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Sample records for supralinear dose dependence

  1. The Dependence of the Dose Response Supralinearity of Peak 5 in TLD-100 on Recombination Temperature

    International Nuclear Information System (INIS)

    Horowitz, Y.S.; Satinger, D.; Oster, L.

    1999-01-01

    Isothermal readout of LiF:Mg,Ti (TLD-700) has recently been used to study the dependence of the supralinearity of peak 5 on recombination temperature. The results were interpreted to be in conflict with earlier results which investigated the effect of readout heating rate on the supralinearity of peak 5 in TLD-100. In this work the two experiments are inspected in greater detail. It is illustrated that the isothermal decay data is not in conflict with the heating rate data. However, the heating rate results do apparently indicate a strong transition in the temperature dependence of the relative strengths of the recombination and competitive cross sections at approximately 235 deg. C, which requires further study and analysis. (author)

  2. Energy dependence of the supralinearity (f(D)max) of peaks 7 and 8 in the high temperature thermoluminescence of LiF:Mg,Ti (TLD-100) : Interpretation using the Unified Interaction Model

    International Nuclear Information System (INIS)

    Datz, H.; Horowitz, Y.S.; Epstein, L.; Oster, L.; Livingstone, J.; Horowitz, A.; Kol, M.; Margaliot, M.

    2011-01-01

    It is demonstrated that the supralinearity of the dose response of glow peaks 7, 8 in the glow curve of LiF:Mg,Ti (TLD-100) are very strongly dependent on photon/electron energy. Previously published data on f(D) max at photon energies of 1.25 MeV, 100 keV and 8.1 keV effective energy coupled with new data at ∼ 540 keV using 90 Sr/ 90 Y beta rays reveals that the maximum supralinearity f(D) max decreases from values of ∼200 and ∼30 at 1.25 MeV, through intermediate values at 540 keV and 100 keV, to values of ∼ 30 and ∼3 at 8.1 keV effective energy. The normalized dose response f(D) for all energies is modeled using the Unified Interaction Model and the dependence of f(D) max on energy is interpreted as arising from strong dependence of the relative intensity of localized recombination on particle energy (ionization density).

  3. measurement of the supralinearity of 7LiF thermoluminescent dosimeters

    International Nuclear Information System (INIS)

    Hancock, I.B.

    1978-04-01

    A study has been made of the supralinearity of the 7 LiF thermoluminesecent dosimeter (T.L.D.) used in the UKAEA personnel criticality dosimeter by exposure to a 60 Co source. the response of the T.L.D. was linear up to approximately 450 rad, above which it became increasingly supralinear, over-reading by about 50% at 2000 rad. The results have been used to produce a correction graph, as a function of apparent dose up to 3500 rad, for routine use in nuclear accident dosimetry. (author)

  4. Supralinearity and particle discrimination in nuclear emulsion

    International Nuclear Information System (INIS)

    Katz, R.; Larsson, L.; Pinkerton, F.E.; Benton, E.V.

    1977-01-01

    Nuclear emulsions may be desensitized in manufacture and/or may be so processed as to discriminate against small latent image sites; to yield supralinear sensitometric response after x-irradiation; and to discriminate against lightly ionizing radiations in favor of heavily ionizing particles. In a circumstance where one electron passing through an emulsion grain is unlikely to generate a latent image sufficiently large to yield a visible grain after development, some larger number of electrons is required, resulting in 'many-hit' statistics, supralinearity, and particle discrimination: for lightly ionizing particles are not likely to generate more than one delta-ray (secondary electron) in their passage through or near a grain. Since these properties are analogous to the response of many biological cells to ionizing radiations, such emulsion-developer combinations have the potential to mimic the response of biological systems to particulate radiations of different charge and speed. (author)

  5. Supralinear detectors in neutron dosimetry

    International Nuclear Information System (INIS)

    Larsson, L.; Roth, R.A.; Katz, R.

    1977-01-01

    Dose-response curves for nuclear emulsions exposed to x-rays and neutrons are presented and discussed. Ilford K.5 plates were used to mimic an initial slope model of biological cell survival curves, and Ilford K-2.5 plates were used to mimic the multi-target survival model after gamma-ray irradiation. The plates were exposed to x-rays from a Torrex-150 x-ray unit and fission neutrons at the 18 kW Triga Mark I reactor. Representative calculations for the response of model detectors to 14 MeV neutrons were made for comparison with experimental findings. Results are presented and discussed

  6. Supralinear photoconductivity of copper doped semi-insulating gallium arsenide

    Energy Technology Data Exchange (ETDEWEB)

    Schoenbach, K.H.; Joshi, R.P.; Peterkin, F. [Physical Electronics Research Institute, Old Dominion University, Norfolk, Virginia 23529 (United States); Druce, R.L. [Lawrence Livermore National Laboratory, Livermore, California 94550 (United States)

    1995-05-15

    We report on the intensity dependent supralinear photoconductivity in GaAs:Si:Cu material. The results of our measurements show that the effective carrier lifetime can change over two orders of magnitude with variations in the intensity of the optical excitation. A threshold intensity level has been observed and can be related to the occupancy of the deep copper level. Numerical simulations have also been carried out to analyze the trapping dynamics. The intensity dependent lifetimes obtained from the simulations match the experimental data very well. Finally, based on the nonlinear intensity dependence of the effective lifetimes, a possible low-energy phototransistor application for the GaAs:Cu material system is presented. {copyright} {ital 1995} {ital American} {ital Institute} {ital of} {ital Physics}.

  7. Supralinear photoconductivity of copper doped semi-insulating gallium arsenide

    Science.gov (United States)

    Schoenbach, K. H.; Joshi, R. P.; Peterkin, F.; Druce, R. L.

    1995-05-01

    The high gain effect was shown to be a threshold effect and was dependent on the photoactivation energy level. For the studied material, laser energy densities in the order of 10 mJ cm(sup - 2) for a laser pulse duration of 200 ps were needed to switch into the high gain mode. The observed supralinear behavior of the peak photoconductivity and the charge carrier lifetime can be accounted by the shifts in quasi Fermi levels and the occupancy of copper states within the forbidden gap. Numerical simulations were also presented that yielded quantitative values for the trapping cross sections and recombination center densities. From the perspective of applications, the GaAs:Si:Cu material had great potential for high-power repetitive switching and photodetection.

  8. Angular dependence of shallow dose

    International Nuclear Information System (INIS)

    Alvarez, J.L.

    1986-01-01

    The theoretical response of a detector is discussed and compared to measurements of shallow dose with tissue and phantom response detectors. A definite energy dependent angular response of dose and measurement was observed which could not be explained by simple trigonometric arguments. The response is back scatter dependent and must be considered in detector design and dose measurements. It is not possible for standard detectors to follow this response

  9. Additive effects on the energy barrier for synaptic vesicle fusion cause supralinear effects on the vesicle fusion rate

    DEFF Research Database (Denmark)

    Schotten, Sebastiaan; Meijer, Marieke; Walter, Alexander Matthias

    2015-01-01

    supralinear effects on the fusion rate. To test this prediction experimentally, we developed a method to assess the number of releasable vesicles, rate constants for vesicle priming, unpriming, and fusion, and the activation energy for fusion by fitting a vesicle state model to synaptic responses induced......-linear effects of genetic/pharmacological perturbations on synaptic transmission and a novel interpretation of the cooperative nature of Ca2+-dependent release....

  10. Thermoluminescence dose response of quartz as a function of irradiation temperature

    International Nuclear Information System (INIS)

    Kitis, G.; Kaldoudi, E.; Charalambous, S.

    1990-01-01

    The thermoluminescence (TL) response of pure Norwegian quartz as a function of irradiation temperature (T irr ) and dose has been investigated. The TL response of the (150-230 o C) and (230-350 o C) glow curve intervals shows a strong dependence on T irr between 77 and 373 K in the dose range from 54 to 8.4 x 10 4 Gy. Both glow curve intervals also show temperature dependent dose response properties. The 150-230 o C interval is supralinear from the lowest dose (54 Gy). Its maximum supralinearity factor appears at T irr = 293 K. The 230-350 o C interval shows sublinear behaviour below T irr = + 193 K, while at T irr ≥ 273 K it shows the well known dose response curves. Its maximum supralinearity factor appears at T irr = 323 K. The linear response is extended up to 460 Gy at T irr = 273 K and falls to 80 Gy at T irr = 373 K. (author)

  11. Changes in optically stimulated luminescent dosimeter (OSLD) dosimetric characteristics with accumulated dose

    International Nuclear Information System (INIS)

    Jursinic, Paul A.

    2010-01-01

    Purpose: A new type of in vivo dosimeter, an optically stimulated luminescent dosimeter (OSLD), has now become commercially available for clinical use. The OSLD is a plastic disk infused with aluminum oxide doped with carbon (Al 2 O 3 :C). Crystals of Al 2 O 3 :C, when exposed to ionizing radiation, store energy that is released as luminescence (420 nm) when the OSLD is illuminated with stimulation light (540 nm). The intensity of the luminescence depends on the dose absorbed by the OSLD and the intensity of the stimulation light. The effects of accumulated dose on OSLD response were investigated. Methods: The OSLDs used in this work were nanodot dosimeters, which were read with a MicroStar reader (Landauer, Inc., Glenwood, IL). Dose to the OSLDs was delivered by 6 MV x rays and gamma rays from Co-60 and Ir-192. The signal on the OSLDs after irradiation is removed by optical annealing with a 150 W tungsten-halogen lamp or a 14 W compact fluorescent lamp was investigated. Results: It was found that OSLD response to dose was supralinear and this response was altered with the amount of accumulated dose to the OSLD. The OSLD response can be modeled by a quadratic and an exponential equation. For accumulated doses up to 60 Gy, the OSLD sensitivity (counts/dose) decreases and the extent of supralinear increases. Above 60 Gy of accumulated dose the sensitivity increases and the extent of supralinearity decreases or reaches a plateau, depending on how the OSLDs were optically annealed. With preirradiation of OSLDs with greater than 1 kGy, it is found that the sensitivity reaches a plateau 2.5 folds greater than that of an OSLD with no accumulated dose and the supralinearity disappears. A regeneration of the luminescence signal in the dark after full optical annealing occurs with a half time of about two days. The extent of this regeneration signal depends on the amount of accumulated dose. Conclusions: For in vivo dosimetric measurements, a precision of ±0.5% can be

  12. Dose-rate dependence of thermoluminescence response

    International Nuclear Information System (INIS)

    McKeever, S.W.S.; Chen, R.; Groom, P.J.; Durrani, S.A.

    1980-01-01

    The previously observed dose-rate effect of thermoluminescence in quartz at high dose-rates is given at theoretical formulation. Computer calculations simulating the experimental conditions yield similar results to the experimental ones. (orig.)

  13. Consideration of the volume dependence of tolerance doses

    International Nuclear Information System (INIS)

    Gremmel, H.; Wendhausen, H.

    1977-01-01

    A general formula for consideration of the dependence of tolerance doses upon volume is obtained by mathematical evaluation of known skin tolerance doses. The validity for different organs is verified using available data of literature. It is recommended to introduce the volume dependence into the Ellis-formula for tolerance doses. (orig.) [de

  14. Theory of thermoluminescence gamma dose response: The unified interaction model

    International Nuclear Information System (INIS)

    Horowitz, Y.S.

    2001-01-01

    We describe the development of a comprehensive theory of thermoluminescence (TL) dose response, the unified interaction model (UNIM). The UNIM is based on both radiation absorption stage and recombination stage mechanisms and can describe dose response for heavy charged particles (in the framework of the extended track interaction model - ETIM) as well as for isotropically ionising gamma rays and electrons (in the framework of the TC/LC geminate recombination model) in a unified and self-consistent conceptual and mathematical formalism. A theory of optical absorption dose response is also incorporated in the UNIM to describe the radiation absorption stage. The UNIM is applied to the dose response supralinearity characteristics of LiF:Mg,Ti and is especially and uniquely successful in explaining the ionisation density dependence of the supralinearity of composite peak 5 in TLD-100. The UNIM is demonstrated to be capable of explaining either qualitatively or quantitatively all of the major features of TL dose response with many of the variable parameters of the model strongly constrained by ancilliary optical absorption and sensitisation measurements

  15. Page 1 ~'----------------------------- Dose-dependent effects ...

    African Journals Online (AJOL)

    Abstract We cOInpared the serwn levels of oestrogen and progesterone and the endoInetrial Inorphology of. nOrInal pregnant rats at 5,5 days' gestation ~th those of pregnant rats given either low (10 IU) or high (20 IU) doses of two gonadotrophins: follicle-. stiInulating hOrInone (FSH) and hwnan chorionic gonadotrophin ...

  16. Dose dependence on stochastic radiobiological effect in radiation risk estimation

    International Nuclear Information System (INIS)

    Komochkov, M.M.

    1999-01-01

    The analysis of the results in dose -- effect relationship observation has been carried out on the cell and organism levels, with the aim to obtain more precise data on the risk coefficients at low doses. The results are represented by two contrasting groups of dose dependence on effect: a downwards concave and a J-shaped curve. Both types of dependence are described by the equation solutions of an assumed unified protective mechanism, which comprises two components: constitutive and adaptive or inducible ones. The latest data analysis of the downwards concave dependence curves shows a considerable underestimation of radiation risk in all types of cancer, except leukemia, for a number of critical groups in a population, at low doses comparing to the ICRP recommendations. With the dose increase, the decrease of the effect value per dose unit is observed. It may be possibly related to the switching of the activity of the adaptive protective mechanism, with some threshold dose values being exceeded

  17. Simulation of the Nonlinear Dose Dependence of Stabilized Point Defects

    International Nuclear Information System (INIS)

    Chen, R; Pagonis, V; Lawless, J L

    2010-01-01

    The dose dependence of the concentration of point defects in alkali-halides as well as other crystals, as exhibited by the dependence of the thermoluminescence (TL), optical absorption and ESR on the dose of non-ionizing UV excitation is studied using numerical simulation. The relevant set of coupled rate equations are first written and plausible sets of trapping parameters are chosen. Instead of using simplifying assumptions previously used for reaching conclusions concerning this dose behavior, exact numerical solutions have now been reached. Depending on the parameters chosen, different dose dependencies are seen. In some cases, linear dose dependence is reached in a broad range. Sublinear dose dependence, close to a D 1/2 dependence when D is the dose of excitation can be reached when retrapping is stronger than trapping in other traps stabilizing the defects. When strong competition between stabilizing traps takes place, an initial linear range is observed followed by strong superlinearity and an approach to saturation. All these behaviors have been observed experimentally in TL measurements as well as ESR and optical absorption in different materials. Similarities and dissimilarities to linear and non-linear dose dependencies obtained experimentally and by simulations when ionizing irradiation is used for excitation are discussed.

  18. Dependence of sputtering coefficient on ion dose

    International Nuclear Information System (INIS)

    Colligon, J.S.; Patel, M.H.

    1977-01-01

    The sputtering coefficient of polycrystalline gold bombarded by 10-40 keV Ar + ions had been measured as a function of total ion dose and shown to exhibit oscillations in magnitude between 30 and 100%. Possible experimental errors which would give rise to such an oscillation have been considered, but it is apparent that these factors are unable to explain the measurements. It is proposed that a change in the Sublimation Energy associated with either bulk damage or formation of surface topographical features arising during ion bombardment may be responsible for the observed variations in sputtering coefficient. (author)

  19. Investigation of the dose rate dependency of the PAGAT gel dosimeter at low dose rates

    International Nuclear Information System (INIS)

    Zehtabian, M.; Faghihi, R.; Zahmatkesh, M.H.; Meigooni, A.S.; Mosleh-Shirazi, M.A.; Mehdizadeh, S.; Sina, S.; Bagheri, S.

    2012-01-01

    Medical physicists need dosimeters such as gel dosimeters capable of determining three-dimensional dose distributions with high spatial resolution. To date, in combination with magnetic resonance imaging (MRI), polyacrylamide gel (PAG) polymers are the most promising gel dosimetry systems. The purpose of this work was to investigate the dose rate dependency of the PAGAT gel dosimeter at low dose rates. The gel dosimeter was used for measurement of the dose distribution around a Cs-137 source from a brachytherapy LDR source to have a range of dose rates from 0.97 Gy h −1 to 0.06 Gy h −1 . After irradiation of the PAGAT gel, it was observed that the dose measured by gel dosimetry was almost the same at different distances (different dose rates) from the source, although the points nearer the source had been expected to receive greater doses. Therefore, it was suspected that the PAGAT gel is dose rate dependent at low dose rates. To test this further, three other sets of measurements were performed by placing vials containing gel at different distances from a Cs-137 source. In the first two measurements, several plastic vials were exposed to equal doses at different dose rates. An ionization chamber was used to measure the dose rate at each distance. In addition, three TLD chips were simultaneously irradiated in order to verify the dose to each vial. In the third measurement, to test the oxygen diffusion through plastic vials, the experiment was repeated again using plastic vials in a nitrogen box and glass vials. The study indicates that oxygen diffusion through plastic vials for dose rates lower than 2 Gy h −1 would affect the gel dosimeter response and it is suggested that the plastic vials or (phantoms) in an oxygen free environment or glass vials should be used for the dosimetry of low dose rate sources using PAGAT gel to avoid oxygen diffusion through the vials.

  20. Dose dependence of complication rates in cervix cancer radiotherapy

    International Nuclear Information System (INIS)

    Orton, C.G.; Wolf-Rosenblum, S.

    1986-01-01

    The population selected for this study was a group of 410 Stage IIB and III squamous cell Ca cervix patients treated at the Radiumhemmet between the years 1958-1966. A total of 48 of these patients developed moderate-to-severe rectal and/or bladder complications. Of these, 33 were evaluable with respect to dose-dependence of complications, that is, complete intracavitary dose measurements and external beam dose calculations, no chemotherapy or electrocautery, and complete clinical radiotherapy records. A group of 57 randomly selected uninjured patients were used as controls. Results show good correlation between dose, expressed in TDF units, and complication rates for both rectal and bladder injuries. Severity of rectal injury was observed to increase with increase in dose, although no such correlation was observed for bladder injuries. Mean delays in the expression of symptoms of injury were 10 months for the rectum and 22 months for the bladder

  1. Dose dependence of complication rates in cervix cancer radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Orton, C.G.; Wolf-Rosenblum, S.

    1986-01-01

    The population selected for this study was a group of 410 Stage IIB and III squamous cell Ca cervix patients treated at the Radiumhemmet between the years 1958-1966. A total of 48 of these patients developed moderate-to-severe rectal and/or bladder complications. Of these, 33 were evaluable with respect to dose-dependence of complications, that is, complete intracavitary dose measurements and external beam dose calculations, no chemotherapy or electrocautery, and complete clinical radiotherapy records. A group of 57 randomly selected uninjured patients were used as controls. Results show good correlation between dose, expressed in TDF units, and complication rates for both rectal and bladder injuries. Severity of rectal injury was observed to increase with increase in dose, although no such correlation was observed for bladder injuries. Mean delays in the expression of symptoms of injury were 10 months for the rectum and 22 months for the bladder.

  2. Dose- and time-dependent pharmacokinetics of apigenin trimethyl ether.

    Science.gov (United States)

    Elhennawy, Mai Gamal; Lin, Hai-Shu

    2018-06-15

    Apigenin trimethyl ether (5,7,4'-trimethoxyflavone, ATE), one of the key polymethoxyflavones present in black ginger (rhizome of Kaempferia parviflora) possesses various health-promoting activities. To optimize its medicinal application, the pharmacokinetics of ATE was assessed in Sprague-Dawley rats with emphases to identify the impacts from dose and repeated dosing on its major pharmacokinetic parameters. Plasma ATE levels were monitored by liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Upon single intravenous administration (2 mg/kg), plasma levels of ATE declined through an apparent first-order process while dose-escalation to 4 and 8 mg/kg led to its non-linear disposition, which could be described by the Michaelis-Menten model. Similarly, dose-dependent oral pharmacokinetics was confirmed and when the dose was escalated from 5 to 15 and 45 mg/kg, much longer mean residence time (MRT 0→last ), higher dose-normalized maximal plasma concentration (C max /Dose) and exposure (AUC/Dose) were observed at 15 and/or 45 mg/kg. One-week daily oral administration of ATE at 15 mg/kg caused its accelerated elimination and the plasma exposure (AUC) after intravenous (2 mg/kg) and oral administration (15 mg/kg) dropped ~40 and 60%, respectively. As ATE displayed both dose- and time-dependent pharmacokinetics, caution is needed in the medicinal applications of ATE and/or black ginger. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Supralinear response and efficiency of LiF:Mg,Ti to 0.7, 1.5 and 3 MeV protons

    International Nuclear Information System (INIS)

    Gamboa-deBuen, I.; Aviles, P.; Rodriguez-Villafuerte, M.; Buenfil, A.E.; Ruiz-Trejo, C.; Brandan, M.E.

    2001-01-01

    The thermoluminescent (TL) response, supralinearity function, and relative efficiency with respect to 60 Co γ-rays, of TLD-100 exposed to 0.7, 1.5 and 3 MeV protons have been measured. The TL response of the glow curve peaks using two different deconvolutions, separating in either 7 (3-9) or 9 peaks (3-10 and peaks 6a and 6b), was investigated. Results for the supralinearity function of peaks 5 and 7-9 and the relative response of peaks 5 and 7 are insensitive to the chosen deconvolution scheme. At all energies we observe that peak 5 is slightly supralinear and that supralinearity increases as a function of the peak temperature. The relative efficiencies, measured for the total TL signal (area under the glow curve) and peaks 5 and 7, decrease with the proton energy having values of 0.33, 0.46 and 0.70 (total TL signal), 0.22, 0.32 and 0.53 (peak 5) and 1.4, 2.6 and 3.6 (peak 7) at 0.7, 1.5 and 3 MeV, respectively. These data agree with the systematics reported in the literature. The measurements of the supralinearity function are compared with Monte Carlo track interaction model calculations. The analysis suggests that the model ion track effective radius and the saturation radius are independent of the incident ion energy

  4. Temperature dependence of dose rate laser simulation adequacy

    International Nuclear Information System (INIS)

    Skorobogatov, P.K.; Nikiforov, A.Y.; Demidov, A.A.

    1999-01-01

    2-D numerical modeling was carried out to analyze the temperature dependence of dose rate laser simulation adequacy in application to p-n junction ionising current. Experimental validation was performed using test structure in the temperature range of 0 to 100 deg.C. (authors)

  5. Age-dependent dose coefficients for tritium in Asian populations

    International Nuclear Information System (INIS)

    Trivedi, A.

    1999-10-01

    The International Commission on Radiological Protection (ICRP) Publications 56 (1989) and 67 (1993) have prescribed the biokinetic models and age-dependent dose coefficients for tritiated water and organically bound tritium. The dose coefficients are computed from values selected to specify the anatomical, morphological and physiological characteristics of a three-month-old, one-year-old, five-year-old, 10-year-old, 15-year-old and adult (Reference Man) Caucasian living in North America and Western Europe. However, values for Reference Man and other age groups are not directly applicable to Asians, because of differences in race, custom, dietary habits and climatic conditions. An Asian Man model, including five age groups, has been proposed by Tanaka and Kawamura (1996, 1998) for use in internal dosimetry. The basic concept of the ICRP Reference Man and the system describing body composition in ICRP Publication 23 (1975) were used. Reference values for Asians were given for the body weight and height, the mass of soft tissue, the mass of body water and the daily fluid balance, and are used to compute the dose coefficients for tritium. The age-dependent dose coefficients for Asians for tritiated water intakes are smaller by 20 to 30% of the currently prescribed values (Trivedi, 1998). The reduction in the dose coefficient values is caused by the increased daily fluid balance among Asians. The dose coefficient for tritiated water is 1.4 x 10 -11 Sv Bq -1 for Asian Man compared to 2.0 x 10 -11 Sv Bq -1 for Reference Man. The dose coefficients for organically bound tritium are only marginally different from those of the ICRP values. The dose coefficient for organically bound tritium for Asian Man is 4.0 x 10 -11 Sv Bq -11 compared to 4.6 x 10 -11 Sv Bq -1 for Reference Man. (author)

  6. Age-dependent dose coefficients for tritium in Asian populations

    Energy Technology Data Exchange (ETDEWEB)

    Trivedi, A

    1999-10-01

    The International Commission on Radiological Protection (ICRP) Publications 56 (1989) and 67 (1993) have prescribed the biokinetic models and age-dependent dose coefficients for tritiated water and organically bound tritium. The dose coefficients are computed from values selected to specify the anatomical, morphological and physiological characteristics of a three-month-old, one-year-old, five-year-old, 10-year-old, 15-year-old and adult (Reference Man) Caucasian living in North America and Western Europe. However, values for Reference Man and other age groups are not directly applicable to Asians, because of differences in race, custom, dietary habits and climatic conditions. An Asian Man model, including five age groups, has been proposed by Tanaka and Kawamura (1996, 1998) for use in internal dosimetry. The basic concept of the ICRP Reference Man and the system describing body composition in ICRP Publication 23 (1975) were used. Reference values for Asians were given for the body weight and height, the mass of soft tissue, the mass of body water and the daily fluid balance, and are used to compute the dose coefficients for tritium. The age-dependent dose coefficients for Asians for tritiated water intakes are smaller by 20 to 30% of the currently prescribed values (Trivedi, 1998). The reduction in the dose coefficient values is caused by the increased daily fluid balance among Asians. The dose coefficient for tritiated water is 1.4 x 10{sup -11} Sv Bq{sup -1} for Asian Man compared to 2.0 x 10{sup -11} Sv Bq{sup -1} for Reference Man. The dose coefficients for organically bound tritium are only marginally different from those of the ICRP values. The dose coefficient for organically bound tritium for Asian Man is 4.0 x 10{sup -11} Sv Bq{sup -11} compared to 4.6 x 10{sup -11} Sv Bq{sup -1} for Reference Man. (author)

  7. Dose-dependent transitions in mechanisms of toxicity: case studies

    International Nuclear Information System (INIS)

    Slikker, William; Andersen, Melvin E.; Bogdanffy, Matthew S.; Bus, James S.; Cohen, Steven D.; Conolly, Rory B.; David, Raymond M.; Doerrer, Nancy G.; Dorman, David C.; Gaylor, David W.; Hattis, Dale; Rogers, John M.; Setzer, R. Woodrow; Swenberg, James A.; Wallace, Kendall

    2004-01-01

    Experience with dose response and mechanisms of toxicity has shown that multiple mechanisms may exist for a single agent along the continuum of the full dose-response curve. It is highly likely that critical, limiting steps in any given mechanistic pathway may become overwhelmed with increasing exposures, signaling the emergence of new modalities of toxic tissue injury at these higher doses. Therefore, dose-dependent transitions in principal mechanisms of toxicity may occur, and could have significant impact on the interpretation of reference data sets for risk assessment. To illustrate the existence of dose-dependent transitions in mechanisms of toxicity, a group of academic, government, and industry scientists, formed under the leadership of the ILSI Health and Environmental Sciences Institute (HESI), developed a series of case studies. These case studies included acetaminophen, butadiene, ethylene glycol, formaldehyde, manganese, methylene chloride, peroxisome proliferator-activated receptor (PPAR), progesterone/hydroxyflutamide, propylene oxide, vinyl acetate, vinyl chloride, vinylidene chloride, and zinc. The case studies formed the basis for technical discourse at two scientific workshops in 2003

  8. The dependence of radiation response on the dose per fraction

    International Nuclear Information System (INIS)

    Joiner, M.C.

    1989-01-01

    The linear-quadratic (LQ) model explains the dependence of total dose in a fractionated course on the dose per fraction, in a very wide range of tumour and normal tissue studies, providing the dose per fraction remains above 2 Gy. In the range 2-1 Gy per fraction, some experimental studies show less increase in total dose than predicted by LQ; a probable explanation is incomplete repair between fractions given 2 seen between 1 and 0.1 Gy per fraction. This cannot be explained by incomplete repair; a modified LQ model where α decreases sharply with increasing dose per fraction in the range 0-1 Gy fits these data. The basic LQ model describes data from neutron fractionation studies, so the relationship between relative biological effectiveness (RBE) and X-ray dose per fraction can be expressed in terms of LQ parameters and fitted directly to RBE data. Results from different experiments, different assays and both top-up and full-course fractionation techniques, can all be included in one analysis. (author)

  9. Dose rate and SDD dependence of commercially available diode detectors

    International Nuclear Information System (INIS)

    Saini, Amarjit S.; Zhu, Timothy C.

    2004-01-01

    The dose-rate dependence of commercially available diode detectors was measured under both high instantaneous dose-rate (pulsed) and low dose rate (continuous, Co-60) radiation. The dose-rate dependence was measured in an acrylic miniphantom at a 5-cm depth in a 10x10 cm 2 collimator setting, by varying source-to-detector distance (SDD) between at least 80 and 200 cm. The ratio of a normalized diode reading to a normalized ion chamber reading (both at SDD=100 cm) was used to determine diode sensitivity ratio for pulsed and continuous radiation at different SDD. The inverse of the diode sensitivity ratio is defined as the SDD correction factor (SDD CF). The diode sensitivity ratio increased with increasing instantaneous dose rate (or decreasing SDD). The ratio of diode sensitivity, normalized to 4000 cGy/s, varied between 0.988 (1490 cGy/s)-1.023 (38 900 cGy/s) for unirradiated n-type Isorad Gold, 0.981 (1460 cGy/s)-1.026 (39 060 cGy/s) for unirradiated QED Red (n type), 0.972 (1490 cGy/s)-1.068 (38 900 cGy/s) for preirradiated Isorad Red (n type), 0.985 (1490 cGy/s)-1.012 (38 990 cGy/s) for n-type Pt-doped Isorad-3 Gold, 0.995 (1450 cGy/s)-1.020 (21 870 cGy/s) for n-type Veridose Green, 0.978 (1450 cGy/s)-1.066 (21 870 cGy/s) for preirradiated Isorad-p Red, 0.994 (1540 cGy/s)-1.028 (17 870 cGy/s) for p-type preirradiated QED, 0.998 (1450 cGy/s)-1.003 (21 870 cGy/s) for the p-type preirradiated Scanditronix EDP20 3G , and 0.998 (1490 cGy/s)-1.015 (38 880 cGy/s) for Scanditronix EDP10 3G diodes. The p-type diodes do not always show less dose-rate dependence than the n-type diodes. Preirradiation does not always reduce diode dose-rate dependence. A comparison between the SDD dependence measured at the surface of a full scatter phantom and that in a miniphantom was made. Using a direct adjustment of radiation pulse height, we concluded that the SDD dependence of diode sensitivity can be explained by the instantaneous dose-rate dependence if sufficient buildup is

  10. The dose dependency of the over-dispersion of quartz OSL single grain dose distributions

    International Nuclear Information System (INIS)

    Thomsen, Kristina J.; Murray, Andrew; Jain, Mayank

    2012-01-01

    The use of single grain quartz OSL dating has become widespread over the past decade, particularly with application to samples likely to have been incompletely bleached before burial. By reducing the aliquot size to a single grain the probability of identifying the grain population most likely to have been well-bleached at deposition is maximised and thus the accuracy with which the equivalent dose can be determined is – at least in principle – improved. However, analysis of single grain dose distributions requires knowledge of the dispersion of the well-bleached part of the dose distribution. This can be estimated by measurement of a suitable analogue, e.g. a well-bleached aeolian sample, but this requires such an analogue to be available, and in addition the assumptions that the sample is in fact a) well-bleached, and b) has a similar dose rate heterogeneity to the fossil deposit. Finally, it is an implicit assumption in such analysis that any over-dispersion is not significantly dose dependent. In this study we have undertaken laboratory investigations of the dose dependency of over-dispersion using a well-bleached modern sample with an average measured dose of 36 ± 3 mGy. This sample was prepared as heated (750 °C for 1 h), bleached and untreated portions which were then given uniform gamma doses ranging from 100 mGy to 208 Gy. We show that for these samples the relative laboratory over-dispersion is not constant as a function of dose and that the over-dispersion is smaller in heated samples. We also show that the dim grains in the distributions have a greater over-dispersion than the bright grains, implying that insensitive samples will have greater values of over-dispersion than sensitive samples.

  11. Energy dependence of contrast-detail-dose and object-detectability-dose curves for CT scanners

    International Nuclear Information System (INIS)

    Wagner, L.K.; Cohen, G.

    1982-01-01

    The energy dependence of contrast-detail-dose (CdD) and object-detectability-dose (OdD) curves for computed tomographic scanners is investigated. The effects of changes in beam energy on perceptibility are shown to be due to changes in signal-to-noise ratio resulting from changes in contrast and photon statistics. Energy-dependence analysis of OdD curves is shown to depend on the atomic composition of the phantom used to generate the curves, while such an analysis of CdD curves is independent of the atomic composition of the phantom. It is also shown that any OdD curve can be generated from CdD curves and that use of this fact rectifies any potential energy-dependent interpretation of CdD curves

  12. Time-Dependent Neutron and Photon Dose-Field Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Wooten, Hasani Omar [Georgia Inst. of Technology, Atlanta, GA (United States)

    2005-08-01

    A unique tool is developed that allows the user to model physical representations of complicated glovebox facilities in two dimensions and determine neutral-particle flux and ambient dose-equivalent fields throughout that geometry. The Pandemonium code, originally designed to determine flux and dose-rates only, is improved to include realistic glovebox geometries, time-dependent source and detector positions, time-dependent shielding thickness calculations, time-integrated doses, a representative criticality accident scenario based on time-dependent reactor kinetics, and more rigorous photon treatment. A primary benefit of this work has been an extensive analysis and improvement of the photon model that is not limited to the application described in this thesis. The photon model has been extended in energy range to 10 MeV to include photons from fission and new photon buildup factors have been included that account for the effects of photon buildup at slant-path thicknesses as a function of angle, where the mean free path thickness has been preserved. The overall system of codes is user-friendly and it is directly applicable to facilities such as the plutonium facility at Los Alamos National Laboratory, where high-intensity neutron and photon emitters are regularly used. The codes may be used to determine a priori doses for given work scenarios in an effort to supply dose information to process models which will in turn assist decision makers on ensuring as low as reasonably achievable (ALARA) compliance. In addition, coupling the computational results of these tools with the process model visualization tools will help to increase worker safety and radiological safety awareness.

  13. Dose-dependent transitions in mechanisms of toxicity

    International Nuclear Information System (INIS)

    Slikker, William; Andersen, Melvin E.; Bogdanffy, Matthew S.; Bus, James S.; Cohen, Steven D.; Conolly, Rory B.; David, Raymond M.; Doerrer, Nancy G.; Dorman, David C.; Gaylor, David W.; Hattis, Dale; Rogers, John M.; Woodrow Setzer, R.; Swenberg, James A.; Wallace, Kendall

    2004-01-01

    Scientists and decision makers from all sectors agree that risk assessments should be based on the best available science. Several years ago, the Health and Environmental Sciences Institute (HESI), a global branch of the International Life Sciences Institute (ILSI), identified the need for better scientific understanding of dose-dependent transitions in mechanisms of toxicity as one avenue by which the best and latest science can be integrated into the decision making process. In July 2001, the HESI Project Committee on Dose-Dependent Transitions in Mechanisms of Toxicity established a group of academic, government, and industry scientists to engage in active technical discourse on the issue of dose-dependent transitions in mechanisms of toxicity. Over the next 18 months, case studies were examined. These case studies included acetaminophen, butadiene, ethylene glycol, formaldehyde, manganese, methylene chloride, the peroxisome proliferator-activated receptor, progesterone/hydroxyflutamide, propylene oxide, vinyl acetate, vinyl chloride, vinylidene chloride, and zinc (Slikker, W., Jr., Andersen, M.E., Bogdanffy, M.S., Bus, J.S., Cohen, S.D., Conolly, R.B., David, R.M., Doerrer, N.G., Dorman, D.C., Gaylor, D.W., Hattis, D., Rogers, J.M., Setzer, R.W., Swenberg, J.A., Wallace, K., 2004. Dose-dependent transitions in mechanisms of toxicity: case studies. Toxicol. Appl. Pharmacol. 201(3), 226-294 (this issue)). The HESI Project Committee sponsored two technical workshops in 2003. The first of these workshops took place on February 12-13, 2003, and was co-sponsored by the Agency for Toxic Substances and Disease Registry, the American Chemistry Council, the National Institute of Environmental Health Sciences, the Society of Toxicology, and the U.S. Environmental Protection Agency. Additional support was provided by Health Canada. Invited experts from government, academia, and industry provided scientific perspectives and recommendations at the workshop. The purpose of

  14. Two separate dose-dependent effects of paroxetine

    DEFF Research Database (Denmark)

    Nielsen, Anette Green; Pedersen, Rasmus Steen; Nøhr-Jensen, Lene

    2010-01-01

    PURPOSE: To investigate paroxetine's putative dose-dependent impact on pupil reaction and inhibition of the O-demethylation of tramadol. METHODS: Twelve healthy CYP2D6 extensive metabolizers participated in this double-blinded randomized five-way placebo controlled cross-over study; they received...... concentrations of (+/-)-tramadol and (+/-)-O-desmethyltramadol (M1) were determined. RESULTS: With placebo, the median maximum pupil diameter was 6.43 mm (range 5.45-7.75 mm) before tramadol and 6.22 mm (4.35-7.65 mm) after 50 mg of tramadol (P = 0.4935). Paroxetine resulted in a statistically significant, dose......-dependent dilatation of the pupil with a geometric mean difference of 1.17 (95% CI 1.10-1.24) after ingestion of 50 mg paroxetine (P inhibition...

  15. TREATMENT OF STEROID DEPENDENT ASTHMATICS WITH LOW DOSES OF CYCLOSPORINE

    Directory of Open Access Journals (Sweden)

    Stanislav Šuškovič

    2004-01-01

    Full Text Available Background. Asthmatics with glucocorticoid dependent asthma should be treated with systemic steroids. Cyclosporine is in many ways a potent anti-inflammatory drug. Cyclosporine is sometimes very effective in treating asthmatics and could allow us to lower the dose of oral steroid. In some randomized, double blind studies steroid dependent asthmatics were treated 12–36 weeks with cyclosporine in dose 5 mg/kg/day. We tried cyclosporine in steroid dependent asthmatics in shorter course and in lower dose.Methods. 13 steroid dependent asthmatics were in the first four weeks of the study treated by their own drugs (phase 1. Then they were for the next four weeks (phase 2 randomly and in double blind fashion treated with either cyclosporine (mean 1.7 mg/kg/day, SD 0.5, 6 patients – group 1 or by identical placebo (7 patients – group 2. To the patients in the group 2 serum concentration of cyclosporine was measured on the eight day of the study.Results. Morning peak expiratory flow (PEF raised significantly in group 1 (200 L/sec to 247 L/sec or for 23%. Patients in group1 had significantly less episodes of nocturnal asthma (2.2 episodes/night to 1.5 episodes/night or for 32%. In group 2 were not found any changes between first phase and second phase of the study. Steroid consumption did not change in any group. Mean serum concentration of cyclosporine in patients of group1 was 35.7 µg/L. We did not find any adverse effects of cyclosporine or placebo.Conclusions. Cyclosporine could have dangerous side effects, which are dependent on its serum concentration. So it should be administered in the lowest possible dose and for the most possible short period. In our study it was found that it is possible to successfully treat steroid dependent asthmatics with lower daily dose and for shorter time, than was found in other similar studies.

  16. A comparison of the angular dependence of effective dose and effective dose equivalent

    International Nuclear Information System (INIS)

    Sitek, M.A.; Gierga, D.P.; Xu, X.G.

    1996-01-01

    In ICRP (International Commission on Radiological Protection) Publication 60, the set of critical organs and their weighing factors were changed, defining the quantity effective dose, E. This quantity replaced the effective dose equivalent, H E , as defined by ICRP 26. Most notably, the esophagus was added to the list of critical organs. The Monte Carlo neutron/photon transport code MCNP was used to determine the effective dose to sex-specific anthropomorphic phantoms. The phantoms, developed in previous research, were modified to include the esophagus. Monte Carlo simulations were performed for monoenergetic photon beams of energies 0.08 MeV, 0.3 MeV, and 1.0 MeV for various azimuthal and polar angles. Separate organ equivalent doses were determined for male and female phantoms. The resulting organ equivalent doses were calculated from arithmetic mean averages. The angular dependence of effective dose was compared with that of effective dose equivalent reported in previous research. The differences between the two definitions and possible implications to regulatory agencies were summarized

  17. Dose-dependent pharmacokinetics and teratogenic activity of topical retinoids

    International Nuclear Information System (INIS)

    Sharma, R.P.; Willhite, C.C.; Berry, D.L.; Allen, P.V.

    1990-01-01

    Oral retinoid treatment can be teratogenic and topical applications are used to treat acne and smooth wrinkles. A single topical trace (2.5 μg; 191 μCi/kg) or high (1.3 mg; 195 μCi/kg) dose of all-trans-[10, 11- 3 H 2 ] retinoic acid (RA) dissolved in acetone was applied to 4 cm 2 shaved dorsal hamster skin. Peak plasma radioactivity (C max ) occurred at 12 and 36 hr and mean t1/2 values for parent PA absorption were 48 min and 2.8 hr, for trace and high dose, respectively. The dermal RA C max values were only 2% of that after an equivalent oral dose, but plasma AUC after dermal treatment was 63% of the oral value. The mean t1/2 for rapid elimination was shorter for the high (57 min) than for the trace (6.9 hr) dose, but t1/2 values for slow elimination were comparable (t1/2 high = 51.2 hr; t1/2 trace = 36.8 hr). Single topical application of 10-30 mg/kg RA or 5 mg/kg etretinate (Ro 10-9359) to pregnant hamsters (day 8) caused local hyperkeratosis, but failed to induce terata. Similar application of 10-1000 μg/kg arotinoid Ro 13-6298 caused dose-dependent terata, being twice as embryolethal by parenteral as enteric dosing. Skin toxicity and attenuated maternal blood levels limit the amount of retinoids that can reach the embryo

  18. Dose-dependent elimination of 8-methoxypsoralen in the mouse

    International Nuclear Information System (INIS)

    Cheney, P.; Pacula, C.M.; Gerber, N.; Mays, D.C.

    1986-01-01

    8-Methoxypsoralen (8-MOP), a photoactive linear furocoumarin, is effective in the treatment of several diseases, including psoriasis, mycosis fungoides and T-cell leukemia. Recently, a specific extraction procedure for 14 C-8-MOP showed that the elimination of 8-MOP in the rat was dose-dependent. Similar pharmacokinetic studies were undertaken in mice. Purity of 14 C-8-MOP, verified by a four-tube countercurrent distribution using hexane (8 ml) and pH 7.4 phosphate buffer (0.1 M 15 ml) as described by Bush, was >98% and distributed with a partition coefficient of 3.86. Male CD-1 mice were each given an i.p. dose of 10 or 50 mg/kg of 14 C-8-MOP (3.4 μCi/mg) sacrificed at timed intervals, homogenized in 150 ml of 0.1 M phosphate buffer (pH 7.4) and a portion (0.8 ml) of the homogenate used to quantify 8-MOP as described above. The elimination half-life measured in the first 45 min was 7.4 min at 10 mg/kg and 95 min at 50 mg/kg. A similar half-life of 9.2 min was measured in mice given an i.v. dose 10 mg/kg of 8-MOP. Explanations of dose-dependent elimination include enzyme saturation, product inhibition or both. Between 58-80% of the administered radioactivity was recovered in the urine within 24 hr. Nine peaks of radioactivity were observed in the urine by HPLC, two of which coeluted with 5,8-dihydroxypsoralen and 6-(7-hydroxy-8-methoxycoumaryl)-acetic acid

  19. Dose rate effect on the yield of radiation induced response with thermal fading

    International Nuclear Information System (INIS)

    Chernov, V.; Rogalev, B.; Barboza-Flores, M.

    2005-01-01

    A model describing the dependences of the accumulation of thermally unstable radiation induced defects on the dose and dose rate is proposed. The model directly takes into account the track nature of the ionizing radiation represented as accumulation processes of defects in tracks averaged over a crystal volume considering various degrees of overlapping in space and time. The accumulation of the defects in the tracks is phenomenologically described. General expressions are obtained that allows radiation yield simulation of defects involving known creation and transformation processes. The cases considered, of linear accumulation (constant increment of the defects in tracks) and accumulation with saturation (complete saturation of the defects in one track), lead to a set of linear dose dependences with saturation, which are routinely used in luminescence and ESR dating. The accumulation, with increase of sensitivity in regions overlapped by two or more tracks, gave a set of dose dependences, from linear-sublinear-linear-saturation, distinctive of quartz up to linear-supralinear-linear-saturation. It is shown that the effect of the dose rate on dose dependences is determined by a dimensionless parameter a=Pτ/D0, where P is the dose rate, τ is the defect lifetime and D0 is the track dose. At a-bar 1 the dose rate influences basically the accumulation of thermally unstable defects. In the reverse case the dose dependences did not seems to be influenced by the dose rate

  20. The impact of the oxygen scavenger on the dose-rate dependence and dose sensitivity of MAGIC type polymer gels

    Science.gov (United States)

    Khan, Muzafar; Heilemann, Gerd; Kuess, Peter; Georg, Dietmar; Berg, Andreas

    2018-03-01

    Recent developments in radiation therapy aimed at more precise dose delivery along with higher dose gradients (dose painting) and more efficient dose delivery with higher dose rates e.g. flattening filter free (FFF) irradiation. Magnetic-resonance-imaging based polymer gel dosimetry offers 3D information for precise dose delivery techniques. Many of the proposed polymer gels have been reported to exhibit a dose response, measured as relaxation rate ΔR2(D), which is dose rate dependent. A lack of or a reduced dose-rate sensitivity is very important for dosimetric accuracy, especially with regard to the increasing clinical use of FFF irradiation protocols with LINACs at high dose rates. Some commonly used polymer gels are based on Methacrylic-Acid-Gel-Initiated-by-Copper (MAGIC). Here, we report on the dose sensitivity (ΔR2/ΔD) of MAGIC-type gels with different oxygen scavenger concentration for their specific dependence on the applied dose rate in order to improve the dosimetric performance, especially for high dose rates. A preclinical x-ray machine (‘Yxlon’, E  =  200 kV) was used for irradiation to cover a range of dose rates from low \\dot{D} min  =  0.6 Gy min-1 to high \\dot{D} max  =  18 Gy min-1. The dose response was evaluated using R2-imaging of the gel on a human high-field (7T) MR-scanner. The results indicate that all of the investigated dose rates had an impact on the dose response in polymer gel dosimeters, being strongest in the high dose region and less effective for low dose levels. The absolute dose rate dependence \\frac{(Δ R2/Δ D)}{Δ \\dot{D}} of the dose response in MAGIC-type gel is significantly reduced using higher concentrations of oxygen scavenger at the expense of reduced dose sensitivity. For quantitative dose evaluations the relative dose rate dependence of a polymer gel, normalized to its sensitivity is important. Based on this normalized sensitivity the dose rate sensitivity was reduced distinctly

  1. Pharmacogenetic analysis of opioid dependence treatment dose and dropout rate.

    Science.gov (United States)

    Crist, Richard C; Li, James; Doyle, Glenn A; Gilbert, Alex; Dechairo, Bryan M; Berrettini, Wade H

    2018-01-01

    Currently, no pharmacogenetic tests for selecting an opioid-dependence pharmacotherapy have been approved by the US Food and Drug Administration. Determine the effects of variants in 11 genes on dropout rate and dose in patients receiving methadone or buprenorphine/naloxone (ClinicalTrials.gov Identifier: NCT00315341). Variants in six pharmacokinetic genes (CYP1A2, CYP2B6, CYP2C19, CYP2C9, CYP2D6, CYP3A4) and five pharmacodynamic genes (HTR2A, OPRM1, ADRA2A, COMT, SLC6A4) were genotyped in samples from a 24-week, randomized, open-label trial of methadone and buprenorphine/naloxone for the treatment of opioid dependence (n = 764; 68.7% male). Genotypes were then used to determine the metabolism phenotype for each pharmacokinetic gene. Phenotypes or genotypes for each gene were analyzed for association with dropout rate and mean dose. Genotype for 5-HTTLPR in the SLC6A4 gene was nominally associated with dropout rate when the methadone and buprenorphine/naloxone groups were combined. When the most significant variants associated with dropout rate were analyzed using pairwise analyses, SLC6A4 (5-HTTLPR) and COMT (Val158Met; rs4860) had nominally significant associations with dropout rate in methadone patients. None of the genes analyzed in the study was associated with mean dose of methadone or buprenorphine/naloxone. This study suggests that functional polymorphisms related to synaptic dopamine or serotonin levels may predict dropout rates during methadone treatment. Patients with the S/S genotype at 5-HTTLPR in SLC6A4 or the Val/Val genotype at Val158Met in COMT may require additional treatment to improve their chances of completing addiction treatment. Replication in other methadone patient populations will be necessary to ensure the validity of these findings.

  2. Dose energy dependence in proton imaging with thin detector

    Energy Technology Data Exchange (ETDEWEB)

    Denyak, V.V., E-mail: denyak@gmail.com [National Science Centre Kharkov Institute of Physics and Technology, St. Akademicheskaya 1, Kharkov 61108 (Ukraine); Federal University of Technology - Parana, Av. Sete de Setembro 3165, Curitiba 80230-901 (Brazil); Schelin, H.R. [Pele Pequeno Principe Research Institute, Av. Silva Jardim 1632, Curitiba 80250-200 (Brazil); Federal University of Technology - Parana, Av. Sete de Setembro 3165, Curitiba 80230-901 (Brazil); Silva, R.C.L.; Kozuki, C.; Paschuk, S.A.; Milhoretto, E. [Federal University of Technology - Parana, Av. Sete de Setembro 3165, Curitiba 80230-901 (Brazil)

    2012-07-15

    Since the earliest works proposing the use of protons for imaging, the main advantage of protons over X-rays was expected to be a result of the specific property of the proton flux dropping off very steeply at the end of the particle range. This idea was declared but was not checked. In the present work, this assumption was investigated using the Monte Carlo simulation for the case of registration of protons with a thin detector. - Highlights: Black-Right-Pointing-Pointer Principal idea of proton imaging 'to work at the end of the range' was tested. Black-Right-Pointing-Pointer The case of thin detector was investigated. Black-Right-Pointing-Pointer The dose energy dependence was calculated using computer simulation.

  3. Pulse and integral optically stimulated luminescence (OSL). Similarities and dissimilarities to thermoluminescence (TL) dose dependence and dose-rate effects

    International Nuclear Information System (INIS)

    Chen, R.; Leung, P.L.

    2000-01-01

    Optically stimulated luminescence (OSL) and thermoluminescence (Tl) are two possible methods to monitor the absorbed radiation in solid samples, and therefore are utilized for dosimetry. For this application, two properties are desirable, namely, linear dose dependence of the measured quantity and dose-rate independence. For Tl, different kinds of super linear dose dependence have been reported in the literature in different materials, and in some cases, dose-rate dependence has also been found. These have been explained as being the result of competition. In OSL, some recent works reported on super linear dose dependence in annealed samples. In the present work, we explain the possible occurrence of these phenomena in OSL by solving numerically the relevant rate equations governing the process during irradiation, relaxation and read-out (heating or light stimulation). The results show that for short pulse OSL, quadratic dose dependence can be expected when only one trapping state and one kind of recombination center are involved and when the excitation starts with empty traps and centers. With the short pulse OSL, the calculation also reveals a possible dose-rate effect. Under the same circumstances, the area under the OSL curve depends linearly on the dose. The dependence of the whole area under the OSL curve on the dose is shown to be super linear when a disconnected trapping state or radiationless center take part in the process. Also, dose-rate effect can be expected in these cases, although no experimental effect of this sort has been reported so far. In pulse OSL, the analogy is made between the measured intensity and the initial rise range of non-first order Tl, whereas for the total area OSL, there is a nearly full analogy with the dose behavior of the Tl maximum. (Author)

  4. Prednisolone dose-dependently influences inflammation and coagulation during human endotoxemia

    NARCIS (Netherlands)

    de Kruif, Martijn D.; Lemaire, Lucienne C.; Giebelen, Ida A.; van Zoelen, Marieke A. D.; Pater, Jennie M.; van den Pangaart, Petra S.; Groot, Angelique P.; de Vos, Alex F.; Elliott, Peter J.; Meijers, Joost C. M.; Levi, Marcel; van der Poll, Tom

    2007-01-01

    The effects of steroids on the outcome of sepsis are dose dependent. Low doses appear to be beneficial, but high doses do not improve outcome for reasons that are insufficiently understood. The effects of steroids on systemic inflammation as a function of dose have not previously been studied in

  5. Dependence of total dose response of bipolar linear microcircuits on applied dose rate

    International Nuclear Information System (INIS)

    McClure, S.; Will, W.; Perry, G.; Pease, R.L.

    1994-01-01

    The effect of dose rate on the total dose radiation hardness of three commercial bipolar linear microcircuits is investigated. Total dose tests of linear bipolar microcircuits show larger degradation at 0.167 rad/s than at 90 rad/s even after the high dose rate test is followed by a room temperature plus a 100 C anneal. No systematic correlation could be found for degradation at low dose rate versus high dose rate and anneal. Comparison of the low dose rate with the high dose rate anneal data indicates that MIL-STD-883, method 1019.4 is not a worst-case test method when applied to bipolar microcircuits for low dose rate space applications

  6. Dose-dependent high-resolution electron ptychography

    International Nuclear Information System (INIS)

    D'Alfonso, A. J.; Allen, L. J.; Sawada, H.; Kirkland, A. I.

    2016-01-01

    Recent reports of electron ptychography at atomic resolution have ushered in a new era of coherent diffractive imaging in the context of electron microscopy. We report and discuss electron ptychography under variable electron dose conditions, exploring the prospects of an approach which has considerable potential for imaging where low dose is needed

  7. Age-dependent conversion coefficients for organ doses and effective doses for external neutron irradiation

    International Nuclear Information System (INIS)

    Nishizaki, Chihiro; Endo, Akira; Takahashi, Fumiaki

    2006-06-01

    To utilize dose assessment of the public for external neutron irradiation, conversion coefficients of absorbed doses of organs and effective doses were calculated using the numerical simulation technique for six different ages (adult, 15, 10, 5 and 1 years and newborn), which represent the member of the public. Calculations were performed using six age-specific anthropomorphic phantoms and a Monte Carlo radiation transport code for two irradiation geometries, anterior-posterior and rotational geometries, for 20 incident energies from thermal to 20 MeV. Effective doses defined by the 1990 Recommendation of ICRP were calculated from the absorbed doses in 21 organs. The calculated results were tabulated in the form of absorbed doses and effective doses per unit neutron fluence. The calculated conversion coefficients are used for dose assessment of the public around nuclear facilities and accelerator facilities. (author)

  8. Dose dependent disposition of gallium-67 in rats

    International Nuclear Information System (INIS)

    Gautam, S.R.

    1982-01-01

    Radioactive gallium-67 has been employed as a diagnostic and follow-up agent for cancer therapy. Currently gallium nitrate is undergoing Phase I clinical studies. A million fold increase in the concentration of the carrier gallium citrate over the range of carrier-free gallium-67 (pgm) to 1.0 μg caused no significant alteration in the disposition of gallium-67 in rats.Gallium-67 was eliminated from blood with a biological t1/2 of 4.1 days. A linear tissue binding profile was observed for gallium-67 over this concentration range. A multi-compartment pharmacokinetic model was developed in which all the tissues studied were treated as separate compartments. At 1.0 mg dose level, significant alteration in the disposition of gallium-67 was observed in rats, > 95% of the initial radioactivity was characteristic reappearance of the radioactivity in the blood approximately 4 hours after dosing leading to a ''hump'' in the blood concentration-time profiles. Following the 1.0 mg dose low tissue levels were observed, except for the kidneys, which contained about 8% of the administered dose per gram of the tissue one-half hour after dosing. A non-linear tissue binding profile was observed to be associated with gallium at high doses. It was hypothesized that the rapid loss of gallium-67 from the vascular system following the high doses of gallium citrate was due to the accumulation of the drug in the kidneys where it was eventually eliminated via urine. The kidneys thus would act as a temporary storage site for gallium. It was concluded that the dose-related renal toxicity associated with gallium therapy may be attributed to the kidney's role as a temporary storage site following high doses

  9. Dose response on the 110 °C thermoluminescence peak of un-heated, synthetic Merck quartz

    Energy Technology Data Exchange (ETDEWEB)

    Kaya Keleş, Şule, E-mail: sule.kaya@ankara.edu.tr; Meriç, Niyazi; Polymeris, George S.

    2016-07-15

    Studies on 110 °C TL peak have been carried out using natural quartz from different origins and synthetic quartz produced by different suppliers. The interest in quartz is due to its usage in dating and retrospective dosimetry as a main material; both synthetic and natural types of quartz yield the 110 °C TL peak in their glow curve. In most studies to understand the physical mechanism behind the TL system, synthetic quartz samples are used and there are many investigations about dose response, in both low and high radiation dose region. In these studies generally synthetic quartz samples produced by Sawyer Research Products are used and the studies showed that both heated and un-heated synthetic quartz samples have intense supra-linear responses. Supra-linearity was enhanced by applying a pre-irradiation while several models have been developed towards an explanation to these supra-linearity effects. In this study commercially available synthetic Merck quartz was used. Different combinations of optical filters were used to obtain dose response curves upto 266 Gy and the effect of pre-dose to these dose response curves was studied. Un-pre-dosed Merck quartz samples dose supra-linearity index is below 1 independently on the optical filters; so Merck quartz showed linear or sub-linear dose response.

  10. Dose-dependent progressive sunscreens. A new strategy for photoprotection?

    Science.gov (United States)

    Gallardo, Adaya; Teixidó, Jordi; Miralles, Ricardo; Raga, Manuel; Guglietta, Antonio; Marquillas, Francisco; Sallarès, Joan; Nonell, Santi

    2010-04-01

    A new generation of UV filters has been developed that act by limiting the dose of radiation rather than by blocking a fraction of the solar irradiance on the skin surface. Such progressive sunscreens are based on the photochemical transformation of suitable precursors upon exposure to sunlight. Broadband sunscreens are thus generated "on demand", affording protection when, where, and to the extent that it is needed, providing higher protection to more exposed areas, and increasing the UV blocking capacity as the radiation dose increases. Encapsulation in silica particles isolates the precursors and transformation products, further improving the efficacy, safety, and environmental impact of the use of sunscreens.

  11. Dose-dependent effects of exogenous gonadotrophins on the ...

    African Journals Online (AJOL)

    We compared the serwn levels of oestrogen and progesterone and the endometrial morphology of normal pregnant rats at 5,5 days' gestation with those of pregnant rats given either low (10 IU) or high (20 IU) doses of two gonadotrophins: follicle-stimulating hormone (FSH) and hwnan chorionic gonadotrophin (HCG).

  12. Dose and time dependent ototoxicity of aspartame in rats.

    Science.gov (United States)

    Ozturan, Orhan; Dogan, Remzi; Tugrul, Selahattin; Gedik, Ozge; Sjostrand, Alev Pektas; Yildirim, Yavuz Selim

    2017-04-01

    Low-dose administration of Aspartame (Ap) did not produce a significant ototoxic effect at the end of the 6th month. However, duration of the ototoxic effect is shortened and severity of the effect is increased as dose and duration of Ap administration is increased. While Ap toxicity has been studied in short- and long-term studies, its effects on hearing have not been investigated. This study was conducted to evaluate the effects of long-term consumption of Ap administered in various doses on hearing status of rats. The study included 54 female Wistar Albino rats. Ap was given for 6 months to the rats. The groups were assigned according to levels of Ap dosage. DPOAE and ABR tests were utilized for serial hearing evaluations. Serial hearing measurement times were designed as baseline, 1st week, 2nd week, 1st, 2nd, 3rd, and 6th months. While audiological parameters deteriorated with 100 mg/kg/day dose after the 3rd month, ABR thresholds were elevated and DPOAE values were significantly decreased in 500 mg/kg/day and 1000 mg/kg/day applications after the 2nd month. In 2000 mg/kg/day and 4000 mg/kg/day applications, deteriorations in audiological parameters were detected as early as the first and second months; respectively.

  13. Dose-dependent teratogenicity of valproate in mono- and polytherapy

    DEFF Research Database (Denmark)

    Tomson, Torbjörn; Battino, Dina; Bonizzoni, Erminio

    2015-01-01

    OBJECTIVE: To assess the risk of major congenital malformations (MCMs) in association with maternal use of valproic acid (VPA) in monotherapy or adjunctive therapy, and its relationship with dose. METHODS: The analysis was based on prospectively acquired data from EURAP, a registry enrolling women...... treated with antiepileptic drugs (AEDs) in early pregnancy, in which the primary outcome is presence of MCMs at 1 year after birth. Exposure was defined as type and dose of AEDs at time of conception. A comparison was made among 3 exposure types: (1) VPA monotherapy (n = 1,224); (2) VPA combined...... with lamotrigine (LTG) (n = 159); and (3) VPA combined with another AED but not LTG (n = 205). RESULTS: The frequency of MCMs at 1 year after birth was 10.0% for VPA monotherapy, 11.3% for exposures to VPA and LTG, and 11.7% for exposures to VPA + another (non-LTG) AED. Regardless of exposure group, the frequency...

  14. Radiation-induced hypopituitarism is dose-dependent

    International Nuclear Information System (INIS)

    Littley, M.D.; Shalet, S.M.; Beardwell, C.G.; Robinson, E.L.; Sutton, M.L.

    1989-01-01

    Radiation-induced hypopituitarism has been studies prospectively for up to 12 years in 251 adult patients treated for pituitary disease with external radiotherapy, ranging in dose from 20 Gy in eight fractions over 11 days to 45 Gy in 15 fractions over 21 days. Ten further patients were studied 2-4 years after whole-body irradiation for haematological malignancies using 12 Gy in six fractions over 3 days and seven patients were studied 3-11 years after whole-brain radiotherapy for a primary brain tumour (30 Gy, eight fractions, 11 days). Five years after treatment, patients who received 20 Gy had an incidence of TSH deficiency of 9% and in patients treated with 35-37 Gy, 40 Gy and 42-45 Gy, the incidence of TSH deficiency increased significantly with increasing dose. A similar relationship was observed for both ACTH and gonadotrophin deficiencies when the 20 Gy group was compared to patients treated with 35-45 Gy. Growth hormone deficiency was universal by 5 years over the dose range 35-45 Gy. In seven patients who were treated with 30 Gy in eight fractions over 11 days, deficiencies were observed at a similar frequency to the 40 Gy group (15 fractions, 21 days). No evidence of pituitary dysfunction was detected in the ten patients who received 12 Gy (six fractions, 3 days). (author)

  15. Investigation of percentage depth dose and dose rate dependence of PAGAT polymer gel dosimeter for photon beams using MRI technique

    International Nuclear Information System (INIS)

    Azadbakht, B.; Hadad, K.; Zahmatkesh, M. H.

    2010-01-01

    In this work, the investigation of the normoxic Pagan polymer-gel dosimeter percentage depth dose and it's dose rate dependence has been made. Using MRI, the formulation to give the maximum change in the transverse relaxation rate R2 was determined to be 4.5% N,N'-methylene-bis-acrylamide(bis), 4.5% acrylamide, 5% gelatine, 5 m M tetrakis (hydroxymethyl) phosphonium chloride, 0.01 m M hydroquinone and 86% HPLC(Water). Irradiation of vials was performed using photon beams of Co-60 therapy unit and an Elec ta linear accelerator. Gel dosimeters were imaged in a Siemens Symphony 1.5 Tesla clinical MRI scanner using a head coil. Post-manufacture irradiation and post imaging times were both selected to be 1 day. For determining the percentage depth dose of the Pagan gel it was found that at the depth of 21 cm, the percentage depth dose for 1.25 MeV γ-ray photons of 60 Co and for 4,6 and 18 MV x-ray photons of Elec ta linear accelerator, are 48%, 52%, 57.3% and 59.73%, respectively. Thus, in the case of the higher energy photon beams, a higher dose can he delivered. to deep-seated tumors. The dose rate dependence of percentage depth dose was studied for 6 MV x-ray photons with the use of dose rates of 80, 160, 240, 320, 400 and 480 c Gy/min. No trend in polymer-gel dosimeter 1/T 2 dependence was found on the mean dose rate and energy for the photon beams.

  16. The dose dependency of the over-dispersion of quartz OSL single grain dose distributions

    DEFF Research Database (Denmark)

    Thomsen, Kristina Jørkov; Murray, Andrew S.; Jain, Mayank

    2012-01-01

    The use of single grain quartz OSL dating has become widespread over the past decade, particularly with application to samples likely to have been incompletely bleached before burial. By reducing the aliquot size to a single grain the probability of identifying the grain population most likely...... to have been well-bleached at deposition is maximised and thus the accuracy with which the equivalent dose can be determined is – at least in principle – improved. However, analysis of single grain dose distributions requires knowledge of the dispersion of the well-bleached part of the dose distribution....... This can be estimated by measurement of a suitable analogue, e.g. a well-bleached aeolian sample, but this requires such an analogue to be available, and in addition the assumptions that the sample is in fact a) well-bleached, and b) has a similar dose rate heterogeneity to the fossil deposit. Finally...

  17. Health Benefits from Nature Experiences Depend on Dose

    Science.gov (United States)

    Shanahan, Danielle F.; Bush, Robert; Gaston, Kevin J.; Lin, Brenda B.; Dean, Julie; Barber, Elizabeth; Fuller, Richard A.

    2016-06-01

    Nature within cities will have a central role in helping address key global public health challenges associated with urbanization. However, there is almost no guidance on how much or how frequently people need to engage with nature, and what types or characteristics of nature need to be incorporated in cities for the best health outcomes. Here we use a nature dose framework to examine the associations between the duration, frequency and intensity of exposure to nature and health in an urban population. We show that people who made long visits to green spaces had lower rates of depression and high blood pressure, and those who visited more frequently had greater social cohesion. Higher levels of physical activity were linked to both duration and frequency of green space visits. A dose-response analysis for depression and high blood pressure suggest that visits to outdoor green spaces of 30 minutes or more during the course of a week could reduce the population prevalence of these illnesses by up to 7% and 9% respectively. Given that the societal costs of depression alone in Australia are estimated at AUD$12.6 billion per annum, savings to public health budgets across all health outcomes could be immense.

  18. Low-dose caffeine physical dependence in humans.

    Science.gov (United States)

    Griffiths, R R; Evans, S M; Heishman, S J; Preston, K L; Sannerud, C A; Wolf, B; Woodson, P P

    1990-12-01

    This study investigated the effects of terminating low dose levels of caffeine (100 mg/day) in 7 normal humans. Substitution of placebo capsules for caffeine capsules occurred under double-blind conditions while subjects rated various dimensions of their mood and behavior. In the first phase of the study, substitution of placebo for 12 consecutive days resulted in an orderly withdrawal syndrome in 4 subjects which peaked on days 1 or 2 and progressively decreased toward prewithdrawal levels over about 1 week. Data from the remaining three subjects provided no evidence of withdrawal. In the second phase of the study, the generality of the withdrawal effect was examined by repeatedly substituting placebo for 100 mg/day of caffeine for 1-day periods separated by an average of 9 days. Despite differences within and across subjects with respect to the presence, nature and magnitude of symptoms, each of the seven subjects demonstrated a statistically significant withdrawal effect. Although the phenomenon of caffeine withdrawal has been described previously, the present report documents that the incidence of caffeine withdrawal is higher (100% of subjects), the daily dose level at which withdrawal occurs is lower (roughly equivalent to the amount of caffeine in a single cup of strong brewed coffee or 3 cans of caffeinated soft drink) and the range of symptoms experienced is broader (including headache, fatigue and other dysphoric mood changes, muscle pain/stiffness, flu-like feelings, nausea/vomiting and craving for caffeine) than heretofore recognized.

  19. Dose dependent sun protective effect of topical melatonin

    DEFF Research Database (Denmark)

    Scheuer, Cecilie; Pommergaard, Hans-Christian; Rosenberg, Jacob

    2016-01-01

    BACKGROUND: Ultraviolet radiation (UVR) by sunlight results in an increasing number of skin conditions. Earlier studies have suggested a protective effect of topical treatment with the pineal hormone melatonin. However, this protective effect has never been evaluated in natural sunlight......-blind study in healthy volunteers. Twenty-three healthy volunteers, 8 male and 15 female, were enrolled. The protective effect of three different doses of melatonin cream (0.5%, 2.5%, 12.5%) against erythema induced by natural sunlight was tested. All participants had their backs exposed to sun from 1:22 PM.......5% concentrations. CONCLUSION: Application of melatonin cream 12.5% protects against natural sunlight induced erythema....

  20. Dose-dependent effects of atorvastatin on myocardial infarction

    Directory of Open Access Journals (Sweden)

    Barbarash O

    2015-06-01

    Full Text Available Olga Barbarash, Olga Gruzdeva, Evgenya Uchasova, Ekaterina Belik, Yulia Dyleva, Victoria KaretnikovaFederal State Budgetary Institution, Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo, the Russian Federation Background: Dyslipidemia is a key factor determining the development of both myocardial infarction (MI and its subsequent complications. Dyslipidemia is associated with endothelial dysfunction, activation of inflammation, thrombogenesis, and formation of insulin resistance. Statin therapy is thought to be effective for primary and secondary prevention of complications associated with atherosclerosis.Methods: This study examined 210 patients with Segment elevated MI (ST elevated MI who were treated with atorvastatin from the first 24 hours after MI. Group 1 (n=110 were given atorvastatin 20 mg/day. Group 2 (n=100 were given atorvastatin 40 mg/day. At days 1 and 12 after MI onset, insulin resistance levels determined by the homeostasis model assessment of insulin resistance index, lipid profiles, and serum glucose, insulin, adipokine, and ghrelin levels were measured.Results: Free fatty acid levels showed a sharp increase during the acute phase of MI. Treatment with atorvastatin 20 mg/day, and especially with 40 mg/day, resulted in a decrease in free fatty acid levels. The positive effect of low-dose atorvastatin (20 mg/day is normalization of the adipokine status. Administration of atorvastatin 20 mg/day was accompanied with a statistically significant reduction in glucose levels (by 14% and C-peptide levels (by 38%, and a decrease in the homeostasis model assessment of insulin resistance index on day 12.Conclusion: Determination of atorvastatin dose and its use during the in-hospital period and subsequent periods should take into account changes in biochemical markers of insulin resistance and adipokine status in patients with MI.Keywords: myocardial infarction, statin, insulin resistance, adipokines

  1. Vitamin D production depends on ultraviolet-B dose but not on dose rate: a randomized controlled trial

    DEFF Research Database (Denmark)

    Bogh, Morten K B; Schmedes, Anne V; Philipsen, Peter A

    2011-01-01

    Ultraviolet-B (UV-B) radiation increases serum vitamin D level expressed as 25-hydroxyvitamin D(3) (25(OH)D), but the dose-response relationship and the importance of dose rate is unclear. Of 172 fair-skinned persons screened for 25(OH)D, 55 with insufficient baseline 25(OH)D=50 nm (mean 31.2 nm...... exposed. Skin pigmentation and 25(OH)D were measured before and after the irradiations. The increase in 25(OH)D after UV-B exposure (adjusted for baseline 25(OH)D) was positively correlated with the UV-B dose (P=0.001; R(2) =0.176) but not to dose rate (1-20 min). 25(OH)D increased in response to four UV......-B treatments of 3 SED with 24.8 nm on average and 14.2 nm after four UV-B treatments of just 0.375 SED. In conclusion, the increase in 25(OH)D after UV-B exposure depends on the dose but not on the dose rate (1-20 min). Further, a significant increase in 25(OH)D was achieved with a very low UV-B dose....

  2. Calculation of age-dependent effective doses for external exposure using the MCNP code

    International Nuclear Information System (INIS)

    Hung, Tran Van

    2013-01-01

    Age-dependent effective dose for external exposure to photons uniformly distributed in air were calculated. Firstly, organ doses were calculated with a series of age-specific MIRD-5 type phantoms using the Monte Carlo code MCNP. The calculations were performed for mono-energetic photon sources with source energies from 10 keV to 5 MeV and for phantoms of newborn, 1, 5, 10, and 15 years-old and adult. Then, the effective doses to the different age-phantoms from the mono-energetic photon sources were estimated based on the obtained organ doses. From the calculated results, it is shown that the effective doses depend on the body size; the effective doses in younger phantoms are higher than those in the older phantoms, especially below 100 keV. (orig.)

  3. Calculation of age-dependent effective doses for external exposure using the MCNP code

    Energy Technology Data Exchange (ETDEWEB)

    Hung, Tran Van [Research and Development Center for Radiation Technology, ThuDuc, HoChiMinh City (VT)

    2013-07-15

    Age-dependent effective dose for external exposure to photons uniformly distributed in air were calculated. Firstly, organ doses were calculated with a series of age-specific MIRD-5 type phantoms using the Monte Carlo code MCNP. The calculations were performed for mono-energetic photon sources with source energies from 10 keV to 5 MeV and for phantoms of newborn, 1, 5, 10, and 15 years-old and adult. Then, the effective doses to the different age-phantoms from the mono-energetic photon sources were estimated based on the obtained organ doses. From the calculated results, it is shown that the effective doses depend on the body size; the effective doses in younger phantoms are higher than those in the older phantoms, especially below 100 keV. (orig.)

  4. Medical and Psychiatric Effects of Long-Term Dependence on High Dose of tramadol.

    Science.gov (United States)

    El-Hadidy, Mohmed Adel; Helaly, Ahmed Mohamed Nabil

    2015-04-01

    Tramadol dependence has been studied recently after large-scale exposure. Although tramadol dependence has increased rapidly in Egypt since 2004, no studies have evaluated the effect of high dose long-term tramadol dependence. To address the chronic sequel of tramadol dependence over at least 5 years duration with a large dose (more than 675 mg/day, three tablets or more, each tablet of 225 mg). The study was aimed to check the physical and psychiatric status during tramadol dependence and 3 months after complete treatment. The present study was applied on 79 patients with single tramadol-dependence dose of 675 mg or more for 5 years or more. We examined the physical and psychological impact of tramadol abuse before and after 3 months of stoppage of the drug. The blood chemistry was nearly within normal parameters, although slight nonsignificant rise in liver enzymes was reported in some cases. Patients during tramadol dependence period were angry, hostile, and aggressive. On the other hand, after treatment the main problem observed was the significant increase in comorbid anxiety, depressive, and obsessive-compulsive symptoms, but no increase was found in psychotic symptoms. Tramadol-dependence dose was more important than duration of use in psychiatric illness. Tramadol dependence on high dose could be physically safe to some limit, but psychiatrically it has many side effects.

  5. Repeated dose studies with pure Epigallocatechin-3-gallate demonstrated dose and route dependant hepatotoxicity with associated dyslipidemia

    Directory of Open Access Journals (Sweden)

    Balaji Ramachandran

    Full Text Available EGCG (Epigallocatechin-3-gallate is the major active principle catechin found in green tea. Skepticism regarding the safety of consuming EGCG is gaining attention, despite the fact that it is widely being touted for its potential health benefits, including anti-cancer properties. The lack of scientific data on safe dose levels of pure EGCG is of concern, while EGCG has been commonly studied as a component of GTE (Green tea extract and not as a single active constituent. This study has been carried out to estimate the maximum tolerated non-toxic dose of pure EGCG and to identify the treatment related risk factors. In a fourteen day consecutive treatment, two different administration modalities were compared, offering an improved [i.p (intraperitoneal] and limited [p.o (oral] bioavailability. A trend of dose and route dependant hepatotoxicity was observed particularly with i.p treatment and EGCG increased serum lipid profile in parallel to hepatotoxicity. Fourteen day tolerable dose of EGCG was established as 21.1 mg/kg for i.p and 67.8 mg/kg for p.o. We also observed that, EGCG induced effects by both treatment routes are reversible, subsequent to an observation period for further fourteen days after cessation of treatment. It was demonstrated that the severity of EGCG induced toxicity appears to be a function of dose, route of administration and period of treatment. Keywords: EGCG, Green tea, Serum lipids, Dose dependant toxicity, Route dependant toxicity, Liver toxicity, Dyslipidemia

  6. Dose-dependent hepatic transcriptional responses in Atlantic salmon (Salmo salar) exposed to sublethal doses of gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Song, You, E-mail: you.song@niva.no [Norwegian University of Life Sciences (NMBU), Faculty of Environmental Science and Technology, Department of Environmental Sciences (IMV), Centre for Environmental Radioactivity - CERAD, P.O. Box 5003, N-1432 Ås (Norway); Norwegian Institute for Water Research (NIVA), Gaustadalléen 21, N-0349 Oslo (Norway); Salbu, Brit; Teien, Hans-Christian; Heier, Lene Sørlie [Norwegian University of Life Sciences (NMBU), Faculty of Environmental Science and Technology, Department of Environmental Sciences (IMV), Centre for Environmental Radioactivity - CERAD, P.O. Box 5003, N-1432 Ås (Norway); Rosseland, Bjørn Olav [Norwegian University of Life Sciences (NMBU), Faculty of Environmental Science and Technology, Department of Environmental Sciences (IMV), Centre for Environmental Radioactivity - CERAD, P.O. Box 5003, N-1432 Ås (Norway); Norwegian University of Life Sciences (NMBU), Department of Ecology and Natural Resource Management, P.O. Box 5003, N-1432 Ås (Norway); Tollefsen, Knut Erik [Norwegian University of Life Sciences (NMBU), Faculty of Environmental Science and Technology, Department of Environmental Sciences (IMV), Centre for Environmental Radioactivity - CERAD, P.O. Box 5003, N-1432 Ås (Norway); Norwegian Institute for Water Research (NIVA), Gaustadalléen 21, N-0349 Oslo (Norway)

    2014-11-15

    Highlights: • First study on early stress responses in salmon exposed to low-dose gamma radiation. • Dramatic dose-dependent transcriptional responses characterized. • Multiple modes of action proposed for gamma radiation. - Abstract: Due to the production of free radicals, gamma radiation may pose a hazard to living organisms. The high-dose radiation effects have been extensively studied, whereas the ecotoxicity data on low-dose gamma radiation is still limited. The present study was therefore performed using Atlantic salmon (Salmo salar) to characterize effects of low-dose (15, 70 and 280 mGy) gamma radiation after short-term (48 h) exposure. Global transcriptional changes were studied using a combination of high-density oligonucleotide microarrays and quantitative real-time reverse transcription polymerase chain reaction (qPCR). Differentially expressed genes (DEGs; in this article the phrase gene expression is taken as a synonym of gene transcription, although it is acknowledged that gene expression can also be regulated, e.g., at protein stability and translational level) were determined and linked to their biological meanings predicted using both Gene Ontology (GO) and mammalian ortholog-based functional analyses. The plasma glucose level was also measured as a general stress biomarker at the organism level. Results from the microarray analysis revealed a dose-dependent pattern of global transcriptional responses, with 222, 495 and 909 DEGs regulated by 15, 70 and 280 mGy gamma radiation, respectively. Among these DEGs, only 34 were commonly regulated by all radiation doses, whereas the majority of differences were dose-specific. No GO functions were identified at low or medium doses, but repression of DEGs associated with GO functions such as DNA replication, cell cycle regulation and response to reactive oxygen species (ROS) were observed after 280 mGy gamma exposure. Ortholog-based toxicity pathway analysis further showed that 15 mGy radiation

  7. SPECIAL CONSIDERATIONS REGARDING WARFARIN DOSE TITRATION IN PATIENTS WITH ATRIAL FIBRILLATION DEPENDING ON CLINICAL FACTORS

    Directory of Open Access Journals (Sweden)

    E. L. Artanova

    2011-01-01

    Full Text Available Aim. To study the relations of clinical characteristics and individual warfarin dose titration in patients with atrial fibrillation. Material and methods. Period of warfarin dose titration was analyzed in 68 patients with atrial fibrillation due to ischemic heart disease. Adjusted warfarin dose in milligram, duration of dose titration in days and maximal international normalized ratio (INR were taken into account. Sex, age, history of myocardial infarction and stroke, concomitant diseases, amiodarone therapy were considered among clinical characteristics. Results. Adjusted warfarin dose was significantly higher in obesity , and it was lower in case of experienced myocardial infarction. The INR highest levels and maximal amplitudes of its fluctuations were observed in patients with thyroid gland nodes and smokers. Period of warfarin dose titration was longer in patients treated with amiodarone. Conclusion. Warfarin dose titration in patients with atrial fibrillation depends on the presence of myocardial infarction, obesity , thyroid nodular changes, smoking and amiodarone treatment.

  8. Estimation of personal dose based on the dependent calibration of personal dosimeters in interventional radiology

    International Nuclear Information System (INIS)

    Mori, Hiroshige; Koshida, Kichiro; Ichikawa, Katsuhiro

    2007-01-01

    The purpose of present study is, in interventional radiology (IVR), to elucidate the differences between each personal dosimeter, and the dependences and calibrations of area or personal dose by measurement with electronic dosimeters in particular. We compare space dose rate distributions measured by an ionization survey meter with the value measured by personal dosimeter: an optically stimulated luminescence, two fluoroglass, and two electronic dosimeters. Furthermore, with electronic dosimeters, we first measured dose rate, energy, and directional dependences. Secondly, we calibrated the dose rate measured by electronic dosimeters with the results, and estimated these methods with coefficient of determination and Akaike's Information Criterion (AIC). The results, especially in electronic dosimeters, revealed that the dose rate measured fell by energy and directional dependences. In terms of methods of calibration, the method is sufficient for energy dependence, but not for directional dependence, because of the lack of stable calibration. This improvement poses a question for the future. The study suggested that these dependences of the personal dosimeter must be considered when area or personal dose is estimated in IVR. (author)

  9. Age-dependent dose factors and dose limits of annual radioactivity uptake with unsealed radioactive substances by occupationally exposed persons

    International Nuclear Information System (INIS)

    Kaul, A.; Nosske, D; Elsasser, U; Roedler, H.D.; Henrichs, K.

    1986-01-01

    The dose factors have been calculated on the basis of the ICRP models for dosimetric and metabolistic assessment, and are laid open in accordance with Annex XI ( to sec. 45 sub-section (2)) of the amended version of the Radiation Protection Ordinance. The contribution in hand explains the scientific fundamentals and results of the calculations of dose factors relating to inhalation and ingestion of unsealed radioactive substances by adult reference man, and age-dependent factors calculated for children and adolescents. Further, annual limits of uptake by occupationally exposed persons, as calculated on the basis of primary dose limits pursunant to the draft amendment presented by the Federal Interior Minister, are compared with relevant data given by the ICRP and EC institutions. (orig./DG) [de

  10. Age-dependent effective doses for radionuclides uniformly distributed in air

    International Nuclear Information System (INIS)

    Hung, Tran Van

    2014-01-01

    Age-dependent effective doses for external exposure to photons emitted by radionuclides uniformly distributed in air are reported. The calculations were performed for 160 radionuclides, which are important for safety assessment of nuclear facilities. The energies and intensities of photons emitted from radionuclides were taken from the decay data DECDC used for dose calculations. The results are tabulated in the form of effective dose per unit concentration and time (Sv per Bq s m -3 ) for 6 age groups: newborn, 1, 5, 10 and 15 years-old and adult. The effective doses for the adult are also compared to values given in the literature.

  11. Moderate- vs high-dose methadone in the treatment of opioid dependence: a randomized trial.

    Science.gov (United States)

    Strain, E C; Bigelow, G E; Liebson, I A; Stitzer, M L

    1999-03-17

    Methadone hydrochloride treatment is the most common pharmacological intervention for opioid dependence, and recent interest has focused on expanding methadone treatment availability beyond traditional specially licensed clinics. However, despite recommendations regarding effective dosing of methadone, controlled clinical trials of higher-dose methadone have not been conducted. To compare the relative clinical efficacy of moderate- vs high-dose methadone in the treatment of opioid dependence. A 40-week randomized, double-blind clinical trial starting in June 1992 and ending in October 1995. Outpatient substance abuse treatment research clinic at the Johns Hopkins University Bayview Campus, Baltimore, Md. One hundred ninety-two eligible clinic patients. Daily oral methadone hydrochloride in the dose range of 40 to 50 mg (n = 97) or 80 to 100 mg (n = 95), with concurrent substance abuse counseling. Opioid-positive urinalysis results and retention in treatment. By intent-to-treat analysis through week 30 patients in the high-dose group had significantly lower rates of opioid-positive urine samples compared with patients in the moderate-dose group (53.0% [95% confidence interval [CI], 46.9%-59.2%] vs 61.9% [95% CI, 55.9%-68.0%]; P = .047. These differences persisted during withdrawal from methadone. Through day 210 no significant difference was evident between dose groups in treatment retention (high-dose group mean retention, 159 days; moderate-dose group mean retention, 157 days). Nineteen (33%) of 57 patients in the high-dose group and 11 (20%) of 54 patients in the moderate-dose group completed detoxification. Both moderate- and high-dose methadone treatment resulted in decreased illicit opioid use during methadone maintenance and detoxification. The high-dose group had significantly greater decreases in illicit opioid use.

  12. Contrast media and glomerular filtration: dose dependence of clearance for three agents

    International Nuclear Information System (INIS)

    Baeck, S.E.K.; Krutzen, E.; Nilsson-Ehle, P.

    1988-01-01

    Determination of plasma clearance of contrast agents has been advocated as a means to assess glomerular filtration rate. To evaluate the feasibility of different agents for this purpose, we have compared, in healthy volunteers, the dose dependence of plasma clearance for three contrast media (iohexol, a nonionic agent, and iothalamate and metrizoate, which are ionic substances), with special emphasis on the lower dose range (2-20 mL corresponding to 0.9-12.9 g, depending on dose and agent). Iohexol and iothalamate were cleared at constant rates, irrespective of given dose, whereas metrizoate clearance increased significantly at lower doses. In general, the clearances or iothalamate and metrizoate were, respectively, moderately and markedly higher than that of iohexol. The clearance of different doses of metrizoate (2 mL versus a radiographic dose of 40 mL or more) was also compared with the clearance of [ 51 Cr]EDTA in two groups of patients with reduced renal function. When compared with [ 51 Cr]EDTA in patients with renal dysfunction, metrizoate was cleared significantly faster after a 2-mL dose, whereas clearances were identical when the metrizoate dose was 40 mL or more. These findings indicate that tubular secretion plays an active role in the elimination of metrizoate. The pharmacokinetic properties of iohexol, in combination with its low toxicity, make it a suitable agent for determination of glomerular filtration rate in clinical practice

  13. Repeated dose studies with pure Epigallocatechin-3-gallate demonstrated dose and route dependant hepatotoxicity with associated dyslipidemia.

    Science.gov (United States)

    Ramachandran, Balaji; Jayavelu, Subramani; Murhekar, Kanchan; Rajkumar, Thangarajan

    2016-01-01

    EGCG (Epigallocatechin-3-gallate) is the major active principle catechin found in green tea. Skepticism regarding the safety of consuming EGCG is gaining attention, despite the fact that it is widely being touted for its potential health benefits, including anti-cancer properties. The lack of scientific data on safe dose levels of pure EGCG is of concern, while EGCG has been commonly studied as a component of GTE (Green tea extract) and not as a single active constituent. This study has been carried out to estimate the maximum tolerated non-toxic dose of pure EGCG and to identify the treatment related risk factors. In a fourteen day consecutive treatment, two different administration modalities were compared, offering an improved [i.p (intraperitoneal)] and limited [p.o (oral)] bioavailability. A trend of dose and route dependant hepatotoxicity was observed particularly with i.p treatment and EGCG increased serum lipid profile in parallel to hepatotoxicity. Fourteen day tolerable dose of EGCG was established as 21.1 mg/kg for i.p and 67.8 mg/kg for p.o. We also observed that, EGCG induced effects by both treatment routes are reversible, subsequent to an observation period for further fourteen days after cessation of treatment. It was demonstrated that the severity of EGCG induced toxicity appears to be a function of dose, route of administration and period of treatment.

  14. Ocular allergy modulation to hi-dose antigen sensitization is a Treg-dependent process.

    Science.gov (United States)

    Lee, Hyun Soo; Schlereth, Simona; Khandelwal, Payal; Saban, Daniel R

    2013-01-01

    A reproducible method to inhibit allergic immune responses is accomplished with hi-dose Ag sensitization, via intraperitoneal (IP) injection. However, the role of CD4+ CD25+ FoxP3+ T regulatory cells (Treg) in this process is unknown, as is whether such modulation extends to ocular allergy. We therefore determined herein whether hi-dose sensitization modulates ocular allergy, and whether CD4+ CD25+ FoxP3+ Treg are involved. C57BL/6 mice were IP sensitized via low-dose (100 µg) versus hi-dose (1000 µg) ovalbumin (OVA), in aluminum hydroxide (1 mg) and pertussis-toxin (300 ng). Other mice received anti-CD25 Ab (PC61) to ablate Treg during sensitization. In another experiment, Treg from hi-dose sensitized mice were adoptively transferred into low-dose sensitized mice. Once daily OVA challenges were administered. Clinical signs, IgE, T cell cytokines, and eosinophils were assessed. Data revealed that hi-dose, but not low-dose, sensitization led to allergy modulation, indicated by decreased clinical signs, serum IgE levels, Th2 recall responses, and eosinophil recruitment. T cells from hi-dose sensitized mice showed a robust increase in TGF-b production, and Treg from these mice were able to efficiently suppress effector T cell proliferation in vitro. In addition, in vivo Treg ablation in hi-dose sensitized mice revoked allergy modulation. Lastly, Treg from hi-dose sensitized mice were able to adoptively transfer allergy modulation to their low-dose sensitized counterparts. Collectively, these findings indicate that modulation to hi-dose sensitization, which is extended to ocular allergy, occurs in a Treg-dependent manner. In addition, our data suggest that hi-dose sensitization may henceforth facilitate the further examination of CD4+ CD25+ FoxP3+ Treg in allergic disease.

  15. Calculation of absorbed dose of anchorage-dependent cells from internal beta-rays irradiation

    International Nuclear Information System (INIS)

    Chen Jianwei; Huang Gang; Li Shijun

    2001-01-01

    Objective: To elicit the formula of internal dosimetry in anchorage-dependent cells by beta-emitting radionuclides from uniformly distributed volume sources. Methods: By means of the definition of absorbed dose and the MIRD (Medical International Radiation Dose) scheme the formula of internal dosimetry was reasonably deduced. Firstly, studying the systems of suspension culture cells. Then, taking account of the speciality of the systems of the anchorage-dependent cells and the directions of irradiation, the absorbed dose of anchorage -dependent cells was calculated by the accumulated radioactivity, beta-ray energy, and the volume of the cultured systems. Results: The formula of internal dosimetry of suspension culture cells and anchorage-dependent cells were achieved. At the same time, the formula of internal dosimetry of suspension culture cells was compared with that of MIRD and was confirmed accurate. Conclusion: The formula of internal dosimetry is concise, reliable and accurate

  16. Dose-dependent metabolic disposition of hydroxytyrosol and formation of mercapturates in rats.

    Science.gov (United States)

    Kotronoulas, Aristotelis; Pizarro, Nieves; Serra, Aida; Robledo, Patricia; Joglar, Jesús; Rubió, Laura; Hernaéz, Alvaro; Tormos, Carmen; Motilva, Ma José; Fitó, Montserrat; Covas, Maria-Isabel; Solà, Rosa; Farré, Magí; Saez, Guillermo; de la Torre, Rafael

    2013-11-01

    Hydroxytyrosol (HT), one of the major polyphenols present in olive oil, is known to possess a high antioxidant capacity. The aim of the present study was to investigate dose dependent (0, 1, 10 and 100 mg/kg) alterations in the metabolism of HT in rats since it has been reported that metabolites may contribute to biological effects. Special attention was paid to the activation of the semiquinone-quinone oxidative cycle and the formation of adducts with potential deleterious effects. Thus, we developed a novel analytical methodology to monitor the in vivo formation of the HT mercapturate, N-acetyl-5-S-cysteinyl-hydroxytyrosol in urine samples. Biomarkers of hepatic and renal toxicity were evaluated within the dose range tested. Following HT administration, dose-dependent effects were observed for the recovery of all the metabolites studied. At the lowest dose of 1 mg/kg, the glucuronidation pathway was the most relevant (25-30%), with lower recoveries for sulfation (14%), while at the highest dose of 100 mg/kg, sulfation was the most prevalent (75%). In addition, we report for the first time the formation of the mercapturate conjugate of HT in a dose-dependent manner. The biochemical data did not reveal significant toxic effects of HT at any of the doses studied. An increase in the GSH/GSSG ratio at the highest dose was observed indicating that the products of HT autoxidation are counteracted by glutathione, resulting in their detoxification. These results indicate that the metabolic disposition of HT is highly dependent on the dose ingested. Copyright © 2013. Published by Elsevier Ltd.

  17. Dose rate dependence for different dosimeters and detectors: TLD, OSL, EBT films, and diamond detectors

    International Nuclear Information System (INIS)

    Karsch, L.; Beyreuther, E.; Burris-Mog, T.; Kraft, S.; Richter, C.; Zeil, K.; Pawelke, J.

    2012-01-01

    Purpose: The use of laser accelerators in radiation therapy can perhaps increase the low number of proton and ion therapy facilities in some years due to the low investment costs and small size. The laser-based acceleration technology leads to a very high peak dose rate of about 10 11 Gy/s. A first dosimetric task is the evaluation of dose rate dependence of clinical dosimeters and other detectors. Methods: The measurements were done at ELBE, a superconductive linear electron accelerator which generates electron pulses with 5 ps length at 20 MeV. The different dose rates are reached by adjusting the number of electrons in one beam pulse. Three clinical dosimeters (TLD, OSL, and EBT radiochromic films) were irradiated with four different dose rates and nearly the same dose. A faraday cup, an integrating current transformer, and an ionization chamber were used to control the particle flux on the dosimeters. Furthermore two diamond detectors were tested. Results: The dosimeters are dose rate independent up to 410 9 Gy/s within 2% (OSL and TLD) and up to 1510 9 Gy/s within 5% (EBT films). The diamond detectors show strong dose rate dependence. Conclusions: TLD, OSL dosimeters, and EBT films are suitable for pulsed beams with a very high pulse dose rate like laser accelerated particle beams.

  18. [Dose rate-dependent cellular and molecular effects of ionizing radiation].

    Science.gov (United States)

    Przybyszewski, Waldemar M; Wideł, Maria; Szurko, Agnieszka; Maniakowski, Zbigniew

    2008-09-11

    The aim of radiation therapy is to kill tumor cells while minimizing damage to normal cells. The ultimate effect of radiation can be apoptotic or necrotic cell death as well as cytogenetic damage resulting in genetic instability and/or cell death. The destructive effects of radiation arise from direct and indirect ionization events leading to peroxidation of macromolecules, especially those present in lipid-rich membrane structures as well as chromatin lipids. Lipid peroxidative end-products may damage DNA and proteins. A characteristic feature of radiation-induced peroxidation is an inverse dose-rate effect (IDRE), defined as an increase in the degree of oxidation(at constant absorbed dose) accompanying a lower dose rate. On the other hand, a low dose rate can lead to the accumulation of cells in G2, the radiosensitive phase of the cell cycle since cell cycle control points are not sensitive to low dose rates. Radiation dose rate may potentially be the main factor improving radiotherapy efficacy as well as affecting the intensity of normal tissue and whole-body side effects. A better understanding of dose rate-dependent biological effects may lead to improved therapeutic intervention and limit normal tissue reaction. The study reviews basic biological effects that depend on the dose rate of ionizing radiation.

  19. Dose-Dependent Effect of Statin Pretreatment on Preventing the Periprocedural Complications of Carotid Artery Stenting.

    Science.gov (United States)

    Hong, Jeong-Ho; Sohn, Sung-Il; Kwak, Jaehyuk; Yoo, Joonsang; Chang, Hyuk Won; Kwon, O-Ki; Jung, Cheolkyu; Chung, Inyoung; Bae, Hee-Joon; Lee, Ji Sung; Han, Moon-Ku

    2017-07-01

    We investigated whether statin pretreatment can dose dependently reduce periprocedural complications in patients undergoing carotid artery stenting because of symptomatic carotid artery stenosis. We enrolled a consecutive series of 397 symptomatic carotid artery stenosis (≥50% stenosis on conventional angiography) treated with carotid artery stenting at 2 tertiary university hospitals over a decade. Definition of periprocedural complications included any stroke, myocardial infarction, and death within 1 month after or during the procedure. Statin pretreatment was divided into 3 categories according to the atorvastatin equivalent dose: none (n=158; 39.8%), standard dose (statin use were 12.0%, 4.5%, and 1.2%. After adjustment, a change in the atorvastatin dose category was associated with reduction in the odds of periprocedural complications for each change in dose category (standard-dose statin: odds ratio, 0.24; 95% confidence interval, 0.07-0.81; high-dose statin: odds ratio, 0.11; 95% confidence interval, 0.01-0.96; P for trend=0.01). Administration of antiplatelet drugs was also an independent factor in periprocedural complications (OR, 0.18; 95% CI, 0.05-0.69). This study shows that statin pretreatment may reduce the incidence of periprocedural complications dose dependently in patients with symptomatic carotid artery stenting. © 2017 American Heart Association, Inc.

  20. Electron dose dependence of signal-to-noise ratio, atom contrast and resolution in transmission electron microscope images

    International Nuclear Information System (INIS)

    Lee, Z.; Rose, H.; Lehtinen, O.; Biskupek, J.; Kaiser, U.

    2014-01-01

    In order to achieve the highest resolution in aberration-corrected (AC) high-resolution transmission electron microscopy (HRTEM) images, high electron doses are required which only a few samples can withstand. In this paper we perform dose-dependent AC-HRTEM image calculations, and study the dependence of the signal-to-noise ratio, atom contrast and resolution on electron dose and sampling. We introduce dose-dependent contrast, which can be used to evaluate the visibility of objects under different dose conditions. Based on our calculations, we determine optimum samplings for high and low electron dose imaging conditions. - Highlights: • The definition of dose-dependent atom contrast is introduced. • The dependence of the signal-to-noise ratio, atom contrast and specimen resolution on electron dose and sampling is explored. • The optimum sampling can be determined according to different dose conditions

  1. Dose-Dependent Effects of Statins for Patients with Aneurysmal Subarachnoid Hemorrhage: Meta-Regression Analysis.

    Science.gov (United States)

    To, Minh-Son; Prakash, Shivesh; Poonnoose, Santosh I; Bihari, Shailesh

    2018-05-01

    The study uses meta-regression analysis to quantify the dose-dependent effects of statin pharmacotherapy on vasospasm, delayed ischemic neurologic deficits (DIND), and mortality in aneurysmal subarachnoid hemorrhage. Prospective, retrospective observational studies, and randomized controlled trials (RCTs) were retrieved by a systematic database search. Summary estimates were expressed as absolute risk (AR) for a given statin dose or control (placebo). Meta-regression using inverse variance weighting and robust variance estimation was performed to assess the effect of statin dose on transformed AR in a random effects model. Dose-dependence of predicted AR with 95% confidence interval (CI) was recovered by using Miller's Freeman-Tukey inverse. The database search and study selection criteria yielded 18 studies (2594 patients) for analysis. These included 12 RCTs, 4 retrospective observational studies, and 2 prospective observational studies. Twelve studies investigated simvastatin, whereas the remaining studies investigated atorvastatin, pravastatin, or pitavastatin, with simvastatin-equivalent doses ranging from 20 to 80 mg. Meta-regression revealed dose-dependent reductions in Freeman-Tukey-transformed AR of vasospasm (slope coefficient -0.00404, 95% CI -0.00720 to -0.00087; P = 0.0321), DIND (slope coefficient -0.00316, 95% CI -0.00586 to -0.00047; P = 0.0392), and mortality (slope coefficient -0.00345, 95% CI -0.00623 to -0.00067; P = 0.0352). The present meta-regression provides weak evidence for dose-dependent reductions in vasospasm, DIND and mortality associated with acute statin use after aneurysmal subarachnoid hemorrhage. However, the analysis was limited by substantial heterogeneity among individual studies. Greater dosing strategies are a potential consideration for future RCTs. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. High-dose zolpidem dependence - Psychostimulant effects? A case report and literature review

    Directory of Open Access Journals (Sweden)

    Abhijna Chandan Chattopadhyay

    2016-01-01

    Full Text Available Zolpidem, an imidazoline nonbenzodiazepine sedative drug, is used widely. Initial reports showed minimal abuse potential. However, multiple reports have appeared of dose escalation and abuse. Subjective effects of high-dose zolpidem are not known. In light of accumulating evidence of abuse potential, we hereby report a case of high-dose dependence and a review of relevant literature. A 33-year-old male presented with 5 years of daily use of 600–1700 mg of zolpidem tartrate. He reported subjective effects of euphoria, intense craving, and inability to stop use. Loss of receptor specificity, pharmacokinetic factors, and different receptor distributions can explain paradoxical stimulatory effects of high-dose zolpidem. Further studies are required to characterize subjective effects of high-dose zolpidem.

  3. The optimal fraction size in high-dose-rate brachytherapy: dependency on tissue repair kinetics and low-dose rate

    International Nuclear Information System (INIS)

    Sminia, Peter; Schneider, Christoph J.; Fowler, Jack F.

    2002-01-01

    Background and Purpose: Indications of the existence of long repair half-times on the order of 2-4 h for late-responding human normal tissues have been obtained from continuous hyperfractionated accelerated radiotherapy (CHART). Recently, these data were used to explain, on the basis of the biologically effective dose (BED), the potential superiority of fractionated high-dose rate (HDR) with large fraction sizes of 5-7 Gy over continuous low-dose rate (LDR) irradiation at 0.5 Gy/h in cervical carcinoma. We investigated the optimal fraction size in HDR brachytherapy and its dependency on treatment choices (overall treatment time, number of HDR fractions, and time interval between fractions) and treatment conditions (reference low-dose rate, tissue repair characteristics). Methods and Materials: Radiobiologic model calculations were performed using the linear-quadratic model for incomplete mono-exponential repair. An irradiation dose of 20 Gy was assumed to be applied either with HDR in 2-12 fractions or continuously with LDR for a range of dose rates. HDR and LDR treatment regimens were compared on the basis of the BED and BED ratio of normal tissue and tumor, assuming repair half-times between 1 h and 4 h. Results: With the assumption that the repair half-time of normal tissue was three times longer than that of the tumor, hypofractionation in HDR relative to LDR could result in relative normal tissue sparing if the optimum fraction size is selected. By dose reduction while keeping the tumor BED constant, absolute normal tissue sparing might therefore be achieved. This optimum HDR fraction size was found to be largely dependent on the LDR dose rate. On the basis of the BED NT/TUM ratio of HDR over LDR, 3 x 6.7 Gy would be the optimal HDR fractionation scheme for replacement of an LDR scheme of 20 Gy in 10-30 h (dose rate 2-0.67 Gy/h), while at a lower dose rate of 0.5 Gy/h, four fractions of 5 Gy would be preferential, still assuming large differences between tumor

  4. Energy and integrated dose dependence of MOSFET dosimeter for clinical electron beams

    International Nuclear Information System (INIS)

    Manigandan, D.; Bharanidharan, G.; Aruna, P.; Ganesan, S.; Tamil Kumar, T.; Rai

    2008-01-01

    In this study, the sensitivity (mV/cGy) and integral dose dependence of a MOSFET detector for different clinical electron beams was studied. Calibrated clinical electron beams (Varian 2100) were used for the exposure. A Markus type parallel plate chamber was used for the absolute dose measurements. In order to study the sensitivity of a MOSFET, the response of the ion chamber and MOSFET for the absorbed dose of 100 cGy was measured. The sensitivity of the MOSFET was then expressed as mV/cGy. Sensitivity was measured for 4-18 MeV electron beams. (author)

  5. Calculation of age-dependent dose conversion coefficients for radionuclides uniformly distributed in air

    International Nuclear Information System (INIS)

    Hung, Tran Van; Satoh, Daiki; Takahashi, Fumiaki; Tsuda, Shuichi; Endo, Akira; Saito, Kimiaki; Yamaguchi, Yasuhiro

    2005-02-01

    Age-dependent dose conversion coefficients for external exposure to photons emitted by radionuclides uniformly distributed in air were calculated. The size of the source region in the calculation was assumed to be effectively semi-infinite in extent. Firstly, organ doses were calculated with a series of age-specific MIRD-5 type phantoms using MCNP code, a Monte Carlo transport code. The calculations were performed for mono-energetic photon sources of twelve energies from 10 keV to 5 MeV and for phantoms of newborn, 1, 5, 10 and 15 years, and adult. Then, the effective doses to the different age-phantoms from the mono-energetic photon sources were estimated based on the obtained organ doses. The calculated effective doses were used to interpolate the conversion coefficients of the effective doses for 160 radionuclides, which are important for dose assessment of nuclear facilities. In the calculation, energies and intensities of emitted photons from radionuclides were taken from DECDC, a recent compilation of decay data for radiation dosimetry developed at JAERI. The results are tabulated in the form of effective dose per unit concentration and time (Sv per Bq s m -3 ). (author)

  6. Dose dependence of true stress parameters in irradiated bcc, fcc, and hcp metals

    Science.gov (United States)

    Byun, T. S.

    2007-04-01

    The dose dependence of true stress parameters has been investigated for nuclear structural materials: A533B pressure vessel steels, modified 9Cr-1Mo and 9Cr-2WVTa ferritic martensitic steels, 316 and 316LN stainless steels, and Zircaloy-4. After irradiation to significant doses, these alloys show radiation-induced strengthening and often experience prompt necking at yield followed by large necking deformation. In the present work, the critical true stresses for deformation and fracture events, such as yield stress (YS), plastic instability stress (PIS), and true fracture stress (FS), were obtained from uniaxial tensile tests or calculated using a linear strain-hardening model for necking deformation. At low dose levels where no significant embrittlement was detected, the true fracture stress was nearly independent of dose. The plastic instability stress was also independent of dose before the critical dose-to-prompt-necking at yield was reached. A few bcc alloys such as ferritic martensitic steels experienced significant embrittlement at doses above ∼1 dpa; and the true fracture stress decreased with dose. The materials fractured before yield at or above 10 dpa.

  7. Space-Time Dependent Transport, Activation, and Dose Rates for Radioactivated Fluids.

    Science.gov (United States)

    Gavazza, Sergio

    Two methods are developed to calculate the space - and time-dependent mass transport of radionuclides, their production and decay, and the associated dose rates generated from the radioactivated fluids flowing through pipes. The work couples space- and time-dependent phenomena, treated as only space- or time-dependent in the open literature. The transport and activation methodology (TAM) is used to numerically calculate space- and time-dependent transport and activation of radionuclides in fluids flowing through pipes exposed to radiation fields, and volumetric radioactive sources created by radionuclide motions. The computer program Radionuclide Activation and Transport in Pipe (RNATPA1) performs the numerical calculations required in TAM. The gamma ray dose methodology (GAM) is used to numerically calculate space- and time-dependent gamma ray dose equivalent rates from the volumetric radioactive sources determined by TAM. The computer program Gamma Ray Dose Equivalent Rate (GRDOSER) performs the numerical calculations required in GAM. The scope of conditions considered by TAM and GAM herein include (a) laminar flow in straight pipe, (b)recirculating flow schemes, (c) time-independent fluid velocity distributions, (d) space-dependent monoenergetic neutron flux distribution, (e) space- and time-dependent activation process of a single parent nuclide and transport and decay of a single daughter radionuclide, and (f) assessment of space- and time-dependent gamma ray dose rates, outside the pipe, generated by the space- and time-dependent source term distributions inside of it. The methodologies, however, can be easily extended to include all the situations of interest for solving the phenomena addressed in this dissertation. A comparison is made from results obtained by the described calculational procedures with analytical expressions. The physics of the problems addressed by the new technique and the increased accuracy versus non -space and time-dependent methods

  8. Field strength and dose dependence of contrast enhancement by gadolinium-based MR contrast agents

    International Nuclear Information System (INIS)

    Rinck, P.A.; Muller, R.N.

    1999-01-01

    The relaxivities r 1 and r 2 of magnetic resonance contrast agents and the T 1 relaxation time values of tissues are strongly field dependent. We present quantitative data and simulations of different gadolinium-based extracellular fluid contrast agents and the modulation of their contrast enhancement by the magnetic field to be able to answer the following questions: How are the dose and field dependences of their contrast enhancement? Is there an interrelationship between dose and field dependence? Should one increase or decrease doses at specific fields? Nuclear magnetic relaxation dispersion data were acquired for the following contrast agents: gadopentetate dimeglumine, gadoterate meglumine, gadodiamide injection, and gadoteridol injection, as well as for several normal and pathological human tissue samples. The magnetic field range stretched from 0.0002 to 4.7 T, including the entire clinical imaging range. The data acquired were then fitted with the appropriate theoretical models. The combination of the diamagnetic relaxation rates (R 1 = 1/T 1 and R 2 = 1/T 2 ) of tissues with the respective paramagnetic contributions of the contrast agents allowed the prediction of image contrast at any magnetic field. The results revealed a nearly identical field and dose-dependent increase of contrast enhancement induced by these contrast agents within a certain dose range. The target tissue concentration (TTC) was an important though nonlinear factor for enhancement. The currently recommended dose of 0.1 mmol/kg body weight seems to be a compromise close to the lower limits of diagnostically sufficient contrast enhancement for clinical imaging at all field strengths. At low field contrast enhancement might be insufficient. Adjustment of dose or concentration, or a new class of contrast agents with optimized relaxivity, would be a valuable contribution to a better diagnostic yield of contrast enhancement at all fields. (orig.)

  9. Assessment of 226Ra age-dependent dose from water intake

    International Nuclear Information System (INIS)

    Porntepkasemsan, Boonsom; Srisuksawad, Kanitha

    2008-01-01

    The radioactivity in canal and ground waters collected in a 2-year long observation from the vicinity of the Rare Earth Research and Development Center (RRDC), Phathumthani Province, Thailand, was measured in order to determine the concentration of 226 Ra and to estimate the age-dependent effective dose to humans due to consumption. 226 Ra activities in both canal and ground waters were well below the WHO guidance level for drinking water quality of 1 Bq L -1 . The highest 226 Ra effective doses per year were found for infants and teens. However, the observed levels of calculated 226 Ra effective doses for all age groups in both canal and ground waters show satisfactory low values (less than 15 μSv yr -1 ). These values are acceptable in accordance with the WHO recommended reference dose level of 100 μSv yr -1 from water intake of 2 L day -1

  10. Dose-dependent pheromone responses of mountain pine beetle in stands of lodgepole pine

    Science.gov (United States)

    Daniel R. Miller; B. Staffan Lindgren; John H. Borden

    2005-01-01

    We conducted seven behavioral choice tests with Lindgren multiple-funnel traps in stands of mature lodgepole pine in British Columbia, from 1988 to 1994, to determine the dosedependent responses of the mountain pine beetle, Dendroctonus ponderosae Hopkins, to its pheromones. Amultifunctional dose-dependent response was exhibited by D. ...

  11. Dose-dependent effects of oral tyrosine administration on plasma tyrosine levels and cognition in aging

    NARCIS (Netherlands)

    Rest, van de Ondine; Bloemendaal, Mirjam; Heus, De Rianne; Aarts, Esther

    2017-01-01

    The effects of tyrosine on plasma response and cognition in aging are unknown. We assessed the dose-dependent response to tyrosine administration in older adults in both plasma tyrosine concentrations and working memory performance. In this double blind randomized cross-over trial 17 older adults

  12. Dose-Dependent Effects of Oral Tyrosine Administration on Plasma Tyrosine Levels and Cognition in Aging

    NARCIS (Netherlands)

    Rest, O. van de; Bloemendaal, M.; Heus, R.A.A. de; Aarts, E.

    2017-01-01

    The effects of tyrosine on plasma response and cognition in aging are unknown. We assessed the dose-dependent response to tyrosine administration in older adults in both plasma tyrosine concentrations and working memory performance. In this double blind randomized cross-over trial 17 older adults

  13. Dose and duration dependent of aluminium in the serum liver and ...

    African Journals Online (AJOL)

    An atomic absorption spectrophotometric analysis on dose and duration dependent aluminum concentration in serum, liver and brain digests of three groups of male Wistar albino rats were investigated after seven and fourteen days of daily 0.38mg/kg, 3.8mg/kg and 38mg/kg aluminum administration respectively.

  14. Induction of IgG memory responses with polyvinylpyrrolidone (PVP) is antigen dose dependent

    International Nuclear Information System (INIS)

    Lite, H.S.; Braley-Mullen, H.

    1981-01-01

    Irradiated recipients of spleen cells from mice primed with a very low dose (0.0025 μ/g) of the thymus-independent (TI) antigen polyvinylpyrrolidone (PVP) produced PVP-specific IgG memory responses after secondary challenge with a T-dependent (TD) form of PVP, PVP-HRBC. The IgG memory responses induced by low doses of PVP were similar in magnitude to those induced by the TD antigen PVP-HRBC. The induction of IgG memory by the TI form of antigen was markedly dependent on the dose of PVP used to prime donor mice. Spleen cells from mice primed with an amount of PVP (0.25 μg) that induces an optimal primary IgM response did not produce significant IgG antibody after challenge with PVP-HRBC. The inability of higher doses of PVP to induce IgG memory may be due, at least in part, to the fact that such doses of PVP were found to induce tolerance in PVP-specific B cells and could suppress the induction of memory induced by PVP-HRBC. Low doses of PVP did not interfere with the induction of memory by PVP-HRBC. Expression of IgG memory responses in recipients of PVP-HRBC or low-dose PVP-primed cells was found to be T cell dependent. Moreover, only primed T cells could reconstitute the respnse of recipients of primed B cells, suggesting that the ability of PVP to induce IgG memory may be related to its ability to prime T helper cells. Expression of the IgG memory response in recipient mice also required the use of a TD antigen for secondary challenge, i.e., mice challenged with PVP did not develop IgG

  15. Delay differential equations and the dose-time dependence of early radiotherapy reactions

    International Nuclear Information System (INIS)

    Fenwick, John D.

    2006-01-01

    The dose-time dependence of early radiotherapy reactions impacts on the design of accelerated fractionation schedules--oral mucositis, for example, can be dose limiting for short treatments designed to avoid tumor repopulation. In this paper a framework for modeling early reaction dose-time dependence is developed. Variation of stem cell number with time after the start of a radiation schedule is modeled using a first-order delay differential equation (DDE), motivated by experimental observations linking the speed of compensatory proliferation in early reacting tissues to the degree of tissue damage. The modeling suggests that two types of early reaction radiation response are possible, stem cell numbers either monotonically approaching equilibrium plateau levels or overshooting before returning to equilibrium. Several formulas have been derived from the delay differential equation, predicting changes in isoeffective total radiation dose with schedule duration for different types of fractionation scheme. The formulas have been fitted to a wide range of published animal early reaction data, the fits all implying a degree of overshoot. Results are presented illustrating the scope of the delay differential model: most of the data are fitted well, although the model struggles with a few datasets measured for schedules with distinctive dose-time patterns. Ways of extending the current model to cope with these particular dose-time patterns are briefly discussed. The DDE approach is conceptually more complex than earlier descriptive dose-time models but potentially more powerful. It can be used to study issues not addressed by simpler models, such as the likely effects of increasing or decreasing the dose-per-day over time, or of splitting radiation courses into intense segments separated by gaps. It may also prove useful for modeling the effects of chemoirradiation

  16. Delay differential equations and the dose-time dependence of early radiotherapy reactions.

    Science.gov (United States)

    Fenwick, John D

    2006-09-01

    The dose-time dependence of early radiotherapy reactions impacts on the design of accelerated fractionation schedules--oral mucositis, for example, can be dose limiting for short treatments designed to avoid tumor repopulation. In this paper a framework for modeling early reaction dose-time dependence is developed. Variation of stem cell number with time after the start of a radiation schedule is modeled using a first-order delay differential equation (DDE), motivated by experimental observations linking the speed of compensatory proliferation in early reacting tissues to the degree of tissue damage. The modeling suggests that two types of early reaction radiation response are possible, stem cell numbers either monotonically approaching equilibrium plateau levels or overshooting before returning to equilibrium. Several formulas have been derived from the delay differential equation, predicting changes in isoeffective total radiation dose with schedule duration for different types of fractionation scheme. The formulas have been fitted to a wide range of published animal early reaction data, the fits all implying a degree of overshoot. Results are presented illustrating the scope of the delay differential model: most of the data are fitted well, although the model struggles with a few datasets measured for schedules with distinctive dose-time patterns. Ways of extending the current model to cope with these particular dose-time patterns are briefly discussed. The DDE approach is conceptually more complex than earlier descriptive dose-time models but potentially more powerful. It can be used to study issues not addressed by simpler models, such as the likely effects of increasing or decreasing the dose-per-day over time, or of splitting radiation courses into intense segments separated by gaps. It may also prove useful for modeling the effects of chemoirradiation.

  17. Dependence on age at intake of committed dose equivalents from radionuclides

    International Nuclear Information System (INIS)

    Adams, N.

    1981-01-01

    The dependence of committed dose equivalents on age at intake is needed to assess the significance of exposures of young persons among the general public resulting from inhaled or ingested radionuclides. The committed dose equivalents, evaluated using ICRP principles, depend on the body dimensions of the young person at the time of intake of a radionuclide and on subsequent body growth. Representation of growth by a series of exponential segments facilitates the derivation of general expressions for the age dependence of committed dose equivalents if metabolic models do not change with age. The additional assumption that intakes of radionuclides in air or food are proportional to a person's energy expenditure (implying age-independent dietary composition) enables the demonstration that the age of the most highly exposed 'critical groups' of the general public from these radionuclides is either about 1 year or 17 years. With the above assumptions the exposure of the critical group is less than three times the exposure of adult members of the general public. Approximate values of committed dose equivalents which avoid both underestimation and excessive overestimation are shown to be obtainable by simplified procedures. Modified procedures are suggested for use if metabolic models change with age. (author)

  18. Gadodiamide injection for enhancement of MRI in the CNS. Applications, dose, field and time dependence

    Energy Technology Data Exchange (ETDEWEB)

    Aakeson, P

    1996-10-01

    Gadodiamide injection was comparable to Gd-DTPA with regard to both safety and diagnostic efficiency in the central nervous system. The contrast effect of Gd contrast agents is higher at 1.5 T than at 0.3 T both in phantoms and patients with a maximum ratio (signal lesion/signal grey matter) more than 50% higher at 1.5 T. To achieve high contrast effect, heavily T1-weighted images are important. Prolonging the TR from 400 ms to 600 ms reduced the ratio by 15-45% depending on concentration. The effective time window for imaging of BBB (Blood-Brain Barrier) damage is between 2-5 and 25-30 minutes after injection and several scans can be performed without loss of enhancement. To provide maximum detectability of BBB damage in patients, higher doses of Gd contrast media should be useful, especially at low field strengths, as the doses used clinically today do not utilize the maximum contrast effect. High-dose (0.3 mmol/kg b.w.) contrast enhanced MRI (0.3 T) with Gadodiamide injection allowed detection of significantly more and smaller metastases (i.e. BBB damage) than standard dose (0.1 mmol/kg b.w.) High dose contrast-enhanced MRI (0.3 T) did not increase the diagnostic information for the evaluation of patients with failed back surgery syndrome compared to standard dose MRI. 55 refs, 9 figs, 10 tabs.

  19. Gadodiamide injection for enhancement of MRI in the CNS. Applications, dose, field and time dependence

    International Nuclear Information System (INIS)

    Aakeson, P.

    1996-01-01

    Gadodiamide injection was comparable to Gd-DTPA with regard to both safety and diagnostic efficiency in the central nervous system. The contrast effect of Gd contrast agents is higher at 1.5 T than at 0.3 T both in phantoms and patients with a maximum ratio (signal lesion/signal grey matter) more than 50% higher at 1.5 T. To achieve high contrast effect, heavily T1-weighted images are important. Prolonging the TR from 400 ms to 600 ms reduced the ratio by 15-45% depending on concentration. The effective time window for imaging of BBB (Blood-Brain Barrier) damage is between 2-5 and 25-30 minutes after injection and several scans can be performed without loss of enhancement. To provide maximum detectability of BBB damage in patients, higher doses of Gd contrast media should be useful, especially at low field strengths, as the doses used clinically today do not utilize the maximum contrast effect. High-dose (0.3 mmol/kg b.w.) contrast enhanced MRI (0.3 T) with Gadodiamide injection allowed detection of significantly more and smaller metastases (i.e. BBB damage) than standard dose (0.1 mmol/kg b.w.) High dose contrast-enhanced MRI (0.3 T) did not increase the diagnostic information for the evaluation of patients with failed back surgery syndrome compared to standard dose MRI. 55 refs, 9 figs, 10 tabs

  20. Non-monotonic dose dependence of the Ge- and Ti-centres in quartz

    International Nuclear Information System (INIS)

    Woda, C.; Wagner, G.A.

    2007-01-01

    The dose response of the Ge- and Ti-centres in quartz is studied over a large dose range. After an initial signal increase in the low dose range, both defects show a pronounced decrease in signal intensities for high doses. The model by Euler and Kahan [1987. Radiation effects and anelastic loss in germanium-doped quartz. Phys. Rev. B 35 (9), 4351-4359], in which the signal drop is explained by an enhanced trapping of holes at the electron trapping site, is critically discussed. A generalization of the model is then developed, following similar considerations by Lawless et al. [2005. A model for non-monotonic dose dependence of thermoluminescence (TL). J. Phys. Condens. Matter 17, 737-753], who explained a signal drop in TL by an enhanced recombination rate with electrons at the recombination centre. Finally, an alternative model for the signal decay is given, based on the competition between single and double electron capture at the electron trapping site. From the critical discussion of the different models it is concluded that the double electron capture mechanism is the most probable effect for the dose response

  1. Different dose-dependent effects of ebselen in sciatic nerve ischemia-reperfusion injury in rats.

    Science.gov (United States)

    Ozyigit, Filiz; Kucuk, Aysegul; Akcer, Sezer; Tosun, Murat; Kocak, Fatma Emel; Kocak, Cengiz; Kocak, Ahmet; Metineren, Hasan; Genc, Osman

    2015-08-26

    Ebselen is an organoselenium compound which has strong antioxidant and anti-inflammatory effects. We investigated the neuroprotective role of ebselen pretreatment in rats with experimental sciatic nerve ischemia-reperfusion (I/R) injury. Adult male Sprague Dawley rats were divided into four groups (N = 7 in each group). Before sciatic nerve I/R was induced, ebselen was injected intraperitoneally at doses of 15 and 30 mg/kg. After a 2 h ischemia and a 3 h reperfusion period, sciatic nerve tissues were excised. Tissue levels of malondialdehyde (MDA) and nitric oxide (NO), and activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were measured. Sciatic nerve tissues were also examined histopathologically. The 15 mg/kg dose of ebselen reduced sciatic nerve damage and apoptosis (pebselen. Conversely, the 30 mg/kg dose of ebselen increased sciatic nerve damage, apoptosis, iNOS positive cells (pebselen may cause different effects depending on the dose employed. Ebselen may be protective against sciatic nerve I/R injury via antioxidant and antiapoptotic activities at a 15 mg/kg dose, conversely higher doses may cause detrimental effects.

  2. High Dose Oral Calcium Treatment in Patients with Vitamin D-dependent Rickets Type II

    Directory of Open Access Journals (Sweden)

    R Vakili

    2017-02-01

    Full Text Available BACKGROUND AND OBJECTIVE: Vitamin D-dependent rickets type II (VDDR2 is a rare genetic disorder caused by mutations in vitamin D receptor (VDR and leads to resistance to biological effects of calcitriol. Based on the type of mutation, this disease is resistant to calcitriol even at high doses of calcitriol and successful treatment of these patients requires hypocalcemic modification through administration of high doses of calcium and bypassing the intestinal defect in VDR signaling. In addition to the need for frequent hospitalization and high costs, intravenous administration of calcium is associated with complications and problems such as arrhythmia and sepsis, venous catheter infection and hypercalciuria. This study aims to report the positive treatment effects of high doses of oral calcium in 4 patients with vitamin D-dependent rickets type II. CASE REPORT: In this study, 4 patients with vitamin D-dependent rickets type II, diagnosed based on clinical and biochemical symptoms of rickets with alopecia, underwent therapy using high doses of oral calcium (300 mg/kg/day in pediatric endocrinology and metabolism center of Imam Reza hospital. After a short period, increased growth rate in height, strength and elasticity of muscles was observed in addition to biochemical improvements without serious side effects and even one patient started walking independently within the first week of therapy for the first time. Patients were regularly followed up in terms of height and weight, growth rate and biochemical factors including calcium, phosphorus and alkaline phosphatase every 3 months for one year. CONCLUSION: Regardless of the type of mutation in vitamin D receptor, it is suggested that a 3-6 months trial of high dose oral calcium be started in each patient with vitamin D-dependent rickets type II, particularly for patients whose disease was diagnosed at lower ages.

  3. Dose dependent effect of progesterone on hypoxic ventilatory response in newborn rats.

    Science.gov (United States)

    Hichri, Oubeidallah; Laurin, Jean-C; Julien, Cécile A; Joseph, Vincent; Bairam, Aida

    2012-01-01

    The effect of progesterone as a respiratory stimulant in newborn subjects is less known than that in adults. This study investigated the dose-response curve (0, 2, 4, and 8 mg/kg, ip) of progesterone on ventilation in non-anesthetized newborn rats at 4- and 12-days old using plethysmography. Progesterone had no effects in the regulation of normoxic ventilation. However, it enhanced the response to moderate hypoxia (FiO(2) 12%, 20 min) in 4- but not in 12-days old pups. This response was similar between the dose of 4 and 8 mg/kg. These observations suggested that progesterone enhances in age- and dose-dependent manner the hypoxic ventilatory response in newborn rats.

  4. Relaxation behavior and dose dependence of radiation induced radicals in irradiated mango

    International Nuclear Information System (INIS)

    Kameya, Hiromi; Kakita, Daisuke; Kaimori, Yoshihiko; Ukai, Mitsuko; Kikuchi, Masahiro; Kobayashi, Yasuhiko; Shimoyama, Yuhei

    2010-01-01

    Mangoes are imported to Japan after treated with hot water. Recently, irradiated mangoes imported to U. S. are widely used. This paper reports on the ESR method for analyzing the radiation induced radicals of irradiated mangoes. Upon the γ ray irradiation, a strong single peak in the flesh and skin of mangoes was observed at g=2.004. This singlet peak may be attributed to organic free radicals. The ESR spectra of the flesh and skin of mangoes showed the radiation induced radicals due to cellulose by irradiation over 12 kGy. The relaxation times (T 1 and T 2 ) of the singlet signal were calculated. T 2 showed dose response according to increasing the irradiation dose levels, while T 1 was almost constant. The value of (T 1 T 2 ) 1/2 showed the dependence of irradiation dose level. (author)

  5. A novel time dependent gamma evaluation function for dynamic 2D and 3D dose distributions

    International Nuclear Information System (INIS)

    Podesta, Mark; Persoon, Lucas CGG; Verhaegen, Frank

    2014-01-01

    Modern external beam radiotherapy requires detailed verification and quality assurance so that confidence can be placed on both the delivery of a single treatment fraction and on the consistency of delivery throughout the treatment course. To verify dose distributions, a comparison between prediction and measurement must be made. Comparisons between two dose distributions are commonly performed using a Gamma evaluation which is a calculation of two quantities on a pixel by pixel basis; the dose difference, and the distance to agreement. By providing acceptance criteria (e.g. 3%, 3 mm), the function will find the most appropriate match within its two degrees of freedom. For complex dynamic treatments such as IMRT or VMAT it is important to verify the dose delivery in a time dependent manner and so a gamma evaluation that includes a degree of freedom in the time domain via a third parameter, time to agreement, is presented here. A C++ (mex) based gamma function was created that could be run on either CPU and GPU computing platforms that would allow a degree of freedom in the time domain. Simple test cases were created in both 2D and 3D comprising of simple geometrical shapes with well-defined boundaries varying over time. Changes of varying magnitude in either space or time were introduced and repeated gamma analyses were performed varying the criteria. A clinical VMAT case was also included, artificial air bubbles of varying size were introduced to a patient geometry, along with shifts of varying magnitude in treatment time. For all test cases where errors in distance, dose or time were introduced, the time dependent gamma evaluation could accurately highlight the errors. The time dependent gamma function presented here allows time to be included as a degree of freedom in gamma evaluations. The function allows for 2D and 3D data sets which are varying over time to be compared using appropriate criteria without penalising minor offsets of subsequent radiation

  6. Angular dependence of depth doses in a tissue slab irradiated with monoenergetic photons

    International Nuclear Information System (INIS)

    Till, E.; Zankl, M.; Drexler, G.

    1995-12-01

    This report presents dose equivalents from external photon irradiation, normalised to air kerma free in air, on the central axis of a cuboid slab of ICRU tissue for various depths, photon energies and angles of beam incidence. The data were calculated by a Monte Carlo method using an idealised planar parallel source of monoenergetic photons. The data presented here aim at facilitating the calibration of individual dosimeters; they provide also an estimate of the quantity 'personal dose equivalent' defined by the ICRU. A detailed evaluation of the dependence of the calculated conversion coefficients on depth in the slab, photon energy and angle of incidence is given. A comparison with published measured an calculated values of angular dependence factors is made. (orig.)

  7. Assessing patient dose in interventional fluoroscopy using patient-dependent hybrid phantoms

    Science.gov (United States)

    Johnson, Perry Barnett

    Interventional fluoroscopy uses ionizing radiation to guide small instruments through blood vessels or other body pathways to sites of clinical interest. The technique represents a tremendous advantage over invasive surgical procedures, as it requires only a small incision, thus reducing the risk of infection and providing for shorter recovery times. The growing use and increasing complexity of interventional procedures, however, has resulted in public health concerns regarding radiation exposures, particularly with respect to localized skin dose. Tracking and documenting patient-specific skin and internal organ dose has been specifically identified for interventional fluoroscopy where extended irradiation times, multiple projections, and repeat procedures can lead to some of the largest doses encountered in radiology. Furthermore, inprocedure knowledge of localized skin doses can be of significant clinical importance to managing patient risk and in training radiology residents. In this dissertation, a framework is presented for monitoring the radiation dose delivered to patients undergoing interventional procedures. The framework is built around two key points, developing better anthropomorphic models, and designing clinically relevant software systems for dose estimation. To begin, a library of 50 hybrid patient-dependent computational phantoms was developed based on the UF hybrid male and female reference phantoms. These phantoms represent a different type of anthropomorphic model whereby anthropometric parameters from an individual patient are used during phantom selection. The patient-dependent library was first validated and then used in two patient-phantom matching studies focused on cumulative organ and local skin dose. In terms of organ dose, patient-phantom matching was shown most beneficial for estimating the dose to large patients where error associated with soft tissue attenuation differences could be minimized. For small patients, inherent difference

  8. Human, recombinant interleukin-2 induces in vitro histamine release in a dose-dependent manner

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Petersen, L J; Skov, P S

    1995-01-01

    significantly in the supernatant from cells stimulated by rIL-2 in a dose-dependent manner both in patients and volunteers. Total cell-bound histamine was 49.3 +/- 4.1 ng/ml in patients compared to 78.5 +/- 7.7 ng/ml in volunteers (p ... was significantly enhanced in cancer patients compared to volunteers (*p manner in both cancer patients and volunteers. This may in part explain the severe toxicity observed during high...

  9. Marijuana’s Dose-Dependent Effects in Daily Marijuana Smokers

    OpenAIRE

    Ramesh, Divya; Haney, Margaret; Cooper, Ziva D.

    2013-01-01

    Active marijuana produces significant subjective, psychomotor, and physiological effects relative to inactive marijuana, yet demonstrating that these effects are dose-dependent has proven difficult. This within-subject, double-blind study was designed to develop a smoking procedure to obtain a marijuana dose–response function. In four outpatient laboratory sessions, daily marijuana smokers (N = 17 males, 1 female) smoked six 5-s puffs from 3 marijuana cigarettes (2 puffs/cigarette). The numbe...

  10. Dosing-time-dependent variation in biliary excretion of flomoxef in rats.

    Science.gov (United States)

    Hishikawa, Shuji; Sugimoto, Koh-ichi; Kobayashi, Eiji; Kumagai, Yuji; Fujimura, Akio

    2003-05-01

    We previously reported that the biliary excretion of flomoxef, an oxacephem antibiotic, was greater after dosing at 21:00 than at 09:00 h in diurnally active human subjects. The present study was undertaken to examine whether the biliary excretion of flomoxef is also dependent on its dosing time in rats. Adult male Wistar rats were housed under light on at 07:00 h and off at 19:00 h. Bile fluid was completely drained through a polyethylene catheter from conscious animals. Flomoxef (20 mg/kg) was injected into the tail vein at 09:00 or 21:00 h by a cross-over design, and drained bile fluid was collected for 8 h after each dosing. The maximum concentration of biliary flomoxef was significantly greater and its total excretion tended to be greater after dosing at 09:00 than 21:00 h. These results suggest the biliary excretion of flomoxef is enhanced after dosing at the beginning of the rest period in rats, as it is in humans.

  11. Dose dependency of time of onset of radiation-induced growth hormone deficiency

    International Nuclear Information System (INIS)

    Clayton, P.E.; Shalet, S.M.

    1991-01-01

    Growth hormone (GH) secretion during insulin-induced hypoglycemia was assessed on 133 occasions in 82 survivors of childhood malignant disease. All had received cranial irradiation with a dose range to the hypothalamic-pituitary axis of 27 to 47.5 Gy (estimated by a schedule of 16 fractions over 3 weeks) and had been tested on one or more occasions between 0.2 and 18.9 years after treatment. Results of one third of the GH tests were defined as normal (GH peak response, greater than 15 mU/L) within the first 5 years, in comparison with 16% after 5 years. Stepwise multiple linear regression analysis showed that dose (p = 0.007) and time from irradiation (p = 0.03), but not age at therapy, had a significant influence on peak GH responses. The late incidence of GH deficiency was similar over the whole dose range (4 of 26 GH test results normal for less than 30 Gy and 4 of 25 normal for greater than or equal to 30 Gy after 5 years), but the speed of onset over the first years was dependent on dose. We conclude that the requirement for GH replacement therapy and the timing of its introduction will be influenced by the dose of irradiation received by the hypothalamic-pituitary axis

  12. Dose-Dependent Cortical Thinning After Partial Brain Irradiation in High-Grade Glioma

    Energy Technology Data Exchange (ETDEWEB)

    Karunamuni, Roshan [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Bartsch, Hauke; White, Nathan S. [Department of Radiology, University of California San Diego, La Jolla, California (United States); Moiseenko, Vitali; Carmona, Ruben; Marshall, Deborah C.; Seibert, Tyler M. [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); McDonald, Carrie R. [Department of Psychiatry, University of California San Diego, La Jolla, California (United States); Farid, Nikdokht; Krishnan, Anithapriya; Kuperman, Joshua [Department of Radiology, University of California San Diego, La Jolla, California (United States); Mell, Loren [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Brewer, James B.; Dale, Anders M. [Department of Radiology, University of California San Diego, La Jolla, California (United States); Hattangadi-Gluth, Jona A., E-mail: jhattangadi@ucsd.edu [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States)

    2016-02-01

    Purpose: Radiation-induced cognitive deficits may be mediated by tissue damage to cortical regions. Volumetric changes in cortex can be reliably measured using high-resolution magnetic resonance imaging (MRI). We used these methods to study the association between radiation therapy (RT) dose and change in cortical thickness in high-grade glioma (HGG) patients. Methods and Materials: We performed a voxel-wise analysis of MRI from 15 HGG patients who underwent fractionated partial brain RT. Three-dimensional MRI was acquired pre- and 1 year post RT. Cortex was parceled with well-validated segmentation software. Surgical cavities were censored. Each cortical voxel was assigned a change in cortical thickness between time points, RT dose value, and neuroanatomic label by lobe. Effects of dose, neuroanatomic location, age, and chemotherapy on cortical thickness were tested using linear mixed effects (LME) modeling. Results: Cortical atrophy was seen after 1 year post RT with greater effects at higher doses. Estimates from LME modeling showed that cortical thickness decreased by −0.0033 mm (P<.001) for every 1-Gy increase in RT dose. Temporal and limbic cortex exhibited the largest changes in cortical thickness per Gy compared to that in other regions (P<.001). Age and chemotherapy were not significantly associated with change in cortical thickness. Conclusions: We found dose-dependent thinning of the cerebral cortex, with varying neuroanatomical regional sensitivity, 1 year after fractionated partial brain RT. The magnitude of thinning parallels 1-year atrophy rates seen in neurodegenerative diseases and may contribute to cognitive decline following high-dose RT.

  13. Induction of oral tolerance with micro-doses of ovomucoid depends on the length of the feeding period

    DEFF Research Database (Denmark)

    Kjær, Tanja; Frøkiær, Hanne

    2002-01-01

    Oral administration of antigen induces antigen-specific immunologic tolerance, which is known to be dose-dependent. We studied the influence of continuous oral administration of nanogram and microgram doses of antigen on oral tolerance induction. Mice were continuously exposed to varying doses (1...

  14. Study of the SEY dependence on the electron beams dose and energy

    International Nuclear Information System (INIS)

    Commisso, M.

    2011-01-01

    During operation, the internal walls of modern particle accelerators are subjected to synchrotron radiation irradiation and/or electron bombardment. Such phenomena do affect surface properties such as the secondary electron yield, (SEY). A low SEY is a key parameter to control and overcome any detrimental effect on the accelerator performance eventually induced by the build-up of an Electron Cloud (E C). In laboratory experiments SEY reduction (called scrubbing) has been studied as a function of dose but the actual kinetic energy dependence has never been considered as an important parameter. For this reason and given the peculiar behavior observed for low-energy electrons, we decided to study this dependence accurately. Here we report results of SEY measurements performed bombarding Cu samples obtained from the Large Hadron Collider (Lhc) with different doses of electron beam with energy in the range 10-500 eV. Our results demonstrate that the potentiality of an electron beam to reduce the SEY does not only depend on its dose, but also on its energy. Furthermore, since E C build-up was predicted and observed also the DAΦNE ring, we report some preliminary measurements on the conditioning of Al samples. An overview of future experiments which we will perform in LNF is then given.

  15. Extent of radiosensitization by the PARP inhibitor olaparib depends on its dose, the radiation dose and the integrity of the homologous recombination pathway of tumor cells

    NARCIS (Netherlands)

    Verhagen, Caroline V. M.; de Haan, Rosemarie; Hageman, Floor; Oostendorp, Tim P. D.; Carli, Annalisa L. E.; O'Connor, Mark J.; Jonkers, Jos; Verheij, Marcel; van den Brekel, Michiel W.; Vens, Conchita

    2015-01-01

    The PARP inhibitor olaparib is currently tested in clinical phase 1 trials to define safe dose levels in combination with RT. However, certain clinically relevant insights are still lacking. Here we test, while comparing to single agent activity, the olaparib dose and genetic background dependence

  16. Kinetic and dose dependences of the SOS-induction in E.coli K-12 (uvrA) cells exposed to the different UV doses

    International Nuclear Information System (INIS)

    Komova, O.V.; Kandiano, E.S.; Malavya, G.

    1999-01-01

    The kinetic and dose dependences of the SOS-induction in E.coli (uvrA) cells exposed to UV light were investigated. Below 2 J/m 2 the rate of the SOS-induction increased with dose. The maximal level of the SOS-response was proportional to the UV dose. Pyrimidine dimers were necessary for the induction. In the dose range 2-10 J/m 2 the rate of the SOS-induction decreased with dose. The dose-response curve was non-linear. Pyrimidine dimers were not required for the induction. The nature of the molecular events leading to the SOS-induction at low and high UV doses was discussed. (author)

  17. Kinetic and dose dependencies of the SOS-induction in E.coli K-12 (uvrA) cells exposed to different UV doses

    International Nuclear Information System (INIS)

    Komova, O.V.; Kandiano, E.S.; Malavina, G.; )

    2000-01-01

    Kinetic and dose dependencies of the SOS-induction in E. coli (uvrA) cells exposed to UV light were investigated. below 2 J/m 2 the rate of the SOS-induction increased with dose. Maximal level of the SOS-response was proportional to the UV dose. Pyrimidine dimers were necessary for the induction. In the dose range 2-10 J/m 2 the rate of SOS-induction decreased with dose. Dose-maximum response curve was non-linear. Pyrimidine dimers were not required for the induction. nature of the molecular events leading to the SOS-induction at low and high doses was discussed [ru

  18. Cerebral Cortex Regions Selectively Vulnerable to Radiation Dose-Dependent Atrophy

    International Nuclear Information System (INIS)

    Seibert, Tyler M.; Karunamuni, Roshan; Kaifi, Samar; Burkeen, Jeffrey; Connor, Michael; Krishnan, Anitha Priya; White, Nathan S.; Farid, Nikdokht; Bartsch, Hauke; Murzin, Vyacheslav; Nguyen, Tanya T.; Moiseenko, Vitali; Brewer, James B.; McDonald, Carrie R.; Dale, Anders M.; Hattangadi-Gluth, Jona A.

    2017-01-01

    Purpose and Objectives: Neurologic deficits after brain radiation therapy (RT) typically involve decline in higher-order cognitive functions such as attention and memory rather than sensory defects or paralysis. We sought to determine whether areas of the cortex critical to cognition are selectively vulnerable to radiation dose-dependent atrophy. Methods and Materials: We measured change in cortical thickness in 54 primary brain tumor patients who underwent fractionated, partial brain RT. The study patients underwent high-resolution, volumetric magnetic resonance imaging (T1-weighted; T2 fluid-attenuated inversion recovery, FLAIR) before RT and 1 year afterward. Semiautomated software was used to segment anatomic regions of the cerebral cortex for each patient. Cortical thickness was measured for each region before RT and 1 year afterward. Two higher-order cortical regions of interest (ROIs) were tested for association between radiation dose and cortical thinning: entorhinal (memory) and inferior parietal (attention/memory). For comparison, 2 primary cortex ROIs were also tested: pericalcarine (vision) and paracentral lobule (somatosensory/motor). Linear mixed-effects analyses were used to test all other cortical regions for significant radiation dose-dependent thickness change. Statistical significance was set at α = 0.05 using 2-tailed tests. Results: Cortical atrophy was significantly associated with radiation dose in the entorhinal (P=.01) and inferior parietal ROIs (P=.02). By contrast, no significant radiation dose-dependent effect was found in the primary cortex ROIs (pericalcarine and paracentral lobule). In the whole-cortex analysis, 9 regions showed significant radiation dose-dependent atrophy, including areas responsible for memory, attention, and executive function (P≤.002). Conclusions: Areas of cerebral cortex important for higher-order cognition may be most vulnerable to radiation-related atrophy. This is consistent with clinical observations

  19. Cerebral Cortex Regions Selectively Vulnerable to Radiation Dose-Dependent Atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Seibert, Tyler M.; Karunamuni, Roshan; Kaifi, Samar; Burkeen, Jeffrey; Connor, Michael [Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California (United States); Krishnan, Anitha Priya; White, Nathan S.; Farid, Nikdokht; Bartsch, Hauke [Department of Radiology, University of California, San Diego, La Jolla, California (United States); Murzin, Vyacheslav [Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California (United States); Nguyen, Tanya T. [Department of Psychiatry, University of California, San Diego, La Jolla, California (United States); Moiseenko, Vitali [Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California (United States); Brewer, James B. [Department of Radiology, University of California, San Diego, La Jolla, California (United States); Department of Neurosciences, University of California, San Diego, La Jolla, California (United States); McDonald, Carrie R. [Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California (United States); Department of Psychiatry, University of California, San Diego, La Jolla, California (United States); Dale, Anders M. [Department of Radiology, University of California, San Diego, La Jolla, California (United States); Department of Psychiatry, University of California, San Diego, La Jolla, California (United States); Department of Neurosciences, University of California, San Diego, La Jolla, California (United States); Hattangadi-Gluth, Jona A., E-mail: jhattangadi@ucsd.edu [Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California (United States)

    2017-04-01

    Purpose and Objectives: Neurologic deficits after brain radiation therapy (RT) typically involve decline in higher-order cognitive functions such as attention and memory rather than sensory defects or paralysis. We sought to determine whether areas of the cortex critical to cognition are selectively vulnerable to radiation dose-dependent atrophy. Methods and Materials: We measured change in cortical thickness in 54 primary brain tumor patients who underwent fractionated, partial brain RT. The study patients underwent high-resolution, volumetric magnetic resonance imaging (T1-weighted; T2 fluid-attenuated inversion recovery, FLAIR) before RT and 1 year afterward. Semiautomated software was used to segment anatomic regions of the cerebral cortex for each patient. Cortical thickness was measured for each region before RT and 1 year afterward. Two higher-order cortical regions of interest (ROIs) were tested for association between radiation dose and cortical thinning: entorhinal (memory) and inferior parietal (attention/memory). For comparison, 2 primary cortex ROIs were also tested: pericalcarine (vision) and paracentral lobule (somatosensory/motor). Linear mixed-effects analyses were used to test all other cortical regions for significant radiation dose-dependent thickness change. Statistical significance was set at α = 0.05 using 2-tailed tests. Results: Cortical atrophy was significantly associated with radiation dose in the entorhinal (P=.01) and inferior parietal ROIs (P=.02). By contrast, no significant radiation dose-dependent effect was found in the primary cortex ROIs (pericalcarine and paracentral lobule). In the whole-cortex analysis, 9 regions showed significant radiation dose-dependent atrophy, including areas responsible for memory, attention, and executive function (P≤.002). Conclusions: Areas of cerebral cortex important for higher-order cognition may be most vulnerable to radiation-related atrophy. This is consistent with clinical observations

  20. Energy-dependency correction factors for the digital dosimeters using in NMD environment dose assessment

    International Nuclear Information System (INIS)

    Lai, Y.C.; Huang, Y. F.; Chen, Y.W.

    2008-01-01

    Full text: Short-term environment dose-rate assessments using real-time digital dosimeters within a Nuclear Medicine Department (NMD) are gaining more world-wide uses recently. In the past, conventional ion chamber-type survey-meters are used dominantly in environmental dose rates evaluation. Although it has suffered less gamma energy-dependency, but it is less sensitive in comparison with other digital dosimeters and more bulky in design that can hardly make it into a pocket size application. With modern electronic advancement and its shrinking in physical size, real-time personal dosimeter nowadays has gaining more popular to use a miniature G-M counter or a solid-state diode sensor, or even a NaI(Tl) scintillation device for ambient radiation monitoring. Radiation sensor operated in pulse-mode can never been used in doses or dose rates determination since each digital pulse has carried no energy information of the impinging gamma ray being interactive with, especially in the G-M counter or the diode sensor case. The raw count rates measured from a pulse-mode device are heavily dependent on the packaging of the sensor to make it less energy-sensitive. The doses or dose rates are then calculated by using a built-in conversion factor, based on a Cs-137 beam source calibration data conducted by various manufacturing vendors, to convert its raw counts into a so-called dose or dose-rate unit. In this study, we have focused our interests in the low energy response of the digital dosimeters from several brands currently for our in-house uses. Mainly, Tc-99m and I-131 in point sources and water phantoms detection configurations have been deployed to simulate our NMD outpatients for environment radiation monitoring purpose. The energy-dependent correction factors of the digital dosimeters will be evaluated by using calibrated Tc-99m or I-131 standard sources directly that has much lower gamma energy than the Cs-137 beam source of 661 keV. In the near future, we would

  1. Dose-Dependent and Lasting Influences of Intranasal Vasopressin on Face Processing in Men

    Directory of Open Access Journals (Sweden)

    Daniel Price

    2017-09-01

    Full Text Available Arginine vasopressin (AVP and related peptides have diverse effects on social behaviors in vertebrates, sometimes promoting affiliative interactions and sometimes aggressive or antisocial responses. The type of influence, in at least some species, depends on social contexts, including the sex of the individuals in the interaction and/or on the levels of peptide within brain circuits that control the behaviors. To determine if AVP promotes different responses to same- and other-sex faces in men, and if those effects are dose dependent, we measured the effects of two doses of AVP on subjective ratings of male and female faces. We also tested if any influences persist beyond the time of drug delivery. When AVP was administered intranasally on an initial test day, 20 IU was associated with decreased social assessments relative to placebo and 40 IU, and some of the effects persisted beyond the initial drug delivery and appeared to generalize to novel faces on subsequent test days. In single men, those influences were most pronounced, but not exclusive, for male faces, whereas in coupled men they were primarily associated with responses to female faces. Similar influences were not observed if AVP was delivered after placebo on a second test day. In a preliminary analysis, the differences in social assessments observed between men who received 20 and 40 IU, which we suggest primarily reflect lowered social assessments induced by the lower dose, appeared most pronounced in subjects who carry what has been identified as a risk allele for the V1a receptor gene. Together, these results suggest that AVP’s effects on face processing, and possibly other social responses, differ according to dose, depend on relationship status, and may be more prolonged than previously recognized.

  2. Quality of life in a cohort of high-dose benzodiazepine dependent patients.

    Science.gov (United States)

    Lugoboni, Fabio; Mirijello, Antonio; Faccini, Marco; Casari, Rebecca; Cossari, Anthony; Musi, Gessica; Bissoli, Giorgia; Quaglio, Gianluca; Addolorato, Giovanni

    2014-09-01

    Benzodiazepines (BZD) are among the most widely prescribed drugs in developed countries. Since BZD can produce tolerance and dependence even in a short time, their use is recommended for a very limited time. However, these recommendations have been largely disregarded. The chronic use of BZD causes a number of serious side effects, i.e., cognitive impairment, falls, traffic accidents, dependence and tolerance. The aim of the present study was to evaluate quality of life (QoL) in a cohort of 62 consecutive high-dose BZD-dependent patients seeking a BZD detoxification. Patients seeking BZD detoxification were evaluated using the General Health Questionnaire (GHQ-12) and the short form-36 questionnaire (SF-36). Patients showed a significant reduction of QoL as measured by either SF-36 or GHQ-12. In particular, the greater impairment was observed in the items exploring physical and emotional status. Physical functioning was the item more influenced by the length of BZD abuse. Female patients showed a greater reduction of QoL compared to male, at least in some of the explored items. Social functioning scores were greatly reduced. The present study shows for the first time that high-doses BZD dependent patients have a reduced QoL and a reduced social functioning, along with high levels of psychological distress. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Establishment Success of the Beetle Tapeworm Hymenolepis diminuta Depends on Dose and Host Body Condition

    Directory of Open Access Journals (Sweden)

    Suraj Dhakal

    2018-02-01

    Full Text Available Parasite effects on host fitness and immunology are often intensity-dependent. Unfortunately, only few experimental studies on insect-parasite interactions attempt to control the level of infection, which may contribute substantial variation to the fitness or immunological parameters of interest. The tapeworm Hymenolepis diminuta—flour beetle Tenebrio molitor model—has been used extensively for ecological and evolutionary host–parasite studies. Successful establishment of H. diminuta cysticercoids in T. molitor relies on ingestion of viable eggs and penetration of the gut wall by the onchosphere. Like in other insect models, there is a lack of standardization of the infection load of cysticercoids in beetles. The aims of this study were to: (1 quantify the relationship between exposure dose and establishment success across several H. diminuta egg concentrations; and (2 test parasite establishment in beetles while experimentally manipulating host body condition and potential immune response to infection. Different egg concentrations of H. diminuta isolated from infected rat feces were fed to individual beetles 7–10 days after eclosion and beetles were exposed to starvation, wounding, or insertion of a nylon filament one hour prior to infection. We found that the establishment of cysticercoids in relation to exposure dose could be accurately predicted using a power function where establishment success was low at three lowest doses and higher at the two highest doses tested. Long-term starvation had a negative effect on cysticercoid establishment success, while insertion of a nylon filament and wounding the beetles did not have any effect compared to control treatment. Thus, our results show that parasite load may be predicted from the exposure dose within the observed range, and that the relationship between dose and parasite establishment success is able to withstand some changes in host body condition.

  4. Establishment Success of the Beetle Tapeworm Hymenolepis diminuta Depends on Dose and Host Body Condition

    Science.gov (United States)

    Jane Cassidy, Elizabeth; Vitt Meyling, Nicolai

    2018-01-01

    Parasite effects on host fitness and immunology are often intensity-dependent. Unfortunately, only few experimental studies on insect-parasite interactions attempt to control the level of infection, which may contribute substantial variation to the fitness or immunological parameters of interest. The tapeworm Hymenolepis diminuta—flour beetle Tenebrio molitor model—has been used extensively for ecological and evolutionary host–parasite studies. Successful establishment of H. diminuta cysticercoids in T. molitor relies on ingestion of viable eggs and penetration of the gut wall by the onchosphere. Like in other insect models, there is a lack of standardization of the infection load of cysticercoids in beetles. The aims of this study were to: (1) quantify the relationship between exposure dose and establishment success across several H. diminuta egg concentrations; and (2) test parasite establishment in beetles while experimentally manipulating host body condition and potential immune response to infection. Different egg concentrations of H. diminuta isolated from infected rat feces were fed to individual beetles 7–10 days after eclosion and beetles were exposed to starvation, wounding, or insertion of a nylon filament one hour prior to infection. We found that the establishment of cysticercoids in relation to exposure dose could be accurately predicted using a power function where establishment success was low at three lowest doses and higher at the two highest doses tested. Long-term starvation had a negative effect on cysticercoid establishment success, while insertion of a nylon filament and wounding the beetles did not have any effect compared to control treatment. Thus, our results show that parasite load may be predicted from the exposure dose within the observed range, and that the relationship between dose and parasite establishment success is able to withstand some changes in host body condition. PMID:29401652

  5. Different dose-dependent effects of ebselen in sciatic nerve ischemia-reperfusion injury in rats

    Directory of Open Access Journals (Sweden)

    Filiz Ozyigit

    2015-08-01

    Full Text Available Ebselen is an organoselenium compound which has strong antioxidant and anti-inflammatory effects. We investigated the neuroprotective role of ebselen pretreatment in rats with experimental sciatic nerve ischemia-reperfusion (I/R injury. Adult male Sprague Dawley rats were divided into four groups (N = 7 in each group. Before sciatic nerve I/R was induced, ebselen was injected intraperitoneally at doses of 15 and 30 mg/kg. After a 2 h ischemia and a 3 h reperfusion period, sciatic nerve tissues were excised. Tissue levels of malondialdehyde (MDA and nitric oxide (NO, and activities of superoxide dismutase (SOD, glutathione peroxidase (GPx, and catalase (CAT were measured. Sciatic nerve tissues were also examined histopathologically. The 15 mg/kg dose of ebselen reduced sciatic nerve damage and apoptosis (P < 0.01, levels of MDA, NO, and inducible nitric oxide synthase (iNOS positive cells (P < 0.01, P < 0.05, respectively, and increased SOD, GPx, and CAT activities (P < 0.001, P < 0.01, P < 0.05, respectively compared with the I/R group that did not receive ebselen. Conversely, the 30 mg/kg dose of ebselen increased sciatic nerve damage, apoptosis, iNOS positive cells (P < 0.01, P < 0.05, P < 0.001 and MDA and NO levels (P < 0.05, P < 0.01 and decreased SOD, GPx, and CAT activities (P < 0.05 compared with the sham group. The results of this study suggest that ebselen may cause different effects depending on the dose employed. Ebselen may be protective against sciatic nerve I/R injury via antioxidant and antiapoptotic activities at a 15 mg/kg dose, conversely higher doses may cause detrimental effects.

  6. Electron Beam Irradiation Dose Dependently Damages the Bacillus Spore Coat and Spore Membrane

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    S. E. Fiester

    2012-01-01

    Full Text Available Effective control of spore-forming bacilli begs suitable physical or chemical methods. While many spore inactivation techniques have been proven effective, electron beam (EB irradiation has been frequently chosen to eradicate Bacillus spores. Despite its widespread use, there are limited data evaluating the effects of EB irradiation on Bacillus spores. To study this, B. atrophaeus spores were purified, suspended in sterile, distilled water, and irradiated with EB (up to 20 kGy. Irradiated spores were found (1 to contain structural damage as observed by electron microscopy, (2 to have spilled cytoplasmic contents as measured by spectroscopy, (3 to have reduced membrane integrity as determined by fluorescence cytometry, and (4 to have fragmented genomic DNA as measured by gel electrophoresis, all in a dose-dependent manner. Additionally, cytometry data reveal decreased spore size, increased surface alterations, and increased uptake of propidium iodide, with increasing EB dose, suggesting spore coat alterations with membrane damage, prior to loss of spore viability. The present study suggests that EB irradiation of spores in water results in substantial structural damage of the spore coat and inner membrane, and that, along with DNA fragmentation, results in dose-dependent spore inactivation.

  7. Operator dependency of the radiation exposure in cardiac interventions: feasibility of ultra low dose levels

    International Nuclear Information System (INIS)

    Emre Ozpelit, Mehmet; Ercan, Ertugrul; Pekel, Nihat; Tengiz, Istemihan; Yilmaz, Akar; Ozpelit, Ebru; Ozyurtlu, Ferhat

    2017-01-01

    Introduction: Mean radiation exposure in invasive cardiology varies greatly between different centres and interventionists. The International Commission on Radiological Protection and the EURATOM Council stipulate that, despite reference values, 'All medical exposure for radiodiagnostic purposes shall be kept as low as reasonably achievable' (ALARA). The purpose of this study is to establish the effects of the routine application of ALARA principles and to determine operator and procedure impact on radiation exposure in interventional cardiology. Materials and methods: A total of 240 consecutive cardiac interventional procedures were analysed. Five operators performed the procedures, two of whom were working in accordance with ALARA principles (Group 1 operators) with the remaining three working in a standard manner (Group 2 operators). Radiation exposure levels of these two groups were compared. Results: Total fluoroscopy time and the number of radiographic runs were similar between groups. However, dose area product and cumulative dose were significantly lower in Group 1 when compared with Group 2. Radiation levels of Group 1 were far below even the reference levels in the literature, thus representing an ultra-low-dose radiation exposure in interventional cardiology. Conclusion: By use of simple radiation reducing techniques, ultra-low-dose radiation exposure is feasible in interventional cardiology. Achievability of such levels depends greatly on operator awareness, desire, knowledge and experience of radiation protection. (authors)

  8. Genetic basis of haloperidol resistance in Saccharomyces cerevisiae is complex and dose dependent.

    Directory of Open Access Journals (Sweden)

    Xin Wang

    2014-12-01

    Full Text Available The genetic basis of most heritable traits is complex. Inhibitory compounds and their effects in model organisms have been used in many studies to gain insights into the genetic architecture underlying quantitative traits. However, the differential effect of compound concentration has not been studied in detail. In this study, we used a large segregant panel from a cross between two genetically divergent yeast strains, BY4724 (a laboratory strain and RM11_1a (a vineyard strain, to study the genetic basis of variation in response to different doses of a drug. Linkage analysis revealed that the genetic architecture of resistance to the small-molecule therapeutic drug haloperidol is highly dose-dependent. Some of the loci identified had effects only at low doses of haloperidol, while other loci had effects primarily at higher concentrations of the drug. We show that a major QTL affecting resistance across all concentrations of haloperidol is caused by polymorphisms in SWH1, a homologue of human oxysterol binding protein. We identify a complex set of interactions among the alleles of the genes SWH1, MKT1, and IRA2 that are most pronounced at a haloperidol dose of 200 µM and are only observed when the remainder of the genome is of the RM background. Our results provide further insight into the genetic basis of drug resistance.

  9. Genetic Basis of Haloperidol Resistance in Saccharomyces cerevisiae Is Complex and Dose Dependent

    Science.gov (United States)

    Wang, Xin; Kruglyak, Leonid

    2014-01-01

    The genetic basis of most heritable traits is complex. Inhibitory compounds and their effects in model organisms have been used in many studies to gain insights into the genetic architecture underlying quantitative traits. However, the differential effect of compound concentration has not been studied in detail. In this study, we used a large segregant panel from a cross between two genetically divergent yeast strains, BY4724 (a laboratory strain) and RM11_1a (a vineyard strain), to study the genetic basis of variation in response to different doses of a drug. Linkage analysis revealed that the genetic architecture of resistance to the small-molecule therapeutic drug haloperidol is highly dose-dependent. Some of the loci identified had effects only at low doses of haloperidol, while other loci had effects primarily at higher concentrations of the drug. We show that a major QTL affecting resistance across all concentrations of haloperidol is caused by polymorphisms in SWH1, a homologue of human oxysterol binding protein. We identify a complex set of interactions among the alleles of the genes SWH1, MKT1, and IRA2 that are most pronounced at a haloperidol dose of 200 µM and are only observed when the remainder of the genome is of the RM background. Our results provide further insight into the genetic basis of drug resistance. PMID:25521586

  10. Dose-dependent response of Trichoderma harzianum in improving drought tolerance in rice genotypes.

    Science.gov (United States)

    Pandey, Veena; Ansari, Mohammad W; Tula, Suresh; Yadav, Sandep; Sahoo, Ranjan K; Shukla, Nandini; Bains, Gurdeep; Badal, Shail; Chandra, Subhash; Gaur, A K; Kumar, Atul; Shukla, Alok; Kumar, J; Tuteja, Narendra

    2016-05-01

    This study demonstrates a dose-dependent response of Trichoderma harzianum Th-56 in improving drought tolerance in rice by modulating proline, SOD, lipid peroxidation product and DHN / AQU transcript level, and the growth attributes. In the present study, the effect of colonization of different doses of T. harzianum Th-56 strain in rice genotypes were evaluated under drought stress. The rice genotypes treated with increasing dose of T. harzianum strain Th-56 showed better drought tolerance as compared with untreated control plant. There was significant change in malondialdehyde, proline, higher superoxide dismutase level, plant height, total dry matter, relative chlorophyll content, leaf rolling, leaf tip burn, and the number of scorched/senesced leaves in T. harzianum Th-56 treated rice genotypes under drought stress. This was corroborated with altered expression of aquaporin and dehydrin genes in T. harzianum Th-56 treated rice genotypes. The present findings suggest that a dose of 30 g/L was the most effective in improving drought tolerance in rice, and its potential exploitation will contribute to the advancement of rice genotypes to sustain crop productivity under drought stress. Interaction studies of T. harzianum with three aromatic rice genotypes suggested that PSD-17 was highly benefitted from T. harzianum colonization under drought stress.

  11. Estimation of average glandular dose depending on the thickness of the breast

    International Nuclear Information System (INIS)

    Real, Jessica V.; Luz, Renata M. da; Fröhlich, Bruna D.; Pertile, Alessandra S.; Silva, Ana Maria Marques da

    2014-01-01

    Breast cancer is the most common type of cancer in women worldwide. Mammography is, to date, the most efficient method for detecting an abnormality in the patient's breast. It is a technique of imaging diagnostic that requires special care because radiographs without adequate quality may lead to a false diagnosis and lead to the need for a repeat examination, increasing the dose of radiation in the patient. This study aimed to evaluate the average glandular dose (AGD), depending on the breast thickness in patients undergoing routine tests, with a digital computer radiography processing system. Analyzed 30 exhibitions in patients aged (65 ± 12) years, in the right and left caudal skull projections, for breasts with thicknesses between 45 mm and 50 mm. The calculated value of the AGD for this track thickness was (1.600 ± 0.009) mGy. The performance of mammography quality control tests was satisfactory and the AGD values obtained for the chosen thickness range is acceptable, since the threshold achievable is 1.6 mGy and the acceptable is 2 mGy. In Brazil, it is only required the input dose calculation in skin for 45 mm breasts. However, the calculation of AGD is required for different thicknesses of the breast, to identify the best mammographic pattern aiming at better image quality at the lowest dose provided the patient

  12. Studies of the sensitivity dependence of float zone silicon diodes on gamma absorbed dose

    International Nuclear Information System (INIS)

    Pascoalino, K.C.S.; Santos, T.C. dos; Barbosa, R.F.; Camargo, F. de; Goncalves, J.A.C.; Bueno, C.C.

    2011-01-01

    Full text: Several advantages of silicon diodes which include small size, low cost, high sensitivity and wide availability, make them suitable for dosimetry and for radiation field mapping. However, the small radiation tolerance of ordinary silicon devices has imposed constraints on their application in intense radiation fields such as found in industrial radiation processes. This scenario has been changed with the development of radiation hard silicon devices to be used as track detectors in high-energy physics experiments. Particularly, in this work it is presented the dosimetric results obtained with a batch of nine junction silicon diodes developed, in the framework of CERN RD50 Collaboration, as good candidates for improved radiation hardness. These diodes were produced with 300 micrometer n-type silicon substrate grown by standard float zone technique and processed by the Microelectronics Center of Helsinki University of Technology. The samples irradiation was performed using a Co-60 irradiator (Gammacell 220) which delivers a dose-rate of 2 kGy/h. During the irradiation, the unbiased diodes were connected through low-noise coaxial cables to the input of a KEITHLEY 617 electrometer, in order to monitor the devices photocurrent as a function of the exposure time. To study the response uniformity of the batch of nine diodes as well the sensitivity dependence on the absorbed dose, they were irradiated with different doses from 5 kGy up to 50 kGy. The sensitivity response of each device was investigated through the on-line measurements of the current signals as a function of the exposure time. For doses up to 5 kGy, all diodes exhibited a current decay of almost six percent in comparison with the value registered at the start-time of the irradiation. However, this decrease in the current sensitivity is much smaller than those observed with ordinary diodes for the same absorbed dose. The dose-response curves of the devices were also investigated through the plot

  13. Salmonella fecal shedding and immune responses are dose- and serotype- dependent in pigs.

    Directory of Open Access Journals (Sweden)

    Renata Ivanek

    Full Text Available Despite the public health importance of Salmonella infection in pigs, little is known about the associated dynamics of fecal shedding and immunity. In this study, we investigated the transitions of pigs through the states of Salmonella fecal shedding and immune response post-Salmonella inoculation as affected by the challenge dose and serotype. Continuous-time multistate Markov models were developed using published experimental data. The model for shedding had four transient states, of which two were shedding (continuous and intermittent shedding and two non-shedding (latency and intermittent non-shedding, and one absorbing state representing permanent cessation of shedding. The immune response model had two transient states representing responses below and above the seroconversion level. The effects of two doses [low (0.65×10(6 CFU/pig and high (0.65×10(9 CFU/pig] and four serotypes (Salmonella Yoruba, Salmonella Cubana, Salmonella Typhimurium, and Salmonella Derby on the models' transition intensities were evaluated using a proportional intensities model. Results indicated statistically significant effects of the challenge dose and serotype on the dynamics of shedding and immune response. The time spent in the specific states was also estimated. Continuous shedding was on average 10-26 days longer, while intermittent non-shedding was 2-4 days shorter, in pigs challenged with the high compared to low dose. Interestingly, among pigs challenged with the high dose, the continuous and intermittent shedding states were on average up to 10-17 and 3-4 days longer, respectively, in pigs infected with S. Cubana compared to the other three serotypes. Pigs challenged with the high dose of S. Typhimurium or S. Derby seroconverted on average up to 8-11 days faster compared to the low dose. These findings highlight that Salmonella fecal shedding and immune response following Salmonella challenge are dose- and serotype-dependent and that the detection of

  14. Dependence of alanine gel dosimeter response as a function of photon clinical beams dose rate

    International Nuclear Information System (INIS)

    Silva, Cleber Feijo; Campos, Leticia Lucente

    2013-01-01

    Gel dosimetry is a new area developed by Gore, it is ery useful for application in radiotherapy because using NMR imaging as evaluation technique is possible to evaluate three dimensional absorbed dose distribution. The measure technique is based on difference of ferrous (Fe 2+ ) and ferric (Fe 3+ ) ) ions concentration that can be measured also by spectrophotometry technique. The Alanine gel dosimeter was developed at IPEN. The alanine is an amino acid and tissue equivalent material that presents significant improvement on previous alanine dosimetry systems. The addition of Alanine increases the production of ferric ions in the solution. This work aims to study the dose rate dependence of photon clinical beams radiation on the alanine gel dosimeter optical response, as well as the response repeatability and gel production reproducibility, since this property is very important for characterization and standardization of any dosimeter. (author)

  15. Age-dependent radiation dose due to intake of uranium through drinking water in India

    International Nuclear Information System (INIS)

    Sahoo, S.K.; Mohapatra, S.; Chakrabarty, A.; Sumesh, C.G.; Tripathi, R.M.; Puranik, V.D.

    2009-01-01

    In the present study, an attempt has been made to estimate the content of uranium in drinking water in various states of India by laser fluorimetry. Depending upon the rate of water intake for the different age groups, the associated radiation dose was calculated. The concentration of uranium varied between 0.1 ± 0.01 and 19.6 ± 1.8 ppb which is much lower than the drinking water guideline value of 60 ppb. The total radiation dose due to ingestion of uranium through drinking water for various age groups is found to vary from 0.14 μSv/y to 48 μSv/y. (author)

  16. Non-linear character of dose dependences of chromosome aberration frequency in radiation-damaged root

    International Nuclear Information System (INIS)

    Kravets, E.A.; Berezhnaya, V.V.; Sakada, V.I.; Rashidov, N.M.; Grodzinskij, D.M.; Kravets, E.A.; Berezhnaya, V.V.; Sakada, V.I.; Rashidov, N.M.; Grodzinskij, D.M.

    2012-01-01

    The dose dependences of the aberrant anaphases in the root meristem in 48 hours after the irradiation have non-linear character and a plateau in the region about 6-8 Gy. The plateau indicates the activation of recovery processes. In the plateau range, the level of damages for this genotype is 33% for aberrant anaphases (FAA), 2.3 aberrations per aberrant anaphase (A/AC), and 0.74 aberrations for the total number of anaphases. At 10 Gy, the dose curve forms the exponential region caused by the involvement of the large number of new cells with unrepaired damages in the mutation process. The increase of A/AC to 1.1 indicate the ''criticality'' of the meristem radiation damage.

  17. Dose-dependent deterioration of swallowing function after induction chemotherapy and definitive chemoradiotherapy for laryngopharyngeal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Haderlein, M.; Semrau, S.; Ott, O.; Speer, S.; Fietkau, R. [University Hospital Erlangen, Department of Radiation Oncology, Erlangen (Germany); Bohr, C. [University Hospital Erlangen, Department of Otorhinolaryngology, Head and Neck Surgery, Erlangen (Germany)

    2014-02-15

    To evaluate the influence of clinical, treatment- and dose-dependent factors on posttreatment swallowing function after induction chemotherapy and definitive chemoradiotherapy in a group of homogeneously treated laryngopharyngeal cancer patients. From 28 May 2008 to 15 February 2013, 45 patients with borderline inoperable laryngopharyngeal cancer that had responded well to induction chemotherapy were treated with definitive chemoradiotherapy. Median follow-up was 22 months. Swallowing function and clinical data were prospectively analyzed using the EORTC QLQ-C30 questionnaire. Swallowing structures were retrospectively delineated on the original treatment planning CT. Dose-volume histograms were calculated for swallowing structures and D{sub mean}, D{sub max} and V50-V64 values (in 2 Gy increments) were determined for each patient. Tumor volume and infiltration of the swallowing apparatus was defined by CT before induction chemotherapy. Of the 45 patients, 26 (57.8 %) fully regained swallowing function after chemoradiotherapy. A further 12 patients (26.7 %) were able to manage soft, pureed and/or liquid foods; the remaining 7 (15.6 %) were completely dependent on percutaneous endoscopic gastrostomy (PEG). Posttreatment swallowing function was significantly influenced by D{sub mean} to the superior pharyngeal constrictor muscle (PCM, p = 0.041). Correlations between late dysphagia and dose-volume relationships in the superior PCM and soft palate were also observed, which were significant from V60 (p = 0.043) and V58 for the soft palate and superior PCM, respectively. Of the evaluated clinical and tumor-related factors, only alcohol abuse (p = 0.024) had an influence on posttreatment swallowing function. Almost 50 % of patients had deterioration of swallowing function after definitive chemoradiotherapy for laryngopharyngeal cancer. The dose to anatomical structures responsible for swallowing function appears to play a role. Therefore, in selected patients, target

  18. Dose-dependent adverse effects of salinomycin on male reproductive organs and fertility in mice.

    Directory of Open Access Journals (Sweden)

    Olajumoke Omolara Ojo

    Full Text Available Salinomycin is used as an antibiotic in animal husbandry. Its implication in cancer therapy has recently been proposed. Present study evaluated the toxic effects of Salinomycin on male reproductive system of mice. Doses of 1, 3 or 5 mg/kg of Salinomycin were administered daily for 28 days. Half of the mice were sacrificed after 24 h of the last treatment and other half were sacrificed 28 days after withdrawal of treatment. Effects of SAL on body and reproductive organ weights were studied. Histoarchitecture of testis and epididymis was evaluated along with ultrastructural changes in Leydig cells. Serum and testicular testosterone and luteinizing hormones were estimated. Superoxide dismutase, reduced glutathione, lipid peroxidation, catalase and lactate dehydrogenase activities were measured. Spermatozoa count, morphology, motility and fertility were evaluated. Expression patterns of steroidogenic acute regulatory protein (StAR and cytochrome P450 side chain cleavage proteins (CYP11A1 were assessed by Western blotting. Salinomycin treatment was lethal to few mice and retarded body growth in others with decreased weight of testes and seminal vesicles in a dose dependent manner. Seminiferous tubules in testes were disrupted and the epithelium of epididymis showed frequent occurrence of vacuolization and necrosis. Leydig cells showed hypertrophied cytoplasm with shrunken nuclei, condensed mitochondria, proliferated endoplasmic reticulum and increased number of lipid droplets. Salinomycin decreased motility and spermatozoa count with increased number of abnormal spermatozoa leading to infertility. The testosterone and luteinizing hormone levels were decreased in testis but increased in serum at higher doses. Depletion of superoxide dismutase and reduced glutathione with increased lipid peroxidation in both testis and epididymis indicated generation of oxidative stress. Suppressed expression of StAR and CYP11A1 proteins indicates inhibition of

  19. Dose-dependent deterioration of swallowing function after induction chemotherapy and definitive chemoradiotherapy for laryngopharyngeal cancer

    International Nuclear Information System (INIS)

    Haderlein, M.; Semrau, S.; Ott, O.; Speer, S.; Fietkau, R.; Bohr, C.

    2014-01-01

    To evaluate the influence of clinical, treatment- and dose-dependent factors on posttreatment swallowing function after induction chemotherapy and definitive chemoradiotherapy in a group of homogeneously treated laryngopharyngeal cancer patients. From 28 May 2008 to 15 February 2013, 45 patients with borderline inoperable laryngopharyngeal cancer that had responded well to induction chemotherapy were treated with definitive chemoradiotherapy. Median follow-up was 22 months. Swallowing function and clinical data were prospectively analyzed using the EORTC QLQ-C30 questionnaire. Swallowing structures were retrospectively delineated on the original treatment planning CT. Dose-volume histograms were calculated for swallowing structures and D mean , D max and V50-V64 values (in 2 Gy increments) were determined for each patient. Tumor volume and infiltration of the swallowing apparatus was defined by CT before induction chemotherapy. Of the 45 patients, 26 (57.8 %) fully regained swallowing function after chemoradiotherapy. A further 12 patients (26.7 %) were able to manage soft, pureed and/or liquid foods; the remaining 7 (15.6 %) were completely dependent on percutaneous endoscopic gastrostomy (PEG). Posttreatment swallowing function was significantly influenced by D mean to the superior pharyngeal constrictor muscle (PCM, p = 0.041). Correlations between late dysphagia and dose-volume relationships in the superior PCM and soft palate were also observed, which were significant from V60 (p = 0.043) and V58 for the soft palate and superior PCM, respectively. Of the evaluated clinical and tumor-related factors, only alcohol abuse (p = 0.024) had an influence on posttreatment swallowing function. Almost 50 % of patients had deterioration of swallowing function after definitive chemoradiotherapy for laryngopharyngeal cancer. The dose to anatomical structures responsible for swallowing function appears to play a role. Therefore, in selected patients, target volume

  20. Silver Nanoparticles Incite Size and Dose-Dependent Developmental Phenotypes and Nanotoxicity in Zebrafish Embryos

    Science.gov (United States)

    Browning, Lauren M.; Lee, Kerry J.; Nallathamby, Prakash D.; Xu, Xiao-Hong Nancy

    2013-01-01

    Nanomaterials possess distinctive physicochemical properties and promise a wide range of applications, from advanced technology to leading-edge medicine. However, their effects on living organisms remain largely unknown. Here we report that the purified silver nanoparticles (Ag NPs, 97 ± 13 nm) incite specific developmental stage embryonic phenotypes and nanotoxicity in a dose-dependent manner, upon acute exposure of given-stage embryos to the NPs (0–24 pM) for only 2 h. The critical concentrations of the NPs that cause 50% of embryos develop normally for cleavage, early-gastrula, early-segmentation, late-segmentation, and hatching stage zebrafish embryos are 3.5, 4, 6, 6, and 8 pM, respectively, showing that the earlier developmental stage embryos are much more sensitive to the effects of the NPs than the later stage. Interestingly, distinctive phenotypes (head abnormality and no eyes) are observed only in cleavage and early-gastrula stage embryos treated with the NPs, showing the stage-specific effects of the NPs. By comparing with our study of the smaller Ag NPs (13.1 ± 2.5 nm), we found that the embryonic phenotypes strikingly depend upon the sizes of Ag NPs and embryonic developmental stages. These notable findings suggest that the Ag NPs are unlike any conventional chemicals or ions. They can potentially enable target specific study and therapy for early embryonic development in size, stage, dose, and exposure-duration dependent manners. PMID:24024906

  1. Silver nanoparticles incite size- and dose-dependent developmental phenotypes and nanotoxicity in zebrafish embryos.

    Science.gov (United States)

    Browning, Lauren M; Lee, Kerry J; Nallathamby, Prakash D; Xu, Xiao-Hong Nancy

    2013-10-21

    Nanomaterials possess distinctive physicochemical properties and promise a wide range of applications, from advanced technology to leading-edge medicine. However, their effects on living organisms remain largely unknown. Here we report that the purified silver nanoparticles (Ag NPs) (97 ± 13 nm) incite specific developmental stage embryonic phenotypes and nanotoxicity in a dose-dependent manner, upon acute exposure of given stage embryos to the NPs (0-24 pM) for only 2 h. The critical concentrations of the NPs that cause 50% of embryos to develop normally for cleavage, early gastrula, early segmentation, late segmentation, and hatching stage zebrafish embryos are 3.5, 4, 6, 6, and 8 pM, respectively, showing that the earlier developmental stage embryos are much more sensitive to the effects of the NPs than the later stage embryos. Interestingly, distinctive phenotypes (head abnormality and no eyes) are observed only in cleavage and early gastrula stage embryos treated with the NPs, showing the stage-specific effects of the NPs. By comparing these Ag NPs with smaller Ag NPs (13.1 ± 2.5 nm), we found that the embryonic phenotypes strikingly depend upon the sizes of Ag NPs and embryonic developmental stages. These notable findings suggest that the Ag NPs are unlike any conventional chemicals or ions. They can potentially enable target-specific study and therapy for early embryonic development in size-, stage-, dose-, and exposure duration-dependent manners.

  2. DNA methyltransferase mediates dose-dependent stimulation of neural stem cell proliferation by folate.

    Science.gov (United States)

    Li, Wen; Yu, Min; Luo, Suhui; Liu, Huan; Gao, Yuxia; Wilson, John X; Huang, Guowei

    2013-07-01

    The proliferative response of neural stem cells (NSCs) to folate may play a critical role in the development, function and repair of the central nervous system. It is important to determine the dose-dependent effects of folate in NSC cultures that are potential sources of transplantable cells for therapies for neurodegenerative diseases. To determine the optimal concentration and mechanism of action of folate for stimulation of NSC proliferation in vitro, NSCs were exposed to folic acid or 5-methyltetrahydrofolate (5-MTHF) (0-200 μmol/L) for 24, 48 or 72 h. Immunocytochemistry and methyl thiazolyl tetrazolium assay showed that the optimal concentration of folic acid for NSC proliferation was 20-40 μmol/L. Stimulation of NSC proliferation by folic acid was associated with DNA methyltransferase (DNMT) activation and was attenuated by the DNMT inhibitor zebularine, which implies that folate dose-dependently stimulates NSC proliferation through a DNMT-dependent mechanism. Based on these new findings and previously published evidence, we have identified a mechanism by which folate stimulates NSC growth. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. The genomic response of Ishikawa cells to bisphenol A exposure is dose- and time-dependent

    International Nuclear Information System (INIS)

    Naciff, Jorge M.; Khambatta, Zubin S.; Reichling, Timothy D.; Carr, Gregory J.; Tiesman, Jay P.; Singleton, David W.; Khan, Sohaib A.; Daston, George P.

    2010-01-01

    A reliable in vitro model to determine the potential estrogenic activity of chemicals of interest is still unavailable. To further investigate the usefulness of a human-derived cell line, we determined the transcriptional changes induced by bisphenol A (BPA) in Ishikawa cells at various doses (1 nM, 100 nM, 10 μM, and 100 μM) and time points (8, 24 and 48 h) by comparing the response of approximately 38,500 human genes and ESTs between treatment groups and controls (vehicle-treated). By trend analysis, we determined that the expression of 2794 genes was modified by BPA in a dose- and time-dependent manner (p ≤ 0.0001). However, the majority of gene expression changes induced in Ishikawa cells were elicited by the highest doses of BPA evaluated (10-100 μM), while the genomic response of the cells exposed to low doses of BPA was essentially negligible. By comparing the Ishikawa cells' response to BPA vs.17α-ethynyl estradiol we determined that the change in the expression of 307 genes was identical in the direction of the change, although the magnitude of the change for some genes was different. Further, the response of Ishikawa cells to high doses of BPA shared similarities to the estrogenic response of the rat uterus, specifically, 362 genes were regulated in a similar manner in vivo as well as in vitro. Gene ontology analysis indicated that BPA results in changes to multiple molecular pathways affecting various biological processes particularly associated with cell organization and biogenesis, regulation of translation, cell proliferation, and intracellular transport; processes also affected by estrogen exposure in the uterus of the rat. These results indicate that Ishikawa cells are capable of generating a biologically relevant estrogenic response after exposure to chemicals with varied estrogenic activity, and offer an in vitro model to assess this mode of action.

  4. Angular dependence on the records of dose in radiochromic films strips

    Energy Technology Data Exchange (ETDEWEB)

    Costa, K. C.; Prata M, A. [Centro Federal de Educacao Tecnologica de Minas Gerais, Centro de Engenharia Biomedica, Av. Amazonas 5253, 30421-169 Nova Suica, Belo Horizonte, Minas Gerais (Brazil); Alonso, T. C. [Centro de Desenvolvimento da Tecnologia Nuclear - CNEN, Av. Pte. Antonio Carlos 6627, 31270-901 Pampulha, Belo Horizonte, Minas Gerais (Brazil); Campo de O, P. M., E-mail: kamilacosta1995@gmail.com [Universidade Federal de Minas Gerais, Departamento de Anatomia e Imagen, Av. Prof. Alfredo Balena 190, 30130-100 Belo Horizonte, Minas Gerais (Brazil)

    2016-10-15

    Radiological images have relevant information both the diagnostic results as to treatment decisions. Then, the diagnostic quality of image that allows a proper analysis should be achieved with the lowest possible deposition of dose in a patient. CT scans produce sectional images that allow the observation of internal structures of the human body without overlap. As in conventional radiology, the contrast which allows obtaining CT images results from the difference in X-ray beam absorption, according to the characteristics of each tissue. The increased of the beam absorption by a tissue means that it appears brighter in the image. In CT scanners, X-ray tube rotates around the patient, and this rotation results in a cross-sectional image of the body. From a sectional image series is possible to obtain a 3-dimensional image that can be viewed from different angles. Among the methods of dose measurement is the use of radiochromic films, which record the energy deposition by darkening its emulsion. The radiochromic films show little sensitivity to visible light and respond better to exposure to ionizing radiation. In this work, strips of the radiochromic film GAFCHROMIC XR-QA2 were irradiated at different angular positions for radiation quality RQT8, defining a beam of X-rays generated from a voltage of 100 kV. The response of radiochromic films depending on the doses was assessed through digital images obtained by H P Scan jet G-4050 scanner. Digital images were analyzed using Image-J software, which allowed obtaining numerical values corresponding to the intensity of darkening for each film. The aim of this study is to evaluate the dose deposition in radiochromic film according to the angular variation in order how is affected the record. So, to examine the use of film strips to record doses in Computed Tomography tests. (Author)

  5. Metformin decreases lung cancer risk in diabetic patients in a dose-dependent manner.

    Science.gov (United States)

    Tsai, Ming-Ju; Yang, Chih-Jen; Kung, Ya-Ting; Sheu, Chau-Chyun; Shen, Yu-Ting; Chang, Pi-Yu; Huang, Ming-Shyan; Chiu, Herng-Chia

    2014-11-01

    Higher risk of lung cancer has been noted in patients with type 2 diabetes mellitus (DM). Some observational studies have shown a reduced risk of lung cancer in DM patients taking metformin, but a dose-response relationship has never been reported. The aim of this study is to exam the association between the dose of metformin and the incidence of lung cancer in a Chinese population. The dataset used for this nationwide population-based study is a cohort of 1 million subjects randomly sampled from individuals enrolled in the Taiwan National Health Insurance system. We enrolled all subjects with newly diagnosed type 2 DM between 1997 and 2007. Subjects with a diagnosis of neoplasm before DM diagnosis, those using metformin before DM diagnosis, those with polycystic ovary syndrome, and those with a DM diagnosis before their 15 years of age were excluded. The demographic data and duration, cumulative dose and intensity of metformin use were compared between patients developing lung cancer and those without lung cancer. Totally, 47,356 subjects were identified. After adjusting for age, gender, and modified Charlson Comorbidity Index score, the utilization of metformin was an independent protecting factor, and the risk of developing lung cancer decreased progressively with either the higher cumulative dose or the higher intensity of metformin use. This study revealed that the use of metformin decreased the risk of lung cancer in a dose-dependent manner in patients with type 2 DM. The chemo-preventive effect of metformin deserves further study. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  6. Linear dose dependence of ion beam mixing of metals on Si

    International Nuclear Information System (INIS)

    Poker, D.B.; Appleton, B.R.

    1985-01-01

    These experiments were conducted to determine the dose dependences of ion beam mixing of various metal-silicon couples. V/Si and Cr/Si were included because these couples were previously suspected of exhibiting a linear dose dependence. Pd/Si was chosen because it had been reported as exhibiting only the square root dependence. Samples were cut from wafers of (100) n-type Si. The samples were cleaned in organic solvents, etched in hydrofluoric acid, and rinsed with methanol before mounting in an oil-free vacuum system for thin-film deposition. Films of Au, V, Cr, or Pd were evaporated onto the Si samples with a nominal deposition rate of 10 A/s. The thicknesses were large compared with those usually used to measure ion beam mixing and were used to ensure that conditions of unlimited supply were met. Samples were mixed with Si ions ranging in energy from 300 to 375 keV, chosen to produce ion ranges that significantly exceeded the metal film depth. Si was used as the mixing ion to prevent impurity doping of the Si substrate and to exclude a background signal from the Rutherford backscattering (RBS) spectra. Samples were mixed at room temperature, with the exception of the Au/Si samples, which were mixed at liquid nitrogen temperature. The samples were alternately mixed and analyzed in situ without exposure to atmosphere between mixing doses. The compositional distributions after mixing were measured using RBS of 2.5-MeV 4 He atoms

  7. Dose-dependent zoning of estranged territory after the Chernobyl power plant accident

    International Nuclear Information System (INIS)

    Savkin, M.N.

    1994-01-01

    The alienation zone was forming in May-September 1986 when the population was evacuated from the areas nearest to the Chernobyl power pilant. The presnet-day contour of the zone is a result of combination of a geographic criterion, a circular with a 30 km radius, and of radiation criteria developed at the earliest stages after the accident. The authors discuss dose-dependent regioning of the alienation zone at the latest stages of the accident and analyze radiation and hygienic aspects of possible reevacuation of the population

  8. Radiation dose to the thyroid due to incorporation of iodine isotopes: Age dependence and reliability of dose factors

    International Nuclear Information System (INIS)

    Henrichs, K.; Mueller-Brunecker, G.; Paretzke, H.G.

    1983-08-01

    This is the first time that dose factors are published in the literature, together with an assessment of their reliability with regard to the quantification of the dose received by the population in the Federal Republic of Germany due to incorporation if iodine isotopes, taking into account the given age distribution among the population. The calculation of dose factors is based on the latest dosimetric and metabolic models issued by the ICRP (ICRP-30), and the impact of the various parameters and their variability on the accuracy of dose factor determination is assessed. The procedure followed to calculate the dose due to incorporation on the basis of metabolic models (ICRP 1978 and ICRP 1979) is explained. The main data (such as half life, mean frequency per decay, mean energy in keV) are given for I-123, I-125, I-129, I-131, I-132, I-133, I-134, and I-135 (ICRP-30) and listed in tables. (orig./HP) [de

  9. Plumbagin Nanoparticles Induce Dose and pH Dependent Toxicity on Prostate Cancer Cells.

    Science.gov (United States)

    Nair, Harikrishnan A; Snima, K S; Kamath, Ravindranath C; Nair, Shantikumar V; Lakshmanan, Vinoth-Kumar

    2015-01-01

    Stable nano-formulation of Plumbagin nanoparticles from Plumbago zeylanica root extract was explored as a potential natural drug against prostate cancer. Size and morphology analysis by DLS, SEM and AFM revealed the average size of nanoparticles prepared was 100±50nm. In vitro cytotoxicity showed concentration and time dependent toxicity on prostate cancer cells. However, plumbagin crude extract found to be highly toxic to normal cells when compared to plumbagin nanoformulation, thus confirming nano plumbagin cytocompatibility with normal cells and dose dependent toxicity to prostate cells. In vitro hemolysis assay confirmed the blood biocompatibility of the plumbagin nanoparticles. In wound healing assay, plumbagin nanoparticles provided clues that it might play an important role in the anti-migration of prostate cancer cells. DNA fragmentation revealed that partial apoptosis induction by plumbagin nanoparticles could be expected as a potent anti-cancer effect towards prostate cancer.

  10. Temperature and dose dependencies of microstructure and hardness of neutron irradiated OFHC copper

    International Nuclear Information System (INIS)

    Singh, B.N.; Horsewell, A.; Toft, P.; Edwards, D.J.

    1995-01-01

    Tensile specimens of pure oxygen free high conductivity (OFHC) copper were irradiated with fission neutrons between 320 and 723 K to fluences in the range 5x10 21 to 1.5x10 24 n/m 2 (E>1 MeV) with a flux of 2.5x10 17 n/m 2 s. Irradiated specimens were investigated by transmission electron microscopy (TEM) and quantitative determinations were made of defect clusters and cavities. The dose dependence of tensile properties of specimens irradiated at 320 K was determined at 295 K. Hardness measurements were made at 295 K on specimens irradiated at different temperatures and doses. Microstructures of tensile tested specimens were also investigated by TEM. Results show that the increase in cluster density and hardening nearly saturate at a dose of similar 0.3 dpa. Irradiations at 320 K cause a drastic decrease in the uniform elongation already at ∼ =0.1 dpa. It is suggested that the irradiation-induced increase in the initial yield stress and a drastic decrease in the ability of copper to deform plastically in a homogeneous fashion are caused by a substantial reduction in the ability of grown-in dislocations to act as efficient dislocation sources. ((orig.))

  11. Technique-dependent decrease in thyroid absorbed dose for dental radiography

    International Nuclear Information System (INIS)

    Wood, R.E.; Bristow, R.G.; Clark, G.M.; Nussbaum, C.; Taylor, K.W.

    1989-01-01

    A LiF thermoluminescent dosimetry (TLD) system, calibrated in the tissue of interest with the beam used for experimentation, was employed to investigate dosages (muGy) to the thyroid region of an anthropomorphic phantom resultant from two dental complete-mouth radiographic procedures. Both techniques were compared in terms of dosages associated with combinations of lead apron and thyroid collar shielding while using a 70-kVp or 90-kVp x-ray beam for a 20-film complete-mouth series. Lead shielding significantly decreased the dose to the thyroid using both techniques (p less than 0.05). The use of the 90-kVp beam resulted in a significant reduction in the thyroid absorbed dose when using the bisecting angle technique (p less than 0.05) but caused a significant increase in the thyroid absorbed dose when the paralleling technique was used (p less than 0.05). The implementation of higher kilovoltage techniques in dental offices must therefore be dependent on the radiographic technique employed

  12. Paraquat poisoning: an experimental model of dose-dependent acute lung injury due to surfactant dysfunction

    Directory of Open Access Journals (Sweden)

    M.F.R. Silva

    1998-03-01

    Full Text Available Since the most characteristic feature of paraquat poisoning is lung damage, a prospective controlled study was performed on excised rat lungs in order to estimate the intensity of lesion after different doses. Twenty-five male, 2-3-month-old non-SPF Wistar rats, divided into 5 groups, received paraquat dichloride in a single intraperitoneal injection (0, 1, 5, 25, or 50 mg/kg body weight 24 h before the experiment. Static pressure-volume (PV curves were performed in air- and saline-filled lungs; an estimator of surface tension and tissue works was computed by integrating the area of both curves and reported as work/ml of volume displacement. Paraquat induced a dose-dependent increase of inspiratory surface tension work that reached a significant two-fold order of magnitude for 25 and 50 mg/kg body weight (P<0.05, ANOVA, sparing lung tissue. This kind of lesion was probably due to functional abnormalities of the surfactant system, as was shown by the increase in the hysteresis of the paraquat groups at the highest doses. Hence, paraquat poisoning provides a suitable model of acute lung injury with alveolar instability that can be easily used in experimental protocols of mechanical ventilation

  13. [Occlusion treatment for amblyopia. Age dependence and dose-response relationship].

    Science.gov (United States)

    Fronius, M

    2016-04-01

    Based on clinical experience and studies on animal models the age of 6-7 years was regarded as the limit for treatment of amblyopia, although functional improvement was also occasionally reported in older patients. New technical developments as well as insights from clinical studies and the neurosciences have attracted considerable attention to this topic. Various aspects of the age dependence of amblyopia treatment are discussed in this article, e. g. prescription, electronic monitoring of occlusion dosage, calculation of indicators for age-dependent plasticity of the visual system, and novel, alternative treatment approaches. Besides a discussion of the recent literature, results of studies by our "Child Vision Research Unit" in Frankfurt are presented: results of a questionnaire about prescription habits concerning age limits of patching, electronic recording of occlusion in patients beyond the conventional treatment age, calculation of dose-response function and efficiency of patching and their age dependence. The results of the questionnaire illustrate the uncertainty about age limits of prescription with significant deviations from the guideline of the German Ophthalmological Society (DOG). Electronic recording of occlusion allowed the quantification of declining dose-response function and treatment efficiency between 5 and 16 years of age. Reports about successful treatment with conventional and novel methods in adults are at variance with the notion of a rigid adult visual system lacking plasticity. Electronic recording of patching allowed new insights into the age-dependent susceptibility of the visual system and contributes to a more evidence-based treatment of amblyopia. Alternative approaches for adults challenge established notions about age limits of amblyopia therapy. Further studies comparing different treatment options are urgently needed.

  14. Energy and angular dependence of the personal dosemeter in use at ITN-DPRSN

    Energy Technology Data Exchange (ETDEWEB)

    Alves, Joao G. [Departamento de Proteccao Radiologica e Seguranca Nuclear, Instituto Tecnologico e Nuclear, EN 10, 2686-953 Sacavem (Portugal)], E-mail: jgalves@itn.pt; Calado, Ana M.; Cardoso, Joao V.; Santos, Luis M. [Departamento de Proteccao Radiologica e Seguranca Nuclear, Instituto Tecnologico e Nuclear, EN 10, 2686-953 Sacavem (Portugal)

    2008-02-15

    In this paper the characterization of the dosimetry system and of the personal dosemeter in terms of the stability of the reader calibration factors and of the linearity of the response for the 137Cs reference radiation is presented. The energy and angular dependence of the whole body dosemeter are also shown. The energy dependence was determined performing irradiations with the X-ray narrow series beams N30, N40, N60, N80, N100, N120 and with the gamma reference radiations of 137Cs and 60Co [ISO 4037-1, 1996. X and Gamma Reference Radiation for Calibrating Dosemeters and Doserate Meters and for Determining Their Response as a Function of Photon Energy-Part 1: Radiation Characteristics and Production Methods. International Organization for Standardization, Geneva] in terms of Hp(10) incident on the ISO water slab phantom. The angular dependence of the dosemeter was determined for the angles 0 deg., {+-}20 deg., {+-}40 deg. and {+-}60 deg. with normal using the above mentioned radiation fields. All irradiations were performed at the Laboratorio de Metrologia das Radiacoes lonizantes of ITN-DPRSN. The experiments presented in this paper show the thermoluminescence dosimetry (TLD) system is stable and presents a linear behaviour over and extended dose range. The measurements allowed the determination of the energy dependence at normal incidence and of the angular dependence of the dosemeter currently in use. Further studies are being carried out in order to implement correction factors for supralinearity and low energy measurements.

  15. SU-F-18C-12: On the Relationship of the Weighted Dose to the Surface Dose In Abdominal CT - Patient Size Dependency

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Y; Scott, A; Allahverdian, J [Cedars-Sinai Medical Center, Los Angeles, CA (United States)

    2014-06-15

    Purpose: It is possible to measure the patient surface dose non-invasively using radiolucent dosimeters. However, the patient size specific weighted dose remains unknown. We attempted to study the weighted dose to surface dose relationship as the patient size varies in abdominal CT. Methods: Seven abdomen phantoms (CIRS TE series) simulating patients from an infant to a large adult were used. Size specific doses were measured with a 100 mm CT chamber under axial scans using a Siemens Sensation 64 (mCT) and a GE 750 HD. The scanner settings were 120 kVp, 200 mAs with fully opened collimations. Additional kVps (80, 100, 140) were added depending on the phantom sizes. The ratios (r) of the weighted CT dose (Dw) to the surface dose (Ds) were related to the phantom size (L) defined as the diameter resulting the equivalent cross-sectional area. Results: The Dw versus Ds ratio (r) was fitted to a linear relationship: r = 1.083 − 0.007L (R square = 0.995), and r = 1.064 − 0.007L (R square = 0.953), for Siemens Sensation 64 and GE 750 HD, respectively. The relationship appears to be independent of the scanner specifics. Conclusion: The surface dose to the weighted dose ratio decreases linearly as the patient size increases. The result is independent of the scanner specifics. The result can be used to obtain in vivo CT dosimetry in abdominal CT.

  16. SU-F-18C-12: On the Relationship of the Weighted Dose to the Surface Dose In Abdominal CT - Patient Size Dependency

    International Nuclear Information System (INIS)

    Zhou, Y; Scott, A; Allahverdian, J

    2014-01-01

    Purpose: It is possible to measure the patient surface dose non-invasively using radiolucent dosimeters. However, the patient size specific weighted dose remains unknown. We attempted to study the weighted dose to surface dose relationship as the patient size varies in abdominal CT. Methods: Seven abdomen phantoms (CIRS TE series) simulating patients from an infant to a large adult were used. Size specific doses were measured with a 100 mm CT chamber under axial scans using a Siemens Sensation 64 (mCT) and a GE 750 HD. The scanner settings were 120 kVp, 200 mAs with fully opened collimations. Additional kVps (80, 100, 140) were added depending on the phantom sizes. The ratios (r) of the weighted CT dose (Dw) to the surface dose (Ds) were related to the phantom size (L) defined as the diameter resulting the equivalent cross-sectional area. Results: The Dw versus Ds ratio (r) was fitted to a linear relationship: r = 1.083 − 0.007L (R square = 0.995), and r = 1.064 − 0.007L (R square = 0.953), for Siemens Sensation 64 and GE 750 HD, respectively. The relationship appears to be independent of the scanner specifics. Conclusion: The surface dose to the weighted dose ratio decreases linearly as the patient size increases. The result is independent of the scanner specifics. The result can be used to obtain in vivo CT dosimetry in abdominal CT

  17. High-dose benzodiazepine dependence: a qualitative study of patients' perception on cessation and withdrawal.

    Science.gov (United States)

    Liebrenz, Michael; Gehring, Marie-Therese; Buadze, Anna; Caflisch, Carlo

    2015-05-13

    Benzodiazepine withdrawal syndrome has been reported following attempts to withdraw even from low or therapeutic doses and has been compared to barbiturate and alcohol withdrawal. This experience is known to deter patients from future cessation attempts. Research on other psychotropic substances shows that the reasons and motivations for withdrawal attempts - as well as the experiences surrounding those attempts - at least partially predict future efforts at discontinuation as well as relapse. We therefore aimed to qualitatively explore what motivates patients to discontinue this medication as well as to examine their experiences surrounding previous and current withdrawal attempts and treatment interventions in order to positively influence future help-seeking behavior and compliance. To understand these patients better, we conducted a series of 41 unstructured, narrative, in-depth interviews among adult Swiss patients with a long-term dependent use of benzodiazepines in doses equivalent to more than 40 mg diazepam per day and/or otherwise problematic use (mixing benzodiazepines, escalating dosage, recreational use or illegal purchase). Mayring's qualitative content analysis was used to evaluate findings. These high-dose benzodiazepine-dependent patients decision to change consumption patterns were affected by health concerns, the feeling of being addicted and social factors. Discontinuation attempts were frequent and not very successful with fast relapse. Withdrawal was perceived to be a difficult, complicated, and highly unpredictable process. The first attempt at withdrawal occurred at home and typically felt better than at the clinic. Inpatient treatment was believed to be more effective with long term treatment (approaches) than short term. Patients preferred gradual reduction of usage to abrupt cessation (and had experienced both). While no clear preferences for withdrawal were found for benzodiazepines with specific pharmacokinetic properties, participants

  18. Age-dependent doses to members of the public from intake of radionuclides: Pt. 5. Compilation of ingestion and inhalation dose coefficients

    International Nuclear Information System (INIS)

    1996-01-01

    The present report is a compilation of age-dependent committed effective dose coefficients for ingestion and inhalation of radionuclides of the 31 elements covered in previous CRP Publications. The biokinetic models for adults given in ICRP Publication 30 are applied to calculate these dose coefficients, except that age-specific excretion rates are used and increased gastrointestinal absorption in infants is assurred. Changes in body mass, and tissue geometry in children are also taken into account. (UK)

  19. Simulation studies of optimum energies for DXA: dependence on tissue type, patient size and dose model

    International Nuclear Information System (INIS)

    Michael, G. J.; Henderson, C. J.

    1999-01-01

    Dual-energy x-ray absorptiometry (DXA) is a well established technique for measuring bone mineral density (BMD). However, in recent years DXA is increasingly being used to measure body composition in terms of fat and fat-free mass. DXA scanners must also determine the soft tissue baseline value from soft-tissue-only regions adjacent to bone. The aim of this work is to determine, using computer simulations, the optimum x- ray energies for a number of dose models, different tissues, i.e. bone mineral, average soft tissue, lean soft tissue and fat; and a range of anatomical sites and patient sizes. Three models for patient dose were evaluated total beam energy, entrance exposure and absorbed dose calculated by Monte Carlo modelling. A range of tissue compositions and thicknesses were chosen to cover typical patient variations for the three sites femoral neck, PA spine and lateral spine. In this work, the optimisation of the energies is based on (1) the uncertainty that arises from the quantum statistical nature of the number of x-rays recorded by the detector, and (2) the radiation dose received by the patient. This study has deliberately not considered other parameters such as detector response, electronic noise, x-ray tube heat load etc, because these are technology dependent parameters, not ones that are inherent to the measuring technique. Optimisation of the energies is achieved by minimisation of the product of variance of density measurement and dose which is independent of the absolute intensities of the x-ray beams. The results obtained indicate that if solving for bone density, then E-low in the range 34 to 42 keV, E-high in the range 100 to 200 keV and incident intensity ratio (low energy/high energy) in the range 3 to 10 is a reasonable compromise for the normal range of patient sizes. The choice of energies is complicated by the fact that the DXA unit must also solve for fat and lean soft tissue in soft- tissue-only regions adjacent to the bone. In this

  20. Dose-Dependent Effects of Radiation Therapy on Cerebral Blood Flow, Metabolism, and Neurocognitive Dysfunction

    International Nuclear Information System (INIS)

    Hahn, Carol A.; Zhou Sumin; Raynor, Renee; Tisch, Andrea; Light, Kim; Shafman, Timothy; Wong, Terence; Kirkpatrick, John; Turkington, Timothy; Hollis, Donna; Marks, Lawrence B.

    2009-01-01

    Purpose: A prospective study was performed to formally relate dose-dependent radiologically defined changes in normal brain induced by radiotherapy (RT) to neurocognitive dysfunction in subjects with primary brain tumors. Methods and Materials: Adult patients receiving three-dimensional RT for central nervous system (CNS) tumors were enrolled. Positron emission tomography (PET) scanning and neuropsychological testing were performed before RT and 3 weeks and 6 months after treatment. Analyses were performed for correlations between changes in 2-deoxy-2-[ 18 F]-fluoro-D-glucose (FDG)-PET (metabolism), 15 O-PET (relative blood flow), regional radiation dose, follow-up time, and neuropsychological test scores. Results: Eleven subjects were enrolled and 6 completed follow-up studies. The PET data showed reduced FDG uptake, with average decreases of 2-6% in regions of the brain receiving greater than 40 Gy at 3 weeks' and 6 months' follow-up. The 15 O-H 2 O PET showed increases (<10%) at 3 weeks in relative regional blood flow in brain receiving greater than 30 Gy, but less at the 6-month follow-up studies. There were significant correlations between decreases in FDG uptake and increased scores from the Symptom Checklist-90-R, with an average increase in T score of 2 (p < 0.0001). The Wisconsin Card Sorting Test showed a significant correlation of decreased FDG uptake with increased errors and perseveration in test performance, with an average decrease in T score of 11 (p = 0.037). Conclusions: A dose-dependent response of CNS tissue was detected using FDG PET in this small number of patients. Decreases in CNS metabolism correlated with decreased performance on neuropsychological tests for problem solving, cognitive flexibility, and global measures of psychopathology. Additional research is needed to verify and define these findings

  1. Extracellular vesicles have variable dose-dependent effects on cultured draining cells in the eye.

    Science.gov (United States)

    Tabak, Saray; Schreiber-Avissar, Sofia; Beit-Yannai, Elie

    2018-03-01

    The role of extracellular vesicles (EVs) as signal mediators has been described in many biological fields. How many EVs are needed to deliver the desired physiological signal is yet unclear. Using a normal trabecular meshwork (NTM) cell culture exposed to non-pigmented ciliary epithelium (NPCE)-derived EVs, a relevant model for studying the human ocular drainage system, we addressed the EVs dose-response effects on the Wnt signaling. The objective of the study was to investigate the dosing effects of NPCE-derived EVs on TM Wnt signaling. EVs were isolated by PEG 8000 method from NPCE and RPE cells (used as controls) conditioned media. Concentrations were determined by Tunable Resistive Pulse Sensing method. Various exosomes concentration were incubated with TM cells, for the determination of mRNA (β-Catenin, Axin2 and LEF1) and protein (β-Catenin, GSK-3β) expression using real-time quantitative PCR and Western blot, respectively. Exposure of NTM cells for 8 hrs to low EVs concentrations was associated with a significant decreased expression of β-Catenin, GSK-3β, as opposed to exposure to high exosomal concentrations. Pro-MMP9 and MMP9 activities were significantly enhanced in NTM cells treated with high EV concentrations of (X10) as compared to low EV concentrations of either NPCE- or RPE-derived EVs and to untreated control. Our data support the concept that EVs biological effects are concentration-dependent at their target site. Specifically in the present study, we described a general dose-response at the gene and MMPs activity and a different dose-response regarding key canonical Wnt proteins expression. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  2. Corticosteroid effects on ventilator-induced diaphragm dysfunction in anesthetized rats depend on the dose administered

    Directory of Open Access Journals (Sweden)

    Decramer Marc

    2010-12-01

    Full Text Available Abstract Background High dose of corticosteroids has been previously shown to protect against controlled mechanical ventilation (CMV-induced diaphragmatic dysfunction while inhibiting calpain activation. Because literature suggests that the calpain inhibiting effect of corticosteroid depends on the dose administered, we determined whether lower doses of corticosteroids would also provide protection of the diaphragm during CMV. This may be important for patients undergoing mechanical ventilation and receiving corticosteroids. Methods Rats were assigned to controls or to 24 hours of CMV while being treated at the start of mechanical ventilation with a single intramuscular administration of either saline, or 5 mg/kg (low MP or 30 mg/kg (high MP of methylprednisolone. Results Diaphragmatic force was decreased after CMV and this was exacerbated in the low MP group while high MP rescued this diaphragmatic dysfunction. Atrophy was more severe in the low MP group than after CMV while no atrophy was observed in the high MP group. A significant and similar increase in calpain activity was observed in both the low MP and CMV groups whereas the high dose prevented calpain activation. Expression of calpastatin, the endogenous inhibitor of calpain, was decreased in the CMV and low MP groups but its level was preserved to controls in the high MP group. Caspase-3 activity increased in all CMV groups but to a lesser extent in the low and high MP groups. The 20S proteasome activity was increased in CMV only. Conclusions Administration of 30 mg/kg methylprednisolone during CMV protected against CMV-induced diaphragm dysfunction while 5 mg/kg was more deleterious. The protective effect is due mainly to an inhibition of the calpain system through preservation of calpastatin levels and to a lesser extent to a caspase-3 inhibition.

  3. New approach to the approximation of «dose – effect» dependence during the human somatic cells irradiation

    Directory of Open Access Journals (Sweden)

    V. F. Chekhun

    2013-09-01

    Full Text Available New data on cytogenetic approximation of the experimental cytogenetic dependence "dose - effect" based on the spline regression model that improves biological dosimetry of human radiological exposure were received. This is achieved by reducing the error of the determination of absorbed dose as compared to the traditional use of linear and linear-quadratic models and makes it possible to predict the effect of dose curves on plateau.

  4. Age- and sex-dependent model for estimating radioiodine dose to a normal thyroid

    International Nuclear Information System (INIS)

    Killough, G.G.; Eckerman, K.F.

    1985-01-01

    This paper describes the derivation of an age- and sex-dependent model of radioiodine dosimetry in the thyroid and the application of the model to estimating the thyroid dose for each of 4215 patients who were exposed to 131 I in diagnostic and therapeutic procedures. The model was made to conform to these data requirements by the use of age-specific estimates of the biological half-time of iodine in the thyroid and an age- and sex-dependent representation of the mass of the thyroid. Also, it was assumed that the thyroid burden was maximum 24 hours after administration (the 131 I dose is not critically sensitive to this assumption). The metabolic model is of the form A(t) = K[exp(-μ 1 t) - exp(-μ 2 t)] (μCi), where μ 1 = lambda/sub r/ + lambda/sub i//sup b/ (i = 1, 2), lambda/sub r/ is the radiological decay-rate coefficient, and lambda/sub i//sup b/ are biological removal rate coefficients. The values of lambda/sub i//sup b/ are determined by solving a nonlinear equation that depends on assumptions about the time of maximum uptake and the eventual biological loss rate (through which age dependence enters). The value of K may then be calculated from knowledge of the uptake at a particular time. The dosimetric S-factor (rad/μCi-day) is based on specific absorbed fractions for photons of energy ranging from 0.01 to 4.0 MeV for thyroid masses from 1.29 to 19.6 g; the functional form of the S-factor also involves the thyroid mass explicitly, through which the dependence on age and sex enters. An analysis of sensitivity of the model to uncertainties in the thyroid mass and the biological removal rate for several age groups is reported. The model could prove useful in the dosimetry of very short-lived radioiodines. Tables of age- and sex-dependent coefficients are provided to enable readers to make their own calculations. 12 refs., 5 figs., 4 tabs

  5. Dose-dependent effect of 8-day cisplatin administration upon the morphology of the albino guinea pig cochlea

    NARCIS (Netherlands)

    Cardinaal, RM; de Groot, JCMJ; Huizing, EH; Veldman, JE; Smoorenburg, GF

    Numerous studies investigating cisplatin ototoxicity in animals have been performed, but it is difficult to derive a clear dose-effect relation from these studies. The degree of cisplatin-induced ototoxicity depends on a multitude of,factors. Many parameters, such as dose, mode of administration,

  6. First-principles X-ray absorption dose calculation for time-dependent mass and optical density.

    Science.gov (United States)

    Berejnov, Viatcheslav; Rubinstein, Boris; Melo, Lis G A; Hitchcock, Adam P

    2018-05-01

    A dose integral of time-dependent X-ray absorption under conditions of variable photon energy and changing sample mass is derived from first principles starting with the Beer-Lambert (BL) absorption model. For a given photon energy the BL dose integral D(e, t) reduces to the product of an effective time integral T(t) and a dose rate R(e). Two approximations of the time-dependent optical density, i.e. exponential A(t) = c + aexp(-bt) for first-order kinetics and hyperbolic A(t) = c + a/(b + t) for second-order kinetics, were considered for BL dose evaluation. For both models three methods of evaluating the effective time integral are considered: analytical integration, approximation by a function, and calculation of the asymptotic behaviour at large times. Data for poly(methyl methacrylate) and perfluorosulfonic acid polymers measured by scanning transmission soft X-ray microscopy were used to test the BL dose calculation. It was found that a previous method to calculate time-dependent dose underestimates the dose in mass loss situations, depending on the applied exposure time. All these methods here show that the BL dose is proportional to the exposure time D(e, t) ≃ K(e)t.

  7. Dose-dependent effects of intravenous lorazepam on cardiovascular activity, plasma catecholamines and psychological function during rest and mental stress

    NARCIS (Netherlands)

    J.H.M. Tulen (Joke); P. Moleman (Peter); F. Boomsma (Frans); H.G. van Steenis (H.); V.J.H.M. van den Heuij (Venantius)

    1991-01-01

    textabstractDose-dependent effects of intravenously administered lorazepam on psychophysiological activity during rest and mental stress were studied in order to examine differential responses to doses which may induce anxiolysis or sedation. In a double-blind randomized cross-over study, nine male

  8. Dose dependency of outcomes of intrapleural fibrinolytic therapy in new rabbit empyema models

    Science.gov (United States)

    Florova, Galina; Azghani, Ali O.; Buchanan, Ann; Boren, Jake; Allen, Timothy; Rahman, Najib M.; Koenig, Kathleen; Chamiso, Mignote; Karandashova, Sophia; Henry, James; Idell, Steven

    2016-01-01

    The incidence of empyema (EMP) is increasing worldwide; EMP generally occurs with pleural loculation and impaired drainage is often treated with intrapleural fibrinolytic therapy (IPFT) or surgery. A number of IPFT options are used clinically with empiric dosing and variable outcomes in adults. To evaluate mechanisms governing intrapleural fibrinolysis and disease outcomes, models of Pasteurella multocida and Streptococcus pneumoniae were generated in rabbits and the animals were treated with either human tissue (tPA) plasminogen activator or prourokinase (scuPA). Rabbit EMP was characterized by the development of pleural adhesions detectable by chest ultrasonography and fibrinous coating of the pleura. Similar to human EMP, rabbits with EMP accumulated sizable, 20- to 40-ml fibrinopurulent pleural effusions associated with extensive intrapleural organization, significantly increased pleural thickness, suppression of fibrinolytic and plasminogen-activating activities, and accumulation of high levels of plasminogen activator inhibitor 1, plasminogen, and extracellular DNA. IPFT with tPA (0.145 mg/kg) or scuPA (0.5 mg/kg) was ineffective in rabbit EMP (n = 9 and 3 for P. multocida and S. pneumoniae, respectively); 2 mg/kg tPA or scuPA IPFT (n = 5) effectively cleared S. pneumoniae-induced EMP collections in 24 h with no bleeding observed. Although intrapleural fibrinolytic activity for up to 40 min after IPFT was similar for effective and ineffective doses of fibrinolysin, it was lower for tPA than for scuPA treatments. These results demonstrate similarities between rabbit and human EMP, the importance of pleural fluid PAI-1 activity, and levels of plasminogen in the regulation of intrapleural fibrinolysis and illustrate the dose dependency of IPFT outcomes in EMP. PMID:27343192

  9. 1H MRS can detect dose dependent effects in irradiated tumor cells and spheroids

    International Nuclear Information System (INIS)

    Grande, S.; Viti, V.; Guidoni, L.; Luciani, A.M.

    2003-01-01

    Full text: 1 H MR spectra of tumour cells are often characterised by the presence of intense signals from the methylene fatty acid chains of mobile lipids (ML), mostly triglycerides (TG). In previous work (Magnetic Resonance in Medicine ,1999, 42:248-257), we showed that the intensity of these signals is modulated by cell proliferation. Polyunsaturation levels of the fatty acid chains were also found higher when mobile lipid signals were intense, in agreement with independent findings by other authors (Nat. Med . 1999, 5:1323-1327). Cells from breast carcinoma (MCF 7) were irradiated at increasing doses (5 - 40 Gy) to detect spectral differences in irradiated cells and to relate them to the metabolic breakdown accompanying cell death. Early and late, metabolism mediated , effects were observed. The main effect observed shortly after treatment was a decrease in ML peak intensity, probably from the oxidative damage to the involved lipid structures. On the other hand, when cells were observed after 24, 48 and 72 hours, irradiated cells displayed more intense ML peaks, with a maximum effect after 48 hours, irrespective of the initial intensity of ML signals. The effect was found dose dependent. Also peaks from lipid polyunsaturation were found higher in irradiated samples. Moreover, also phosphorylcholine and glutathione signals were affected by irradiation. Similar effects were found in multicellular spheroids from the same cell strain. Association of the observed changes with apoptotic death is currently under consideration

  10. Angular dependence of dose equivalent response of an albedo neutron dosimeter

    International Nuclear Information System (INIS)

    Torres, B.A.; Boswell, E.; Schwartz, R.B.

    1994-01-01

    The ANSI provides procedures for testing the performance of dosimetry services. Although neutron dose equivalent angular response studies are not now mandated, future standards may well require that such studies be performed. Current studies with an albedo dosimeter will yield information regarding the angular dependence of dose equivalent response for this type of personnel dosimeter. Preliminary data for bare 252 Cf fluences show a marked decrease in dosimeter reading with increasing angle. The response decreased by an approximate factor of four. For the horizontal orientation, the same response was noted from both positive and negative angles. However, for the vertical orientation, the response was unexplainably assymetric. We are also examining the response of the personnel badge in moderated 252 Cf fluences. Responses from the moderated and unmoderated 252 Cf fields and theoretical calculations of the neutron angular response will be compared. This information will assist in building a data base for future comparisons of neutron angular responses with other neutron albedo dosimeters and phantoms

  11. Psilocybin dose-dependently causes delayed, transient headaches in healthy volunteers.

    Science.gov (United States)

    Johnson, Matthew W; Sewell, R Andrew; Griffiths, Roland R

    2012-06-01

    Psilocybin is a well-characterized classic hallucinogen (psychedelic) with a long history of religious use by indigenous cultures, and nonmedical use in modern societies. Although psilocybin is structurally related to migraine medications, and case studies suggest that psilocybin may be efficacious in treatment of cluster headache, little is known about the relationship between psilocybin and headache. This double-blind study examined a broad range of psilocybin doses (0, 5, 10, 20, and 30 mg/70 kg) on headache in 18 healthy participants. Psilocybin frequently caused headache, the incidence, duration, and severity of which increased in a dose-dependent manner. All headaches had delayed onset, were transient, and lasted no more than a day after psilocybin administration. Possible mechanisms for these observations are discussed, and include induction of delayed headache through nitric oxide release. These data suggest that headache is an adverse event to be expected with the nonmedical use of psilocybin-containing mushrooms as well as the administration of psilocybin in human research. Headaches were neither severe nor disabling, and should not present a barrier to future psilocybin research. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  12. Dose-Dependent Lowering of Mutant Huntingtin Using Antisense Oligonucleotides in Huntington Disease Patients.

    Science.gov (United States)

    van Roon-Mom, Willeke M C; Roos, Raymund A C; de Bot, Susanne T

    2018-04-01

    On December 11 of 2017, Ionis Pharmaceuticals published a press release announcing dose-dependent reductions of mutant huntingtin protein in their HTTRx Phase 1/2a study in Huntington disease (HD) patients. The results from this Ionis trial have gained much attention from the patient community and the oligonucleotide therapeutics field, since it is the first trial targeting the cause of HD, namely the mutant huntingtin protein, using antisense oligonucleotides (ASOs). The press release also states that the primary endpoints of the study (safety and tolerability) were met, but does not contain data. This news follows the approval of another therapeutic ASO nusinersen (trade name Spinraza) for a neurological disease, spinal muscular atrophy, by the U.S. Food and Drug Administration and European Medicines Agency, in 2016 and 2017, respectively. Combined, this offers hope for the development of the HTTRx therapy for HD patients.

  13. Dose Dependent Survival Response in Chronic Myeloid Leukemia under Continuous and Pulsed Targeted Therapy

    International Nuclear Information System (INIS)

    Pizzolato, N.; Valenti, D.; Spagnolo, B.; Persano Adorno, D.

    2010-01-01

    A simulative study of cancer growth dynamics in patients affected by Chronic Myeloid Leukemia (CML), under the effect of a targeted dose dependent continuous or pulsed therapy, is presented. We have developed a model for the dynamics of CML in which the stochastic evolution of white blood cell populations are simulated by adopting a Monte Carlo approach. Several scenarios in the evolutionary dynamics of white blood cells, as a consequence of the efficacy of the different modelled therapies, pulsed or continuous, are described. The best results, in terms of a permanent disappearance of the leukemic phenotype, are achieved with a continuous therapy and higher dosage. However, our findings demonstrate that an intermittent therapy could represent a valid choice in patients with high risk of toxicity, when a long-term therapy is considered. A suitably tuned pulsed therapy can enhance the treatment efficacy and reduce the percentage of patients developing resistance. (authors)

  14. Dose-dependent neuroprotective effect of enoxaparin on cold-induced traumatic brain injury.

    Science.gov (United States)

    Keskin, Ilknur; Gunal, M Yalcin; Ayturk, Nilufer; Kilic, Ulkan; Ozansoy, Mehmet; Kilic, Ertugrul

    2017-05-01

    Recent evidence exists that enoxaparin can reduce brain injury because of its anticoagulant activity. To investigate the potential therapeutic effect of enoxaparin on cold-induced traumatic brain injury, at 20 minutes after modeling, male BALB/c mouse models of cold-induced traumatic brain injury were intraperitoneally administered 3 and 10 mg/kg enoxaparin or isotonic saline solution. Twenty-four hours later, enoxaparin at 10 mg/kg greatly reduced infarct volume, decreased cell apoptosis in the cortex and obviously increased serum level of total antioxidant status. By contrast, administration of enoxaparin at 3 mg/kg did not lead to these changes. These findings suggest that enoxaparin exhibits neuroprotective effect on cold-induced traumatic brain injury in a dose-dependent manner.

  15. Gamma Low-Dose-Rate Ionizing Radiation Stimulates Adaptive Functional and Molecular Response in Human Aortic Endothelial Cells in a Threshold-, Dose-, and Dose Rate-Dependent Manner.

    Science.gov (United States)

    Vieira Dias, Juliana; Gloaguen, Celine; Kereselidze, Dimitri; Manens, Line; Tack, Karine; Ebrahimian, Teni G

    2018-01-01

    A central question in radiation protection research is whether low-dose and low-dose-rate (LDR) exposures to ionizing radiation play a role in progression of cardiovascular disease. The response of endothelial cells to different LDR exposures may help estimate risk of cardiovascular disease by providing the biological mechanism involved. We investigated the effect of chronic LDR radiation on functional and molecular responses of human aorta endothelial cells (HAoECs). Human aorta endothelial cells were continuously irradiated at LDR (6 mGy/h) for 15 days and analyzed at time points when the cumulative dose reached 0.05, 0.5, 1.0, and 2.0 Gy. The same doses were administered acutely at high-dose rate (HDR; 1 Gy/min). The threshold for the loss of angiogenic capacity for both LDR and HDR radiations was between 0.5 and 1.0 Gy. At 2.0 Gy, angiogenic capacity returned to normal only for HAoEC exposed to LDR radiation, associated with increased expression of antioxidant and anti-inflammatory genes. Pre-LDR, but not pre-HDR, radiation, followed by a single acute 2.0 Gy challenge dose sustained the expression of antioxidant and anti-inflammatory genes and stimulated angiogenesis. Our results suggest that dose rate is important in cellular response and that a radioadaptive response is involved for a 2.0 Gy dose at LDR.

  16. Gamma Low-Dose-Rate Ionizing Radiation Stimulates Adaptive Functional and Molecular Response in Human Aortic Endothelial Cells in a Threshold-, Dose-, and Dose Rate–Dependent Manner

    Science.gov (United States)

    Vieira Dias, Juliana; Gloaguen, Celine; Kereselidze, Dimitri; Manens, Line; Tack, Karine; Ebrahimian, Teni G

    2018-01-01

    A central question in radiation protection research is whether low-dose and low-dose-rate (LDR) exposures to ionizing radiation play a role in progression of cardiovascular disease. The response of endothelial cells to different LDR exposures may help estimate risk of cardiovascular disease by providing the biological mechanism involved. We investigated the effect of chronic LDR radiation on functional and molecular responses of human aorta endothelial cells (HAoECs). Human aorta endothelial cells were continuously irradiated at LDR (6 mGy/h) for 15 days and analyzed at time points when the cumulative dose reached 0.05, 0.5, 1.0, and 2.0 Gy. The same doses were administered acutely at high-dose rate (HDR; 1 Gy/min). The threshold for the loss of angiogenic capacity for both LDR and HDR radiations was between 0.5 and 1.0 Gy. At 2.0 Gy, angiogenic capacity returned to normal only for HAoEC exposed to LDR radiation, associated with increased expression of antioxidant and anti-inflammatory genes. Pre-LDR, but not pre-HDR, radiation, followed by a single acute 2.0 Gy challenge dose sustained the expression of antioxidant and anti-inflammatory genes and stimulated angiogenesis. Our results suggest that dose rate is important in cellular response and that a radioadaptive response is involved for a 2.0 Gy dose at LDR. PMID:29531508

  17. MO-E-17A-06: Organ Dose in Abdomen-Pelvis CT: Does TG 111 Equilibrium Dose Concept Better Accounts for KVp Dependence Than Conventional CTDI?

    International Nuclear Information System (INIS)

    Li, X; Morgan, A; Davros, W; Dong, F; Primak, A; Segars, W

    2014-01-01

    Purpose: In CT imaging, a desirable quality assurance (QA) dose quantity should account for the dose variability across scan parameters and scanner models. Recently, AAPM TG 111 proposed to use equilibrium dose-pitch product, in place of CT dose index (CTDI100), for scan modes involving table translation. The purpose of this work is to investigate whether this new concept better accounts for the kVp dependence of organ dose than the conventional CTDI concept. Methods: The adult reference female extended cardiac-torso (XCAT) phantom was used for this study. A Monte Carlo program developed and validated for a 128-slice CT system (Definition Flash, Siemens Healthcare) was used to simulate organ dose for abdomenpelvis scans at five tube voltages (70, 80, 100, 120, 140 kVp) with a pitch of 0.8 and a detector configuration of 2x64x0.6 mm. The same Monte Carlo program was used to simulate CTDI100 and equilibrium dose-pitch product. For both metrics, the central and peripheral values were used together with helical pitch to calculate a volume-weighted average, i.e., CTDIvol and (Deq)vol, respectively. Results: While other scan parameters were kept constant, organ dose depended strongly on kVp; the coefficient of variation (COV) across the five kVp values ranged between 70–75% for liver, spleen, stomach, pancreas, kidneys, colon, small intestine, bladder, and ovaries, all of which were inside the primary radiation beam. One-way analysis of variance (ANOVA) for the effect of kVp was highly significant (p=3e−30). When organ dose was normalized by CTDIvol, the COV across the five kVp values reduced to 7–16%. The effect of kVp was still highly significant (p=4e−4). When organ dose was normalized by (Deq)vol, the COV further reduced to 4−12%. The effect of kVp was borderline significant (p=0.04). Conclusion: In abdomen-pelvis CT, TG 111 equilibrium dose concept better accounts for kVp dependence than the conventional CTDI. This work is supported by a faculty startup

  18. MO-E-17A-06: Organ Dose in Abdomen-Pelvis CT: Does TG 111 Equilibrium Dose Concept Better Accounts for KVp Dependence Than Conventional CTDI?

    Energy Technology Data Exchange (ETDEWEB)

    Li, X [Cleveland State University, Cleveland, OH (United States); Morgan, A; Davros, W [Cleveland State University, Cleveland, OH (United States); Cleveland Clinic, Cleveland, Ohio (United States); Dong, F [Cleveland Clinic, Cleveland, Ohio (United States); Primak, A [Siemens Medical Solutions USA, Inc. (United States); Segars, W [Duke University, Durham, NC (United States)

    2014-06-15

    Purpose: In CT imaging, a desirable quality assurance (QA) dose quantity should account for the dose variability across scan parameters and scanner models. Recently, AAPM TG 111 proposed to use equilibrium dose-pitch product, in place of CT dose index (CTDI100), for scan modes involving table translation. The purpose of this work is to investigate whether this new concept better accounts for the kVp dependence of organ dose than the conventional CTDI concept. Methods: The adult reference female extended cardiac-torso (XCAT) phantom was used for this study. A Monte Carlo program developed and validated for a 128-slice CT system (Definition Flash, Siemens Healthcare) was used to simulate organ dose for abdomenpelvis scans at five tube voltages (70, 80, 100, 120, 140 kVp) with a pitch of 0.8 and a detector configuration of 2x64x0.6 mm. The same Monte Carlo program was used to simulate CTDI100 and equilibrium dose-pitch product. For both metrics, the central and peripheral values were used together with helical pitch to calculate a volume-weighted average, i.e., CTDIvol and (Deq)vol, respectively. Results: While other scan parameters were kept constant, organ dose depended strongly on kVp; the coefficient of variation (COV) across the five kVp values ranged between 70–75% for liver, spleen, stomach, pancreas, kidneys, colon, small intestine, bladder, and ovaries, all of which were inside the primary radiation beam. One-way analysis of variance (ANOVA) for the effect of kVp was highly significant (p=3e−30). When organ dose was normalized by CTDIvol, the COV across the five kVp values reduced to 7–16%. The effect of kVp was still highly significant (p=4e−4). When organ dose was normalized by (Deq)vol, the COV further reduced to 4−12%. The effect of kVp was borderline significant (p=0.04). Conclusion: In abdomen-pelvis CT, TG 111 equilibrium dose concept better accounts for kVp dependence than the conventional CTDI. This work is supported by a faculty startup

  19. Adiponectin influences progesterone production from MA-10 Leydig cells in a dose-dependent manner.

    Science.gov (United States)

    Landry, David; Paré, Aurélie; Jean, Stéphanie; Martin, Luc J

    2015-04-01

    Obesity in men is associated with lower testosterone levels, related to reduced sperm concentration and the development of various diseases with aging. Hormones produced by the adipose tissue may have influences on both metabolism and reproductive function. Among them, the production and secretion of adiponectin is inversely correlated to total body fat. Adiponectin receptors (AdipoR1 and AdipoR2) have been found to be expressed in testicular Leydig cells (producing testosterone). Since StAR and Cyp11a1 are essential for testosterone synthesis and adiponectin has been shown to regulate StAR mRNA in swine granulosa cells, we hypothesized that adiponectin might also regulate these genes in Leydig cells. Our objective was to determine whether adiponectin regulates StAR and Cyp11a1 genes in Leydig cells and to better define its mechanisms of action. Methods used in the current study are qPCR for the mRNA levels, transfections for promoter activities, and enzyme-linked immunosorbent assay for the progesterone concentration. We have found that adiponectin cooperates with cAMP-dependent stimulation to activate StAR and Cyp11a1 mRNA expressions in a dose-dependent manner in MA-10 Leydig cells as demonstrated by transfection of a luciferase reporter plasmid. These results led to a significant increase in progesterone production from MA-10 cells. Thus, our data suggest that high doses of adiponectin typical of normal body weight may promote testosterone production from Leydig cells.

  20. Dose and batch-dependent hepatobiliary toxicity of 10 nm silver nanoparticles

    Directory of Open Access Journals (Sweden)

    Marcella De Maglie

    2015-07-01

    Full Text Available Silver nanoparticles (AgNPs are widely used because of their antimicrobial properties in medical devices and in a variety of consumer products. The extensive use of AgNPs raises concerns about their potential toxicity, although it is still difficult to draw definite conclusions about their toxicity based on published data. Our preliminary studies performed to compare the effect of the AgNPs size (10-40-100 nm on toxicity, demonstrated that the smallest AgNPs determine the most severe toxicological effects. In order to best investigate the impact of physicochemical characteristics of 10 nm AgNPs on toxicity, we compare three different batches of 10 nm AgNPs slightly different in size distribution (Batch A: 8.8±1.7 nm; Batch B: 9.4±1.7 nm; Batch C: 10.0±1.8 nm. Mice were intravenously treated with two doses (5 and 10 mg/kg of the 3 AgNPs. 24 hours after the treatment, mice were euthanized and underwent complete necropsy. Tissues were collected for histopathological examination and total silver content was determined in tissues by inductively coupled plasma mass spectrometry (ICP-MS. All batches induced severe hepatobiliary lesions, i.e. marked hepatocellular necrosis and massive hemorrhage of the gall bladder. The toxicity was dose-dependent and interestingly, the toxic effects were more severe in mice treated with batches A and B that contained smaller AgNPs. Since the total silver mass concentration was similar, the observed batch-dependent toxicity suggest that even subtle differences in size may contribute to relevant changes in the toxicological outcomes, confirming the fundamental involvement of physicochemical features with respect to toxicity.

  1. Age- and sex-dependent model for estimating radioiodine dose to a normal thyroid

    International Nuclear Information System (INIS)

    Killough, G.G.; Eckerman, K.F.

    1986-01-01

    This paper describes the derivation of an age- and sex-dependent model of radioiodine dosimetry in the thyroid and the application of the model to estimating the thyroid dose for each of 4215 patients who were exposed to 131 I in diagnostic and therapeutic procedures. In most cases, the available data consisted of the patient's age at the time of administration, the patient's sex, the quantity of activity administered, the clinically-determined uptake of radioiodine by the thyroid, and the time after administration at which the uptake was determined. The metabolic model is of the form A(t) = K[exp(-μ 1 t) -exp(-μ 2 t)] (μCi), where μ 1 = λ/sub r/ - λ/sub i//sup b/ (i = 1, 2), λ/sub r/ is the radiological decay-rate coefficient, and λ/sub i//sup b/ are biological removal rate coefficients. The values of λ/sub i//sup b/ are determined by solving a nonlinear equation that depends on assumptions about the time or maximum uptake an the eventual biological loss rate (through which age dependence enters). The value of K may then be calculated from knowledge of the uptakes at a particular time. The dosimetric S-factor (rad/μCi-day) is based on specific absorbed fractions for photons of energy ranging from 0.01 to 4.0 MeV for thyroid masses from 1.29 to 19.6 g; the functional form of the S-factor also involves the thyroid mass explicitly, through which the dependence on age and sex enters. An analysis of sensitivity of the model to uncertainties in the thyroid mass and the biological removal rate for several age groups is reported. 12 references, 5 figures, 5 tables

  2. Analysis of the response dependence of Ebt3 radiochromic film with energy, dose rate, wavelength, scanning mode and humidity

    International Nuclear Information System (INIS)

    Leon M, E. Y.; Camacho L, M. A.; Herrera G, J. A.; Garcia G, O. A.; Villarreal B, J. E.

    2016-10-01

    With the development of new modalities in radiotherapy treatments, the use of radiochromic films has increased considerably. Because the characteristics that presented, they are suitable for quality control and dose measurement. In this work and analysis of the dependence of the response of Ebt3 radiochromic films with energy, dose rate, wavelength, scan mode and humidity, for a dose range of 0-70 Gy is presented. According to the results, the response of Ebt3 radiochromic films has low dependence on energy, dose rate, scan mode and humidity. However, the sensitivity of the response Ebt3 radiochromic films has a high dependence on the wavelength of the optical system used for reading. (Author)

  3. Dose-dependent interaction between gemfibrozil and repaglinide in humans: strong inhibition of CYP2C8 with subtherapeutic gemfibrozil doses.

    Science.gov (United States)

    Honkalammi, Johanna; Niemi, Mikko; Neuvonen, Pertti J; Backman, Janne T

    2011-10-01

    Gemfibrozil 1-O-β-glucuronide inactivates CYP2C8 irreversibly. We investigated the effect of gemfibrozil dose on CYP2C8 activity in humans using repaglinide as a probe drug. In a randomized, five-phase crossover study, 10 healthy volunteers ingested 0.25 mg of repaglinide 1 h after different doses of gemfibrozil or placebo. Concentrations of plasma repaglinide, gemfibrozil, their metabolites, and blood glucose were measured. A single gemfibrozil dose of 30, 100, 300, and 900 mg increased the area under the concentration-time curve of repaglinide 1.8-, 4.5-, 6.7-, and 8.3-fold (P Gemfibrozil pharmacokinetics was characterized by a slightly more than dose-proportional increase in the area under the curve of gemfibrozil and its glucuronide. The gemfibrozil-repaglinide interaction could be mainly explained by gemfibrozil 1-O-β-glucuronide concentration-dependent, mechanism-based inhibition of CYP2C8, with a minor contribution by competitive inhibition of organic anion-transporting polypeptide 1B1 at the highest gemfibrozil dose. The findings are consistent with ∼50% inhibition of CYP2C8 already with a single 30-mg dose of gemfibrozil and >95% inhibition with 900 mg. In clinical drug-drug interaction studies, a single 900-mg dose of gemfibrozil can be used to achieve nearly complete inactivation of CYP2C8.

  4. Theoretical analysis of the dose dependence of the oxygen enhancement ratio and its relevance for clinical applications

    International Nuclear Information System (INIS)

    Wenzl, Tatiana; Wilkens, Jan J

    2011-01-01

    The increased resistance of hypoxic cells to ionizing radiation is usually believed to be the primary reason for treatment failure in tumors with oxygen-deficient areas. This oxygen effect can be expressed quantitatively by the oxygen enhancement ratio (OER). Here we investigate theoretically the dependence of the OER on the applied local dose for different types of ionizing irradiation and discuss its importance for clinical applications in radiotherapy for two scenarios: small dose variations during hypoxia-based dose painting and larger dose changes introduced by altered fractionation schemes. Using the widespread Alper-Howard-Flanders and standard linear-quadratic (LQ) models, OER calculations are performed for T1 human kidney and V79 Chinese hamster cells for various dose levels and various hypoxic oxygen partial pressures (pO2) between 0.01 and 20 mmHg as present in clinical situations in vivo. Our work comprises the analysis for both low linear energy transfer (LET) treatment with photons or protons and high-LET treatment with heavy ions. A detailed analysis of experimental data from the literature with respect to the dose dependence of the oxygen effect is performed, revealing controversial opinions whether the OER increases, decreases or stays constant with dose. The behavior of the OER with dose per fraction depends primarily on the ratios of the LQ parameters alpha and beta under hypoxic and aerobic conditions, which themselves depend on LET, pO2 and the cell or tissue type. According to our calculations, the OER variations with dose in vivo for low-LET treatments are moderate, with changes in the OER up to 11% for dose painting (1 or 3 Gy per fraction compared to 2 Gy) and up to 22% in hyper-/hypofractionation (0.5 or 20 Gy per fraction compared to 2 Gy) for oxygen tensions between 0.2 and 20 mmHg typically measured clinically in hypoxic tumors. For extremely hypoxic cells (0.01 mmHg), the dose dependence of the OER becomes more pronounced (up to 36

  5. Radioiodine therapy induces dose-dependent in-vivo oxidation injury

    International Nuclear Information System (INIS)

    Sinzinger, H.; Resch, U.; Tatzber, F.; Weiss, K.

    2002-01-01

    Until now, radiation hazards as a consequence of radioiodine therapy are not examined in detail. Oxidation of lipoproteins may favour vasculopathy. We studied the influence of a single radioiodine therapy with 5 (n=8; 46-71a), 10 (n=6; 54-75a), 20 (n=11; 45-73a), 80 (n=6; 37-75a) or 200 (n=6; 43-67a) mCi on in-vivo oxidation injury in blood (plasma [P], serum [Se]), urine (U) and saliva (Sa) in patients suffering from hyperthyroidism opr thyroid cancer, respectively. The isoprostane 8-epi-prostaglandin (PG) F 2α as a marker of in-vivo oxidation injury (Sa, Se, P, U), oxidation of lipoproteins (LDL, HDL), thromboxane B2 (Sa, Se, P, U), PGE 2 , PGF 2α and circulating endothelial cells (CEC) were examined before therapy, daily for 7 days and weekly thereafter for 6 weeks. Blood was also analyzed for thiobarbituric acid reactive substances (TBARS), relative electrophoretic mobility (REM), baseline dienes (BD), endogenous peroxides (POX) and formation of conjugated dienes in copper-mediated oxidation (CD) expressed in lag-time and rate of propagation. There is a dose-dependent increase in 8-epi-PGF 2α being most pronounced in saliva (p 2 and HDL 3 subfractions 24 h after application, but 48 h and 72 h after application there was a significant increase in TBARS, REM, BD, POX and rate of propagation and a decrease in lag-time in HDL-subfractions independently from applied dose. Also HDL 2 showed more TBARS, REM, BD, POX and shorter lag-time than HDL 3 48 h after application, but this effect was reversed 72 h after application. HDL is the lipoprotein most prone to oxidation by radioiodine treatment. Apparently, when LDL becomes oxidized, it shifts metabolically its oxidation products to HDL. These findings show a significant temporary and dose-dependent endothelial desquamation, oxidation of lipoproteins and long-lasting in-vivo oxidation injury (saliva > urine > blood) as side effect of radioiodine therapy, altogether being potentially proatherogenic

  6. Dose rate-dependent marrow toxicity of TBI in dogs and marrow sparing effect at high dose rate by dose fractionation.

    Science.gov (United States)

    Storb, R; Raff, R F; Graham, T; Appelbaum, F R; Deeg, H J; Schuening, F G; Sale, G; Seidel, K

    1999-01-01

    We evaluated the marrow toxicity of 200 and 300 cGy total-body irradiation (TBI) delivered at 10 and 60 cGy/min, respectively, in dogs not rescued by marrow transplant. Additionally, we compared toxicities after 300 cGy fractionated TBI (100 cGy fractions) to that after single-dose TBI at 10 and 60 cGy/min. Marrow toxicities were assessed on the basis of peripheral blood cell count changes and mortality from radiation-induced pancytopenia. TBI doses studied were just below the dose at which all dogs die despite optimal support. Specifically, 18 dogs were given single doses of 200 cGy TBI, delivered at either 10 (n=13) or 60 (n=5) cGy/min. Thirty-one dogs received 300 cGy TBI at 10 cGy/min, delivered as either single doses (n=21) or three fractions of 100 cGy each (n=10). Seventeen dogs were given 300 cGy TBI at 60 cGy/min, administered either as single doses (n=5) or three fractions of 100 cGy each (n=10). Within the limitations of the experimental design, three conclusions were drawn: 1) with 200 and 300 cGy single-dose TBI, an increase of dose rate from 10 to 60 cGy/min, respectively, caused significant increases in marrow toxicity; 2) at 60 cGy/min, dose fractionation resulted in a significant decrease in marrow toxicities, whereas such a protective effect was not seen at 10 cGy/min; and 3) with fractionated TBI, no significant differences in marrow toxicity were seen between dogs irradiated at 60 and 10 cGy/min. The reduced effectiveness of TBI when a dose of 300 cGy was divided into three fractions of 100 cGy or when dose rate was reduced from 60 cGy/min to 10 cGy/min was consistent with models of radiation toxicity that allow for repair of sublethal injury in DNA.

  7. Angular dependence of the MOSFET dosimeter and its impact on in vivo surface dose measurement in breast cancer treatment.

    Science.gov (United States)

    Qin, S; Chen, T; Wang, L; Tu, Y; Yue, N; Zhou, J

    2014-08-01

    The focus of this study is the angular dependence of two types of Metal Oxide Semiconductor Field Effect Transistor (MOSFET) dosimeters (MOSFET20 and OneDose/OneDosePlus) when used for surface dose measurements. External beam radiationat different gantry angles were delivered to a cubic solid water phantom with a MOSFET placed on the top surface at CAX. The long axis of the MOSFET was oriented along the gantry axis of rotation, with the dosimeter (bubble side) facing the radiation source. MOSFET-measured surface doses were compared against calibrated radiochromic film readings. It was found that both types of MOSFET dosimeters exhibited larger than previously reported angular dependence when measuring surface dose in beams at large oblique angles. For the MOSFET20 dosimeter the measured surface dose deviation against film readings was as high as 17% when the incident angle was 72 degrees to the norm of the phantom surface. It is concluded that some MOSFET dosimeters may have a strong angular dependence when placed on the surface of water-equivalent material, even though they may have an isotropic angular response when surrounded by uniform medium. Extra on-surface calibration maybe necessary before using MOSFET dosimeters for skin dose measurement in tangential fields.

  8. Dose rate and total dose dependence of the 1/f noise performance of a GaAs operational amplifier during irradiation

    International Nuclear Information System (INIS)

    Hiemstra, D.M.

    1995-01-01

    A pictorial of a sectioned view of the torus of the International Thermonuclear Experimental Reactor (ITER) is shown. Maintenance and inspection of the reactor are required to be performed remotely. This is due to the high gamma radiation environment in vessel during inspection and maintenance activities. The custom GaAs operational amplifier is to be used to readout sensors on the in-vessel manipulator and inspection equipment. The gamma dose rate during maintenance and inspection is anticipated to be 3 Mrad(GaAs)/hour. Here, dose rate and total dose dependence of the 1/f noise performance of a custom GaAs MESFET operational amplifier during irradiation are presented. Dose rate dependent 1/f noise degradation during irradiation is believed to be due to electron trapping in deep levels, enhanced by backgating and shallow traps excited during irradiation. The reduction of this affect with accumulated total dose is believed to be due a reduction of deep level site concentration associated with substitutional oxygen. Post irradiation 1/f noise degradation is also presented.The generation-recombination noise observed post irradiation can be attributed to the production of shallow traps due to ionizing radiation

  9. The dependence of dose recovery experiments on the bleaching of natural quartz OSL using different light sources

    International Nuclear Information System (INIS)

    Choi, J.H.; Murray, A.S.; Cheong, C.-S.; Hong, S.C.

    2009-01-01

    In this paper, the dependence of dose recovery tests on the different bleaching light sources (blue-LEDs, solar simulator, natural sunlight) is investigated with a variety of sedimentary quartz samples, selected so that their OSL signals are dominated by the fast OSL component. We observed that when long solar simulator bleaching was applied, various known doses were underestimated in an SAR-based dose recovery test. However, when blue-LEDs and short solar simulator bleaching were used (10 s and 60 s) the known doses were accurately recovered. In repeated measurement of the OSL signals induced by the same regeneration and test dose, we observed a considerable increase in quartz OSL sensitivity during or after the first OSL measurement when long solar simulator bleaching was used; this seems to provide a possible explanation for the observed underestimation of the laboratory known doses. A series of experimental results using a sample from a modern aeolian dune surface shows that there are no subsequent sensitivity changes when the naturally zeroed samples are bleached with sunlight for long time. It seems that there is a dependence of the sensitivity change on the amount of dose administered before solar simulator bleaching and on the light intensity of solar simulator. When small doses were given to the naturally zeroed sample, the sensitivity change during or after the first OSL measurement was not significant. However, when a considerable amount of beta dose (∼4000 Gy) is administered to the sample, a clear sensitivity change during or after the first OSL measurement (∼20%) was observed. Such a sensitivity change was not observed when the bleaching light intensity of solar simulator was reduced by increasing the distance between samples and the UV lamp. Our results show that, at least for the samples described here, the outcomes of dose recovery experiments are dependent on the bleaching conditions.

  10. Normal tissue complication probabilities: dependence on choice of biological model and dose-volume histogram reduction scheme

    International Nuclear Information System (INIS)

    Moiseenko, Vitali; Battista, Jerry; Van Dyk, Jake

    2000-01-01

    Purpose: To evaluate the impact of dose-volume histogram (DVH) reduction schemes and models of normal tissue complication probability (NTCP) on ranking of radiation treatment plans. Methods and Materials: Data for liver complications in humans and for spinal cord in rats were used to derive input parameters of four different NTCP models. DVH reduction was performed using two schemes: 'effective volume' and 'preferred Lyman'. DVHs for competing treatment plans were derived from a sample DVH by varying dose uniformity in a high dose region so that the obtained cumulative DVHs intersected. Treatment plans were ranked according to the calculated NTCP values. Results: Whenever the preferred Lyman scheme was used to reduce the DVH, competing plans were indistinguishable as long as the mean dose was constant. The effective volume DVH reduction scheme did allow us to distinguish between these competing treatment plans. However, plan ranking depended on the radiobiological model used and its input parameters. Conclusions: Dose escalation will be a significant part of radiation treatment planning using new technologies, such as 3-D conformal radiotherapy and tomotherapy. Such dose escalation will depend on how the dose distributions in organs at risk are interpreted in terms of expected complication probabilities. The present study indicates considerable variability in predicted NTCP values because of the methods used for DVH reduction and radiobiological models and their input parameters. Animal studies and collection of standardized clinical data are needed to ascertain the effects of non-uniform dose distributions and to test the validity of the models currently in use

  11. Anti-Allergic Drugs Tranilast and Ketotifen Dose-Dependently Exert Mast Cell-Stabilizing Properties

    Directory of Open Access Journals (Sweden)

    Asuka Baba

    2016-01-01

    Full Text Available Background: Anti-allergic drugs, such as tranilast and ketotifen, inhibit the release of chemokines from mast cells. However, we know little about their direct effects on the exocytotic process of mast cells. Since exocytosis in mast cells can be monitored electrophysiologically by changes in the whole-cell membrane capacitance (Cm, the absence of such changes by these drugs indicates their mast cell-stabilizing properties. Methods: Employing the standard patch-clamp whole-cell recording technique in rat peritoneal mast cells, we examined the effects of tranilast and ketotifen on the Cm during exocytosis. Using confocal imaging of a water-soluble fluorescent dye, lucifer yellow, we also examined their effects on the deformation of the plasma membrane. Results: Relatively lower concentrations of tranilast (100, 250 µM and ketotifen (1, 10 µM did not significantly affect the GTP-γ-S-induced increase in the Cm. However, higher concentrations of tranilast (500 µM, 1 mM and ketotifen (50, 100 µM almost totally suppressed the increase in the Cm, and washed out the trapping of the dye on the surface of the mast cells. Compared to tranilast, ketotifen required much lower doses to similarly inhibit the degranulation of mast cells or the increase in the Cm. Conclusions: This study provides electrophysiological evidence for the first time that tranilast and ketotifen dose-dependently inhibit the process of exocytosis, and that ketotifen is more potent than tranilast in stabilizing mast cells. The mast cell-stabilizing properties of these drugs may be attributed to their ability to counteract the plasma membrane deformation in degranulating mast cells.

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-04-15

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

  14. Hearing preservation after low dose linac radiosurgery for acoustic neuroma depends on initial hearing and time

    International Nuclear Information System (INIS)

    Roos, Daniel E.; Potter, Andrew E.; Zacest, Andrew C.

    2011-01-01

    Purpose: To assess long term outcomes and factors determining hearing preservation after low dose linac stereotactic radiosurgery (SRS) for acoustic neuroma (AN) at the Royal Adelaide Hospital using prospectively collected data. Material and methods: Between 1994 and 2010, 102 patients had SRS for AN. Five patients had neurofibromatosis type 2, six sporadic cases had relapsed after surgery, and the remaining 91 sporadic cases had primary SRS. Dose was 12 or 14 Gy. Sustained changes ⩾ 2 mm in any diameter were deemed significant, and useful hearing was defined as inter-aural pure tone average (PTA) ⩽ 50 dB. Possible prognostic factors for hearing retention were tested by dividing the patients at pre-specified cutpoints: age (60 years), maximum tumour diameter (20 mm), initial PTA (20 dB) and dose (12 vs 14 Gy). Results: Eighty-four of the 91 sporadic primary SRS cases were evaluable for tumour control with at least one post-treatment MRI. Their median follow-up was 65 mo (range 10–184 mo). Eighty-two (97.6%) were controlled, the remaining two requiring salvage surgery for progression at 5.75 and 9.75 years. Also, one of the post-operative cases required surgery at 2.1 years after SRS. For the 50 sporadic primary SRS patients with initially useful hearing, median age was 56 (range 21–76), median initial PTA 16 dB (range −11 to +45 dB) and median tumour diameter 21 mm (range 10–33 mm). Four received 14 Gy, the rest 12 Gy. After SRS, 19 patients (38%) retained useful hearing. The Kaplan–Meier estimated preservation rate at 5 years was 50% (95% CI 36–64%) but by 10 years, this had fallen to 23% (95% CI 12–41%). On univariate analysis, the only significant factor was initial PTA (P < 0.0001). The estimated risk of hearing loss after SRS for patients with initial PTA ⩾ 20 dB was 5.0 (95% CI 2.2–11.2) times that with PTA < 20 dB. Conclusions: Tumour control was excellent (99/102 = 97% freedom from surgical salvage). Hearing preservation was strongly

  15. Dose-dependent headache response and dilatation of limb and extracranial arteries after three doses of 5-isosorbide-mononitrate

    DEFF Research Database (Denmark)

    Iversen, Helle Klingenberg; Nielsen, T H; Garre, K

    1992-01-01

    of the temporal artery, but not for the radial artery. It is concluded that headache after 5-ISMN is caused by arterial dilatation or by mechanisms responsible for the arterial dilatation. Ultrasound monitoring of arterial diameters is an important and sensitive tool in the evaluation of nitrates and other...... and placebo on separate days. The diameters of the radial and superficial temporal arteries were repeatedly measured with high frequency ultrasound and pain was scored using a 10 point verbal scale. A clear dose-relationship was found for plasma concentrations and headache, and for changes in the diameter...

  16. SPECIAL CONSIDERATIONS REGARDING WARFARIN DOSE TITRATION IN PATIENTS WITH ATRIAL FIBRILLATION DEPENDING ON CLINICAL FACTORS

    OpenAIRE

    E. L. Artanova; E. V. Saleeva; I. M. Sokolov; Y. G. Shvarts

    2011-01-01

    Aim. To study the relations of clinical characteristics and individual warfarin dose titration in patients with atrial fibrillation. Material and methods. Period of warfarin dose titration was analyzed in 68 patients with atrial fibrillation due to ischemic heart disease. Adjusted warfarin dose in milligram, duration of dose titration in days and maximal international normalized ratio (INR) were taken into account. Sex, age, history of myocardial infarction and stroke, concomitant diseases, a...

  17. Dose-dependent pharmacokinetics of delavirdine in combination with amprenavir in healthy volunteers

    DEFF Research Database (Denmark)

    Justesen, Ulrik S; Klitgaard, Niels A; Brosen, Kim

    2004-01-01

    OBJECTIVES: To investigate different dose combinations of amprenavir and delavirdine in order to assess an optimal dose suitable for clinical use. METHODS: This was a prospective, open-label, controlled, three-period, multiple-dose study with nine healthy volunteers. The volunteers received three...

  18. Dependence of the average life span, mortality and osteosarcoma occurence in rats on the radiation dose absorbed (Sr 90)

    International Nuclear Information System (INIS)

    Shvedov, V.L.; Panteleev, L.I.

    1975-01-01

    The dose dependence of mortality and osteosarcoma development frequency is studied in white rats which have received 0.00005-5.0μCi/day of strontium-90 throughout their lives. It is shown that total mortality in the dose range 0-10 krad is a more sensitive test than osteosarcoma frequency, osteosarcomatosis hardly reducing the mean life span of the irradiated rats. (author)

  19. Red Light-Dose or Wavelength-Dependent Photoresponse of Antioxidants in Herb Microgreens.

    Directory of Open Access Journals (Sweden)

    Giedė Samuolienė

    Full Text Available The purpose of this study was to evaluate the role of 638-nm and 665-nm LEDs on changes of antioxidants of basil (Ocimum basilicum and parsley (Petroselinum crispum, and to assess the effect of light quality on antioxidative status. Plants were grown in peat substrate for 19 days (21/17 ±2°C, 16 h. Experiments were performed in (I a controlled-environment: B455,R638,R665,FR731(control; B455,R*638,R665,FR731; B455,R638,R*665,FR731; R638; R665 (B-blue, R- red, FR-far-red light. PPFD was set from 231 during growth, upto 300 μmol m-2 s-1 during 3-day treatment changing R638 or R665 PPFD level; in (II greenhouse (November: high-pressure sodium lamps (HPS (control-300 μmol m-2s-1; and HPS + 638 (HPS generated 90 and red LEDs-210 μmol m-2s-1. In general, under supplemental or increased red 638 nm light, amounts of tested antioxidants were greater in basil, whereas sole 665 nm or sole 638 nm is more favourable for parsley. Increased or supplemental red light significantly increased contents of phenolics, α-tocopherol, ascorbic acid and DPPH• but suppressed accumulation of lutein and β-carotene in basil, whereas an increase of β-carotene and DPPH• was observed in parsley. Hereby, the photoresponse of antioxidant compounds suggests that photoprotective mechanism is stimulated by both light-dose-dependent and wavelength-dependent reactions.

  20. Sex- and dose-dependency in the pharmacokinetics and pharmacodynamics of (+)-methamphetamine and its metabolite (+)-amphetamine in rats

    International Nuclear Information System (INIS)

    Milesi-Halle, Alessandra; Hendrickson, Howard P.; Laurenzana, Elizabeth M.; Gentry, W. Brooks; Owens, S. Michael

    2005-01-01

    These studies investigated how (+)-methamphetamine (METH) dose and rat sex affect the pharmacological response to METH in Sprague-Dawley rats. The first set of experiments determined the pharmacokinetics of METH and its pharmacologically active metabolite (+)-amphetamine (AMP) in male and female Sprague-Dawley rats after 1.0 and 3.0 mg/kg METH doses. The results showed significant sex-dependent changes in METH pharmacokinetics, and females formed significantly lower amounts of AMP. While the area under the serum concentration-time curve in males increased proportionately with the METH dose, the females showed a disproportional increase. The sex differences in systemic clearance, renal clearance, volume of distribution, and percentage of unchanged METH eliminated in the urine suggested dose-dependent pharmacokinetics in female rats. The second set of studies sought to determine the behavioral implications of these pharmacokinetic differences by quantifying locomotor activity in male and female rats after saline, 1.0, and 3.0 mg/kg METH. The results showed sex- and dose-dependent differences in METH-induced locomotion, including profound differences in the temporal profile of effects at higher dose. These findings show that the pharmacokinetic and metabolic profile of METH (slower METH clearance and lower AMP metabolite formation) plays a significant role in the differential pharmacological response to METH in male and female rats

  1. Temperature and ion-mass dependence of amorphization dose for ion beam irradiated zircon (ZrSiO4)

    International Nuclear Information System (INIS)

    Wang, L.M.; Ewing, R.C.; Eby, R.K.

    1992-12-01

    The temperature dependence of amorphization dose for zircon under 1.5 MeV Kr ion irradiation has been investigated using the ANL HVEM-Tandem Facility. Three regimes were observed in the amorphization dose-temperature curve. In the first regime (15 to 300 K), the critical amorphization dose increased from 3.06 to 4.5 ions/nm 2 . In the second regime (300 to 473 K), there is little change in the amorphizationdose. In the third regime (> 473 K), the amorphization dose increased exponentially to 8.3 ions/nm 2 at 913 K. This temperature dependence of amorphization dose can be described by two processes with different activation energies (0.018 and 0.31 eV respectively) which are attributed to close pair recombination in the cascades at low temperatures and radiation-enhanced epitaxial recrystallization at higher temperatures. The upper temperature limit for amorphization of zircon is estimated to be 1100 K. The ion-mass dependence of the amorphization dose (in dpa) has also been discussed in terms of the energy to recoils based on data obtained from He, Ne, Ar, Kr, Xe irradiations and a 238 Pu-doped sample

  2. Vitamin D Dependent Rickets Type II: Late Onset of Disease and Response to High Doses of Vitamin D

    Directory of Open Access Journals (Sweden)

    Soni Sachin

    2008-01-01

    Full Text Available Vitamin D dependent rickets Type II is a rare autosomal recessive disorder. The disorder is characterized by end organ hyporesponsiveness to vitamin D. Common presentation of the disorder is total body alopecia and onset of rickets during the second half of the first year of life. Patients may display progressive rachitic bone changes, hypocalcemia and secondary hyper-parathyroidism. It is differentiated from vitamin D dependent rickets type I by virtue of response to physiological doses of exogenous vitamin D in the later. Target organ hyporesponsiveness can be overcome by higher doses of vitamin D or its analogues. We report a case of vitamin D dependent rickets type II with onset of rickets at the age of thirteen years without alopecia progressing to marked disability by twenty three years of age. She responded to massive doses of vitamin D with significant clinical improvement after six months of therapy.

  3. Entrance doses during lateral lumbar spine and antero-posterior abdomen examinations: generator waveform dependence

    International Nuclear Information System (INIS)

    Morrison, G.D.; Underwood, A.C.

    1995-01-01

    In North Trent, UK, an entrance dose survey of lateral lumbar spine and antero-posterior (AP) abdomen examinations has been carried out in 17 radiology departments. The survey comprised 294 lateral lumbar spine and 322 AP abdomen entrance dose measurements. The mean entrance doses were found to be approximately half of the relevant national reference entrance dose levels of 30 mGy and 10 mGy, respectively. The effect of generator waveform on entrance dose was studied by separating the generators into two types: ''pulsating potential'' (PP) generators and ''constant potential'' (CP) generators for each examination. PP generators comprised 23% of the total number of examinations. The mean entrance dose and radiographic exposure factors from CP generators were found to be significantly lower than those from PP generators. The use of CP type generators, together with low attenuation components can significantly reduce patient entrance doses for these examinations. (author)

  4. High-dose total-body irradiation and autologous marrow reconstitution in dogs: dose-rate-related acute toxicity and fractionation-dependent long-term survival

    International Nuclear Information System (INIS)

    Deeg, H.J.; Storb, R.; Weiden, P.L.; Schumacher, D.; Shulman, H.; Graham, T.; Thomas, E.D.

    1981-01-01

    Beagle dogs treated by total-body irradiation (TBI) were given autologous marrow grafts in order to avoid death from marrow toxicity. Acute and delayed non-marrow toxicities of high single-dose (27 dogs) and fractionated TBI (20 dogs) delivered at 0.05 or 0.1 Gy/min were compared. Fractionated TBI was given in increments of 2 Gy every 6 hr for three increments per day. Acute toxicity and early mortality (<1 month) at identical total irradiation doses were comparable for dogs given fractionated or single-dose TBI. With single-dose TBI, 14, 16, and 18 Gy, respectively, given at 0.05 Gy/min, 0/5, 5/5, and 2/2 dogs died from acute toxicity; with 10, 12, and 14 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 5/5 dogs died acutely. With fractionated TBI, 14 and 16 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 2/2 dogs died auctely. Early deaths were due to radiation enteritis with or without associated septicemia (29 dogs; less than or equal to Day 10). Three dogs given 10 Gy of TBI at 0.1 Gy/min died from bacterial pneumonia; one (Day 18) had been given fractionated and two (Days 14, 22) single-dose TBI. Fifteen dogs survived beyond 1 month; eight of these had single-dose TBI (10-14 Gy) and all died within 7 months of irradiation from a syndrome consisting of hepatic damage, pancreatic fibrosis, malnutrition, wasting, and anemia. Seven of the 15 had fractionated TBI, and only one (14 Gy) died on Day 33 from hepatic failure, whereas 6 (10-14 Gy) are alive and well 250 to 500 days after irradiation. In conclusion, fractionated TBI did not offer advantages over single-dose TBI with regard to acute toxicity and early mortality; rather, these were dependent upon the total dose of TBI. The total acutely tolerated dose was dependent upon the exposure rate; however, only dogs given fractionated TBI became healthy long-term survivors

  5. Dose- and Time-Dependent Response of Human Leukemia (HL-60 Cells to Arsenic Trioxide Treatment

    Directory of Open Access Journals (Sweden)

    Paul B. Tchounwou

    2006-06-01

    Full Text Available The treatment of acute promyelocytic leukemia (APL has been based on the administration of all-trans retinoic acid plus anthracycline chemotherapy, which is very effective as first line therapy; however 25 to 30% of patients will relapse with their disease becoming refractory to conventional therapy. Recently, studies have shown arsenic trioxide to be effective in the treatment of acute promyelocytic leukemia. In this study, we used the human leukemia (HL-60 cell line as a model to evaluate the cytoxicity of arsenic trioxide based on the MTT assay. Data obtained from this assay indicated that arsenic trioxide significantly reduced the viability of HL-60 cells, showing LD50 values of 14.26 + 0.5μg/mL, 12.54 + 0.3μg/mL, and 6.4 + 0.6μg/mL upon 6, 12, and 24 hours of exposure, respectively; indicating a dose- and time-dependent response relationship. Findings from the present study indicate that arsenic trioxide is highly cytotoxic to human leukemia (HL-60 cells, supporting its use as an effective therapeutic agent in the management of acute promyelocytic leukemia.

  6. Cytotoxicity and Genotoxicity of Cypermethrin in Hepatocarcinoma Cells: A Dose- and Time-Dependent Study.

    Science.gov (United States)

    AlKahtane, Abdullah A; Alarifi, Saud; Al-Qahtani, Ahmed A; Ali, Daoud; Alomar, Suliman Y; Aleissia, Mohammed S; Alkahtani, Saad

    2018-01-01

    Most of the agricultural workers are potentially exposed to pesticides through different routes. Inhalation exposures may result in numerous diseases that can adversely affect an individual's health and capacity to perform at work. The aim of this study was to determine the cytotoxic potential of cypermethrin pesticide on cultured human hepatocarcinoma (HepG2) cells. The HepG2 cells were exposed to cypermethrin (0, 5, 15, 40 ng/mL) for 24 and 48 hours. We observed that cypermethrin caused cell death of HepG2 cells using 3-(4, 5-dimethylthiozolyl-2)-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase tests. Furthermore, cypermethrin reduced HepG2 cells viability in a time and dose dependent basis, that was probably mediated through the induction of reactive oxygen species (ROS) and apoptosis. An increase in ROS generation with a concomitant increase in expression of the proapoptotic protein Bcl-2 and cytochrome c and decrease in the antiapoptosis protein Bax suggested that a mitochondria-mediated pathway was involved in cypermethrin-induced apoptosis. These findings provide insights into the underlying mechanisms involved in cytotoxicity of cypermethrin in HepG2 cells.

  7. Morning administration of oral methamphetamine dose-dependently disrupts nighttime sleep in recreational stimulant users.

    Science.gov (United States)

    Herrmann, Evan S; Johnson, Patrick S; Bruner, Natalie R; Vandrey, Ryan; Johnson, Matthew W

    2017-09-01

    Use of amphetamine-type stimulants (e.g., methamphetamine) is associated with acute sleep disruptions. No prior reports have characterized the acute effects of methamphetamine on sleep using polysomnography, the gold standard for objective sleep monitoring. Recreational stimulant users (n=19) completed a baseline assessment, which included questionnaires assessing demographic and substance use characteristics, and the Pittsburgh Sleep Quality Index (PSQI), which assesses sleep quality over the past month. Participants were administered 0mg (placebo), 20mg, or 40mg oral methamphetamine at 08:15h on study days, using a double-blind, randomized, within-subjects design. Sleep was monitored using polysomnography from 22:20 that evening until 06:15 the following morning. PSQI scores indicated more than half of participants reported poor sleep quality at baseline. Methamphetamine dose-dependently increased sleep latency, and decreased total sleep time, sleep efficiency, time in NREM 2 sleep, number of REM periods, and total time in REM sleep. Sleep under placebo conditions was consistent with what would be expected from healthy adults. Morning oral administration of methamphetamine produces robust disruptions in nighttime sleep. Future research should examine relations between stimulant use and sleep disruption in naturalistic settings, with regard to both stimulant abuse and licit prescription use. Copyright © 2017. Published by Elsevier B.V.

  8. Dose-dependent cytotoxicity of clinically relevant cobalt nanoparticles and ions on macrophages in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Young-Min; Xia Zhidao; Glyn-Jones, Sion; Beard, David; Gill, Harinderjit S; Murray, David W, E-mail: young-min.kwon@ndos.ox.ac.u [Nuffield Department of Orthopaedic Surgery, University of Oxford, Oxford OX3 7LD (United Kingdom)

    2009-04-15

    Despite the satisfactory short-term implant survivorship of metal-on-metal hip resurfacing arthroplasty, periprosthetic soft-tissue masses such as pseudotumours are being increasingly reported. Cytotoxic effects of cobalt or chromium have been suggested to play a role in its aetiology. The aim of this study was to investigate the effects of clinically relevant metal nanoparticles and ions on the viability of macrophages in vitro. A RAW 264.7 murine macrophage cell line was cultured in the presence of either: (1) cobalt, chromium and titanium nanoparticles sized 30-35 nm; or (2) cobalt sulphate and chromium chloride. Two methods were used to quantify cell viability: Alamar Blue assay and Live/Dead assay. The cytotoxicity was observed only with cobalt. Cobalt nanoparticles and ions demonstrated dose-dependent cytotoxic effects on macrophages in vitro: the cytotoxic concentrations of nanoparticles and ions were 1 x 10{sup 12} particles ml{sup -1} and 1000 {mu}M, respectively. The high concentration of cobalt nanoparticles required for cytotoxicity of macrophages in vitro suggests that increased production of cobalt nanoparticles in vivo, due to excessive MoM implant wear, may lead to local adverse biological effects. Therefore, cytotoxicity of high concentrations of metal nanoparticles phagocytosed by macrophages located in the periprosthetic tissues may be an important factor in pathogenesis of pseudotumours.

  9. Dose-dependent effects of ouabain on spiral ganglion neurons and Schwann cells in mouse cochlea.

    Science.gov (United States)

    Zhang, Zhi-Jian; Guan, Hong-Xia; Yang, Kun; Xiao, Bo-Kui; Liao, Hua; Jiang, Yang; Zhou, Tao; Hua, Qing-Quan

    2017-10-01

    This study aimed in fully investigating the toxicities of ouabain to mouse cochlea and the related cellular environment, and providing an optimal animal model system for cell transplantation in the treatment of auditory neuropathy (AN) and sensorineural hearing loss (SNHL). Different dosages of ouabain were applied to mouse round window. The auditory brainstem responses and distortion product otoacoustic emissions were used to evaluate the cochlear function. The immunohistochemical staining and cochlea surface preparation were performed to detect the spiral ganglion neurons (SGNs), Schwann cells and hair cells. Ouabain at the dosages of 0.5 mM, 1 mM and 3 mM selectively and permanently destroyed SGNs and their functions, while leaving the hair cells relatively intact. Ouabain at 3 mM resulted in the most severe SGNs loss and induced significant loss of Schwann cells started as early as 7 days and with further damages at 14 and 30 days after ouabain exposure. The application of ouabain to mouse round window induces damages of SGNs and Schwann cells in a dose- and time-dependent manner, this study established a reliable and accurate animal model system of AN and SNHL.

  10. Carbon dioxide inhalation induces dose-dependent and age-related negative affectivity.

    Directory of Open Access Journals (Sweden)

    Eric J Griez

    Full Text Available BACKGROUND: Carbon dioxide inhalation is known to induce an emotion similar to spontaneous panic in Panic Disorder patients. The affective response to carbon dioxide in healthy subjects was not clearly characterized yet. METHODOLOGY/PRINCIPAL FINDINGS: Sixty-four healthy subjects underwent a double inhalation of four mixtures containing respectively 0, 9, 17.5 and 35% CO(2 in compressed air, following a double blind, cross-over, randomized design. Affective responses were assessed according to DSM IV criteria for panic, using an Electronic Visual Analogue Scale and the Panic Symptom List. It was demonstrated that carbon dioxide challenges induced a dose dependent negative affect (p<0.0001. This affect was semantically identical to the DSM IV definition of panic. Older individuals were subjectively less sensitive to Carbon Dioxide (p<0.05. CONCLUSIONS/SIGNIFICANCE: CO(2 induced affectivity may lay on a continuum with pathological panic attacks. Consistent with earlier suggestions that panic is a false biological alarm, the affective response to CO(2 may be part of a protective system triggered by suffocation and acute metabolic distress.

  11. Revised age-dependent doses to members of the public from intake of radionuclides using the new tissue weighting factors

    International Nuclear Information System (INIS)

    Jain, S.C.; Gupta, M.M.; Nagaratnam, A.; Reddy, A.R.; Mehta, S.C.

    1992-01-01

    ICRP 56 gave age-dependent dose coefficients to members of the public from intake of most radiologically significant radionuclides that might be released to the environment due to various human activities. It has computed effective dose equivalent (now called effective dose) from these dose coefficients utilising the tissue weighting factors as given by ICRP 26. The recent ICRP 1990 recommendations have revised the tissue weighting factors based on new information on risk estimates of fatal cancer and hereditary disorders. This change in the tissue weighting factors will subsequently affect the computation of effective dose due to intake of various radio-nuclides considered by ICRP 56. The revised effective doses for ingested as well as inhaled radionuclides have been worked out and compared from corresponding earlier values. No change was found in the case of tritiated water, organically bound tritium and 14 C. For the majority of the radionuclides, the revised effective dose was within ± 20% of the earlier values. Larger variations in effective dose were noted for radionuclides which deposit preferentially in one or two organs. (author)

  12. Chronic UVA (365-nm) irradiation induced scratching in hairless mice: dose-time dependency and the effect of ketanserin

    International Nuclear Information System (INIS)

    Laat, J.M.T. de; Groenendijk, M.; Vloten, W.A. van; Gruijl, F.R. de; Seite, S.

    1997-01-01

    In a study on the dose-response relationship for longwave UVA (UVA1; 340-400 nm) carcinogenesis in hairless mice scratch marks appeared after months of daily exposure as an unwanted side effect. Tumor induction in the highest of the 4 tested dose groups (receiving a daily dose of 430 kJ/m 2 of 365-nm radiation) could not be determined because extensive scarification occurred prior to the development of any tumors. The induction of scratch marks could be scored and quantified in all 4 dose groups tested. The UVA1 dose-dependencies for the induction of tumors and scratch marks were compared. We found that the induction of scratch marks depended mainly on the cumulative UVA1 exposure, whereas tumor induction showed a lesser dose-dependency. An attempt was made to prevent the apparent pruritogenic effect of UVA1 irradiation and to understand its mechanism. The influence of ketanserin, a serotonin/histamine antagonist, on the UVA1 induction of scratch marks was tested in groups of 8 mice daily irradiated with 430 kJ/m 2 . No difference was found between treated and untreated animals. Histological examination of skin biopsies from irradiated mice from the 430-kJ/m 2 dose group from the UVA1 carcinogenic experiment, showed no changes in numbers of mast cells or other inflammatory features when compared to skin biopsies from unirradiated control mice. This indicated that UVA1-induced scratching is not mediated through mast cell release of serotonin and/or histamine. An adequate therapeutic treatment which can prevent UVA1-induced scratching would enable us to test tumor induction with UVA1 over a larger dose range, and may provide additional insight in how this radiation damages the skin. It remains conjectural whether there exists and analogous UVA-induced pruritus in human skin. (au)

  13. SU-F-18C-11: Diameter Dependency of the Radial Dose Distribution in a Long Polyethylene Cylinder

    Energy Technology Data Exchange (ETDEWEB)

    Bakalyar, D; McKenney, S [Henry Ford Health System, Detroit, MI (United States); Feng, W [New York Presbyterian Hospital, Tenafly, NJ (United States)

    2014-06-15

    Purpose: The radial dose distribution in the central plane of a long cylinder following a long CT scan depends upon the diameter and composition of the cylinder. An understanding of this behavior is required for determining the spatial average of the dose in the central plane. Polyethylene, the material for construction of the TG200/ICRU phantom (30 cm in diameter) was used for this study. Size effects are germane to the principles incorporated in size specific dose estimates (SSDE); thus diameter dependency was explored as well. Method: ssuming a uniform cylinder and cylindrically symmetric conditions of irradiation, the dose distribution can be described using a radial function. This function must be an even function of the radial distance due to the conditions of symmetry. Two effects are accounted for: The direct beam makes its weakest contribution at the center while the contribution due to scatter is strongest at the center and drops off abruptly at the outer radius. An analytic function incorporating these features was fit to Monte Carlo results determined for infinite polyethylene cylinders of various diameters. A further feature of this function is that it is integrable. Results: Symmetry and continuity dictate a local extremum at the center which is a minimum for the larger sizes. The competing effects described above can Resultin an absolute maximum occurring between the center and outer edge of the cylinders. For the smallest cylinders, the maximum dose may occur at the center. Conclusion: An integrable, analytic function can be used to characterize the radial dependency of dose for cylindrical CT phantoms of various sizes. One use for this is to help determine average dose distribution over the central cylinder plane when equilibrium dose has been reached.

  14. Biophysical analysis of the dose-dependent overdispersion and the restricted linear energy transfer dependence expressed in dicentric chromosome data from alpha-irradiated human lymphocytes.

    Science.gov (United States)

    Greinert, R; Harder, D

    1997-06-01

    Experimental data for the induction of dicentric chromosomes in phytohemagglutinin (PHA)-stimulated human T lymphocytes by 241Am alpha-particles obtained by Schmid et al. have been analyzed in the light of biophysical theory. As usual in experiments with alpha-particles, the relative variance of the intercellular distribution of the number of aberrations per cell exceeds unity, and the multiplicity of the aberrations per particle traversal through the cell is understood as the basic effect causing this overdispersion. However, the clearly expressed dose dependence of the relative variance differs from the dose-independent relative variance predicted by the multiplicity effect alone. Since such dose dependence is often observed in experiments with alpha-particles, protons, and high-energy neutrons, the interpretation of the overdispersion needs to be supplemented. In a new, more general statistical model, the distribution function of the number of aberrations is interpreted as resulting from the convolution of a Poisson distribution for the spontaneous aberrations with the overdispersed distributions for the aberrations caused by intratrack or intertrack lesion interaction, and the fluctuation of the cross-sectional area of the cellular chromatin must also be considered. Using a suitable mathematical formulation of the resulting dose-dependent over-dispersion, the mean number lambda 1 of the aberrations produced by a single particle traversal through the cell nucleus and the mean number lambda 2 of the aberrations per pairwise approach between two alpha-particle tracks could be estimated. Coefficient alpha of the dose-proportional yield component, when compared between 241Am alpha-particle irradiation and 137Cs gamma-ray exposure, is found to increase approximately in proportion to dose-mean restricted linear energy transfer, which indicates an underlying pairwise molecular lesion interaction on the nanometer scale.

  15. SU-E-T-44: Angular Dependence of Surface Dose Enhancement Measured On Several Inhomogeneities Using Radiochromic EBT3 Films

    International Nuclear Information System (INIS)

    Jansen, A; Schoenfeld, A; Poppinga, D; Chofor, N; Poppe, B

    2014-01-01

    Purpose: The quantification of the relative surface dose enhancement in dependence on the angle of incidence and the atomic number Z of the surface material. Methods: Experiments were performed with slabs made of aluminum, titanium, copper, silver, dental gold and lead. The metal slabs with equal sizes of 1.0×8.0×8.8mm 3 were embedded in an Octavius 4D phantom (PTW Freiburg, Germany). Radiochromic EBT3 films were used to measure the surface dose for angles of incidence ranging from 0° to 90°. The setup with the metals slabs at the isocenter was irradiated with acceleration voltages of 6MV and 10MV. Water reference measurements were taken under equal conditions. Results: The surface dose enhancement is highest for angles of incidence below 30° and drops significantly for higher. The surface dose enhancement produced by lead and dental gold at 6MV showed a peak of 65%. At 90°, the surface dose enhancement dropped to 15% for both materials. The surface dose enhancements for silver, copper, titanium and aluminum were 45%, 32%, 22% and 12% at 0°, respectively. At an angle of incidence of 80°, the values dropped to 22%, 18%, 12% und 6%. The values for 10MV were very similar. Lead and dental gold showed peaks of 65% und 60%. Their values dropped to 18% at an angle of 90°. The surface dose enhancements for silver, copper, titanium and aluminum were 45%, 30%, 20% and 8% at 0°. At 80° the values dropped to 30%, 20%, 12% and 5%. A dependence of the magnitude of the surface dose enhancement on the atomic number of the surface material can be seen, which is in consistence with literature. Conclusion: The results show that the surface dose enhancements near implant materials with high Z-values should be taken into consideration in radio therapy, even when the angle of incidence is flat

  16. Absorbed dose/melting heat dependence studies for the PVDF homopolymer

    International Nuclear Information System (INIS)

    Batista, Adriana S.M.; Gual, Maritza R.; Pereira, Claubia

    2013-01-01

    Differential Scanning Calorimetry (DSC) of gamma irradiated Poly (vinylidene Fluoride) [PVDF] homopolymer has been studied in connection with the use of material in industrial high gamma dose measurement. Interaction between gamma radiation and PVDF leads to the radio-induction of C=O and conjugated C=C bonds, as it can be inferred from previous infrared (FTIR) and ultraviolet-visible (UV-Vis) spectrometric data. These induced defects result in a decrease of the polymer crystallinity that can be followed with DSC scans, by measuring the latent heat during the melting transition (Hmelt). After a systematic investigation, we have found that Hmelt is unambiguously related to the delivered doses ranging from 100 to 2,000 kGy of gamma radiation. One the other hand, further fading investigation analysis has proved that the Hmelt x Dose relationship can be fitted by an exponential function that remains constant for several months. Both the very large range of dose measurement and also the possibility of evaluating high gamma doses until five months after irradiation make PVDF homopolymers very good candidates to be investigated as commercial high gamma dose dosimeters. The high gamma dose irradiation facilities in Brazil used to develop high dose dosimeters are all devoted to industrial and medical purposes. Therefore, in view of the uncertainties involved in the dose measurements related to the electronic equilibrium correction factors and backscattering in the isodose curves used at the irradiation setup, a validation process is required to correctly evaluate the delivered absorbed doses. The sample irradiations were performed with a Co-60 source, at 12kGy/h and 2,592 kGy/h, in the high gamma dose facilities at Centro de Desenvolvimento da Tecnologia Nuclear CDTN/CNEN, Belo Horizonte, Brazil. The comparison of the curve of the Hmelt vs Dose is presented in this paper. (author)

  17. A recalculation of the age dependent dose-effect-relationship of the life span study of Hiroshima and Nagasaki

    International Nuclear Information System (INIS)

    Kottbauer, M.M.; Fleck, C.M.; Schoellnberger, H.

    1996-01-01

    The basis of the presented model is the multistage process of carcinogenesis as a biological effect. It provides simultaneously the age-dependent mortality of spontaneous and radiation induced solid tumors and dose-effect relationships at any age after exposure. The model has been used to describe the solid cancer mortality rates of the atomic bomb survivors of Hiroshima and Nagasaki. It has characteristics of both relative and absolute risk projections depending on the age of exposure. (author)

  18. The protein corona protects against size- and dose-dependent toxicity of amorphous silica nanoparticles

    Directory of Open Access Journals (Sweden)

    Dominic Docter

    2014-08-01

    Full Text Available Besides the lung and skin, the gastrointestinal (GI tract is one of the main targets for accidental exposure or biomedical applications of nanoparticles (NP. Biological responses to NP, including nanotoxicology, are caused by the interaction of the NP with cellular membranes and/or cellular entry. Here, the physico-chemical characteristics of NP are widely discussed as critical determinants, albeit the exact mechanisms remain to be resolved. Moreover, proteins associate with NP in physiological fluids, forming the protein corona potentially transforming the biological identity of the particle and thus, adding an additional level of complexity for the bio–nano responses.Here, we employed amorphous silica nanoparticles (ASP and epithelial GI tract Caco-2 cells as a model to study the biological impact of particle size as well as of the protein corona. Caco-2 or mucus-producing HT-29 cells were exposed to thoroughly characterized, negatively charged ASP of different size in the absence or presence of proteins. Comprehensive experimental approaches, such as quantifying cellular metabolic activity, microscopic observation of cell morphology, and high-throughput cell analysis revealed a dose- and time-dependent toxicity primarily upon exposure with ASP30 (Ø = 30 nm. Albeit smaller (ASP20, Ø = 20 nm or larger particles (ASP100; Ø = 100 nm showed a similar zeta potential, they both displayed only low toxicity. Importantly, the adverse effects triggered by ASP30/ASP30L were significantly ameliorated upon formation of the protein corona, which we found was efficiently established on all ASP studied. As a potential explanation, corona formation reduced ASP30 cellular uptake, which was however not significantly affected by ASP surface charge in our model. Collectively, our study uncovers an impact of ASP size as well as of the protein corona on cellular toxicity, which might be relevant for processes at the nano–bio interface in general.

  19. Dose-Dependent Effect of Curcumin on Learning and Memory Deficit in Kainate-Epileptic Rats

    Directory of Open Access Journals (Sweden)

    Zahra Kiasalari

    2014-09-01

    Full Text Available Background & objectives : Epileptic seizures accompany disturbances in learning, memory, and cognitive skills. With regard to antiepileptic potential of curcumin and its beneficial effect on memory, the effect of its administration on learning and memory in kainate-epileptic rats was investigated.   Methods: Forty male rats were divided into sham, positive control ( valproate-treated epileptic, epileptic, and two curcumin-treated epileptic groups. Rat model of epilepsy was induced by unilateral intrahippocampal administration of 4 μg of kainate per rat. Rats received intraperitoneal injection of curcumin (50 and 100 mg/kg daily for 1 week before surgery. For evaluation of learning and memory, initial (IL and step-through latencies (STL were determined using passive avoidance test and alternation behavior percentage was obtained according to Y maze test.   Results: Regarding IL, there was no significant difference between the groups. In contrast, STL significantly decreased in curcumin-50-treated epileptic group (p<0.05 (a change from 263.1 to 184.5 s. However, this parameter significantly increased in curcumin-100-treated epileptic group as compared to epileptic group (p<0.01 (a change from 263.1 to 220.3 s. In addition, STL was also significantly higher in valproic acid-treated epileptic group versus epileptic group (p<0.05 (a change from 145.7 to 210.3 s. Alternation percentage was also significantly higher in curcumin-50- and curcumin-100-treated epileptic groups relative to epileptic group (p<0.05 (a change from 60.5 to 77.6 and 80.3%.   Conclusion: Curcumin could dose-dependently enhance the consolidation and recall in epileptic animals and could improve spatial memory in such animals.

  20. Induced terpene accumulation in Norway spruce inhibits bark beetle colonization in a dose-dependent manner.

    Directory of Open Access Journals (Sweden)

    Tao Zhao

    Full Text Available Tree-killing bark beetles (Coleoptera, Scolytinae are among the most economically and ecologically important forest pests in the northern hemisphere. Induction of terpenoid-based oleoresin has long been considered important in conifer defense against bark beetles, but it has been difficult to demonstrate a direct correlation between terpene levels and resistance to bark beetle colonization.To test for inhibitory effects of induced terpenes on colonization by the spruce bark beetle Ips typographus (L. we inoculated 20 mature Norway spruce Picea abies (L. Karsten trees with a virulent fungus associated with the beetle, Ceratocystis polonica (Siem. C. Moreau, and investigated induced terpene levels and beetle colonization in the bark.Fungal inoculation induced very strong and highly variable terpene accumulation 35 days after inoculation. Trees with high induced terpene levels (n = 7 had only 4.9% as many beetle attacks (5.1 vs. 103.5 attacks m(-2 and 2.6% as much gallery length (0.029 m m(-2 vs. 1.11 m m(-2 as trees with low terpene levels (n = 6. There was a highly significant rank correlation between terpene levels at day 35 and beetle colonization in individual trees. The relationship between induced terpene levels and beetle colonization was not linear but thresholded: above a low threshold concentration of ∼100 mg terpene g(-1 dry phloem trees suffered only moderate beetle colonization, and above a high threshold of ∼200 mg terpene g(-1 dry phloem trees were virtually unattacked.This is the first study demonstrating a dose-dependent relationship between induced terpenes and tree resistance to bark beetle colonization under field conditions, indicating that terpene induction may be instrumental in tree resistance. This knowledge could be useful for developing management strategies that decrease the impact of tree-killing bark beetles.

  1. Modulation of DNA polymerase beta-dependent base excision repair in cultured human cells after low dose exposure to arsenite

    International Nuclear Information System (INIS)

    Sykora, Peter; Snow, Elizabeth T.

    2008-01-01

    Base excision repair (BER) is crucial for development and for the repair of endogenous DNA damage. However, unlike nucleotide excision repair, the regulation of BER is not well understood. Arsenic, a well-established human carcinogen, is known to produce oxidative DNA damage, which is repaired primarily by BER, whilst high doses of arsenic can also inhibit DNA repair. However, the mechanism of repair inhibition by arsenic and the steps inhibited are not well defined. To address this question we have investigated the regulation of DNA polymerase β (Pol β) and AP endonuclease (APE1), in response to low, physiologically relevant doses of arsenic. GM847 lung fibroblasts and HaCaT keratinocytes were exposed to sodium arsenite, As(III), and mRNA, protein levels and BER activity were assessed. Both Pol β and APE1 mRNA exhibited significant dose-dependant down regulation at doses of As(III) above 1 μM. However, at lower doses Pol β mRNA and protein levels, and consequently, BER activity were significantly increased. In contrast, APE1 protein levels were only marginally increased by low doses of As(III) and there was no correlation between APE1 and overall BER activity. Enzyme supplementation of nuclear extracts confirmed that Pol β was rate limiting. These changes in BER correlated with overall protection against sunlight UV-induced toxicity at low doses of As(III) and produced synergistic toxicity at high doses. The results provide evidence that changes in BER due to low doses of arsenic could contribute to a non-linear, threshold dose response for arsenic carcinogenesis

  2. Dose- and time-dependent radiation inhibition of RNA and glycosaminoglycan synthesis in embryonic cartilage: an in vitro study

    Energy Technology Data Exchange (ETDEWEB)

    Cornelissen, M.; Thierens, H.; De Ridder, L. (Ghent Rijksuniversiteit (Belgium))

    1990-05-01

    Radiation effects on the RNA and glycosaminoglycan (GAG) synthesis of embryonic cartilaginous tibiae were studied in vitro during a 4- or 7-day culture period. Before culture, tibiae received single radiation doses of 20, 50 or 100 Gy. A limited, dose-dependent immediate effect on RNA and GAG synthesis was found. This effect was unchanged for 2 days. After this period a time-dependent delayed effect was observed. For each radiation dose, and for each precursor, the same time-related pattern was found. At the end of the culture period acid phosphatase activity, an early indicator of apoptosis, was higher in irradiated tibiae than in controls. No other morphological ultrastructural differences were observed at this time. The authors conclude that metabolic alterations are probably due to stimulation of initial stages of the apoptotic process in the irradiated cartilage cells. (author).

  3. {sup 131}I age-dependent inhalation dose in Southern Poland from Fukushima accident

    Energy Technology Data Exchange (ETDEWEB)

    Brudecki, K.; Szufa, K.; Mietelski, J.W. [Polish Academy of Sciences, Institute of Nuclear Physics, Krakow (Poland)

    2017-03-15

    A general method for calculating doses absorbed from isotopes released in nuclear accidents is presented. As an example, this method was used to calculate doses for inhabitants of Southern Poland due to inhalation of {sup 131}I released due to the Fukushima nuclear plant accident. {sup 131}I activity measurements in the air of that region provided the basis for the study. The proposed model is based on a complex biokinetic model for iodine merging the Leggett model developed in 2010 with the human respiratory tract and gastrointestinal tract models recommended by the International Commission on Radiological Protection (ICRP). This model is described here, and it is demonstrated that resulting dose estimates are consistent with those obtained using the ICRP methodology. Using the developed model, total doses were calculated for six age groups of both genders, for gaseous and aerosol fractions alike. The committed effective dose, H{sub 50}, for an adult man reached 16 nSv, which is lower than 0.001% of the background dose. The dose for the thyroid of an adult reached 0.33 μSv, which corresponds to circa 0.0007% of the dose to the population of Southern Poland after the Chernobyl nuclear plant accident. (orig.)

  4. Verbenone: Dose-Dependent Interruption of Pheromone-Based Attraction of Three Sympatric Species of Pine Bark Beetles (Coleoptera: Scolytidae)

    Science.gov (United States)

    Daniel R. Miller; John H. Borden; B. Staffan Lindgren

    1995-01-01

    Verbenone significantly reduced catches of Ips latidens (LeConte), I. pini (Say), and Dendroctonus ponderosae Hopkins in multiple-funnel traps, baited with aggregation pheromones, in stands of lodgepole pine in southern British Columbia. Interruption of attraction was dose dependent for all three species. There...

  5. Quantitative simulation of intracellular signaling cascades in a Virtual Liver: estimating dose dependent changes in hepatocellular proliferation and apoptosis

    Science.gov (United States)

    The US EPA Virtual Liver (v-Liver™) is developing an approach to predict dose-dependent hepatotoxicity as an in vivo tissue level response using in vitro data. The v-Liver accomplishes this using an in silico agent-based systems model that dynamically integrates environmental exp...

  6. Fibrinolytic Activity and Dose-Dependent Effect of Incubating Human Blood Clots in Caffeic Acid Phenethyl Ester: In Vitro Assays

    Directory of Open Access Journals (Sweden)

    Abuzar Elnager

    2015-01-01

    Full Text Available Background. Caffeic acid phenethyl ester (CAPE has been reported to possess time-dependent fibrinolytic activity by in vitro assay. This study is aimed at investigating fibrinolytic dose-dependent activity of CAPE using in vitro assays. Methods. Standardized human whole blood (WB clots were incubated in either blank controls or different concentrations of CAPE (3.75, 7.50, 15.00, 22.50, and 30.00 mM. After 3 hours, D-dimer (DD levels and WB clot weights were measured for each concentration. Thromboelastography (TEG parameters were recorded following CAPE incubation, and fibrin morphology was examined under a confocal microscope. Results. Overall, mean DD (μg/mL levels were significantly different across samples incubated with different CAPE concentrations, and the median pre- and postincubation WB clot weights (grams were significantly decreased for each CAPE concentration. Fibrin removal was observed microscopically and indicated dose-dependent effects. Based on the TEG test, the Ly30 fibrinolytic parameter was significantly different between samples incubated with two different CAPE concentrations (15.0 and 22.50 mM. The 50% effective dose (ED50 of CAPE (based on DD was 1.99 mg/mL. Conclusions. This study suggests that CAPE possesses fibrinolytic activity following in vitro incubation and that it has dose-dependent activities. Therefore, further investigation into CAPE as a potential alternative thrombolytic agent should be conducted.

  7. Dose-Dependent Protective Effect of Inhalational Anesthetics Against Postoperative Respiratory Complications

    DEFF Research Database (Denmark)

    Grabitz, Stephanie D; Farhan, Hassan N; Ruscic, Katarina J

    2017-01-01

    OBJECTIVES: Inhalational anesthetics are bronchodilators with immunomodulatory effects. We sought to determine the effect of inhalational anesthetic dose on risk of severe postoperative respiratory complications. DESIGN: Prospective analysis of data on file in surgical cases between January 2007...... with endotracheal intubation. INTERVENTIONS: Median effective dose equivalent of inhalational anesthetics during surgery (derived from mean end-tidal inhalational anesthetic concentrations). MEASUREMENTS AND MAIN RESULTS: Postoperative respiratory complications occurred in 6,979 of 124,497 cases (5.61%). High...... inhalational anesthetic dose of 1.20 (1.13-1.30) (median [interquartile range])-fold median effective dose equivalent versus 0.57 (0.45-0.64)-fold median effective dose equivalent was associated with lower odds of postoperative respiratory complications (odds ratio, 0.59; 95% CI, 0.53-0.65; p

  8. Dose and energy dependence of response of Gafchromic XR-QA film for kilovoltage x-ray beams.

    Science.gov (United States)

    Rampado, O; Garelli, E; Deagostini, S; Ropolo, R

    2006-06-07

    There is a growing interest in Gafchromic films for patient dosimetry in radiotherapy and in radiology. A new model (XR-QA) with high sensitivity to low dose was tested in this study. The response of the film to different x-ray beam energies (range 28-145 kVp with various filtrations, dose range 0-100 mGy) and to visible light was investigated, together with the after exposure darkening properties. Exposed films were digitized with a commercially available, optical flatbed scanner. A single functional form for dose versus net pixel value variation has been determined for all the obtained calibration curves, with a unique fit parameter different for each of the used x-ray beams. The film response was dependent on beam energy, with higher colour variations for the beams in the range 80-140 kVp. Different sources of uncertainties in dose measurements, governed by the digitalization process, the film response uniformity and the calibration curve fit procedure, have been considered. The overall one-sigma dose measurement uncertainty depended on the beam energy and decreased with increasing absorbed dose. For doses above 10 mGy and beam energies in the range 80-140 kVp the total uncertainty was less than 5%, whereas for the 28 kVp beam the total uncertainty at 10 mGy was about 10%. The post-exposure colour variation was not negligible in the first 24 h after the exposure, with a consequent increase in the calculated dose of about 10%. Results of the analysis of the sensitivity to visible light indicated that a short exposure of this film to ambient and scanner light during the measurements will not have a significant impact on the radiation dosimetry.

  9. Dose and energy dependence of response of Gafchromic (registered) XR-QA film for kilovoltage x-ray beams

    Energy Technology Data Exchange (ETDEWEB)

    Rampado, O; Garelli, E; Deagostini, S; Ropolo, R [Struttura Complessa fisica Sanitaria, Azienda Ospedaliera San Giovanni Battista, Corso Bramante 88, 10126 Turin (Italy)

    2006-06-07

    There is a growing interest in Gafchromic (registered) films for patient dosimetry in radiotherapy and in radiology. A new model (XR-QA) with high sensitivity to low dose was tested in this study. The response of the film to different x-ray beam energies (range 28-145 kVp with various filtrations, dose range 0-100 mGy) and to visible light was investigated, together with the after exposure darkening properties. Exposed films were digitized with a commercially available, optical flatbed scanner. A single functional form for dose versus net pixel value variation has been determined for all the obtained calibration curves, with a unique fit parameter different for each of the used x-ray beams. The film response was dependent on beam energy, with higher colour variations for the beams in the range 80-140 kVp. Different sources of uncertainties in dose measurements, governed by the digitalization process, the film response uniformity and the calibration curve fit procedure, have been considered. The overall one-sigma dose measurement uncertainty depended on the beam energy and decreased with increasing absorbed dose. For doses above 10 mGy and beam energies in the range 80-140 kVp the total uncertainty was less than 5%, whereas for the 28 kVp beam the total uncertainty at 10 mGy was about 10%. The post-exposure colour variation was not negligible in the first 24 h after the exposure, with a consequent increase in the calculated dose of about 10%. Results of the analysis of the sensitivity to visible light indicated that a short exposure of this film to ambient and scanner light during the measurements will not have a significant impact on the radiation dosimetry.

  10. Time-dependent, low-dose reporting limit for dosimeters that are taken home at the end of the workday

    International Nuclear Information System (INIS)

    Sonder, E.

    1994-01-01

    In routine personnel dosimetry, it is usual to report doses only where th occupational dose (measured dose with background subtracted) is greater than previously determined reporting limit. The reporting limit, although se administratively, should be justified by an assessment of the errors inherent in th personnel and background dose measurements, and estimates of the probability that a zero exposure will yield a dosimeter response equal to the reporting limit. For background subtraction and reporting limits, it was realized that the source of low-dose uncertainty is very much dependent on whether dosimeters are held in racks at the work site or remain with the employee. The External dosimetry Program for the DOE facilities at Oak Ridge, Tennessee, is operated such that dosimeters are taken home by the employee at the end of each workday. This report is a summary measurements of background radiation in a variety of home locations, and calculations of the effect of the variation of this background on the uncertainty low-level occupational dose and on the reporting level. When dosimeters are stored at a given location (e.g., the facility gate), it theoretically possible to determine the background there to any desired accuracy; the errors in occupational dose are then those due to measurement noise and dosimeter calibration. However, when different dosimeters are stored in different homes, th difference in background between a particular location and the average for a locations appears as an added uncertainty in the occupational dose. Since this difference is not random, but fixed for a given location, the error due to this difference increases linearly with assignment time. From the background measurements, time-dependent values of the standard deviation of occupational do and critical levels are derived and used to define an expression for the reporting limit

  11. Estimation of average glandular dose depending on the thickness of the breast; Estimativa da dose glandular media em funcao da espessura da mama

    Energy Technology Data Exchange (ETDEWEB)

    Real, Jessica V.; Luz, Renata M. da, E-mail: jessica.real@pucrs.br, E-mail: renata.luz@pucrs.br [Hospital Sao Lucas (HSL/PUCRS), Porto Alegre, RS (Brazil); Fröhlich, Bruna D.; Pertile, Alessandra S.; Silva, Ana Maria Marques da, E-mail: bruna.frohlich@acad.pucrs.br, E-mail: lessandra.pertile@acad.pucrs.br, E-mail: ana.marques@pucrs.br [Pontificia Universidade Catolica do Rio Grande do Sul (PUCRS), Porto Alegre, RS (Brazil)

    2014-07-01

    Breast cancer is the most common type of cancer in women worldwide. Mammography is, to date, the most efficient method for detecting an abnormality in the patient's breast. It is a technique of imaging diagnostic that requires special care because radiographs without adequate quality may lead to a false diagnosis and lead to the need for a repeat examination, increasing the dose of radiation in the patient. This study aimed to evaluate the average glandular dose (AGD), depending on the breast thickness in patients undergoing routine tests, with a digital computer radiography processing system. Analyzed 30 exhibitions in patients aged (65 ± 12) years, in the right and left caudal skull projections, for breasts with thicknesses between 45 mm and 50 mm. The calculated value of the AGD for this track thickness was (1.600 ± 0.009) mGy. The performance of mammography quality control tests was satisfactory and the AGD values obtained for the chosen thickness range is acceptable, since the threshold achievable is 1.6 mGy and the acceptable is 2 mGy. In Brazil, it is only required the input dose calculation in skin for 45 mm breasts. However, the calculation of AGD is required for different thicknesses of the breast, to identify the best mammographic pattern aiming at better image quality at the lowest dose provided the patient.

  12. Human Dose-Response Data for Francisella tularensis and a Dose- and Time-Dependent Mathematical Model of Early-Phase Fever Associated with Tularemia After Inhalation Exposure.

    Science.gov (United States)

    McClellan, Gene; Coleman, Margaret; Crary, David; Thurman, Alec; Thran, Brandolyn

    2018-04-25

    Military health risk assessors, medical planners, operational planners, and defense system developers require knowledge of human responses to doses of biothreat agents to support force health protection and chemical, biological, radiological, nuclear (CBRN) defense missions. This article reviews extensive data from 118 human volunteers administered aerosols of the bacterial agent Francisella tularensis, strain Schu S4, which causes tularemia. The data set includes incidence of early-phase febrile illness following administration of well-characterized inhaled doses of F. tularensis. Supplemental data on human body temperature profiles over time available from de-identified case reports is also presented. A unified, logically consistent model of early-phase febrile illness is described as a lognormal dose-response function for febrile illness linked with a stochastic time profile of fever. Three parameters are estimated from the human data to describe the time profile: incubation period or onset time for fever; rise time of fever; and near-maximum body temperature. Inhaled dose-dependence and variability are characterized for each of the three parameters. These parameters enable a stochastic model for the response of an exposed population through incorporation of individual-by-individual variability by drawing random samples from the statistical distributions of these three parameters for each individual. This model provides risk assessors and medical decisionmakers reliable representations of the predicted health impacts of early-phase febrile illness for as long as one week after aerosol exposures of human populations to F. tularensis. © 2018 Society for Risk Analysis.

  13. SU-E-T-96: Energy Dependence of the New GafChromic- EBT3 Film's Dose Response-Curve.

    Science.gov (United States)

    Chiu-Tsao, S; Massillon-Jl, G; Domingo-Muñoz, I; Chan, M

    2012-06-01

    To study and compare the dose response curves of the new GafChromic EBT3 film for megavoltage and kilovoltage x-ray beams, with different spatial resolution. Two sets of EBT3 films (lot#A101711-02) were exposed to each x-ray beam (6MV, 15MV and 50kV) at 8 dose values (50-3200cGy). The megavoltage beams were calibrated per AAPM TG-51 protocol while the kilovoltage beam was calibrated following the TG-61 using an ionization chamber calibrated at NIST. Each film piece was scanned three consecutive times in the center of Epson 10000XL flatbed scanner in transmission mode, landscape orientation, 48-bit color at two separate spatial resolutions of 75 and 300 dpi. The data were analyzed using ImageJ and, for each scanned image, a region of interest (ROI) of 2×2cm 2 at the field center was selected to obtain the mean pixel value with its standard deviation in the ROI. For each energy, dose value and spatial resolution, the average netOD and its associated uncertainty were determined. The Student's t-test was performed to evaluate the statistical differences between the netOD/dose values of the three energy modalities, with different color channels and spatial resolutions. The dose response curves for the three energy modalities were compared in three color channels with 75 and 300dpi. Weak energy dependence was found. For doses above 100cGy, no statistical differences were observed between 6 and 15MV beams, regardless of spatial resolution. However, statistical differences were observed between 50kV and the megavoltage beams. The degree of energy dependence (from MV to 50kV) was found to be function of color channel, dose level and spatial resolution. The dose response curves for GafChromic EBT3 films were found to be weakly dependent on the energy of the photon beams from 6MV to 50kV. The degree of energy dependence varies with color channel, dose and spatial resolution. GafChromic EBT3 films were supplied by Ashland Corp. This work was partially supported by DGAPA

  14. Tumor cell survival dependence on helical tomotherapy, continuous arc and segmented dose delivery

    International Nuclear Information System (INIS)

    Yang Wensha; Wang Li; Larner, James; Read, Paul; Benedict, Stan; Sheng Ke

    2009-01-01

    The temporal pattern of radiation delivery has been shown to influence the tumor cell survival fractions for the same radiation dose. To study the effect more specifically for state of the art rotational radiation delivery modalities, 2 Gy of radiation dose was delivered to H460 lung carcinoma, PC3 prostate cancer cells and MCF-7 breast tumor cells by helical tomotherapy (HT), seven-field LINAC (7F), and continuous dose delivery (CDD) over 2 min that simulates volumetric rotational arc therapy. Cell survival was measured by the clonogenic assay. The number of viable H460 cell colonies was 23.2 ± 14.4% and 27.7 ± 15.6% lower when irradiated by CDD compared with HT and 7F, respectively, and the corresponding values were 36.8 ± 18.9% and 35.3 ± 18.9% lower for MCF7 cells (p < 0.01). The survival of PC3 was also lower when irradiated by CDD than by HT or 7F but the difference was not as significant (p = 0.06 and 0.04, respectively). The higher survival fraction from HT delivery was unexpected because 90% of the 2 Gy was delivered in less than 1 min at a significantly higher dose rate than the other two delivery techniques. The results suggest that continuous dose delivery at a constant dose rate results in superior in vitro tumor cell killing compared with prolonged, segmented or variable dose rate delivery.

  15. Polimixina B: efeito dose e tempo dependente na nefrotoxicidade in vitro Polymyxin B: dose and time dependent nephrotoxicity effect in vitro

    Directory of Open Access Journals (Sweden)

    Luciana Barros de Moura Neiva

    2013-01-01

    Full Text Available OBJETIVO: Caracterizar a toxicidade da polimixina B (PmxB em células renais em dosagem e tempos diferentes. MÉTODOS: Células LLC-PK1, cultivadas em placas multiwell de 12 poços, foram divididas nos seguintes grupos: Controle (CTL - células mantidas em meio DMEM suplementado a 5%; G1 - células expostas à concentração de 75mM de PmxB; G2 - células expostas à concentração de 375mM de PmxB. Cada grupo foi avaliado nos tempos de 24, 48 e 72 horas quanto à viabilidade celular (Acridine Orange/Brometo de Etídio e apoptose (Hoechst 33342. RESULTADOS: Os dados demonstraram a viabilidade celular e a apoptose à exposição de três doses de PmxB em três intervalos de tempo, com um aumento significativo da toxicidade à elevação das doses e ao maior tempo de permanência no antibiótico para apoptose. CONCLUSÃO: A citotoxicidade pela PmxB, no modelo de cultivo celular, se mostrou tempo e dose dependente, aumentando com a maior exposição e maior dose de antibiótico.OBJECTIVE: To characterize the toxicity of polymyxin B (PmxB in renal cell in different dosage and times. METHODS: LLC-PK1 cells grown in 12 well multiwell plates were divided into the following groups: Control (CTL - cells maintained in DMEM supplemented with 5%; G1 - cells exposed to concentration of 75µM PmxB G2 - cells exposed to concentration of 375µM PmxB. Each group was assessed at 24,48 and 72 hours as for cell viability (Acridine orange/ethidium bromide and apoptosis (Hoechst 33342. RESULTS: The data demonstrate the cell viability and apoptosis exposure of three doses of PmxB in three time intervals, with a significant increase in toxicity to high doses and longer duration of stay in the antibiotic to apoptosis. CONCLUSION: Cytotoxicity by PmxB in cell culture model, showed to be time and dose dependent, increasing with increased exposure and higher dose of antibiotic.

  16. Dose-dependent effects of a microbial phytase on phosphorus digestibility of common feedstuffs in pigs

    Directory of Open Access Journals (Sweden)

    Ferdinando N. Almeida

    2017-07-01

    Full Text Available Objective The objective of this study was to evaluate increasing doses of a novel microbial phytase (Cibenza Phytaverse, Novus International, St. Charles, MO, USA on standardized total tract digestibility (STTD of P in canola meal (CM, corn, corn-derived distiller’s dried grains with solubles (DDGS, rice bran (RB, sorghum, soybean meal (SBM, sunflower meal (SFM, and wheat. Methods Two cohorts of 36 pigs each (initial body weight = 78.5±3.7 kg were randomly assigned to 2 rooms, each housing 36 pigs, and then allotted to 6 diets with 6 replicates per diet in a randomized complete block design. Test ingredient was the only dietary source of P and diets contained 6 concentrations of phytase (0, 125, 250, 500, 1,000, or 2,000 phytase units [FTU]/kg with 0.4% of TiO2 as a digestibility marker. Feeding schedule for each ingredient was 5 d acclimation, 5 d fecal collection, and 4 d washout. The STTD of P increased (linear or exponential p≤0.001 with the inclusion of phytase for all ingredients. Results Basal STTD of P was 37.6% for CM, 37.6% for corn, 68.6% for DDGS, 10.3% for RB, 41.2% for sorghum, 36.7% for SBM, 26.2% for SFM, and 55.1% for wheat. The efficiency of this novel phytase to hydrolyze phytate is best described with a broken-line model for corn, an exponential model for CM, RB, SBM, SFM, and wheat, and a linear model for DDGS and sorghum. Based on best-fit model the phytase dose (FTU/kg needed for highest STTD of P (%, respectively, was 735 for 64.3% in CM, 550 for 69.4% in corn, 160 for 55.5% in SBM, 1,219 for 57.8% in SFM, and 881 for 64.0% in wheat, whereas a maximum response was not obtained for sorghum, DDGS and RB within the evaluated phytase range of 0 to 2,000 FTU/kg. These differences in the phytase concentration needed to maximize the STTD of P clearly indicate that the enzyme does not have the same hydrolysis efficiency among the evaluated ingredients. Conclusion Variations in enzyme efficacy to release P from phytate in

  17. Experimental determination of the angular dependence factor for the dose equivalent for photons in calibration phantoms of PMMA

    International Nuclear Information System (INIS)

    Lund, E.; Carlsson, C.A.; Pernicka, F.

    1994-01-01

    The conversion coefficients from air kerma to dose equivalent at a depth of 10 mm in both a spherical and a slab phantom of PMMA have been determined for the X ray qualities: 40, 80 and 295 kV, ISO 'narrow' spectra; and for 137 Cs γ rays. The angular dependence factors have been experimentally determined for the same qualities and for different angles between 0 o and 180 o . The absorbed doses have been measured with thermoluminescence LiF dosemeters. The conversion coefficients and the angular dependence factors are generally found to agree well with calculated ones. Some minor discrepancies are found for the angular dependence factors and the 30 x 30 x 15 cm 3 PMMA slab phantom. (Author)

  18. Calculation of effective dose in whole body in dependence of angle of collimator for photon fields

    International Nuclear Information System (INIS)

    Fuenzalida, M.; Varon, C.; Piriz, G.; Banguero, Y.; Lozano, E.; Mancilla, C.

    2011-01-01

    The objective of this work is to obtain quantifiable data of whole body effective dose for photons fields of 6 MV and 18 MV in function of the collimator angle of a Varian Clinac 21EX lineal accelerator. It has been made a variety of studies which investigate the form to reduce the dose in whole body with photons fields, specially over the potential risks and the influence of the collimator angle, as performed Stanthakis et al. [1] with the Monte Carlo method. As a result of this work, the values of whole body effective doses are higher with a 0 deg collimator than with a 90 deg collimator, and as the field size increases, the effective doses difference in whole body, between 0 deg and 90 deg collimator angle, for both energies, becomes smaller. (author)

  19. Calculation of effective dose in whole body in dependence of angle of collimator for photon fields

    Energy Technology Data Exchange (ETDEWEB)

    Fuenzalida, M. [Universidad de la Frontera, Temuco (Chile). Programa de Magister en Fisica Medica; Varon, C.; Piriz, G.; Banguero, Y.; Lozano, E.; Mancilla, C., E-mail: fisicamedica@incancer.c [Instituto Nacional del Cancer, Santiago (Chile). Unidad de Fisica Medica

    2011-07-01

    The objective of this work is to obtain quantifiable data of whole body effective dose for photons fields of 6 MV and 18 MV in function of the collimator angle of a Varian Clinac 21EX lineal accelerator. It has been made a variety of studies which investigate the form to reduce the dose in whole body with photons fields, specially over the potential risks and the influence of the collimator angle, as performed Stanthakis et al. [1] with the Monte Carlo method. As a result of this work, the values of whole body effective doses are higher with a 0 deg collimator than with a 90 deg collimator, and as the field size increases, the effective doses difference in whole body, between 0 deg and 90 deg collimator angle, for both energies, becomes smaller. (author)

  20. Dose-rate dependent stochastic effects in radiation cell-survival models

    International Nuclear Information System (INIS)

    Sachs, R.K.; Hlatky, L.R.

    1990-01-01

    When cells are subjected to ionizing radiation the specific energy rate (microscopic analog of dose-rate) varies from cell to cell. Within one cell, this rate fluctuates during the course of time; a crossing of a sensitive cellular site by a high energy charged particle produces many ionizations almost simultaneously, but during the interval between events no ionizations occur. In any cell-survival model one can incorporate the effect of such fluctuations without changing the basic biological assumptions. Using stochastic differential equations and Monte Carlo methods to take into account stochastic effects we calculated the dose-survival rfelationships in a number of current cell survival models. Some of the models assume quadratic misrepair; others assume saturable repair enzyme systems. It was found that a significant effect of random fluctuations is to decrease the theoretically predicted amount of dose-rate sparing. In the limit of low dose-rates neglecting the stochastic nature of specific energy rates often leads to qualitatively misleading results by overestimating the surviving fraction drastically. In the opposite limit of acute irradiation, analyzing the fluctuations in rates merely amounts to analyzing fluctuations in total specific energy via the usual microdosimetric specific energy distribution function, and neglecting fluctuations usually underestimates the surviving fraction. The Monte Carlo methods interpolate systematically between the low dose-rate and high dose-rate limits. As in other approaches, the slope of the survival curve at low dose-rates is virtually independent of dose and equals the initial slope of the survival curve for acute radiation. (orig.)

  1. Dose-dependent EEG effects of zolpidem provide evidence for GABA(A) receptor subtype selectivity in vivo.

    Science.gov (United States)

    Visser, S A G; Wolters, F L C; van der Graaf, P H; Peletier, L A; Danhof, M

    2003-03-01

    Zolpidem is a nonbenzodiazepine GABA(A) receptor modulator that binds in vitro with high affinity to GABA(A) receptors expressing alpha(1) subunits but with relatively low affinity to receptors expressing alpha(2), alpha(3), and alpha(5) subunits. In the present study, it was investigated whether this subtype selectivity could be detected and quantified in vivo. Three doses (1.25, 5, and 25 mg) of zolpidem were administered to rats in an intravenous infusion over 5 min. The time course of the plasma concentrations was determined in conjunction with the change in the beta-frequency range of the EEG as pharmacodynamic endpoint. The concentration-effect relationship of the three doses showed a dose-dependent maximum effect and a dose-dependent potency. The data were analyzed for one- or two-site binding using two pharmacodynamic models based on 1) the descriptive model and 2) a novel mechanism-based pharmacokinetic/pharmacodynamic (PK/PD) model for GABA(A) receptor modulators that aims to separates drug- and system-specific properties, thereby allowing the estimation of in vivo affinity and efficacy. The application of two-site models significantly improved the fits compared with one-site models. Furthermore, in contrast to the descriptive model, the mechanism-based PK/PD model yielded dose-independent estimates for affinity (97 +/- 40 and 33,100 +/- 14,800 ng x ml(-1)). In conclusion, the mechanism-based PK/PD model is able to describe and explain the observed dose-dependent EEG effects of zolpidem and suggests the subtype selectivity of zolpidem in vivo.

  2. Dose- and time-dependence of the host-mediated response to paclitaxel therapy: a mathematical modeling approach.

    Science.gov (United States)

    Benguigui, Madeleine; Alishekevitz, Dror; Timaner, Michael; Shechter, Dvir; Raviv, Ziv; Benzekry, Sebastien; Shaked, Yuval

    2018-01-05

    It has recently been suggested that pro-tumorigenic host-mediated processes induced in response to chemotherapy counteract the anti-tumor activity of therapy, and thereby decrease net therapeutic outcome. Here we use experimental data to formulate a mathematical model describing the host response to different doses of paclitaxel (PTX) chemotherapy as well as the duration of the response. Three previously described host-mediated effects are used as readouts for the host response to therapy. These include the levels of circulating endothelial progenitor cells in peripheral blood and the effect of plasma derived from PTX-treated mice on migratory and invasive properties of tumor cells in vitro . A first set of mathematical models, based on basic principles of pharmacokinetics/pharmacodynamics, did not appropriately describe the dose-dependence and duration of the host response regarding the effects on invasion. We therefore provide an alternative mathematical model with a dose-dependent threshold, instead of a concentration-dependent one, that describes better the data. This model is integrated into a global model defining all three host-mediated effects. It not only precisely describes the data, but also correctly predicts host-mediated effects at different doses as well as the duration of the host response. This mathematical model may serve as a tool to predict the host response to chemotherapy in cancer patients, and therefore may be used to design chemotherapy regimens with improved therapeutic outcome by minimizing host mediated effects.

  3. Peripubertal Caffeine Exposure Impairs Longitudinal Bone Growth in Immature Male Rats in a Dose- and Time-Dependent Manner.

    Science.gov (United States)

    Choi, Yun-Young; Choi, Yuri; Kim, Jisook; Choi, Hyeonhae; Shin, Jiwon; Roh, Jaesook

    2016-01-01

    This study investigated the dose- and time-dependent effects of caffeine consumption throughout puberty in peripubertal rats. A total of 85 male SD rats were randomly divided into four groups: control and caffeine-fed groups with 20, 60, or 120 mg/kg/day through oral gavage for 10, 20, 30, or 40 days. Caffeine decreased body weight gain and food consumption in a dose- and time-dependent manner, accompanied by a reduction in muscle and body fat. In addition, it caused a shortening and lightening of leg bones and spinal column. The total height of the growth plate decreased sharply at 40 days in the controls, but not in the caffeine-fed groups, and the height of hypertrophic zone in the caffeine-fed groups was lower than in the control. Caffeine increased the height of the secondary spongiosa, whereas parameters related to bone formation, such as bone area ratio, thickness and number of trabeculae, and bone perimeter, were significantly reduced. Furthermore, serum levels of IGF-1, estradiol, and testosterone were also reduced by the dose of caffeine exposure. Our results demonstrate that caffeine consumption can dose- and time-dependently inhibit longitudinal bone growth in immature male rats, possibly by blocking the physiologic changes in body composition and hormones relevant to bone growth.

  4. Time- and dose-dependent effects of total-body ionizing radiation on muscle stem cells

    Science.gov (United States)

    Masuda, Shinya; Hisamatsu, Tsubasa; Seko, Daiki; Urata, Yoshishige; Goto, Shinji; Li, Tao-Sheng; Ono, Yusuke

    2015-01-01

    Exposure to high levels of genotoxic stress, such as high-dose ionizing radiation, increases both cancer and noncancer risks. However, it remains debatable whether low-dose ionizing radiation reduces cellular function, or rather induces hormetic health benefits. Here, we investigated the effects of total-body γ-ray radiation on muscle stem cells, called satellite cells. Adult C57BL/6 mice were exposed to γ-radiation at low- to high-dose rates (low, 2 or 10 mGy/day; moderate, 50 mGy/day; high, 250 mGy/day) for 30 days. No hormetic responses in proliferation, differentiation, or self-renewal of satellite cells were observed in low-dose radiation-exposed mice at the acute phase. However, at the chronic phase, population expansion of satellite cell-derived progeny was slightly decreased in mice exposed to low-dose radiation. Taken together, low-dose ionizing irradiation may suppress satellite cell function, rather than induce hormetic health benefits, in skeletal muscle in adult mice. PMID:25869487

  5. Hydrocortisone infusion exerts dose- and sex-dependent effects on attention to emotional stimuli.

    Science.gov (United States)

    Breitberg, Alaina; Drevets, Wayne C; Wood, Suzanne E; Mah, Linda; Schulkin, Jay; Sahakian, Barbara J; Erickson, Kristine

    2013-03-01

    Glucocorticoid administration has been shown to exert complex effects on cognitive and emotional processing. In the current study we investigated the effects of glucocorticoid administration on attention towards emotional words, using an Affective Go/No-go task on which healthy humans have shown an attentional bias towards positive as compared to negative words. Healthy volunteers received placebo and either low-dose (0.15mg/kg) or high-dose (0.45mg/kg) hydrocortisone intravenously during two separate visits in a double-blind, randomized design. Seventy-five minutes post-infusion, the subjects performed tests of attention (Rapid Visual Information Processing [RVIP]), spatial working memory (Spatial Span) and emotional processing (Affective Go/No-go task [AGNG]). On the attention task, performance was impaired under both hydrocortisone doses relative to placebo, though the effect on error rate was not significant after controlling for age; Spatial Span performance was unaffected by hydrocortisone administration. On the AGNG task, relative to the placebo condition the low-dose hydrocortisone infusion decreased response time to emotional words while high-dose hydrocortisone increased response time. In the females specifically, both high and low dose hydrocortisone administration attenuated the normal attentional bias toward positively valenced words. These data suggest that, in healthy women, the modulation of attention by the emotional salience of stimuli is influenced by glucocorticoid hormone concentrations. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Dose-response relationships and risk estimates for the induction of cancer due to low doses of low-LET radiation

    International Nuclear Information System (INIS)

    Elaguppillai, V.

    1981-01-01

    Risk estimates for radiation-induced cancer at low doses can be obtained only by extrapolation from the known effects at high doses and high dose rates, using a suitable dose-response model. The applicability of three different models, linear, sublinear and supralinear, are discussed in this paper. Several experimental studies tend to favour a sublinear dose-response model (linear-quadratic model) for low-LET radiation. However, human epidemiological studies do not exclude any of the dose-response relationships. The risk estimates based on linear and linear quadratic dose-response models are compared and it is concluded that, for low-LET radiation, the linear dose-response model would probably over-estimate the actual risk of cancer by a factor of two or more. (author)

  7. Radioprotection by murine and human tumor-necrosis factor; Dose-dependent effects on hematopoiesis in the mouse

    Energy Technology Data Exchange (ETDEWEB)

    Sloerdal, L; Muench, M O; Warren, D J; Moore, M A.S. [James Ewing Laboratory of Developmental Hematopoiesis, Memorial Sloan-Kettering Cancer Center, New York (USA)

    1989-01-01

    Tumor-necrosis factor (TNF) has been shown to confer significant radioprotection in murine models. Herein, we demonstrate a dose-dependent enhancement of hematological recovery when single doses of either murine or human recombinant TNF are administered prior to irradiation. In addition to its action upon leukocytes and erythocytes, TNF also alleviates radiation-induced thrombocytopenia in the mouse. These effects on circulating blood constituents are further reflected in increased numbers of both primitive (CFU-S) and more differentiated (CFU-GM, CFU-Mega) hematopoietic progenitors in TNF-treated animals. This suggests that TNF exerts it radioprotective effects on a pool of primitive multi-potential hematopoietic cells. (author).

  8. Cocoa consumption dose-dependently improves flow-mediated dilation and arterial stiffness decreasing blood pressure in healthy individuals.

    Science.gov (United States)

    Grassi, Davide; Desideri, Giovambattista; Necozione, Stefano; di Giosia, Paolo; Barnabei, Remo; Allegaert, Leen; Bernaert, Herwig; Ferri, Claudio

    2015-02-01

    Cocoa flavonoids exert beneficial vascular effects and reduce the risk of cardiovascular morbidity and mortality. Nevertheless, the involved mechanisms have not been clarified and no study has yet focused on the dose-response effects. We aimed to investigate the effects of different doses of cocoa flavonoids on flow-mediated dilation (FMD), endothelin-1 (ET-1), pulse wave velocity (PWV), and SBP and DBP. According to a randomized, double-blind, controlled, cross-over design, 20 healthy volunteers (1.5% improvement in FMD in 20 individuals: 0.99 at alpha = 0.05) were assigned to receive either five treatments with daily intake of 10 g cocoa (0, 80, 200, 500 and 800 mg cocoa flavonoids/day) in five periods lasting 1 week each. Cocoa dose-dependently increased FMD from 6.2% (control) to 7.3, 7.6, 8.1 and 8.2% after the different flavonoid doses, respectively (P cocoa flavonoids per day increased FMD (P Cocoa dose-dependently decreased PWV (P Cocoa intake decreased office blood pressure (BP) (SBP: -4.8 ± 1.03  mmHg, P cocoa ingestion decreased 24-h (P = 0.05) and daytime (P = 0.038) SBP, and 24-h (P = 0.0064), daytime (P = 0.0088) and night-time (P = 0.0352) pulse pressure. Compared with the control, cocoa dose-dependently decreased ET-1 levels [from 17.1 (control) to 15.2, 14.5, 14.2 and 14.1 pg/ml, after the different flavonoid doses, respectively (P for treatment cocoa dose-dependently improved FMD and decreased PWV and ET-1 also by ameliorating office and monitored BP. Our findings are clinically relevant, suggesting cocoa, with very low calorie intake, might be reasonably incorporated into a dietary approach, representing a consistent tool in cardiovascular prevention.

  9. No compelling evidence that sibutramine prolongs life in rodents despite providing a dose-dependent reduction in body weight

    Science.gov (United States)

    Smith, Daniel L.; Robertson, Henry; Desmond, Renee; Nagy, Tim R.; Allison, David B.

    2010-01-01

    Objective The health and longevity effects of body weight reduction resulting from exercise and caloric restriction in rodents are well known, but less is known about whether similar effects occur with weight reduction from the use of a pharmaceutical agent such as sibutramine, a serotonin-norepinephrine reuptake inhibitor. Results & Conclusion Using data from a two-year toxicology study of sibutramine in CD rats and CD-1 mice, despite a dose-dependent reduction in food intake and body weight in rats compared to controls, and a body weight reduction in mice at the highest dose, there was no compelling evidence for reductions in mortality rate. PMID:21079617

  10. Magnetic-field-induced dose effects in MR-guided radiotherapy systems: dependence on the magnetic field strength.

    Science.gov (United States)

    Raaijmakers, A J E; Raaymakers, B W; Lagendijk, J J W

    2008-02-21

    Several institutes are currently working on the development of a radiotherapy treatment system with online MR imaging (MRI) modality. The main difference between their designs is the magnetic field strength of the MRI system. While we have chosen a 1.5 Tesla (T) magnetic field strength, the Cross Cancer Institute in Edmonton will be using a 0.2 T MRI scanner and the company Viewray aims to use 0.3 T. The magnetic field strength will affect the severity of magnetic field dose effects, such as the electron return effect (ERE): considerable dose increase at tissue air boundaries due to returning electrons. This paper has investigated how the ERE dose increase depends on the magnetic field strength. Therefore, four situations where the ERE occurs have been simulated: ERE at the distal side of the beam, the lateral ERE, ERE in cylindrical air cavities and ERE in the lungs. The magnetic field comparison values were 0.2, 0.75, 1.5 and 3 T. Results show that, in general, magnetic field dose effects are reduced at lower magnetic field strengths. At the distal side, the ERE dose increase is largest for B = 0.75 T and depends on the irradiation field size for B = 0.2 T. The lateral ERE is strongest for B = 3 T but shows no effect for B = 0.2 T. Around cylindrical air cavities, dose inhomogeneities disappear if the radius of the cavity becomes small relative to the in-air radius of the secondary electron trajectories. At larger cavities (r > 1 cm), dose inhomogeneities exist for all magnetic field strengths. In water-lung-water phantoms, the ERE dose increase takes place at the water-lung transition and the dose decreases at the lung-water transition, but these effects are minimal for B = 0.2 T. These results will contribute to evaluating the trade-off between magnetic field dose effects and image quality of MR-guided radiotherapy systems.

  11. Magnetic-field-induced dose effects in MR-guided radiotherapy systems: dependence on the magnetic field strength

    International Nuclear Information System (INIS)

    Raaijmakers, A J E; Raaymakers, B W; Lagendijk, J J W

    2008-01-01

    Several institutes are currently working on the development of a radiotherapy treatment system with online MR imaging (MRI) modality. The main difference between their designs is the magnetic field strength of the MRI system. While we have chosen a 1.5 Tesla (T) magnetic field strength, the Cross Cancer Institute in Edmonton will be using a 0.2 T MRI scanner and the company Viewray aims to use 0.3 T. The magnetic field strength will affect the severity of magnetic field dose effects, such as the electron return effect (ERE): considerable dose increase at tissue air boundaries due to returning electrons. This paper has investigated how the ERE dose increase depends on the magnetic field strength. Therefore, four situations where the ERE occurs have been simulated: ERE at the distal side of the beam, the lateral ERE, ERE in cylindrical air cavities and ERE in the lungs. The magnetic field comparison values were 0.2, 0.75, 1.5 and 3 T. Results show that, in general, magnetic field dose effects are reduced at lower magnetic field strengths. At the distal side, the ERE dose increase is largest for B = 0.75 T and depends on the irradiation field size for B = 0.2 T. The lateral ERE is strongest for B = 3 T but shows no effect for B = 0.2 T. Around cylindrical air cavities, dose inhomogeneities disappear if the radius of the cavity becomes small relative to the in-air radius of the secondary electron trajectories. At larger cavities (r > 1 cm), dose inhomogeneities exist for all magnetic field strengths. In water-lung-water phantoms, the ERE dose increase takes place at the water-lung transition and the dose decreases at the lung-water transition, but these effects are minimal for B = 0.2 T. These results will contribute to evaluating the trade-off between magnetic field dose effects and image quality of MR-guided radiotherapy systems

  12. Dose-dependent effects of celecoxib on CB-1 agonist-induced antinociception in the mice

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Zarrindast

    2009-04-01

    Full Text Available "nObjective: Endocannabinoid produce analgesia that is comparable which of opioids. The mechanism of antinociceptive effects of (∆ - 9 tetrahydrocannabinol (THC is suggested to be through cyclooxygenase (COX pathway. In the present work, the effect of two extreme dose ranges of celecoxib (mg/kg and ng/kg, a cyclooxygenase-2 (COX-2 antagonist, on arachidonylcyclopropylamide (ACPA, a selective CB1 agonist induced antinociception in mice was examined. "nMethods: We have investigated the interaction between celecoxib, at the doses of mg/kg (50, 100, 200 and 400 i.p.  and ultra low dose (ULD (25 and 50 ng/kg, i.p., on the antinociceptive effect of intracerebroventricular (i.c.v. administration of ACPA (0.004, 0.0625 and 1 μg/mice, using formalin test in mice. "nResults: I.C.V. administration of ACPA induced antinociception. Intraperitoneal administration of celecoxib (mg/kg and its ULD (ng/kg attenuated and potentiated, ACPA antinociceptive effects, respectively. "nConclusion: It is concluded that the mg/kg doses of COX-2 antagonist showed opposite effects compare to the ultra-low dose of the drug.

  13. Dose-rate-dependent damage of cerium dioxide in the scanning transmission electron microscope.

    Science.gov (United States)

    Johnston-Peck, Aaron C; DuChene, Joseph S; Roberts, Alan D; Wei, Wei David; Herzing, Andrew A

    2016-11-01

    Beam damage caused by energetic electrons in the transmission electron microscope is a fundamental constraint limiting the collection of artifact-free information. Through understanding the influence of the electron beam, experimental routines may be adjusted to improve the data collection process. Investigations of CeO 2 indicate that there is not a critical dose required for the accumulation of electron beam damage. Instead, measurements using annular dark field scanning transmission electron microscopy and electron energy loss spectroscopy demonstrate that the onset of measurable damage occurs when a critical dose rate is exceeded. The mechanism behind this phenomenon is that oxygen vacancies created by exposure to a 300keV electron beam are actively annihilated as the sample re-oxidizes in the microscope environment. As a result, only when the rate of vacancy creation exceeds the recovery rate will beam damage begin to accumulate. This observation suggests that dose-intensive experiments can be accomplished without disrupting the native structure of the sample when executed using dose rates below the appropriate threshold. Furthermore, the presence of an encapsulating carbonaceous layer inhibits processes that cause beam damage, markedly increasing the dose rate threshold for the accumulation of damage. Published by Elsevier B.V.

  14. Dose dependent oxidation kinetics of lipids in fish during irradiation processing

    International Nuclear Information System (INIS)

    Tukenmez, I.; Ersen, M.S.; Bakioglu, A.T.; Bicer, A.; Pamuk, V.

    1997-01-01

    Kinetic aspects of the development of lipid oxidation in complex foods as fish in the course of irradiation were analyzed with respect to the associated formation of malonaldehyde (MA) through the reactions modified so as to be consistent with those in complex foods as fish. Air-packed anchovy (Engraulis encrasicholus) samples in polyethylene pouches were irradiated at the doses of 1, 2, 5, 10, 15,20 and 25 kGy at 20 o C in a Cs-137 gamma irradiator of 1.806 kGy/h dose rate. Immediately after each irradiation, MA contents of irradiated and unirradiated samples were determined by thiobarbituric acid test. Based on the MA formation, a kinetic model to simulate the apparent oxidation of lipid in fish as a function of irradiation dose was derived from the rate equations consistent with modified reactions. Kinetic parameters and simulation were related to conditions of lipid oxidation, and associated rancidity state of fish with respect to the doses applied in different irradiation-preservation processes. Numerical values of kinetic parameters based on the MA formation were found as a threshold dose of 0.375 kGy, an apparent yield of 1.871 μmol/kg kGy, and a maximum attainable concentration of 15.853 μmol/kg which may be used for process control and dosimetry. (author)

  15. Intermittent hypoxia alters dose dependent caffeine effects on renal prostanoids and receptors in neonatal rats.

    Science.gov (United States)

    Beharry, Kay D; Cai, Charles L; Soontarapornchai, Kultida; Ahmad, Taimur; Valencia, Gloria B; Aranda, Jacob V

    2018-01-01

    Caffeine, one of the most commonly prescribed drugs in preterm neonates, is given in standard or suprapharmacologic doses. Although known as a diuretic, its effects in the neonatal kidneys are not well studied. We tested the hypothesis that neonatal intermittent hypoxia (IH) and high caffeine doses (HCD) alter renal regulators of vasomotor tone and water balance. Newborn rats were randomized to room air, hyperoxia, or IH and treated with standard or high caffeine doses; or placebo saline. Renal prostanoids; histopathology; and cyclooxygenase (COX), prostanoid receptor, and aquaporin (AQP) immunoreactivity were determined. HCD in IH caused severe pathological changes in the glomeruli and proximal tubules, consistent with acute kidney injury. This was associated with reductions in anthropometric growth, PGI 2, and IP, DP, and AQP-4 immunoreactivity, well as a robust increase in COX-2, suggesting that the use of HCD should be avoided in preterm infants who experience frequent IH episodes. Published by Elsevier Inc.

  16. Dose dependence of radiation-induced segregation in Ni-1 at% Si

    International Nuclear Information System (INIS)

    Rehn, L.E.; Okamoto, P.R.; Wiedersich, H.

    1979-01-01

    Measurements have been made of alloy composition as a function of depth from the external surface in Ni-1 at% Si specimens after irradiation with 3-MeV 58 Ni + ions to several different doses at nominal temperatures of 525 and 600 0 C. Very rapid segregation of Si toward the external surface ocurred during irradiation. Surface concentrations of Si in excess of the 10 at% solubility limit were found at both irradiation temperatures after a dose of only approximately 0.05 dpa. The rate of segregation decreased markedly in the dose range from approximately 1-10 dpa. Qualitative agreement was found between the experimental observations and calculations made using a modified Johnson-Lam segregation mode (1976). The present investigation suggests that radiation-induced segregation may significantly alter the mechanical behavior of irradiated alloys long before the onset of void swelling. (Auth.)

  17. Dose-dependency of radiation on enzyme production in Trichoderma reesei

    International Nuclear Information System (INIS)

    Kumakura, Minoru

    1993-01-01

    Effect of irradiation dose on the production of cellulase and amylase related enzymes in Trichoderma reesei was studied in which post-irradiation time response pattern was measured. The damage of the cells irradiated with certain irradiation doses (1.40±0.20x10 5 , 2.20±0.10x10 5 , 3.00±0.50x10 5 and 3.50±0.20x10 5 rad) was rapidly recovered. The increased enzyme production in the culture of the irradiated cells resulted from the recovery of radiation damage after irradiation. The function of cell growth was not affected by irradiation below dose of 5x10 5 rad, though the function of enzyme synthesis was drastically affected. (orig.)

  18. Dose- and age-dependent cardiovascular mortality among inhabitants of the Chornobyl contaminated areas. 1988-2010 observation period

    International Nuclear Information System (INIS)

    Buzunov, V.O.; Prikashchikova, K.Je.; Domashevs'ka, T.Je.; Kostyuk, G.V.; Gubyina, Yi.G.; Tereshchenko, S.O.

    2014-01-01

    Cardiovascular mortality among inhabitants of contaminated areas of Ukraine is dependent on the total cumulative effective doses and age at the time of the Chornobyl accident. It is proved by a significantly higher (p < 0.05) mortality in people exposed to 21.00-50.0 mSv radiation doses compared to those having 5.6-20.99 mSv exposures. Mortality was significantly higher (p < 0.05) in age groups with higher doses as opposed to those with low ones. Maximum mortality was observed among inhabitants aged 40-60, while the lowest death rate - in patients younger than 18 years old. The data obtained also suggest that the radiation factor can be considered here as one accelerating the aging and pathophysiological abnormalities in survivors. Coronary heart disease, cerebrovascular disease, arterial hypertension, diseases of arteries, arterioles and capillaries are the main causes of death from cardiovascular disease in people under investigation

  19. Juvenile Hormone Analogues, Methoprene and Fenoxycarb Dose-Dependently Enhance Certain Enzyme Activities in the Silkworm Bombyx Mori (L

    Directory of Open Access Journals (Sweden)

    M. Rajeswara Rao

    2008-06-01

    Full Text Available Use of Juvenile Hormone Analogues (JHA in sericulture practices has been shown to boost good cocoon yield; their effect has been determined to be dose-dependent. We studied the impact of low doses of JHA compounds such as methoprene and fenoxycarb on selected key enzymatic activities of the silkworm Bombyx mori. Methoprene and fenoxycarb at doses of 1.0 μg and 3.0fg/larvae/48 hours showed enhancement of the 5th instar B. mori larval muscle and silkgland protease, aspartate aminotransaminase (AAT and alanine aminotransaminase (ALAT, adenosine triphosphate synthase (ATPase and cytochrome-c-oxidase (CCO activity levels, indicating an upsurge in the overall oxidative metabolism of the B.mori larval tissues.

  20. Dose-dependent effects of endotoxin on neurobehavioral functions in humans.

    Directory of Open Access Journals (Sweden)

    Jan-Sebastian Grigoleit

    Full Text Available Clinical and experimental evidence document that inflammation and increased peripheral cytokine levels are associated with depression-like symptoms and neuropsychological disturbances in humans. However, it remains unclear whether and to what extent cognitive functions like memory and attention are affected by and related to the dose of the inflammatory stimulus. Thus, in a cross-over, double-blind, experimental approach, healthy male volunteers were administered with either placebo or bacterial lipopolysaccharide (LPS at doses of 0.4 (n = 18 or 0.8 ng/kg of body weight (n = 16. Pro- and anti-inflammatory cytokines, norephinephrine and cortisol concentrations were analyzed before and 1, 1.75, 3, 4, 6, and 24 h after injection. In addition, changes in mood and anxiety levels were determined together with working memory (n-back task and long term memory performance (recall of emotional and neutral pictures of the International Affective Picture System. Endotoxin administration caused a profound transient physiological response with dose-related elevations in body temperature and heart rate, increases in plasma interleukin (IL-6, IL-10, tumor necrosis factor (TNF-α and IL-1 receptor antagonist (IL-1ra, salivary and plasma cortisol, and plasma norepinephrine. These changes were accompanied by dose-related decreased mood and increased anxiety levels. LPS administration did not affect accuracy in working memory performance but improved reaction time in the high-dose LPS condition compared to the control conditon. In contrast, long-term memory performance was impaired selectively for emotional stimuli after administration of the lower but not of the higher dose of LPS. These data suggest the existence of at least two counter-acting mechanisms, one promoting and one inhibiting cognitive performance during acute systemic inflammation.

  1. Dose-dependent optically stimulated luminescence of synthetic quartz at room temperature

    International Nuclear Information System (INIS)

    Kale, Y.D.; Gandhi, Y.H.; Gartia, R.K.

    2008-01-01

    Physical conditions such as annealing temperature, duration of annealing, ionizing radiation, etc., play a significant role in the applications of optically stimulated luminescence (OSL) dating as well as OSL dosimetry. Many efforts are made to understand the effect of these physical parameters on quartz specimens owing to its use in such applications. Such factors induce changes in OSL decay pattern. The definite correlation between color centers and luminescence sensitivity can be established on account of such pre-treatments to the specimen. The purpose of present investigations is to study the effect of ionizing radiation under identical physical conditions on OSL properties measured at room temperature. The shapes of decay curve and dose-response data are considered for this purpose. This study can reveal the changes in color centers in response to the pre-conditions to the specimen. It was found that the OSL decay remains slow and OSL properties change systematically with the rise in beta dose up to a critical dose; however, it changes the pattern when the beta exposure to the specimen was increased higher than the critical dose. This critical dose was found to be different for different temperature of annealing. The shape of decay curve up to the critical dose was also studied by considering the difference of OSL intensities between two successive durations from the observed OSL decay data. The results are explained based on the changes in available shallow traps during OSL measurement at room temperature with changes in pre-conditions to the specimens. The results also have been confirmed with the corresponding changes in ESR signals

  2. Photobiomodulation delays the onset of skeletal muscle fatigue in a dose-dependent manner.

    Science.gov (United States)

    Larkin-Kaiser, Kelly A; Borsa, Paul A; Baweja, Harsimran S; Moore, Molly A; Tillman, Mark D; George, Steven Z; Christou, Evangelos A

    2016-09-01

    Photobiomodulation (PBM) therapy has been implicated as an effective ergogenic aid to delay the onset of muscle fatigue. The purpose of this study was to examine the dose-response ergogenic properties of PBM therapy and its ability to prolong time to task failure by enhancing muscle activity and delaying the onset of muscle fatigue using a static positioning task. Nine participants (24.3 ± 4.9 years) received three doses of near-infrared (NIR) light therapy randomly on three separate sessions (sham, 240, and 480 J). For the positioning task, participants held a 30 % one-repetition maximum (1-RM) load using the index finger until volitional fatigue. Surface electromyography (sEMG) of the first dorsal interosseous muscle was recorded for the length of the positioning task. Outcomes included time to task failure (TTF), muscle fatigue, movement accuracy, motor output variability, and muscle activity (sEMG). The 240-J dose significantly extended TTF by 26 % (p = 0.032) compared with the sham dose. TTF for the 240-J dose was strongly associated with a decrease in muscle fatigue (R (2) = 0.54, p = 0.024). Our findings show that a 240-J dose of NIR light therapy is efficacious in delaying the onset and extent of muscle fatigue during submaximal isometric positioning tasks. Our findings suggest that NIR light therapy may be used as an ergogenic aid during functional tasks or post-injury rehabilitation.

  3. Efficacy and Safety of Daikenchuto for Constipation and Dose-Dependent Differences in Clinical Effects

    Directory of Open Access Journals (Sweden)

    Tatsuya Hirose

    2018-01-01

    Full Text Available Background. Daikenchuto (DKT is a Kampo medicine used for the treatment of constipation. In this study, we evaluated the effectiveness of DKT against constipation. Patients and Methods. Thirty-three patients administered DKT for constipation were selected and divided into low-dose (7.5 g DKT; n=22 and high-dose (15 g DKT; n=11 groups. We retrospectively evaluated weekly defaecation frequency, side effects, and clinical laboratory data. Results. Median defaecation frequencies after DKT administration (5, 5.5, 5, and 8 for the first, second, third, and fourth weeks, resp. were significantly higher than that before DKT administration (2 in all 33 cases (P<0.01. One case (3% of watery stool, one case of loose stools (3%, and no cases of abdominal pain (0% were observed. Median defaecation frequencies in the high-dose group (7 and 9 were significantly higher than those in the low-dose group (4 and 3 in the first (P=0.0133 and second (P=0.0101 weeks, respectively. There was no significant change in clinical laboratory values. Conclusion. We suggest that DKT increases defaecation frequency and is safe for treating constipation.

  4. The dependence of percentage depth dose on the source-to-skin ...

    African Journals Online (AJOL)

    The variation of percentage depth dose (PDD) with source-to-skin distance (SSD) for kilovoltage X-rays used in radiotherapy has been investigated. Based on physical parameters of photon fluence, absorption and scatter during interaction of radiation with tissue, a mathematical model was developed to predict the PDDs at ...

  5. Liposome accumulation in irradiated tumors display important tumor and dose dependent differences

    DEFF Research Database (Denmark)

    Hansen, Anders Elias; Fliedner, Frederikke Petrine; Henriksen, Jonas Rosager

    2018-01-01

    Radiation therapy may affect several important parameters in the tumor microenvironment and thereby influence the accumulation of liposomes by the enhanced permeability and retention (EPR)-effect. Here we investigate the effect of single dose radiation therapy on liposome tumor accumulation by PET...

  6. Age and sex dependent inhalation doses to members of the public from indoor thoron progeny

    Energy Technology Data Exchange (ETDEWEB)

    Bi, L; Tschiersch, J [Helmholtz Zentrum Muenchen-German Research Center for Environmental Health, Institute of Radiation Protection, D-85764, Neuherberg (Germany); Li, W B [Helmholtz Zentrum Muenchen-German Research Center for Environmental Health, Department of Medical Radiation Physics and Diagnostics, D-85764, Neuherberg (Germany); Li, J L, E-mail: bilei1983@gmail.com [Department of Engineering Physics, Tsinghua University, Beijing 100084 (China)

    2010-12-01

    The increased indoor thoron level in Europe, North America and Asia has shown that the exposure to thoron and its decay products cannot be ignored in some environments. The contribution of thoron and its progeny can be a significant component of the total exposure from radon and thoron. In the present paper, radiation dose assessment of members of the public of different age and sex exposed to {sup 220}Rn progeny under different daily life activities is performed through a dosimetric approach. Dose conversion coefficients under typical indoor conditions were estimated to be in the range of 107 nSv (Bq h m{sup -3}){sup -1} for infant to 81.7 nSv (Bq h m{sup -3}){sup -1} for adult. The results of this work emphasized that small children receive a radiation dose of 25% more than adults under the same conditions, and people performing exercise receive a radiation dose 100% more than when sleeping. The results of this work are appropriate to the risk assessment of thoron exposure to members of the public who live in areas with high radon and thoron concentrations.

  7. Measurement bias dependence of enhanced bipolar gain degradation at low dose rates

    International Nuclear Information System (INIS)

    Witczak, S.C.; Lacoe, R.C.; Mayer, D.C.; Fleetwood, D.M.

    1998-03-01

    Oxide trapped charge, field effects from emitter metallization, and high level injection phenomena moderate enhanced gain degradation of lateral pnp transistors at low dose rates. Hardness assurance tests at elevated irradiation temperatures require larger design margins for low power measurement biases

  8. The dose dependence of fracture toughness Of F82H steel

    Energy Technology Data Exchange (ETDEWEB)

    Sokolov, M. [Oak Ridge National Laboratory, Materials Science and Technology Div., TN (United States); Tanigawa, H.; Ando, M.; Shiba, K. [Japan Atomic Energy Agency, Tokai-mura, Naga-gun, Ibaraki-ken (Japan); Odette, G. [UCSB, Santa-Barbara, Dept. of Mechanical Engineering UCSB, AK (United States); Hirose, T. [Blanket Engineering Group, Japan Atomic Energy Agency, Naka, Ibaraki (Japan); Klueh, R.L. [Oak Ridge Noational Laboratory, TN (United States)

    2007-07-01

    Full text of publication follows: The ferritic-martensitic steel F82H is a primary candidate low-activation material for fusion applications, and it is being investigated in the joint U.S. Department of Energy-Japan Atomic Energy Agency. As a part of this program, several capsules containing fracture toughness specimens were irradiated in High-Flux Isotope Reactor. These specimens were irradiated to a wide range of doses from 3.5 to 25 dpa. The range of irradiation temperature was from 250 deg. C to 500 deg. C. This paper summarizes the changes in fracture toughness transition temperature and decrease in the ductile fracture toughness as result of various irradiation conditions. It is shown that in the 3.5 to 25 dpa dose range, irradiation temperature plays the key rote in determination of the shift of the transition temperature. Highest embrittlement observed at 250 deg.C and the lowest at 500 deg. C. At a given irradiation temperature, shift of the fracture toughness transition temperature increases slightly with dose within the studied dose range. It appears that main gain in transition temperature shift occurred during initial {approx}5 dpa of irradiation. The present data are compared to the available published trends. (authors)

  9. Gender and dose dependent ovalbumin induced hypersensitivity responses in murine model of food allergy

    Science.gov (United States)

    While federal regulations mandate the labeling of major food allergens, allowable food allergen thresholds have yet to be determined. Therefore the aim of this project was to identify the lowest egg allergen ovalbumin (OVA) dose causing hypersensitization using a validated murine model. Mice were or...

  10. Time- and dose-dependent changes in neuronal activity produced by X radiation in brain slices

    International Nuclear Information System (INIS)

    Pellmar, T.C.; Schauer, D.A.; Zeman, G.H.

    1990-01-01

    A new method of exposing tissues to X rays in a lead Faraday cage has made it possible to examine directly radiation damage to isolated neuronal tissue. Thin slices of hippocampus from brains of euthanized guinea pigs were exposed to 17.4 ke V X radiation. Electrophysiological recordings were made before, during, and after exposure to doses between 5 and 65 Gy at a dose rate of 1.54 Gy/min. Following exposure to doses of 40 Gy and greater, the synaptic potential was enhanced, reaching a steady level soon after exposure. The ability of the synaptic potential to generate a spike was reduced and damage progressed after termination of the radiation exposure. Recovery was not observed following termination of exposure. These results demonstrate that an isolated neuronal network can show complex changes in electrophysiological properties following moderate doses of ionizing radiation. An investigation of radiation damage directly to neurons in vitro will contribute to the understanding of the underlying mechanisms of radiation-induced nervous system dysfunction

  11. Dose-dependent LDL-cholesterol lowering effect by plant stanol ester consumption: clinical evidence

    Directory of Open Access Journals (Sweden)

    Laitinen Kirsi

    2012-10-01

    Full Text Available Abstract Elevated serum lipids are linked to cardiovascular diseases calling for effective therapeutic means to reduce particularly LDL-cholesterol (LDL-C levels. Plant stanols reduce levels of LDL-C by partly blocking cholesterol absorption. Accordingly the consumption of foods with added plant stanols, typically esterified with vegetable oil fatty acids in commercial food products, are recommended for lowering serum cholesterol levels. A daily intake of 1.5 to 2.4 g of plant stanols has been scientifically evaluated to lower LDL-C by 7 to 10% in different populations, ages and with different diseases. Based on earlier studies, a general understanding is that no further reduction may be achieved in intakes in excess of approximately 2.5 g/day. Recent studies however suggest that plant stanols show a continuous dose–response effect in serum LDL-C lowering. This review discusses the evidence for a dose-effect relationship between plant stanol ester consumption and reduction of LDL-C concentrations with daily intakes of plant stanols of 4 g/day or more. We identified five such studies and the overall data demonstrate a linear dose-effect relationship with the most pertinent LDL-Cholesterol lowering outcome, 18%, achieved by a daily intake of 9 to 10 g of plant stanols. Along with reduction in LDL-C, the studies demonstrated a decrease in cholesterol absorption markers, the serum plant sterol to cholesterol ratios, by increasing the dose of plant stanol intake. None of the studies with daily intakes up to 10 g of plant stanols reported adverse clinical or biochemical effects from plant stanols. In a like manner, the magnitude of decrease in serum antioxidant vitamins was not related to the dose of plant stanols consumed and the differences between plant stanol ester consumers and controls were minor and insignificant or nonexisting. Consumption of plant stanols in high doses is feasible as a range of food products are commercially available for

  12. Angular dependence of dose sensitivity of nanoDot optically stimulated luminescent dosimeters in different radiation geometries

    Energy Technology Data Exchange (ETDEWEB)

    Jursinic, Paul A., E-mail: pjursinic@wmcc.org [West Michigan Cancer Center, 200 North Park Street, Kalamazoo, Michigan 49007 (United States)

    2015-10-15

    Purpose: A type of in vivo dosimeter, an optically stimulated luminescent dosimeter, OSLD, may have dose sensitivity that depends on the angle of incidence of radiation. This work measures how angular dependence of a nanoDot changes with the geometry of the phantom in which irradiation occurs and with the intrinsic structure of the nanoDot. Methods: The OSLDs used in this work were nanoDot dosimeters (Landauer, Inc., Glenwood, IL), which were read with a MicroStar reader (Landauer, Inc., Glenwood, IL). Dose to the OSLDs was delivered by 6 MV x-rays. NanoDots with various intrinsic sensitivities were irradiated in numerous phantoms that had geometric shapes of cylinders, rectangles, and a cube. Results: No angular dependence was seen in cylindrical phantoms, cubic phantoms, or rectangular phantoms with a thickness to width ratio of 0.3 or 1.5. An angular dependence of 1% was observed in rectangular phantoms with a thickness to width of 0.433–0.633. A group of nanoDots had sensitive layers with mass density of 2.42–2.58 g/cm{sup 3} and relative sensitivity of 0.92–1.09 and no difference in their angular dependence. Within experimental uncertainty, nanoDot measurements agree with a parallel-plate ion chamber at a depth of maximum dose. Conclusions: When irradiated in cylindrical, rectangular, and cubic phantoms, nanoDots show a maximum angular dependence of 1% or less at an incidence angle of 90°. For a sample of 78 new nanoDots, the range of their relative intrinsic sensitivity is 0.92–1.09. For a sample of ten nanoDots, on average, the mass in the sensitive layer is 73.1% Al{sub 2}O{sub 3}:C and 26.9% polyester. The mass density of the sensitive layer of a nanoDot disc is between 2.42 and 2.58 g/cm{sup 3}. The angular dependence is not related to Al{sub 2}O{sub 3}:C loading of the nanoDot disc. The nanoDot at the depth of maximum dose has no more angular dependence than a parallel-plate ion chamber.

  13. Dependence of malformation upon gestational age and exposed dose of gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sung-Ho; Lee, Jong-Hwan; Oh, Heon; Kim, Se-Ra [Chonnam National Univ., Kwangju (Korea, Republic of). Coll. of Veterinary Medicine; Lee, Cha-Soo; Jo, Sung-Kee; Kim, Tae-Hwan; Lee, Yun-Sil

    2001-09-01

    In order to evaluate the importance of gestational age and the dose-incidence relationship by gamma radiation, pregnant ICR mice at gestational days from 2.5 to 15.5 days post-coitus (p.c.) were exposed to a single dose of 2.0 Gy and also at day 11.5 after conception, which was the most sensitive stage for the induction of major congenital malformations. The animals were sacrificed on day 18 of gestation and the fetuses were examined for mortality, growth retardation, changes in head size and other morphological abnormalities. The only demonstrable effect of irradiation during the pre-implantation period was an increase in prenatal mortality. Resorptions were maximal on exposure at day 2.5 after conception. The pre-implantation irradiated embryos which survived did not show any major fetal abnormalities. A small head, growth retardation, a cleft palate, dilatation of the cerebral ventricle, a renal pelvis, and abnormalities of the extremities and tail after exposure were prominent during the organogenesis period, especially on day 11.5 of gestation. As for the dose-incidence relationship, the incidence of a small head, growth-retarded fetuses, a cleft palate, dilatation of cerebral ventricle and abnormalities of the extremities in live fetuses rose as the radiation dose increased. The result indicated that the late period of organogenesis in the development of the brain, skull and extremities of a mouse was a particularly sensitive phase. The threshold doses of radiation that induced a cleft palate and dilatation of the cerebral ventricle, and abnormal extremities were between 1.0 and 2.0 Gy, and between 0.5 and 1.0 Gy, respectively. (author)

  14. Dependence of malformation upon gestational age and exposed dose of gamma radiation

    International Nuclear Information System (INIS)

    Kim, Sung-Ho; Lee, Jong-Hwan; Oh, Heon; Kim, Se-Ra; Lee, Cha-Soo; Jo, Sung-Kee; Kim, Tae-Hwan; Lee, Yun-Sil

    2001-01-01

    In order to evaluate the importance of gestational age and the dose-incidence relationship by gamma radiation, pregnant ICR mice at gestational days from 2.5 to 15.5 days post-coitus (p.c.) were exposed to a single dose of 2.0 Gy and also at day 11.5 after conception, which was the most sensitive stage for the induction of major congenital malformations. The animals were sacrificed on day 18 of gestation and the fetuses were examined for mortality, growth retardation, changes in head size and other morphological abnormalities. The only demonstrable effect of irradiation during the pre-implantation period was an increase in prenatal mortality. Resorptions were maximal on exposure at day 2.5 after conception. The pre-implantation irradiated embryos which survived did not show any major fetal abnormalities. A small head, growth retardation, a cleft palate, dilatation of the cerebral ventricle, a renal pelvis, and abnormalities of the extremities and tail after exposure were prominent during the organogenesis period, especially on day 11.5 of gestation. As for the dose-incidence relationship, the incidence of a small head, growth-retarded fetuses, a cleft palate, dilatation of cerebral ventricle and abnormalities of the extremities in live fetuses rose as the radiation dose increased. The result indicated that the late period of organogenesis in the development of the brain, skull and extremities of a mouse was a particularly sensitive phase. The threshold doses of radiation that induced a cleft palate and dilatation of the cerebral ventricle, and abnormal extremities were between 1.0 and 2.0 Gy, and between 0.5 and 1.0 Gy, respectively. (author)

  15. Dose- and time-dependent effects of clodronate on orthodontic tooth movement

    Directory of Open Access Journals (Sweden)

    Enita Nakaš

    2017-02-01

    Full Text Available Orthodontic tooth movement is the result of bone remodeling that occurs in periodontal ligament and alveolar bone tissue as a response to mechanical loading of the tooth. The aim of this study is to investigate the time- and dose-response effects of locally administered clodronate on tooth movement. Sixty Wistar rats were randomly assigned to 4 groups of 15 specimens: E1 - application of 10 mMol of clodronate in 3-day intervals; E2 - application of 2.5 mMol of clodronate in 3-day intervals; E3 - application of 10 mMol of clodronate in 7-day intervals; E4 - application of 2.5 mMol of clodronate in 7-day intervals. A 50 μL clodronate solution was injected into a subperiosteal area to the right maxillary incisor. The left maxillary incisor served as a control, with an injection of saline solution. In 3-day interval application regime, there was no effect of clodronate dosing on tooth movement. In 7-day interval application regime, decreased tooth movement was observed with 10 mMol compared with 2.5 mMol clodronate concentration. However, decreased tooth movement was also observed when 2.5 mMol of clodronate was applied in 7-versus 3-day intervals. Conversely, no difference was observed when 10 mMol concentration was applied in 3- versus 7-day intervals. When clodronate is applied subperiosteally in the root area, it decreases the tooth movement. Tooth movement is impeded by the higher clodronate dosing, as well as by shorter application interval even with lower dosing. The purpose of future trials should, therefore, be to determine a safe therapeutic dose/interval application of clodronate in humans and their potential side effects.

  16. Dose dependency of the frequency of micronucleated binucleated clone cells and of division related median clone sizes difference. Pt. 2

    International Nuclear Information System (INIS)

    Hagemann, G,; Kreczik, A.; Treichel, M.

    1996-01-01

    Following irradiation of the progenitor cells the clone growth of CHO cells decreases as a result of cell losses. Lethally acting expressions of micronuclei are produced by heritable lethal mutations. The dependency of the frequency of micronucleated binucleated clone cells and of the median clone sizes difference on the radiation dose was measured and compared to non-irradiated controls. Using the cytokinesis-block-micronucleus-method binucleated cells with micronuclei were counted as ratio of all binucleated cells within a clone size distribution. This ratio (shortened: micronucleus yield) was determined for all clone size distributions, which had been exposed to different irradiation doses and incubation times. The micronucleus yields were compared to the corresponding median clone sizes differences. The micronucleus yield is linearly dependent on the dose and is independent of the incubation time. The same holds true for the division related median clone sizes difference, which as a result is also linearly dependent on the micronucleus yield. Due to the inevitably errors of the cell count of micronucleated binucleated cells, an automatic measurement of the median clone sizes differences is the preferred method for evaluation of cellular radiation sensitivity for heritable lethal mutations. This value should always be determined in addition, if clone survival fractions are used as predictive test because it allows for an estimation of the remission probability of surviving cells. (orig.) [de

  17. Time-, Sex-, and Dose-Dependent Alterations of the Gut Microbiota by Consumption of Dietary Daikenchuto (TU-100

    Directory of Open Access Journals (Sweden)

    Jun Miyoshi

    2018-01-01

    Full Text Available Medications or dietary components can affect both the host and the host’s gut microbiota. Changes in the microbiota may influence medication efficacy and interactions. Daikenchuto (TU-100, a herbal medication, comprised of ginger, ginseng, and Japanese pepper, is widely used in Japanese traditional Kampo medicine for intestinal motility and postoperative paralytic ileus. We previously showed in mice that consumption of TU-100 for 4 weeks changed the gut microbiota and increased bioavailability of bacterial ginsenoside metabolites. Since TU-100 is prescribed in humans for months to years, we examined the time- and sex-dependent effects of TU-100 on mouse gut microbiota. Oral administration of 1.5% TU-100 for 24 weeks caused more pronounced changes in gut microbiota in female than in male mice. Changes in both sexes largely reverted to baseline upon TU-100 withdrawal. Effects were time and dose dependent. The microbial profiles reverted to baseline within 4 weeks after withdrawal of 0.75% TU-100 but were sustained after withdrawal of 3% TU-100. In summary, dietary TU-100 changed mouse microbiota in a time-, sex-, and dose-dependent manner. These findings may be taken into consideration when determining optimizing dose for conditions of human health and disease with the consideration of differences in composition and response of the human intestinal microbiota.

  18. Dose-Dependent AMPK-Dependent and Independent Mechanisms of Berberine and Metformin Inhibition of mTORC1, ERK, DNA Synthesis and Proliferation in Pancreatic Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Ming Ming

    Full Text Available Natural products represent a rich reservoir of potential small chemical molecules exhibiting anti-proliferative and chemopreventive properties. Here, we show that treatment of pancreatic ductal adenocarcinoma (PDAC cells (PANC-1, MiaPaCa-2 with the isoquinoline alkaloid berberine (0.3-6 µM inhibited DNA synthesis and proliferation of these cells and delay the progression of their cell cycle in G1. Berberine treatment also reduced (by 70% the growth of MiaPaCa-2 cell growth when implanted into the flanks of nu/nu mice. Mechanistic studies revealed that berberine decreased mitochondrial membrane potential and intracellular ATP levels and induced potent AMPK activation, as shown by phosphorylation of AMPK α subunit at Thr-172 and acetyl-CoA carboxylase (ACC at Ser79. Furthermore, berberine dose-dependently inhibited mTORC1 (phosphorylation of S6K at Thr389 and S6 at Ser240/244 and ERK activation in PDAC cells stimulated by insulin and neurotensin or fetal bovine serum. Knockdown of α1 and α2 catalytic subunit expression of AMPK reversed the inhibitory effect produced by treatment with low concentrations of berberine on mTORC1, ERK and DNA synthesis in PDAC cells. However, at higher concentrations, berberine inhibited mitogenic signaling (mTORC1 and ERK and DNA synthesis through an AMPK-independent mechanism. Similar results were obtained with metformin used at doses that induced either modest or pronounced reductions in intracellular ATP levels, which were virtually identical to the decreases in ATP levels obtained in response to berberine. We propose that berberine and metformin inhibit mitogenic signaling in PDAC cells through dose-dependent AMPK-dependent and independent pathways.

  19. Efficacy and Safety of Daikenchuto for Constipation and Dose-Dependent Differences in Clinical Effects.

    Science.gov (United States)

    Hirose, Tatsuya; Shinoda, Yasutaka; Kuroda, Ayaka; Yoshida, Aya; Mitsuoka, Machiko; Mori, Kouki; Kawachi, Yuki; Moriya, Akihiro; Tanaka, Kouji; Takeda, Atsuko; Yoshimura, Tomoaki; Sugiyama, Tadashi

    2018-01-01

    Daikenchuto (DKT) is a Kampo medicine used for the treatment of constipation. In this study, we evaluated the effectiveness of DKT against constipation. Thirty-three patients administered DKT for constipation were selected and divided into low-dose (7.5 g DKT; n = 22) and high-dose (15 g DKT; n = 11) groups. We retrospectively evaluated weekly defaecation frequency, side effects, and clinical laboratory data. Median defaecation frequencies after DKT administration (5, 5.5, 5, and 8 for the first, second, third, and fourth weeks, resp.) were significantly higher than that before DKT administration (2) in all 33 cases ( P DKT increases defaecation frequency and is safe for treating constipation.

  20. The Dose Rate Dependence of the Yield of Trapped Electrons in Crystalline Ice

    DEFF Research Database (Denmark)

    Nilsson, Johan Daniel Göran; Pagsberg, Palle Bjørn

    1980-01-01

    in competition with other reactions and we propose a simple model where we assume that the mobile electrons can undergo bimolecular bulk reactions with protons and OH radicals. Rate constants of 3.0 × 1015 M−1 S−1 and 1.4 × 1014 M−1 S−1 for the two reactions were required in the model in order to account......The yield of localized excess electrons in crystalline H2O ice has been studied as a function of the dose rate at various temperatures in the range −10 to −40°C. The G value was found to decrease significantly with increasing dose rate. Thus it appears that the localization of electrons takes place...

  1. Ethylene regulates Apple (Malus x domestica) fruit softening through a dose x time-dependent mechanism and through differential sensitivities and dependencies of cell wall-modifying genes.

    Science.gov (United States)

    Ireland, Hilary S; Gunaseelan, Kularajathevan; Muddumage, Ratnasiri; Tacken, Emma J; Putterill, Jo; Johnston, Jason W; Schaffer, Robert J

    2014-05-01

    In fleshy fruit species that have a strong requirement for ethylene to ripen, ethylene is synthesized autocatalytically, producing increasing concentrations as the fruits ripen. Apple fruit with the ACC OXIDASE 1 (ACO1) gene suppressed cannot produce ethylene autocatalytically at ripening. Using these apple lines, an ethylene sensitivity dependency model was previously proposed, with traits such as softening showing a high dependency for ethylene as well as low sensitivity. In this study, it is shown that the molecular control of fruit softening is a complex process, with different cell wall-related genes being independently regulated and exhibiting differential sensitivities to and dependencies on ethylene at the transcriptional level. This regulation is controlled through a dose × time mechanism, which results in a temporal transcriptional response that would allow for progressive cell wall disassembly and thus softening. This research builds on the sensitivity dependency model and shows that ethylene-dependent traits can progress over time to the same degree with lower levels of ethylene. This suggests that a developmental clock measuring cumulative ethylene controls the fruit ripening process.

  2. Dose-Dependent Effects of Methadone on QT interval in Patients under Methadone Maintenance Treatment

    Directory of Open Access Journals (Sweden)

    Farzad Gheshlaghi

    2013-03-01

    Full Text Available Background: The role of methadone in QTc prolongation, Torsades de Pointes (TdP arrhythmia and sudden cardiac death has been debated. Because of widespread use of methadone in methadone maintenance treatment (MMT centers, we aimed to study dose-related effects of methadone on QTc prolongation. Methods: In a comparative observational study, 90 patients who were under MMT were evaluated. Patients were divided into three groups according to methadone daily dose (G1: 0-59 mg, G2: 60-109 mg, G3: 110-150 mg. Twelve-lead electrocardiograms (ECG were performed at baseline and two months later, after reaching the maximum daily dose of methadone. The QTc were calculated for each patient. Comparison of mean QTc and mean QTc prolongation between baseline and follow up ECGs were analyzed. Results: In total, mean (SD age was 32.4 (8.5. TdP was not detected in any patients. Mean QTc was 405.2 (17.0 and 418.5 (23.1 msec before and two months after MMT respectively. There was a significant difference between mean QTc in each group before and after treatment (P

  3. Dose-dependent antiinflammatory effect of ursodeoxycholic acid in experimental colitis.

    Science.gov (United States)

    Martínez-Moya, Patricia; Romero-Calvo, Isabel; Requena, Pilar; Hernández-Chirlaque, Cristina; Aranda, Carlos J; González, Raquel; Zarzuelo, Antonio; Suárez, María Dolores; Martínez-Augustin, Olga; Marín, José Juan G; de Medina, Fermín Sánchez

    2013-02-01

    The denomination of inflammatory bowel disease comprises a group of chronic inflammatory diseases of the digestive tract, ulcerative colitis and Crohn's disease being the most important conditions. Bile acids may play a role both in etiology and pharmacology of this disease. Thus, although deoxycholic acid is regarded as a proinflammatory agent ursodeoxycholic acid, which is currently being used to treat certain types of cholestasis and primary biliary cirrhosis, because of their choleretic, cytoprotective and immunomodulatory effects, it has been reported to exert an anti-inflammatory activity. We aim to confirm and characterize the intestinal antiinflammatory activity of ursodeoxycholic acid. The experimental model trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats has been used. Animal status was characterized by a number of macroscopic and biochemical parameters. Oral administration of ursodeoxycholic acid was able to ameliorate experimental colonic inflammation. This occurred only at a relatively high dose (50 mg/kg day), whereas ursodeoxycholic acid was without significant effect at doses of 10 and 25 mg/kg day. The therapeutic effect was evidenced, among others, by a higher body weight recovery, a diminished affected to total mucosal area and lower alkaline phosphatase activity in treated vs. control (TNBS treated) animals. These results indicate that, at the appropriate dose, ursodeoxycholic acid is a potentially useful drug to reduce intestinal inflammation and could be envisaged to be incorporated in the treatment of inflammatory bowel diseases. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. The mode of lymphoblastoid cell death in response to gas phase cigarette smoke is dose-dependent

    Directory of Open Access Journals (Sweden)

    Baltatzis George E

    2009-09-01

    Full Text Available Abstract Background Cigarette smoke (CS is the main cause in the development of chronic obstructive pulmonary disease (COPD, the pathogenesis of which is related to an extended inflammatory response. In this study, we investigated the effect of low and high doses of gas phase cigarette smoke (GPS on cultured lymphocyte progenitor cells, using techniques to assess cell viability and to elucidate whether cells die of apoptosis or necrosis upon exposure to different doses of GPS. Methods In our approach we utilised a newly-established system of exposure of cells to GPS that is highly controlled, accurately reproducible and simulates CS dosage and kinetics that take place in the smokers' lung. This system was used to study the mode of cell death upon exposure to GPS in conjunction with a range of techniques widely used for cell death studies such as Annexin V staining, activation of caspase -3, cytoplasmic release of cytochrome C, loss of mitochondrial membrane potential and DNA fragmentation. Results Low doses of GPS induced specific apoptotic indexes in CCRF-CEM cells. Specifically, cytochrome C release and cleaved caspase-3 were detected by immunofluorescence, upon treatment with 1-3 puffs GPS. At 4 h post-exposure, caspase-3 activation was observed in western blot analysis, showing a decreasing pattern as GPS doses increased. Concomitant with this behaviour, a dose-dependent change in Δψm depolarization was monitored by flow cytometry 2 h post-exposure, while at 4 h Δψm collapse was observed at the higher doses, indicative of a shift to a necrotic demise. A reduction in DNA fragmentation events produced by 5 puffs GPS as compared to those provoked by 3 puffs GPS, also pointed towards a necrotic response at the higher dose of GPS. Conclusion Collectively, our results support that at low doses gas phase cigarette smoke induces apoptosis in cultured T-lymphocytes, whereas at high doses GPS leads to necrotic death, by-passing the characteristic

  5. Comparative pharmacokinetics and bioavailability of albendazole sulfoxide in sheep and goats, and dose-dependent plasma disposition in goats.

    Science.gov (United States)

    Aksit, Dilek; Yalinkilinc, Hande Sultan; Sekkin, Selim; Boyacioğlu, Murat; Cirak, Veli Yilgor; Ayaz, Erol; Gokbulut, Cengiz

    2015-05-27

    The aims of this study were to compare the pharmacokinetics of albendazole sulfoxide (ABZ-SO, ricobendazole) in goats and sheep at a dose of 5 g/kg bodyweight (BW), after intravenous (IV) and subcutaneous (SC) administrations, and to investigate the effects of increased doses (10 and 15 mg/kg BW) on the plasma disposition of ABZ-SO in goats following SC administration. A total of 16 goats (Capra aegagrus hircus, eight males and eight females) and 8 sheep (Ovis aries, four males and four females) 12-16 months old and weighing 20-32 kg, were used. The study was designed according to two-phase crossover study protocol. In Phase-1, eight sheep were assigned as Group I and 16 goats were allocated into two groups (Group II and Group III). ABZ-SO was applied to Group I (sheep) and Group II (goats) animals subcutaneously, and to Group III (goats) animals intravenously, all at a dose rate of 5 mg/kg BW. In Phase-2, the sheep in the Group I received ABZ-SO intravenously in a dose of 5 mg/kg BW; the goats in Group II and Group III received ABZ-SO subcutaneously at a dose of 10 mg/kg and 15 mg/kg BW, respectively. Blood samples were collected from the jugular vein at different times between 1 and 120 h after drug administrations. The plasma concentrations of ABZ-SO and its metabolites were analysed by high performance liquid chromatography. In goats, the area under the curve, terminal half-life and plasma persistence of ABZ-SO were significantly smaller and shorter, respectively, compared with those observed in sheep following both IV and SC administrations at a dose of 5 mg/kg BW. On the other side, dose-dependent plasma dispositions of ABZ-SO were observed following SC administration at increased doses (10 and 15 mg/kg) in goats. Consequently, ABZ-SO might be used at higher doses to provide higher plasma concentration and thus to achieve greater efficacy against the target parasites.

  6. Dose dependence of microstructural evolution and mechanical properties of neutron irradiated copper and copper alloys

    Energy Technology Data Exchange (ETDEWEB)

    Singh, B N; Edwards, D J; Horsewell, A; Toft, P

    1995-09-01

    The present investigation of the effects of neutron irradiation on microstructures and mechanical properties of copper alloys is a part of the ITER (International Thermonuclear Experimental Reactor) programme. Tensile specimens of the candidate alloys Cu-Al{sub 2}O{sub 3}, CuCrZr and CuNiBe were irradiated with fission neutrons in the DR-3 reactor at Risoe with a flux of 2.5 x 10{sup 17} n/m{sup 2}s (E > 1 MeV, i.e. a dose rate of {approx}5 x 10{sup -8} dpa/s) to fluences of 5 x 10{sup 22}, 5 x 10{sup 23} and 1 x 10{sup 24} n/m{sup 2} (E > 1 MeV, i.e. displacement doses of 0.01, 0.1 and 0.2 dpa) at 47 deg. C. The Cu-Al{sub 2}O{sub 3} (CuA125) specimens, were irradiated in the as-cold worked state. Tensile properties and Vickers hardness of both irradiated and unirradiated specimens were determined at 22 deg. C. Pre- and post-deformation microstructures of irradiated as well as unirradiated specimens were examined using a transmission electron microscope. The fractured surfaces of tensile tested specimens were investigated in a scanning electron microscope. The results show the following general trend: (a) that the CuNiBe alloy is stronger than CuCrZr as well as Cu Al{sub 2}O{sub 3}, (b) that even relatively low dose irradiations cause significant increase in the yield strength, but rather drastic decreases in the uniform elongation of CuCrZr and CuNiBe alloys and that the low dose irradiation of the cold-worked Cu-Al{sub 2}O{sub 3} alloy causes a decrease in the yield strength and an increase in the uniform elongation, at higher doses irradiation hardening occurs. The SEM examinations of the fractured surfaces demonstrate that both unirradiated and irradiated specimens fracture in a ductile manner. The lack of uniform elongation in the irradiated copper alloys may be understood in terms of difficulty in dislocation generation due to pinning of grown-in dislocation by defect clusters (loops) at or around them. (EG) 5 tabs., 18 ills., 13 refs.

  7. Dose dependence of microstructural evolution and mechanical properties of neutron irradiated copper and copper alloys

    International Nuclear Information System (INIS)

    Singh, B.N.; Edwards, D.J.; Horsewell, A.; Toft, P.

    1995-09-01

    The present investigation of the effects of neutron irradiation on microstructures and mechanical properties of copper alloys is a part of the ITER (International Thermonuclear Experimental Reactor) programme. Tensile specimens of the candidate alloys Cu-Al 2 O 3 , CuCrZr and CuNiBe were irradiated with fission neutrons in the DR-3 reactor at Risoe with a flux of 2.5 x 10 17 n/m 2 s (E > 1 MeV, i.e. a dose rate of ∼5 x 10 -8 dpa/s) to fluences of 5 x 10 22 , 5 x 10 23 and 1 x 10 24 n/m 2 (E > 1 MeV, i.e. displacement doses of 0.01, 0.1 and 0.2 dpa) at 47 deg. C. The Cu-Al 2 O 3 (CuA125) specimens, were irradiated in the as-cold worked state. Tensile properties and Vickers hardness of both irradiated and unirradiated specimens were determined at 22 deg. C. Pre- and post-deformation microstructures of irradiated as well as unirradiated specimens were examined using a transmission electron microscope. The fractured surfaces of tensile tested specimens were investigated in a scanning electron microscope. The results show the following general trend: (a) that the CuNiBe alloy is stronger than CuCrZr as well as Cu Al 2 O 3 , (b) that even relatively low dose irradiations cause significant increase in the yield strength, but rather drastic decreases in the uniform elongation of CuCrZr and CuNiBe alloys and that the low dose irradiation of the cold-worked Cu-Al 2 O 3 alloy causes a decrease in the yield strength and an increase in the uniform elongation, at higher doses irradiation hardening occurs. The SEM examinations of the fractured surfaces demonstrate that both unirradiated and irradiated specimens fracture in a ductile manner. The lack of uniform elongation in the irradiated copper alloys may be understood in terms of difficulty in dislocation generation due to pinning of grown-in dislocation by defect clusters (loops) at or around them. (EG) 5 tabs., 18 ills., 13 refs

  8. Intranasal infection with Chlamydia abortus induces dose-dependent latency and abortion in sheep.

    Science.gov (United States)

    Longbottom, David; Livingstone, Morag; Maley, Stephen; van der Zon, Arjan; Rocchi, Mara; Wilson, Kim; Wheelhouse, Nicholas; Dagleish, Mark; Aitchison, Kevin; Wattegedera, Sean; Nath, Mintu; Entrican, Gary; Buxton, David

    2013-01-01

    Latency is a key feature of the animal pathogen Chlamydia abortus, where infection remains inapparent in the non-pregnant animal and only becomes evident during a subsequent pregnancy. Often the first sign that an animal is infected is abortion occurring late in gestation. Despite this, little is understood of the underlying mechanisms that control latency or the recrudescence of infection that occurs during subsequent pregnancy. The aim of this study was to develop an experimental model of latency by mimicking the natural route of infection through the intranasal inoculation of non-pregnant sheep with C. abortus. Three groups of sheep (groups 1, 2 and 3) were experimentally infected with different doses of C. abortus (5×10(3), 5×10(5) and 5×10(7) inclusion forming units (IFU), respectively) prior to mating and monitored over 2 breeding cycles for clinical, microbiological, pathological, immunological and serological outcomes. Two further groups received either negative control inoculum (group 4a,b) or were inoculated subcutaneously on day 70 of gestation with 2×10(6) IFU C. abortus (group 5). Animals in groups 1, 2 and 5 experienced an abortion rate of 50-67%, while only one animal aborted in group 3 and none in group 4a,b. Pathological, microbiological, immunological and serological analyses support the view that the maternal protective immune response is influenced by initial exposure to the bacterium. The results show that intranasal administration of non-pregnant sheep with a low/medium dose of C. abortus results in a latent infection that leads in a subsequent pregnancy to infection of the placenta and abortion. In contrast a high dose stimulates protective immunity, resulting in a much lower abortion rate. This model will be useful in understanding the mechanisms of infection underlying latency and onset of disease, as well as in the development of novel therapeutics and vaccines for controlling infection.

  9. Intranasal infection with Chlamydia abortus induces dose-dependent latency and abortion in sheep.

    Directory of Open Access Journals (Sweden)

    David Longbottom

    Full Text Available Latency is a key feature of the animal pathogen Chlamydia abortus, where infection remains inapparent in the non-pregnant animal and only becomes evident during a subsequent pregnancy. Often the first sign that an animal is infected is abortion occurring late in gestation. Despite this, little is understood of the underlying mechanisms that control latency or the recrudescence of infection that occurs during subsequent pregnancy. The aim of this study was to develop an experimental model of latency by mimicking the natural route of infection through the intranasal inoculation of non-pregnant sheep with C. abortus.Three groups of sheep (groups 1, 2 and 3 were experimentally infected with different doses of C. abortus (5×10(3, 5×10(5 and 5×10(7 inclusion forming units (IFU, respectively prior to mating and monitored over 2 breeding cycles for clinical, microbiological, pathological, immunological and serological outcomes. Two further groups received either negative control inoculum (group 4a,b or were inoculated subcutaneously on day 70 of gestation with 2×10(6 IFU C. abortus (group 5. Animals in groups 1, 2 and 5 experienced an abortion rate of 50-67%, while only one animal aborted in group 3 and none in group 4a,b. Pathological, microbiological, immunological and serological analyses support the view that the maternal protective immune response is influenced by initial exposure to the bacterium.The results show that intranasal administration of non-pregnant sheep with a low/medium dose of C. abortus results in a latent infection that leads in a subsequent pregnancy to infection of the placenta and abortion. In contrast a high dose stimulates protective immunity, resulting in a much lower abortion rate. This model will be useful in understanding the mechanisms of infection underlying latency and onset of disease, as well as in the development of novel therapeutics and vaccines for controlling infection.

  10. Low-dose sevoflurane promotes hippocampal neurogenesis and facilitates the development of dentate gyrus-dependent learning in neonatal rats.

    Science.gov (United States)

    Chen, Chong; Shen, Feng-Yan; Zhao, Xuan; Zhou, Tao; Xu, Dao-Jie; Wang, Zhi-Ru; Wang, Ying-Wei

    2015-01-01

    Huge body of evidences demonstrated that volatile anesthetics affect the hippocampal neurogenesis and neurocognitive functions, and most of them showed impairment at anesthetic dose. Here, we investigated the effect of low dose (1.8%) sevoflurane on hippocampal neurogenesis and dentate gyrus-dependent learning. Neonatal rats at postnatal day 4 to 6 (P4-6) were treated with 1.8% sevoflurane for 6 hours. Neurogenesis was quantified by bromodeoxyuridine labeling and electrophysiology recording. Four and seven weeks after treatment, the Morris water maze and contextual-fear discrimination learning tests were performed to determine the influence on spatial learning and pattern separation. A 6-hour treatment with 1.8% sevoflurane promoted hippocampal neurogenesis and increased the survival of newborn cells and the proportion of immature granular cells in the dentate gyrus of neonatal rats. Sevoflurane-treated rats performed better during the training days of the Morris water maze test and in contextual-fear discrimination learning test. These results suggest that a subanesthetic dose of sevoflurane promotes hippocampal neurogenesis in neonatal rats and facilitates their performance in dentate gyrus-dependent learning tasks. © The Author(s) 2015.

  11. Low-Dose Sevoflurane Promotes Hippocampal Neurogenesis and Facilitates the Development of Dentate Gyrus-Dependent Learning in Neonatal Rats

    Directory of Open Access Journals (Sweden)

    Chong Chen

    2015-04-01

    Full Text Available Huge body of evidences demonstrated that volatile anesthetics affect the hippocampal neurogenesis and neurocognitive functions, and most of them showed impairment at anesthetic dose. Here, we investigated the effect of low dose (1.8% sevoflurane on hippocampal neurogenesis and dentate gyrus-dependent learning. Neonatal rats at postnatal day 4 to 6 (P4–6 were treated with 1.8% sevoflurane for 6 hours. Neurogenesis was quantified by bromodeoxyuridine labeling and electrophysiology recording. Four and seven weeks after treatment, the Morris water maze and contextual-fear discrimination learning tests were performed to determine the influence on spatial learning and pattern separation. A 6-hour treatment with 1.8% sevoflurane promoted hippocampal neurogenesis and increased the survival of newborn cells and the proportion of immature granular cells in the dentate gyrus of neonatal rats. Sevoflurane-treated rats performed better during the training days of the Morris water maze test and in contextual-fear discrimination learning test. These results suggest that a subanesthetic dose of sevoflurane promotes hippocampal neurogenesis in neonatal rats and facilitates their performance in dentate gyrus-dependent learning tasks.

  12. A UV-Induced Genetic Network Links the RSC Complex to Nucleotide Excision Repair and Shows Dose-Dependent Rewiring

    Directory of Open Access Journals (Sweden)

    Rohith Srivas

    2013-12-01

    Full Text Available Efficient repair of UV-induced DNA damage requires the precise coordination of nucleotide excision repair (NER with numerous other biological processes. To map this crosstalk, we generated a differential genetic interaction map centered on quantitative growth measurements of >45,000 double mutants before and after different doses of UV radiation. Integration of genetic data with physical interaction networks identified a global map of 89 UV-induced functional interactions among 62 protein complexes, including a number of links between the RSC complex and several NER factors. We show that RSC is recruited to both silenced and transcribed loci following UV damage where it facilitates efficient repair by promoting nucleosome remodeling. Finally, a comparison of the response to high versus low levels of UV shows that the degree of genetic rewiring correlates with dose of UV and reveals a network of dose-specific interactions. This study makes available a large resource of UV-induced interactions, and it illustrates a methodology for identifying dose-dependent interactions based on quantitative shifts in genetic networks.

  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. Ultraviolet Radiation Induces Dose-Dependent Pigment Dispersion in Crustacean Chromatophores

    OpenAIRE

    Gouveia, Glauce Ribeiro; Lopes, Thaís Martins; Neves, Carla Amorim; Nery, Luiz Eduardo Maia; Trindade, Gilma Santos

    2004-01-01

    Pigment dispersion in chromatophores as a response to UV radiation was investigated in two species of crustaceans, the crab Chasmagnathus granulata and the shrimp Palaemonetes argentinus. Eyestalkless crabs and shrimps maintained on either a black or a white background were irradiated with different UV bands. In eyestalkless crabs the significant minimal effective dose inducing pigment dispersion was 0.42 J/cm2 for UVA and 2.15 J/cm2 for UVB. Maximal response was achieved with 10.0 J/cm...

  15. Mycorrhizal dependency of mangaba tree under increasing phosphorus levels Dependência micorrízica de mangabeira em doses crescentes de fósforo

    Directory of Open Access Journals (Sweden)

    Júlio Alves Cardoso Filho

    2008-07-01

    Full Text Available The objective of this study was to evaluate the mycorrhizal dependency of mangaba tree (Hancornia speciosa plantlets, under increasing levels of phosphorus fertilization. The experimental design was completely randomized in a 4×5 factorial arrangement with three mycorrhizal fungi inocula - Gigaspora margarita, Glomus etunicatum, or a pool of native mycorrhizal fungi (Acaulospora longula, Glomus clarum, Gigaspora albida, Paraglomus sp. -, and a nonmycorrhizal control, in combination with five levels of phosphorus applied to the substrate: 0, 25, 50, 75, and 100 mg kg-1. After 180 days of growth, plantlets with inoculation of native mycorrhizal pool produced more shoot and root dry biomass and had higher shoot phosphorus content and accumulation. The noninoculated control showed the lowest values, independently of the phosphorus level. The highest relative mycorrhizal dependency occurred with the inoculation of native mycorrhizal fungi. Plants with mycorrhizal fungi did not respond to phosphorus addition above 50 mg kg-1. Mangaba tree is highly dependent on mycorrhiza, but the degree of dependency varies according to phosphorus levels and fungal inocula. In general, mangaba tree is more responsive to mycorrhizal fungi inoculation than to phosphorus addition.O objetivo deste trabalho foi avaliar a dependência micorrízica de mudas de mangaba (Hancornia speciosa, em doses crescentes de fósforo. O delineamento experimental foi inteiramente casualizado, em arranjo fatorial 4´5 com três inóculos de fungos micorrízicos - Gigaspora margarita, Glomus etunicatum, ou uma mistura de espécies de fungos micorrízicos nativos (Acaulospora longula, Glomus clarum, Gigaspora albida e Paraglomus sp. -, e um controle não micorrízico, combinados a cinco doses de fósforo no substrato: 0, 25, 50, 75 e 100 mg kg-1. Após 180 dias, as mudas com inoculação dos fungos micorrízicos nativos produziram mais biomassa seca de parte aérea e raízes e apresentaram

  16. Dose dependence of the microstructural evolution in neutron-irradiated austenitic stainless steel

    International Nuclear Information System (INIS)

    Zinkle, S.J.; Maziasz, P.J.; Stoller, R.E.

    1993-01-01

    Microstructural data on the evolution of the dislocation loop, cavity, and precipitate populations in neutron-irradiated austenitic stainless steels are reviewed in order to estimate the displacement damage levels needed to achieve the 'steady state' condition. The microstructural data can be conveniently divided into two temperature regimes. In the low temperature regime (below about 200 degrees C) the microstructure of austenitic stainless steel is dominated by 'black spot' defect clusters and faulted interstitial dislocation loops. The dose needed to approach saturation of the loop and defect cluster densities is generally on the order of 1 displacement per atom (dpa) in this regime. In the high temperature regime (∼300 to 700 degrees C), cavities, precipitates, loops and network dislocations are all produced during irradiation; doses in excess of 10 dpa are generally required to approach a 'steady state' microstructural condition. Due to complex interactions between the various microstructural components that form during irradiation, a secondary transient regime is typically observed in commercial stainless steels during irradiation at elevated temperatures. This slowly evolving secondary transient may extend to damage levels in excess of 50 dpa in typical 300-series stainless steels, and to >100 dpa in radiation-resistant developmental steels. The detailed evolution of any given microstructural component in the high-temperature regime is sensitive to slight variations in numerous experimental variables, including heat-to-heat composition changes and neutron spectrum

  17. Co-administration of morphine and gabapentin leads to dose dependent synergistic effects in a rat model of postoperative pain

    DEFF Research Database (Denmark)

    Papathanasiou, Theodoros; Juul, Rasmus Vestergaard; Heegaard, Anne-Marie

    2016-01-01

    dose combinations and investigate whether co-administration leads to synergistic effects in a preclinical model of postoperative pain. The pharmacodynamic effects of morphine (1, 3 and 7 mg/kg), gabapentin (10, 30 and 100 mg/kg) or their combination (9 combinations in total) were evaluated in the rat...... plantar incision model using an electronic von Frey device. The percentage of maximum possible effect (%MPE) and the area under the response curve (AUC) were used for evaluation of the antihyperalgesic effects of the drugs. Identification of synergistic interactions was based on Loewe additivity response...... surface analyses. The combination of morphine and gabapentin resulted in synergistic antihyperalgesic effects in a preclinical model of postoperative pain. The synergistic interactions were found to be dose dependent and the increase in observed response compared to the theoretical additive response...

  18. Tl response of KMgF3 :Lu+PTFE depending on the dose of gamma radiation of 60Co

    International Nuclear Information System (INIS)

    Lopez, A.; Gonzalez, P.R.; Furetta, C.; Azorin, J; Rivera, T.; Sepulveda, F.

    2002-01-01

    Due to the great interest in Tl dosimetry for measuring the levels of radiation doses, as environmental as in the different medical radiation applications in different laboratories of the World it is continued in the searching of new Tl materials with optimum dosimetric characteristics and low cost. In this work the obtained results when irradiating Tl dosemeters of KMgF 3 :Lu + PTFE with gamma radiation of 60 Co are presented. Such results showed that this material presents linearity of response depending on the dose between 0.016 to 100 Gy. Although it is continued with the characterization tests it is able to say that this Tl new material can be used for dosimetric aims. (Author)

  19. Time-dependent recovery of in vivo binding sites after drug dosing: A method for radiotracer evaluation

    International Nuclear Information System (INIS)

    Kilbourn, Michael R.

    1997-01-01

    The recovery of in vivo binding sites for (±)-α-[ 11 C]methoxytetrabenazine, a radioligand for the monoamine vesicular transporter (VMAT2), was determined in mouse brain at various times following a pharmacological dose of tetrabenazine. Concentrations of in vivo radioligand binding sites progressively increased and had reached control values by 8.5 h, and this recovery was consistent with the pharmacokinetics of the competing drug tetrabenazine and its active metabolite, dihydrotetrabenazine. This study demonstrates a simple experimental protocol of using a single dose of a reversible competing drug and time-dependent measurements of in vivo binding of a radioligand. This protocol is suitable for testing the sensitivity of an in vivo radiotracer for measurement of varying concentrations of in vivo binding sites

  20. Effects of different doses of glucose and insulin on morphine state-dependent memory of passive avoidance in mice.

    Science.gov (United States)

    Jafari, M R; Zarrindast, M R; Djahanguiri, B

    2004-10-01

    Behavioral effects of morphine, including its effect on memory, have been demonstrated to be influenced by glucose pretreatment. The measurement of step-down latency in passive avoidance has been used to study memory in laboratory animals. The pre-training injection of 5 mg/kg morphine impaired memory, which was restored when 24 h later the same dose of the drug was administered. To investigate the effects of glucose and insulin alone or in combination with morphine, on pre-test day, on memory recall in mice. The effects of different doses of glucose (50, 100, and 200 mg/kg, IP) and insulin (5, 10, and 20 IU/kg, IP) alone or in combination with morphine, have been studied in mice. The blood glucose level and locomotor activity of the animals were also measured. Although the administration of glucose alone showed no effect on morphine-induced memory impairment, its co-administration with morphine resulted in a significant and dose-dependent memory enhancement compared with the effects of morphine administration alone. Like glucose, the administration of different doses of insulin alone produced no change in the memory, but when the drug was co-administered with morphine, it significantly reduced morphine-induced memory retrieval. The effect of insulin was the opposite of glucose. None of the animals subjected to insulin treatment showed convulsions. Glucose is suggested to increase, on the test day, the morphine-induced memory enhancement by three different mechanisms: cholinergic or opioidergic modulations, or regulation of the ATP-dependent potassium channels.

  1. Effect of low-dose heparin on urinary albumin excretion in insulin-dependent diabetes mellitus

    DEFF Research Database (Denmark)

    Myrup, B; Hansen, P M; Jensen, T

    1995-01-01

    We investigated the effect of heparin on urinary albumin excretion in patients with insulin-dependent diabetes mellitus. 39 patients with persistent urinary albumin excretion of 30-300 mg/24 h were randomly treated for 3 months with subcutaneous injections twice daily of isotonic saline, 5000 IU...

  2. Effect of low-dose heparin on urinary albumin excretion in insulin-dependent diabetes mellitus

    NARCIS (Netherlands)

    Myrup, B.; Hansen, P.M.; Jensen, T.; Kofoed-Enevoldsen, A.; Feldt-Rasmussen, B.; Gram, J.; Kluft, C.; Jespersen, J.; Deckert, T.

    1995-01-01

    We investigated the effect of heparin on urinary albumin excretion in patients with insulin-dependent diabetes mellitus. 39 patients with persistent urinary albumin excretion of 30-300 mg/24 h were randomly treated for 3 months with subcutaneous injections twice daily of isotonic saline, 5000 IU

  3. Age, Dose, and Time-Dependency of Plasma and Tissue Distribution of Deltamethrine in Immature Rats

    Science.gov (United States)

    The major objective of this project was to characterize the systemic disposition of the pyrethroid, deltamethrin (DLT), in immature rats, with emphasis on the age-dependence of target organ (brain) dosimetry. Postnatal day (PND) 10, 21, and 40 male Sprague-Dawley rats received 0...

  4. Determination of dose correction factor for energy and directional dependence of the MOSFET dosimeter in an anthropomorphic phantom

    International Nuclear Information System (INIS)

    Cho, Sung Koo; Choi, Sang Hyoun; Kim, Chan Hyeong; Na, Seong Ho

    2006-01-01

    In recent years, the MOSFET dosimeter has been widely used in various medical applications such as dose verification in radiation therapeutic and diagnostic applications. The MOSFET dosimeter is, however, mainly made of silicon and shows some energy dependence for low energy photons. Therefore, the MOSFET dosimeter tends to overestimate the dose for low energy scattered photons in a phantom. This study determines the correction factors to compensate these dependences of the MOSFET dosimeter in ATOM phantom. For this, we first constructed a computational model of the ATOM phantom based on the 3D CT image data of the phantom. The voxel phantom was then implemented in a Monte Carlo simulation code and used to calculate the energy spectrum of the photon field at each of the MOSFET dosimeter locations in the phantom. Finally, the correction factors were calculated based on the energy spectrum of the photon field at the dosimeter locations and the pre-determined energy and directional dependence of the MOSFET dosimeter. Our result for 60 Co and 137 Cs photon fields shows that the correction factors are distributed within the range of 0.89 and 0.97 considering all the MOSFET dosimeter locations in the phantom

  5. Sex-dependent behavioral changes in rat offspring after in utero administration of a single low dose PBDE 47

    Energy Technology Data Exchange (ETDEWEB)

    Kuriyama, S.N.; Talsness, C.E.; Chahoud, I. [Charite Univ. Medical School Berlin (Germany). Inst. of Clinical Pharmacology and Toxicology, Dept. Toxicology, Campus Benjamin Franklin

    2004-09-15

    Increasing levels of polybrominated diphenyl ethers (PBDEs) in environmental and human samples has resulted in intensive discussion regarding possible hazard identification and risk assessment in the last years. In rodents, exposure to PBDE mixtures or single congeners has resulted in a mixed induction of CYP450- dependent enzymes, showing increased activity of hepatic EROD and PROD. In addition, genotoxicity has been observed in recombination assays, and neurotoxicity has been reported in mice exposed during development. Acute and sub-chronic exposures of mice and rats to a PBDE mixture (DE-71) cause dose-dependent reductions in serum concentrations of thyroxin (T4), and stressinduced elevations in plasma corticosterone. Further, some hydroxylated metabolites of PBDE congeners exhibit a higher potency in vivo than T4 in competitive binding to human transthyretin (TTR), the transport protein mediating transfer of thyroid hormones across the placenta and into the brain. The available information in the literature clearly indicates that PBDEs are potent neurotoxicants, causing effects at doses lower than that able to disrupt thyroid hormone profiles and change CYP 450 activities. Neurobehavior effects, which includes defects in learning and memory, and changes in nicotinic receptors were found at doses starting at 0.45 ppm in mouse (9). The congeners, PBDE 47 and PBDE 99, have also been shown to cause permanent aberrations in spontaneous behavior in mice which was more pronounced with increasing age. PBDE 47 is the most predominant congener found in environmental and human samples, including human breast milk. Its presence in breast milk highlights the importance of evaluating possible effects following early developmental exposure and because this period represents a critical time which an organism is extremely susceptible to minor changes in hormonal milieu. Variances in terms of time point and concentration of exposure to steroids can lead to an organizational

  6. The effect of chronic corticosterone on fear learning and memory depends on dose and the testing protocol.

    Science.gov (United States)

    Marks, W N; Fenton, E Y; Guskjolen, A J; Kalynchuk, L E

    2015-03-19

    Chronic exposure to the stress hormone corticosterone (CORT) is known to alter plasticity within hippocampal and amygdalar circuits that mediate fear learning and memory. The purpose of this experiment was to clarify the effects of chronic CORT on Pavlovian fear conditioning, which is dependent on intact hippocampal and amygdalar activity. In particular, we assessed whether the effect of chronic CORT on fear learning and memory is influenced by two factors-the dose of CORT and the order in which rats are tested for freezing to context versus tone cues. Male Long-Evans rats received low-dose CORT (5mg/kg), high-dose CORT (40mg/kg), or vehicle injections once daily for 21days. On day 22, the rats were trained in a fear-conditioning paradigm. On days 23 and 24, the rats were tested for the retrieval of fear memories to context and tone cues in a counterbalanced way-half the rats received context testing on day 23 and then tone testing on day 24 and half the rats received tone testing on day 23 followed by context testing on day 24. Our results revealed dose-dependent effects of CORT on memory retrieval: Rats injected with high-dose CORT froze significantly more than control rats to both context and tone cues regardless of what testing day these cues were presented. However, rats injected with low-dose CORT froze significantly more than control rats to tone cues only. We also found an order effect in that the effects of CORT on freezing were greater on the second day of testing, regardless of whether that testing was to context or tones cues. This order effect may be due to a lack of extinction in the CORT rats. Overall, these results suggest a relationship between stress intensity and testing conditions that should be taken into account when assessing the effect of stress on fear memories. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Dose-dependent effect of ghrelin on gastric emptying in rats and the related mechanism of action

    Directory of Open Access Journals (Sweden)

    Shu-Guang Cao

    2016-03-01

    Full Text Available The aim of this study was to investigate the dose-dependent effect of ghrelin on gastric emptying in rats and the related mechanism of action. Sixty Wistar rats were randomized into control and test groups, which respectively received intraperitoneal injection of normal saline and ghrelin at different doses (0.5 nmol/kg, 1.0 nmol/kg, 1.5 nmol/kg, 2.0 nmol/kg, and 2.5 nmol/kg. After 45 minutes, all rats were gavaged with semisolid paste. The gastric emptying rate was determined 30 minutes later, and the plasma cholecystokinin level was tested by radioimmunoassay. The mean gastric emptying rate in the test groups was significantly higher than in the control group (38.24 ± 7.15% and 27.18 ± 2.37%, respectively, p < 0.05. Medium and high doses of ghrelin (1.0 nmol/kg, 1.5 nmol/kg, 2.0 nmol/kg, and 2.5 nmol/kg, but not low dose (0.5 nmol/kg, accelerated the gastric emptying. In addition, the plasma cholecystokinin level in the test groups was significantly higher than in the control group (p < 0.01. The gastric emptying rate was positively correlated with the plasma cholecystokinin level (p < 0.01. Intraperitoneal injection of ghrelin at medium and high doses significantly accelerated gastric emptying in rats.

  8. Radiation dose dependent risk of liver cancer mortality in the German uranium miners cohort 1946–2003

    International Nuclear Information System (INIS)

    Dufey, F; Walsh, L; Sogl, M; Tschense, A; Schnelzer, M; Kreuzer, M

    2013-01-01

    An increased risk of mortality from primary liver cancers among uranium miners has been observed in various studies. An analysis of the data from a German uranium miner cohort (the ‘Wismut cohort’) was used to assess the relationship with ionising radiation. To that end the absorbed organ dose due to high and low linear energy transfer radiation was calculated for 58 987 miners with complete information on radiation exposure from a detailed job–exposure matrix. 159 deaths from liver cancer were observed in the follow-up period from 1946 to 2003. Relative risk models with either linear or categorical dependence on high and low linear energy transfer radiation liver doses were fitted by Poisson regression, stratified on age and calendar year. The linear trend of excess relative risk in a model with both low and high linear transfer radiation is −0.8 (95% confidence interval (CI): −3.7, 2.1) Gy −1 and 48.3 (95% CI: −32.0, 128.6) Gy −1 for low and high linear energy transfer radiation, respectively, and thus not statistically significant for either dose. The increase of excess relative risk with equivalent liver dose is 0.57 (95% CI: −0.69, 1.82) Sv −1 . Adjustment for arsenic only had a negligible effect on the radiation risk. In conclusion, there is only weak evidence for an increase of liver cancer mortality with increasing radiation dose in the German uranium miners cohort considered. However, both a lack of statistical power and potential misclassification of primary liver cancer are issues. (paper)

  9. Pressureless mechanical induction of stem cell differentiation is dose and frequency dependent.

    Directory of Open Access Journals (Sweden)

    Roland Fuhrer

    Full Text Available Movement is a key characteristic of higher organisms. During mammalian embryogenesis fetal movements have been found critical to normal tissue development. On the single cell level, however, our current understanding of stem cell differentiation concentrates on inducing factors through cytokine mediated biochemical signaling. In this study, human mesenchymal stem cells and chondrogenesis were investigated as representative examples. We show that pressureless, soft mechanical stimulation precipitated by the cyclic deformation of soft, magnetic hydrogel scaffolds with an external magnetic field, can induce chondrogenesis in mesenchymal stem cells without any additional chondrogenesis transcription factors (TGF-β1 and dexamethasone. A systematic study on the role of movement frequency revealed a classical dose-response relationship for human mesenchymal stem cells differentiation towards cartilage using mere mechanical stimulation. This effect could even be synergistically amplified when exogenous chondrogenic factors and movement were combined.

  10. A capacitively coupled dose-rate-dependent transient upset mechanism in a bipolar memory

    International Nuclear Information System (INIS)

    Turfler, R.M.; Pease, R.L.; Dinger, G.; Armstrong, B.

    1992-01-01

    This paper reports on a pattern sensitivity that was observed in the threshold dose rate response of a bipolar 16K PROM for radiation pulse widths of 20-100 ns. For the worst case pattern, the upset threshold was a factor of three lower than for the commonly used checkerboard pattern. The mechanism for this pattern sensitivity was found to be a capacitively coupled voltage transient on a sensitive node which caused a low-to-high transition at the output. A design fix was implemented to significantly alter the ratio of the two parasitic capacitances in a capacitive divider which reduced the amplitude of the voltage transient at the sensitive node. It was demonstrated that in the redesign, the pattern sensitivity was eliminated

  11. Dose-rate and temperature dependent statistical damage accumulation model for ion implantation into silicon

    Energy Technology Data Exchange (ETDEWEB)

    Hernandez-Mangas, J.M. [Dpto. de Electricidad y Electronica, Universidad de Valladolid, ETSI Telecomunicaciones, Campus Miguel Delibes, Valladolid E-47011 (Spain)]. E-mail: jesus.hernandez.mangas@tel.uva.es; Arias, J. [Dpto. de Electricidad y Electronica, Universidad de Valladolid, ETSI Telecomunicaciones, Campus Miguel Delibes, Valladolid E-47011 (Spain); Marques, L.A. [Dpto. de Electricidad y Electronica, Universidad de Valladolid, ETSI Telecomunicaciones, Campus Miguel Delibes, Valladolid E-47011 (Spain); Ruiz-Bueno, A. [Dpto. de Electricidad y Electronica, Universidad de Valladolid, ETSI Telecomunicaciones, Campus Miguel Delibes, Valladolid E-47011 (Spain); Bailon, L. [Dpto. de Electricidad y Electronica, Universidad de Valladolid, ETSI Telecomunicaciones, Campus Miguel Delibes, Valladolid E-47011 (Spain)

    2005-01-01

    Currently there are extensive atomistic studies that model some characteristics of the damage buildup due to ion irradiation (e.g. L. Pelaz et al., Appl. Phys. Lett. 82 (2003) 2038-2040). Our interest is to develop a novel statistical damage buildup model for our BCA ion implant simulator (IIS) code in order to extend its ranges of applicability. The model takes into account the abrupt regime of the crystal-amorphous transition. It works with different temperatures and dose-rates and also models the transition temperature. We have tested it with some projectiles (Ge, P) implanted into silicon. In this work we describe the new statistical damage accumulation model based on the modified Kinchin-Pease model. The results obtained have been compared with existing experimental results.

  12. Dose-rate and temperature dependent statistical damage accumulation model for ion implantation into silicon

    International Nuclear Information System (INIS)

    Hernandez-Mangas, J.M.; Arias, J.; Marques, L.A.; Ruiz-Bueno, A.; Bailon, L.

    2005-01-01

    Currently there are extensive atomistic studies that model some characteristics of the damage buildup due to ion irradiation (e.g. L. Pelaz et al., Appl. Phys. Lett. 82 (2003) 2038-2040). Our interest is to develop a novel statistical damage buildup model for our BCA ion implant simulator (IIS) code in order to extend its ranges of applicability. The model takes into account the abrupt regime of the crystal-amorphous transition. It works with different temperatures and dose-rates and also models the transition temperature. We have tested it with some projectiles (Ge, P) implanted into silicon. In this work we describe the new statistical damage accumulation model based on the modified Kinchin-Pease model. The results obtained have been compared with existing experimental results

  13. Dose-Dependent Response to 3-Nitrobenzanthrone Exposure in Human Urothelial Cancer Cells.

    Science.gov (United States)

    Pink, Mario; Verma, Nisha; Zerries, Anna; Schmitz-Spanke, Simone

    2017-10-16

    A product of incomplete combustion of diesel fuel, 3-nitrobenzanthrone (3-NBA), has been classified as a cancer-causing substance. It first gained attention as a potential urinary bladder carcinogen due to the presence of its metabolite in urine and formation of DNA adducts. The aim of the present study was to characterize the dose-response relationship of 3-NBA in human urothelial cancer cell line (RT4) exposed to concentrations ranging from 0.0003 μM (environmentally relevant) to 80 μM by utilizing toxicological and metabolomic approaches. We observed that the RT4 cells were capable of bioactivation of 3-NBA within 30 min of exposure. Activity measurements of various enzymes involved in the conversion of 3-NBA in RT4 cells demonstrated NAD(P)H:quinone oxidoreductase (NQO1) as the main contributor for its bioactivation. Moreover, cytotoxicity assessment exhibited an initiation of adaptive mechanisms at low dosages, which diminished at higher doses, indicating that the capacity of these mechanisms no longer suffices, resulting in increased levels of intracellular reactive oxygen species, reduced proliferation, and hyperpolarisation of the mitochondrial membrane. To characterize the underlying mechanisms of this cellular response, the metabolism of 3-NBA and metabolomic changes in the cells were analyzed. The metabolomic analysis of the cells (0.0003, 0.01, 0.08, 10, and 80 μM 3-NBA) showed elevated levels of various antioxidants at low concentrations of 3-NBA. However, at higher exposure concentrations, it appeared that the cells reprogrammed their metabolism to maintain the cell homeostasis via activation of pentose phosphate pathway (PPP).

  14. Dose-dependent suppression by ethanol of transient auditory 40-Hz response.

    Science.gov (United States)

    Jääskeläinen, I P; Hirvonen, J; Saher, M; Pekkonen, E; Sillanaukee, P; Näätänen, R; Tiitinen, H

    2000-02-01

    Acute alcohol (ethanol) challenge is known to induce various cognitive disturbances, yet the neural basis of the effect is poorly known. The auditory transient evoked gamma-band (40-Hz) oscillatory responses have been suggested to be associated with various perceptual and cognitive functions in humans; however, alcohol effects on auditory 40-Hz responses have not been investigated to date. The objective of the study was to test the dose-related impact of alcohol on auditory transient evoked 40-Hz responses during a selective-attention task. Ten healthy social drinkers ingested, in four separate sessions, 0.00, 0. 25, 0.50, or 0.75 g/kg of 10% (v/v) alcohol solution. The order of the sessions was randomized and a double-blind procedure was employed. During a selective attention task, 300-Hz standard and 330-Hz deviant tones were presented to the left ear, and 1000-Hz standards and 1100-Hz deviants to the right ear of the subjects (P=0. 425 for each standard, P=0.075 for each deviant). The subjects attended to a designated ear, and were to detect the deviants therein while ignoring tones to the other ear. The auditory transient evoked 40-Hz responses elicited by both the attended and unattended standard tones were significantly suppressed by the 0.50 and 0.75 g/kg alcohol doses. Alcohol suppresses auditory transient evoked 40-Hz oscillations already with moderate blood alcohol concentrations. Given the putative role of gamma-band oscillations in cognition, this finding could be associated with certain alcohol-induced cognitive deficits.

  15. Insulin is essential for in vitro chondrogenesis of mesenchymal progenitor cells and influences chondrogenesis in a dose-dependent manner.

    Science.gov (United States)

    Mueller, Michael B; Blunk, Torsten; Appel, Bernhard; Maschke, Angelika; Goepferich, Achim; Zellner, Johannes; Englert, Carsten; Prantl, Lukas; Kujat, Richard; Nerlich, Michael; Angele, Peter

    2013-01-01

    Insulin is a commonly used additive in chondrogenic media for differentiating mesenchymal stem cells (MSCs). The indispensability of other bioactive factors like TGF-β or dexamethasone in these medium formulations has been shown, but the role of insulin is unclear. The purpose of this study was to investigate whether insulin is essential for MSC chondrogenesis and if there is a dose-dependent effect of insulin on MSC chondrogenesis. We cultivated human MSCs in pellet culture in serum-free chondrogenic medium with insulin concentrations between 0 and 50 μg/ml and assessed the grade of chondrogenic differentiation by histological evaluation and determination of glycosaminoglycan (GAG), total collagen and DNA content. We further tested whether insulin can be delivered in an amount sufficient for MSC chondrogenesis via a drug delivery system in insulin-free medium. Chondrogenesis was not induced by standard chondrogenic medium without insulin and the expression of cartilage differentiation markers was dose-dependent at insulin concentrations between 0 and 10 μg/ml. An insulin concentration of 50 μg/ml had no additional effect compared with 10 μg/ml. Insulin was delivered by a release system into the cell culture under insulin-free conditions in an amount sufficient to induce chondrogenesis. Insulin is essential for MSC chondrogenesis in this system and chondrogenic differentiation is influenced by insulin in a dose-dependent manner. Insulin can be provided in a sufficient amount by a drug delivery system. Therefore, insulin is a suitable and inexpensive indicator substance for testing drug release systems in vitro.

  16. Size- and dose-dependent toxicity of cellulose nanocrystals (CNC) on human fibroblasts and colon adenocarcinoma.

    Science.gov (United States)

    Hanif, Zahid; Ahmed, Farrukh R; Shin, Seung Won; Kim, Young-Kee; Um, Soong Ho

    2014-07-01

    A controlled preparation of cellulose nanocrystals of different sizes and shapes has been carried out by acid hydrolysis of microcrystalline cellulose. The size- and concentration-dependent toxicity effects of the resulting cellulose nanocrystals were evaluated against two different cell lines, NIH3T3 murine embryo fibroblasts and HCT116 colon adenocarcinoma. It could serve as a therapeutic platform for cancer treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Change of notch impact strength depending on radiation dose and test temperature

    Directory of Open Access Journals (Sweden)

    Martin Bednarik

    2017-01-01

    Full Text Available The main purpose of this paper has been determine the effect of radiation crosslinking on the notch impact strength of polyamides filled with fiberglass. These properties were examined in dependence on the dosage of the ionizing beta radiation (non-irradiated samples and those irradiated by dosage 66 and 132 kGy were compared and on the test temperature (23–150 °C.

  18. Towards the development of lipid multilayer microarrays for dose dependent in vitro delivery and screening

    Science.gov (United States)

    Kusi-Appiah, Aubrey Emmanuel

    Screening for effects of small molecules on cells grown in culture is a well-established method for drug discovery and testing, and faster throughput at lower cost is needed especially for lipophilic materials. Small-molecule arrays present a promising approach. However, it has been a challenge to use them to obtain quantitative surface based dose-response curves in vitro, especially for lipophilic compounds. This thesis first introduces a simple novel method of surface-mediated delivery of drugs to cells from a microarray of phospholipid multilayers (layers thicker than a bilayer) encapsulating small molecules. The capability of controlling the dosage of the lipophilic molecules delivered to cells using the lipid multilayer microarray assay is further demonstrated using the nanointaglio printing method. This control enabled the variation of the volumes of surface supported lipid micro- and nanostructure arrays fabricated with nanointaglio. The volumes of the lipophilic drug-containing nanostructures were determined using a fluorescence microscope calibrated by atomic-force microscopy. The surface supported lipid volume information was used to obtain EC-50 values for the response of HeLa cells to treatment with three FDA-approved lipophilic anticancer drugs, docetaxel, imiquimod and triethylenemelamine, which were found to be significantly different from neat lipid controls. Features with sub-cellular lateral dimensions were found to be necessary to obtain normal cell adhesion with HeLa cells. Comparison of the microarray data to dose-response curves for the same drugs delivered liposomally from solution revealed quantitative differences in the efficacy values, which may be explained in terms of cell-adhesion playing a more important role in the surface-based assay. Finally, solution encapsulation was done for a library of hydrophilic silicon nanocrystals in order to set a solution standard for comparison with future surface supported delivery of the library. The

  19. Radiation dose-dependent change in brain 1H-MRS

    International Nuclear Information System (INIS)

    Matsushima, Shigeru; Muroka, Mamoru; Uchiyama, Yukio; Morita, Kozo; Nomoto, Yoshihito; Kinosada, Yasutomi.

    1994-01-01

    We have investigated the usefulness of 1 H-magnetic resonance spectroscopy ( 1 H-MRS) for the assessment of acute radiation damage of the human brain. Nineteen patients were treated with the whole brain irradiation. Biochemical changes in white matter were measured by in vivo 1 H-MRS. The measurement was performed 1 or 2 times in each case at radiation doses ranging from 0 to 44.4 Gy with conventional fractionation (2 Gy per fraction, once a day) or accelerated hyperfractionation (1.5 Gy per fraction, twice a day). For the measurement of 1 H-MRS, 1.5T whole body MR system was used and stimulated echo acquisition mode (STEAM) with chemical shift selective (CHESS) pulse was applied. Volume of the interest (VOI) was 2.5 x 2.5 x 2.5 cm 3 , and the repetition time and echo time were 2000 ms and 272 ms, respectively. The acute radiation damage of the brain was evaluated by the change of peak area ratio (PAR) of choline, creatine and N-acetylaspartate (NAA). 1 H-MR spectra obtained before irradiation were different from those observed during irradiation. There were statistically significant (p 1 H-MRS can be useful for assessment of acute radiation damage. (author)

  20. Ultraviolet radiation induces dose-dependent pigment dispersion in crustacean chromatophores.

    Science.gov (United States)

    Gouveia, Glauce Ribeiro; Lopes, Thaís Martins; Neves, Carla Amorim; Nery, Luiz Eduardo Maia; Trindade, Gilma Santos

    2004-10-01

    Pigment dispersion in chromatophores as a response to UV radiation was investigated in two species of crustaceans, the crab Chasmagnathus granulata and the shrimp Palaemonetes argentinus. Eyestalkless crabs and shrimps maintained on either a black or a white background were irradiated with different UV bands. In eyestalkless crabs the significant minimal effective dose inducing pigment dispersion was 0.42 J/cm(2) for UVA and 2.15 J/cm(2) for UVB. Maximal response was achieved with 10.0 J/cm(2) UVA and 8.6 J/cm(2) UVB. UVA was more effective than UVB in inducing pigment dispersion. Soon after UV exposure, melanophores once again reached the initial stage of pigment aggregation after 45 min. Aggregated erythrophores of shrimps adapted to a white background showed significant pigment dispersion with 2.5 J/cm(2) UVA and 0.29 J/cm(2) UVC. Dispersed erythrophores of shrimps adapted to a black background did not show any significant response to UVA, UVB or UVC radiation. UVB did not induce any significant pigment dispersion in shrimps adapted to either a white or a black background. As opposed to the tanning response, which only protects against future UV exposure, the pigment dispersion response could be an important agent protecting against the harmful effects of UV radiation exposure.

  1. Dose dependent transfer of 203lead to milk and tissue uptake in suckling offspring studied in rats and mice

    International Nuclear Information System (INIS)

    Palminger Hallen, I.; Oskarsson, A.

    1993-01-01

    The dose-dependent transfer of 203 Pb to milk and uptake in suckling rats and mice during a three-day nursing period was studied. On day 14 of lactation, the dams were administered a single intravenous dose of lead, labelled with 203 Pb, in four or five doses from 0.0005 to 2.0 mg Pb/kg b.wt. There was a linear relationship between Pb levels in plasma and milk of both species. The Pb milk: plasma ratios at 24 hr after administration were 119 and 89 in mice and rats, respectively. At 72 hr the Pb milk: plasma ratio had decreased to 72 in mice and 35 in rats. The tissue levels of lead in the suckling rats and mice were also linearly correlated with lead concentration in milk at 72 hr, showing that milk could be used as an indicator of lead exposure to the suckling offspring. It is concluded that lead is transported into rat and mouse milk to a very high extent and the excretion into milk is more efficient in mice than in rats. On the other hand, rat pups had higher lead levels in tissues than mice pups, which might be due to a higher bioavailability and/or a lower excretion of lead in rat pups. Thus, lead in breast milk could be used as a biological indicator of lead exposure in the mother as well as in the suckling offspring. (au) (38 refs.)

  2. Regulation of number and size of digits by posterior Hox genes: a dose-dependent mechanism with potential evolutionary implications.

    Science.gov (United States)

    Zákány, J; Fromental-Ramain, C; Warot, X; Duboule, D

    1997-12-09

    The proper development of digits, in tetrapods, requires the activity of several genes of the HoxA and HoxD homeobox gene complexes. By using a variety of loss-of-function alleles involving the five Hox genes that have been described to affect digit patterning, we report here that the group 11, 12, and 13 genes control both the size and number of murine digits in a dose-dependent fashion, rather than through a Hox code involving differential qualitative functions. A similar dose-response is observed in the morphogenesis of the penian bone, the baculum, which further suggests that digits and external genitalia share this genetic control mechanism. A progressive reduction in the dose of Hox gene products led first to ectrodactyly, then to olygodactyly and adactyly. Interestingly, this transition between the pentadactyl to the adactyl formula went through a step of polydactyly. We propose that in the distal appendage of polydactylous short-digited ancestral tetrapods, such as Acanthostega, the HoxA complex was predominantly active. Subsequent recruitment of the HoxD complex contributed to both reductions in digit number and increase in digit length. Thus, transition through a polydactylous limb before reaching and stabilizing the pentadactyl pattern may have relied, at least in part, on asynchronous and independent changes in the regulation of HoxA and HoxD gene complexes.

  3. Short communication: Experimental toxocarosis in Chinese Kun Ming mice: Dose-dependent larval distribution and modulation of immune responses.

    Science.gov (United States)

    Ma, Guangxu; Tan, Yancai; Hu, Ling; Luo, Yongfang; Zhu, Honghong; Zhou, Rongqiong

    2015-12-01

    Toxocarosis is an important parasitic zoonosis which is mainly caused by the infective larvae of Toxocara canis. To identify whether there are correlations among the infectious dose, the larval migrans and immune modulation in inbred Chinese Kun Ming (KM) mice, experimental infections were carried out with a range of dosages of 100, 500, 1000, 2000, and 3000 embryonated eggs (EE). Pathogenic reactions were observed in terms of physical and central nervous symptoms. Distributions of T. canis larvae in liver, lung, kidney, heart and brain organs were respectively detected by scanning tissue sections. Moreover, quantitative real-time PCR was employed to identify the variations of Th2 immune response. The results showed that high inocula resulted in advanced larval emergences and arrested migrations in liver, lung, kidney and brain. However, no larvae were found in any of the histological sections of heart tissues. Higher levels of interleukin (IL)-4, IL-5, and IL-10 were detected along with the increasing inoculation doses, but the heaviest inoculum (3000 EE in this study) resulted in the sharp reduction of these ILs. Although no neurological symptoms or mortalities were noticed, these results indicated dose-dependent distribution patterns and immune regulations of T. canis larvae infection in KM mice. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Lack of Radiation Dose or Quality Dependence of Epithelial-to-Mesenchymal Transition (EMT) Mediated by Transforming Growth Factor β

    International Nuclear Information System (INIS)

    Andarawewa, Kumari L.; Costes, Sylvain V.; Fernandez-Garcia, Ignacio; Chou, William S.; Ravani, Shraddha A.; Park, Howard; Barcellos-Hoff, Mary Helen

    2011-01-01

    Purpose: Epithelial-to-mesenchymal transition (EMT) is a phenotype that alters cell morphology, disrupts morphogenesis, and increases motility. Our prior studies have shown that the progeny of human mammary epithelial cells (HMECs) irradiated with 2 Gy undergoes transforming growth factor β (TGF-β)-mediated EMT. In this study we determined whether radiation dose or quality affected TGF-β-mediated EMT. Methods and Materials: HMECs were cultured on tissue culture plastic or in Matrigel (BD Biosciences, San Jose, CA) and exposed to low or high linear energy transfer (LET) and TGF-β (400 pg/mL). Image analysis was used to measure membrane-associated E-cadherin, a marker of functional epithelia, or fibronectin, a product of mesenchymal cells, as a function of radiation dose and quality. Results: E-cadherin was reduced in TGF-β-treated cells irradiated with low-LET radiation doses between 0.03 and 2 Gy compared with untreated, unirradiated cells or TGF-β treatment alone. The radiation quality dependence of TGF-β-mediated EMT was determined by use of 1 GeV/amu (gigaelectron volt / atomic mass unit) 56 Fe ion particles at the National Aeronautics and Space Administration's Space Radiation Laboratory. On the basis of the relative biological effectiveness of 2 for 56 Fe ion particles' clonogenic survival, TGF-β-treated HMECs were irradiated with equitoxic 1-Gy 56 Fe ion or 2-Gy 137 Cs radiation in monolayer. Furthermore, TGF-β-treated HMECs irradiated with either high- or low-LET radiation exhibited similar loss of E-cadherin and gain of fibronectin and resulted in similar large, poorly organized colonies when embedded in Matrigel. Moreover, the progeny of HMECs exposed to different fluences of 56 Fe ion underwent TGF-β-mediated EMT even when only one-third of the cells were directly traversed by the particle. Conclusions: Thus TGF-β-mediated EMT, like other non-targeted radiation effects, is neither radiation dose nor quality dependent at the doses examined.

  5. Doxycycline-loaded nanotube-modified adhesives inhibit MMP in a dose-dependent fashion.

    Science.gov (United States)

    Palasuk, Jadesada; Windsor, L Jack; Platt, Jeffrey A; Lvov, Yuri; Geraldeli, Saulo; Bottino, Marco C

    2018-04-01

    This article evaluated the drug loading, release kinetics, and matrix metalloproteinase (MMP) inhibition of doxycycline (DOX) released from DOX-loaded nanotube-modified adhesives. DOX was chosen as the model drug, since it is the only MMP inhibitor approved by the U.S. Food and Drug Administration. Drug loading into the nanotubes was accomplished using DOX solution at distinct concentrations. Increased concentrations of DOX significantly improved the amount of loaded DOX. The modified adhesives were fabricated by incorporating DOX-loaded nanotubes into the adhesive resin of a commercial product. The degree of conversion (DC), Knoop microhardness, DOX release kinetics, antimicrobial, cytocompatibility, and anti-MMP activity of the modified adhesives were investigated. Incorporation of DOX-loaded nanotubes did not compromise DC, Knoop microhardness, or cell compatibility. Higher concentrations of DOX led to an increase in DOX release in a concentration-dependent manner from the modified adhesives. DOX released from the modified adhesives did not inhibit the growth of caries-related bacteria, but more importantly, it did inhibit MMP-1 activity. The loading of DOX into the nanotube-modified adhesives did not compromise the physicochemical properties of the adhesives and the released levels of DOX were able to inhibit MMP activity without cytotoxicity. Doxycycline released from the nanotube-modified adhesives inhibited MMP activity in a concentration-dependent fashion. Therefore, the proposed nanotube-modified adhesive may hold clinical potential as a strategy to preserve resin/dentin bond stability.

  6. Melatonin has dose-dependent effects on folliculogenesis, oocyte maturation capacity and steroidogenesis

    International Nuclear Information System (INIS)

    Adriaens, I.; Jacquet, P.; Cortvrindt, R.; Janssen, K.; Smitz, J.

    2006-01-01

    Chemo and/or radiotherapy applied to young cancer patients most often have severe effects upon female fertility. Today, few options are available to protect ovarian function in females. However, these options are either ineffective, belong to the field of experimental research or/and are not applicable to all patients. Drugs that could protect the oocyte and its surrounding feeder cells from damage can be of great importance. Melatonin, being an important indirect antioxidant and a powerful direct free radical scavenger could be such a reagent. This paper reports the direct effects of different melatonin concentrations (range: 1 nM to 2 mM) on folliculogenesis and oogenesis of in vitro cultured mouse ovarian follicles. Early secondary mouse follicles were cultured in vitro for 12 days under different melatonin regimes. Every fourth day, survival rates were scored, follicles were morphologically evaluated and medium was collected for steroid analyses. On day 12, in vitro ovulation was induced by hCG/EGF. Eighteen hours later, oocytes were measured, oocyte maturation was evaluated and normality of spindle and chromosomes ascertained. Results obtained in this study indicated that 2 mM melatonin is toxic. One mM negatively influenced oocyte maturation capacity. In the presence of 100 μM melatonin, androstenedione and progesterone were increased whereas estradiol was not influenced. Lower melatonin concentrations had no effect on the evaluated parameters. These data indicate an effect of melatonin on theca cell steroidogenesis. For prophylactic use, a dose of 10 μM could be suitable to reduce oxidative stress in cultured follicles

  7. Schistosoma mansoni: is acquired immunity induced by highly x-irradiated cercariae dependent on the size of the challenging dose

    International Nuclear Information System (INIS)

    Hsue, S.Y.; Hsue, H.F.; Osborne, J.W.; Johnson, S.C.

    1982-01-01

    A high degree of immunity, as shown by a 91% reduction of the number of worms recovered was found in five groups of mice that were immunized five times with highly X-irradiated cercariae and then challenged with 10, 20, 50, 100, or 500 normal Schistosoma mansoni cercariae. The results indicated that there were no significant differences in worm reduction in immunized mice challenged with different numbers of cercariae; consequently the immunity induced by this immunization method did not appear to be challenge-dose-dependent. However, the results also showed that when immunized mice were challenged with 500, 100, 50, 20, and 10 cercariae, 0, 13, 26, 56, and 68%, respectively, of the experimental animals were free of worms. Thus, the percentage of worm-negative cases increased as the number of challenge cercariae decreased. When viewed in this manner, the acquired immunity may be considered challenge-dose-dependent as well. If this method of vaccination is used for schistosomiasis control, we may anticipate that in both hypo- and hyperendemic areas, the intensity of infection and the severity of the disease will be reduced owing to a reduction in worms burdens, and in hypoendemic areas, there will be a number of worm-free cases

  8. Dependence of the bystander effect for micronucleus formation on dose of heavy-ion radiation in normal human fibroblasts

    International Nuclear Information System (INIS)

    Matsumoto, Yoshitaka; Hamada, Nobuyuki; Aoki-Nakano, Mizuho; Furusawa, Yoshiya; Funayama, Tomoo; Sakashita, Tetsuya; Kobayashi, Yasuhiko; Wada, Seiichi; Kakizaki, Takehiko

    2015-01-01

    Ionising radiation-induced bystander effects are well recognised, but its dependence on dose or linear energy transfer (LET) is still a matter of debate. To test this, 49 sites in confluent cultures of AG01522D normal human fibroblasts were targeted with microbeams of carbon (103 keV μm -1 ), neon (375 keV μm -1 ) and argon ions (1260 keV μm -1 ) and evaluated for the bystander-induced formation of micronucleus that is a kind of a chromosome aberration. Targeted exposure to neon and argon ions significantly increased the micronucleus frequency in bystander cells to the similar extent irrespective of the particle numbers per site of 1- 6. In contrast, the bystander micronucleus frequency increased with increasing the number of carbon-ion particles in a range between 1 and 3 particles per site and was similar in a range between 3 and 8 particles per site. These results suggest that the bystander effect of heavy ions for micronucleus formation depends on dose. (authors)

  9. [Value of desmopressin stimulation test and high dose dexamethasone suppression testin the etiologic diagnosis of ACTH dependent Cushing's syndrome].

    Science.gov (United States)

    Zhang, Weiwei; Yu, Yerong; Tan, Huiwen; Wang, Chun; Li, Jianwei; An, Zhenmei; Liu, Yuping

    2016-03-22

    To investigate the value of desmopressin (DDAVP) stimulation test and high dose dexamethasone suppression test (HDDST) in establishing the cause of ACTH dependent Cushing's syndrome. The clinical data of patients with ACTH dependent Cushing's syndrome at West China Hospital from January 1, 2010 to September 30, 2015 was analyzed. The sensitivity and specificity of DDAVP stimulation test, HDDST, and the diagnostic accordance rate when the two tests were combined, were evaluated based on the diagnostic gold standard. A total of 85 patients with Cushing's disease and 10 patients with ectopic ACTH syndrome were included. The sensitivity and specificity of DDAVP stimulation test were 87% and 5/5, respectively, whereas those of HDDST were 79% and 8/10, respectively. The standard high dose dexamethasone suppression test showed a higher sensitivity than overnight 8 mg dexamethasone suppression test. When the two tests had consistent results, the diagnostic accordance rate was 100%. DDAVP stimulation test and HDDST are both efficient modalities for the diagnosis of Cushing's Disease and ectopic ACTH syndrome. The accuracy of diagnosis can be further improved by combining the two tests.

  10. Dose and time-dependent effects of cyanide on thiosulfate sulfurtransferase, 3-mercaptopyruvate sulfurtransferase, and cystathionine λ-lyase activities.

    Science.gov (United States)

    Singh, Poonam; Rao, Pooja; Bhattacharya, Rahul

    2013-12-01

    We assessed the dose-dependent effect of potassium cyanide (KCN) on thiosulfate sulfurtransferase (TST), 3-mercaptopyruvate sulfurtransferase (3-MPST), and cystathionine λ-lyase (CST) activities in mice. The time-dependent effect of 0.5 LD50 KCN on cyanide level and cytochrome c oxidase (CCO), TST, 3-MPST, and CST activities was also examined. Furthermore, TST, 3-MPST, and CST activities were measured in stored mice cadavers. Hepatic and renal TST activity increased by 0.5 LD50 KCN but diminished by ≥2.0 LD50. After 0.5 LD50 KCN, the elevated hepatic cyanide level was accompanied by increased TST, 3-MPST, and CST activities, and CCO inhibition. Elevated renal cyanide level was only accompanied by increased 3-MPST activity. No appreciable change in enzyme activities was observed in mice cadavers. The study concludes that high doses of cyanide exert saturating effects on its detoxification enzymes, indicating their exogenous use during cyanide poisoning. Also, these enzymes are not reliable markers of cyanide poisoning in autopsied samples. © 2013 Wiley Periodicals, Inc.

  11. High-Dose Benzodiazepine Dependence: A Qualitative Study of Patients' Perceptions on Initiation, Reasons for Use, and Obtainment.

    Directory of Open Access Journals (Sweden)

    Michael Liebrenz

    Full Text Available High-dose benzodiazepine (BZD dependence is associated with a wide variety of negative health consequences. Affected individuals are reported to suffer from severe mental disorders and are often unable to achieve long-term abstinence via recommended discontinuation strategies. Although it is increasingly understood that treatment interventions should take subjective experiences and beliefs into account, the perceptions of this group of individuals remain under-investigated.We conducted an exploratory qualitative study with 41 adult subjects meeting criteria for (high-dose BZD-dependence, as defined by ICD-10. One-on-one in-depth interviews allowed for an exploration of this group's views on the reasons behind their initial and then continued use of BZDs, as well as their procurement strategies. Mayring's qualitative content analysis was used to evaluate our data.In this sample, all participants had developed explanatory models for why they began using BZDs. We identified a multitude of reasons that we grouped into four broad categories, as explaining continued BZD use: (1 to cope with symptoms of psychological distress or mental disorder other than substance use, (2 to manage symptoms of physical or psychological discomfort associated with somatic disorder, (3 to alleviate symptoms of substance-related disorders, and (4 for recreational purposes, that is, sensation-seeking and other social reasons. Subjects often considered BZDs less dangerous than other substances and associated their use more often with harm reduction than as recreational. Specific obtainment strategies varied widely: the majority of participants oscillated between legal and illegal methods, often relying on the black market when faced with treatment termination.Irrespective of comorbidity, participants expressed a clear preference for medically related explanatory models for their BZD use. We therefore suggest that clinicians consider patients' motives for long-term, high-dose

  12. Sodium bicarbonate causes dose-dependent increases in cerebral blood flow in infants and children with single ventricle physiology

    Science.gov (United States)

    Buckley, Erin M.; Naim, Maryam Y.; Lynch, Jennifer M.; Goff, Donna A.; Schwab, Peter J.; Diaz, Laura K.; Nicolson, Susan C.; Montenegro, Lisa M.; Lavin, Natasha A.; Durduran, Turgut; Spray, Thomas L.; Gaynor, J. William; Putt, Mary E.; Yodh, A.G.; Fogel, Mark A.; Licht, Daniel J.

    2013-01-01

    Background Sodium bicarbonate (NaHCO3) is a common treatment for metabolic acidemia, however little definitive information exists regarding its treatment efficacy and cerebral hemodynamic effects. This pilot observational study quantifies relative changes in cerebral blood flow (rCBF) and oxy and deoxy-hemoglobin concentrations (ΔHbO2 and ΔHb) due to bolus administration of NaHCO3 in patients with mild base deficits. Methods Infants and children with hypoplastic left heart syndrome (HLHS) were recruited prior to cardiac surgery. NaHCO3 was given as needed for treatment of base deficit. Diffuse optical spectroscopies were employed for 15 minutes post-injection to non-invasively monitor ΔHb, ΔHbO2 and rCBF relative to baseline prior to NaHCO3 administration. Results Twenty-two anesthetized and mechanically ventilated HLHS patients (1 day to 4 years old) received a median (interquartile range) dose of 1.1 (0.8, 1.8) mEq/kg NaHCO3 administered intravenously over 10–20 seconds to treat a base deficit of −4 (−6, −3) mEq/l. NaHCO3 caused significant dose-dependent increases in rCBF, however population averaged ΔHb or Δ4HbO2 compared to controls were not significant. Conclusions Dose-dependent increases in cerebral blood flow (CBF) caused by bolus NaHCO3 are an important consideration in vulnerable populations wherein risk of rapid CBF fluctuations does not outweigh the benefit of treating a base deficit. PMID:23403802

  13. Dose-dependent effects of an immune challenge at both ultimate and proximate levels in Drosophila melanogaster.

    Science.gov (United States)

    Nystrand, M; Dowling, D K

    2014-05-01

    Immune responses are highly dynamic. The magnitude and efficiency of an immune response to a pathogen can change markedly across individuals, and such changes may be influenced by variance in a range of intrinsic (e.g. age, genotype, sex) and external (e.g. abiotic stress, pathogen identity, strain) factors. Life history theory predicts that up-regulation of the immune system will come at a physiological cost, and studies have confirmed that increased investment in immunity can reduce reproductive output and survival. Furthermore, males and females often have divergent reproductive strategies, and this might drive the evolution of sex-specific life history trade-offs involving immunity, and sexual dimorphism in immune responses per se. Here, we employ an experiment design to elucidate dose-dependent and sex-specific responses to exposure to a nonpathogenic immune elicitor at two scales--the 'ultimate' life history and the underlying 'proximate' immune level in Drosophila melanogaster. We found dose-dependent effects of immune challenges on both male and female components of reproductive success, but not on survival, as well as a response in antimicrobial activity. These results indicate that even in the absence of the direct pathogenic effects that are associated with actual disease, individual life histories respond to a perceived immune challenge--but with the magnitude of this response being contingent on the initial dose of exposure. Furthermore, the results indicate that immune responses at the ultimate life history level may indeed reflect underlying processes that occur at the proximate level. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

  14. The effects of steroids during sepsis depend on dose and severity of illness: an updated meta-analysis

    Science.gov (United States)

    Minneci, P. C.; Deans, K. J.; Eichacker, P. Q.; Natanson, C.

    2012-01-01

    A previous meta-analysis determined that the effects of steroids during sepsis were dose-dependent; since then, additional trials have been published. The current analysis updates our previous analysis examining the effects of steroids during sepsis. A literature search from 2004 to 2008 identified seven randomized controlled trials in adult patients; these were added to 14 previously identified trials. The effects of steroids on mortality were highly variable among the 21 trials (p steroids, steroids increased mortality (n = 8, I2 = 14%, OR of death 1.39 (95% CI 1.04–1.86), p 0.03). In trials published after 1997, which involved longer courses of lower-dose steroids, steroids consistently improved shock reversal (n = 7, I2 = 0%, OR of shock reversal 1.66 [95% CI 1.25–2.20), p effect on mortality (n = 12, I2 = 25%, OR of death 0.64 (95% CI 0.45–0.93), p 0.02). An inverse linear relationship between severity of illness and the effects of steroids on mortality was identified across all trials (p 0.03) and within the subgroup of trials published after 1997 (p 0.03); steroids were harmful in less severely ill patient populations and beneficial in more severely ill patient populations. There was no effect of response to adrenocorticotrophic hormone (ACTH) stimulation testing concerning the effects of steroids and no increase in steroid-associated adverse events. Low-dose steroids appear to improve mortality rates in patients with septic shock who are at high risk of death; however, additional trials in this subpopulation are necessary to definitively determine the role of low-dose steroids during sepsis. PMID:19416302

  15. Methyl jasmonate-induced emission of biogenic volatiles is biphasic in cucumber: a high-resolution analysis of dose dependence.

    Science.gov (United States)

    Jiang, Yifan; Ye, Jiayan; Li, Shuai; Niinemets, Ülo

    2017-07-20

    Methyl jasmonate (MeJA) is a key airborne elicitor activating jasmonate-dependent signaling pathways, including induction of stress-related volatile emissions, but how the magnitude and timing of these emissions scale with MeJA dose is not known. Treatments with exogenous MeJA concentrations ranging from mild (0.2 mM) to lethal (50 mM) were used to investigate quantitative relationships among MeJA dose and the kinetics and magnitude of volatile release in Cucumis sativus by combining high-resolution measurements with a proton-transfer reaction time-of-flight mass spectrometer (PTR-TOF-MS) and GC-MS. The results highlighted biphasic kinetics of elicitation of volatiles. The early phase, peaking in 0.1-1 h after the MeJA treatment, was characterized by emissions of lipoxygenase (LOX) pathway volatiles and methanol. In the subsequent phase, starting in 6-12 h and reaching a maximum in 15-25 h after the treatment, secondary emissions of LOX compounds as well as emissions of monoterpenes and sesquiterpenes were elicited. For both phases, the maximum emission rates and total integrated emissions increased with applied MeJA concentration. Furthermore, the rates of induction and decay, and the duration of emission bursts were positively, and the timing of emission maxima were negatively associated with MeJA dose for LOX compounds and terpenoids, except for the duration of the first LOX burst. These results demonstrate major effects of MeJA dose on the kinetics and magnitude of volatile response, underscoring the importance of biotic stress severity in deciphering the downstream events of biological impacts. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  16. Testing Dose-Dependent Effects of the Nectar Alkaloid Anabasine on Trypanosome Parasite Loads in Adult Bumble Bees.

    Science.gov (United States)

    Anthony, Winston E; Palmer-Young, Evan C; Leonard, Anne S; Irwin, Rebecca E; Adler, Lynn S

    2015-01-01

    The impact of consuming biologically active compounds is often dose-dependent, where small quantities can be medicinal while larger doses are toxic. The consumption of plant secondary compounds can be toxic to herbivores in large doses, but can also improve survival in parasitized herbivores. In addition, recent studies have found that consuming nectar secondary compounds may decrease parasite loads in pollinators. However, the effect of compound dose on bee survival and parasite loads has not been assessed. To determine how secondary compound consumption affects survival and pathogen load in Bombus impatiens, we manipulated the presence of a common gut parasite, Crithidia bombi, and dietary concentration of anabasine, a nectar alkaloid produced by Nicotiana spp. using four concentrations naturally observed in floral nectar. We hypothesized that increased consumption of secondary compounds at concentrations found in nature would decrease survival of uninfected bees, but improve survival and ameliorate parasite loads in infected bees. We found medicinal effects of anabasine in infected bees; the high-anabasine diet decreased parasite loads and increased the probability of clearing the infection entirely. However, survival time was not affected by any level of anabasine concentration, or by interactive effects of anabasine concentration and infection. Crithidia infection reduced survival time by more than two days, but this effect was not significant. Our results support a medicinal role for anabasine at the highest concentration; moreover, we found no evidence for a survival-related cost of anabasine consumption across the concentration range found in nectar. Our results suggest that consuming anabasine at the higher levels of the natural range could reduce or clear pathogen loads without incurring costs for healthy bees.

  17. Dose-dependent effects of (anti)folate preinjection on 99mTc-radiofolate uptake in tumors and kidneys

    International Nuclear Information System (INIS)

    Mueller, Cristina; Schibli, Roger; Forrer, Flavio; Krenning, Eric P.; Jong, Marion de

    2007-01-01

    Introduction: The folate receptor (FR) is frequently overexpressed in tumors and can be targeted with folate-based (radio)pharmaceuticals. However, significant accumulation of radiofolates in FR-positive kidneys represents a drawback. We have shown that preadministration of the antifolate pemetrexed (PMX) significantly improved the tumor-to-kidney ratio of radiofolates in mice. The aim of this study was to investigate the dose dependence of these effects and whether the same results could be achieved with folic acid (FA) or 5-methyl-tetrahydrofolate (5-Me-THF). Methods: Biodistribution was assessed 4 h postinjection of the organometallic 99m Tc-picolylamine monoacetic acid folate in nude mice bearing FR-positive KB tumor xenografts. PMX (50-400 μg/mouse) was injected 1 h previous to radioactivity. The effects of FA and 5-Me-THF (0.5-50 μg/mouse) were investigated likewise. Tissues and organs were collected and counted for radioactivity and the values tabulated as percentage of injected dose per gram tissue (% ID/g). Results: PMX administration reduced renal retention ( 10% ID/g), while the tumor uptake (average 1.35%±0.40% ID/g vs. control: 1.79%±0.49% ID/g) was only slightly affected independent of the PMX dose. Replacement of PMX by FA or 5-Me-THF (50 μg/mouse) resulted in a significant renal blockade (<0.1% ID/g) but at the same time in an undesired reduction of tumor uptake (<0.2% ID/g). Conclusions: Selective reduction of radiofolate uptake in kidneys under retention of high tumor accumulation could be achieved in combination with PMX over a broad dose range but not with FA or 5-Me-THF

  18. Testing Dose-Dependent Effects of the Nectar Alkaloid Anabasine on Trypanosome Parasite Loads in Adult Bumble Bees.

    Directory of Open Access Journals (Sweden)

    Winston E Anthony

    Full Text Available The impact of consuming biologically active compounds is often dose-dependent, where small quantities can be medicinal while larger doses are toxic. The consumption of plant secondary compounds can be toxic to herbivores in large doses, but can also improve survival in parasitized herbivores. In addition, recent studies have found that consuming nectar secondary compounds may decrease parasite loads in pollinators. However, the effect of compound dose on bee survival and parasite loads has not been assessed. To determine how secondary compound consumption affects survival and pathogen load in Bombus impatiens, we manipulated the presence of a common gut parasite, Crithidia bombi, and dietary concentration of anabasine, a nectar alkaloid produced by Nicotiana spp. using four concentrations naturally observed in floral nectar. We hypothesized that increased consumption of secondary compounds at concentrations found in nature would decrease survival of uninfected bees, but improve survival and ameliorate parasite loads in infected bees. We found medicinal effects of anabasine in infected bees; the high-anabasine diet decreased parasite loads and increased the probability of clearing the infection entirely. However, survival time was not affected by any level of anabasine concentration, or by interactive effects of anabasine concentration and infection. Crithidia infection reduced survival time by more than two days, but this effect was not significant. Our results support a medicinal role for anabasine at the highest concentration; moreover, we found no evidence for a survival-related cost of anabasine consumption across the concentration range found in nectar. Our results suggest that consuming anabasine at the higher levels of the natural range could reduce or clear pathogen loads without incurring costs for healthy bees.

  19. Angular and dose dependence of CR-39 neutron response for shape-selected tracks

    CERN Document Server

    Tam, N C; Lakosi, L

    1999-01-01

    A shape selection method corresponding to an energy discrimination was used to eliminate unwanted events disturbing evaluation of CR-39 detectors in detecting tracks induced by particles both of perpendicular and oblique incidence. The angular dependence of the response was examined, detecting fast neutrons from sup 2 sup 5 sup 2 Cf with shape selection technique at various angles and distances. Also, the CR-39 track detectors with the sup 2 sup 5 sup 2 Cf source were exposed to high gamma-intensity of a sup 6 sup 0 Co irradiation facility in the range 0.1 to 4.5 kGy, similar to the exposures inside spent fuel assemblies. Using the two functions the lower limit of burnup could be determined by the method.

  20. Reduction of entrance surface dose depending on shielding methods for panoramagraphy

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jung Hyun; Han, DongKyoon [Dept. of Radiological Science, The Graduate School, Eulji University, Sungnam (Korea, Republic of); Kim, Sung Chul [Dept. of Radiological, Science Gachon, University, Incheon (Korea, Republic of)

    2015-09-15

    Panoramagraphy was the second most used intraoral radiography utilized in Korea, resulting in 17.8% in university dental hospitals, 24.8% in dental hospitals, and 31.4% in dental clinics. Depending on increased demand like orthodontics and implant, panoromagraphy tends to consistently increase. This study were used lead glasses and lead shielding to reduce unnecessary radiation to the eyeballs and thyroid. ESD was 41.4% when radiation was shielded with the lead glasses while reducing 47.3% of ESD by shielding the X-ray tube area with shielding lead. There was no statistically significant difference. The lead glasses is appropriated to reduce unnecessary radiation exposure to the eyeballs.

  1. Reduction of entrance surface dose depending on shielding methods for panoramagraphy

    International Nuclear Information System (INIS)

    Choi, Jung Hyun; Han, DongKyoon; Kim, Sung Chul

    2015-01-01

    Panoramagraphy was the second most used intraoral radiography utilized in Korea, resulting in 17.8% in university dental hospitals, 24.8% in dental hospitals, and 31.4% in dental clinics. Depending on increased demand like orthodontics and implant, panoromagraphy tends to consistently increase. This study were used lead glasses and lead shielding to reduce unnecessary radiation to the eyeballs and thyroid. ESD was 41.4% when radiation was shielded with the lead glasses while reducing 47.3% of ESD by shielding the X-ray tube area with shielding lead. There was no statistically significant difference. The lead glasses is appropriated to reduce unnecessary radiation exposure to the eyeballs

  2. Nanosilica induced dose-dependent cytotoxicity and cell type-dependent multinucleation in HepG2 and L-02 cells

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Yongbo [Capital Medical University, Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, Beijing Pediatric Research Institute, Beijing Children’s Hospital (China); Duan, Junchao; Li, Yang; Yu, Yang; Hu, Hejing; Wu, Jing; Zhang, Yannan; Li, Yanbo; CaixiaGuo; Zhou, Xianqing; Sun, Zhiwei, E-mail: zwsun@ccmu.edu.cn [Capital Medical University, School of Public Health (China)

    2016-11-15

    The prevalent exposure to nanosilica gained concerns about health effects of these particles on human beings. Although nanosilica-induced multinucleation has been confirmed previously, the underlying mechanism was still not clear; this study was to investigate the origination of multinucleated cells caused by nanosilica (62 nm) in both HepG2 and L-02 cells. Cell viability and cellular uptake was determined by MTT assay and transmission electron microscope (TEM), respectively. Giemsa staining was applied to detect multinucleation. To clarify the origination of multinucleated cells, fluorescent probes, PKH26 and PKH67, time-lapse observation were further conducted by confocal microscopy. Results indicated that nanosilica particles were internalized into cells and induced cytotoxicity in a dose-dependent manner. Quantification analysis showed that nanosilica significantly increased the rates of binucleated and multinucleated cells, which suggested mitotic catastrophe induction. Moreover, dynamic visualization verified that multinucleation resulted from cell fusion in HepG2 cells not in L-02 cells after nanosilica exposure, suggesting cell type-dependent multinucleation formation. Both multinucleation and cell fusion were involved in genetic instability, which emphasized the significance to explore the multinucleation induced by nanosilica via environmental, occupational and consumer product exposure.

  3. Stability of the response and dependence of the optical signal as function of dose rate of the alanine gel dosimeter for electron clinic beams

    International Nuclear Information System (INIS)

    Silva, Cleber Feijo; Dias, Daniel Menezes; Campos, Leticia Lucente

    2009-01-01

    This work evaluates the stability of response and the dependence on the optical response of dose rate of the alanine gel solution developed at the IPEN, Sao Paulo, Brazil, for possible future usage as 3D dosemeter in the medical area, as the area is lack of measure instrumentation for three dimension dose

  4. Dose-dependent platelet stimulation and inhibition induced by anti-PIA1 IgG

    International Nuclear Information System (INIS)

    Ryu, T.; Davis, J.M.; Schwartz, K.A.

    1990-01-01

    The PIA1 antibody produces several clinically distinct and severe thrombocytopenias. Investigations have demonstrated divergent effects on platelet function; prior reports demonstrated inhibition, while a conflicting publication showed platelet activation. We have resolved this conflict using anti-PIA1 IgG produced by a patient with posttransfusion purpura. Relatively low concentrations stimulated platelet aggregation and release of adenosine triphosphate (ATP) whereas high concentrations inhibited platelet function, producing a thrombasthenia-like state. The number of molecules of platelet-associated IgG necessary to initiate aggregation and ATP release (2,086 +/- 556) or produce maximum aggregation (23,420 +/- 3,706) or complete inhibition (63,582 +/- 2654) were measured with a quantitative radiometric assay for bound anti-PIA1. Preincubation of platelets with high concentrations of PIA1 antibody inhibited platelet aggregation with 10 mumol/L adenosine diphosphate and blocked 125I-labeled fibrinogen platelet binding. Platelet activation with nonfibrinogen dependent agonist, 1 U/ml thrombin, was not inhibited by this high concentration of PIA1 IgG. In conclusion, anti-PIAI IgG produces (1) stimulation of platelet aggregation and ATP release that is initiated with 2000 molecules IgG per platelet and is associated with an increase of 125I-fibrinogen binding; (2) conversely, inhibition of platelet aggregation is observed with maximum antibody binding, 63,000 molecules IgG per platelet, and is mediated via a blockade of fibrinogen binding

  5. Dose-dependent dual effects of cholesterol and desmosterol on J774 macrophage proliferation

    International Nuclear Information System (INIS)

    Rodriguez-Acebes, Sara; Cueva, Paloma de la; Ferruelo, Antonio J.; Fernandez-Hernando, Carlos; Lasuncion, Miguel A.; Martinez-Botas, Javier; Gomez-Coronado, Diego

    2008-01-01

    We addressed the ability of native, oxidized and acetylated low-density lipoproteins (nLDL, oxLDL and acLDL, respectively) and desmosterol to act as sources of sterol for the proliferation of J774A.1 macrophages. Treatment with 0.5 μM lovastatin and lipoprotein-deficient serum suppressed cell proliferation. This inhibition was effectively prevented by nLDL, but only to a lesser extent by oxLDL. AcLDL, despite its ability to deliver a higher amount of cholesterol to J774 macrophages than the other LDLs, was dependent on mevalonate supply to sustain cell proliferation. Similarly, exogenous desmosterol, which is not converted into cholesterol in J774 cells, required the simultaneous addition of mevalonate to support optimal cell growth. Expression of hydroxymethyl glutaryl coenzyme A reductase mRNA was potently down-regulated by acLDL and exogenous desmosterol, but the effect was weaker with other sterol sources. We conclude that nLDL is more efficient than modified LDL in sustaining macrophage proliferation. Despite the requirement of cholesterol or desmosterol for J774 cell proliferation, excessive provision of either sterol limits mevalonate availability, thus suppressing cell proliferation.

  6. Dose-dependent dual effects of cholesterol and desmosterol on J774 macrophage proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez-Acebes, Sara [Servicio de Bioquimica-Investigacion, Hospital Ramon y Cajal, Carretera de Colmenar, km 9, 28034 Madrid (Spain); CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid (Spain); Cueva, Paloma de la; Ferruelo, Antonio J; Fernandez-Hernando, Carlos [Servicio de Bioquimica-Investigacion, Hospital Ramon y Cajal, Carretera de Colmenar, km 9, 28034 Madrid (Spain); Lasuncion, Miguel A [Servicio de Bioquimica-Investigacion, Hospital Ramon y Cajal, Carretera de Colmenar, km 9, 28034 Madrid (Spain); CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid (Spain); Departamento de Bioquimica y Biologia Molecular, Universidad de Alcala, Alcala de Henares (Spain); Martinez-Botas, Javier [Servicio de Bioquimica-Investigacion, Hospital Ramon y Cajal, Carretera de Colmenar, km 9, 28034 Madrid (Spain); CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid (Spain); Gomez-Coronado, Diego [Servicio de Bioquimica-Investigacion, Hospital Ramon y Cajal, Carretera de Colmenar, km 9, 28034 Madrid (Spain); CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid (Spain)], E-mail: diego.gomez@hrc.es

    2008-12-12

    We addressed the ability of native, oxidized and acetylated low-density lipoproteins (nLDL, oxLDL and acLDL, respectively) and desmosterol to act as sources of sterol for the proliferation of J774A.1 macrophages. Treatment with 0.5 {mu}M lovastatin and lipoprotein-deficient serum suppressed cell proliferation. This inhibition was effectively prevented by nLDL, but only to a lesser extent by oxLDL. AcLDL, despite its ability to deliver a higher amount of cholesterol to J774 macrophages than the other LDLs, was dependent on mevalonate supply to sustain cell proliferation. Similarly, exogenous desmosterol, which is not converted into cholesterol in J774 cells, required the simultaneous addition of mevalonate to support optimal cell growth. Expression of hydroxymethyl glutaryl coenzyme A reductase mRNA was potently down-regulated by acLDL and exogenous desmosterol, but the effect was weaker with other sterol sources. We conclude that nLDL is more efficient than modified LDL in sustaining macrophage proliferation. Despite the requirement of cholesterol or desmosterol for J774 cell proliferation, excessive provision of either sterol limits mevalonate availability, thus suppressing cell proliferation.

  7. Time and dose dependent expression in the proteome of human peripheral blood mononuclear cells with γ-irradiation

    International Nuclear Information System (INIS)

    Nishad, S.; Ghosh, Anu

    2014-01-01

    The aim of present study is to investigate time and dose dependent differential protein expression pattern of human peripheral blood mononuclear cells (PBMCs) after acute gamma irradiation. For this purpose, PBMCs extracted from eight healthy individuals were irradiated using 60 Co gamma rays (0.3 Gy and 1 Gy) and compared with sham irradiated controls. Total proteins were extracted 1 and 4 hour post irradiation and analyzed using 2-D gel electrophoresis. A fold change of 1.5 in spot intensity was considered as 'biological significant'. Protein identification was performed by MALDI-TOF mass spectrometry. The MS/MS spectra were interrogated using Mascot 2.1 for searching against SWISS-PROT database. One-hour post irradiation, 18 proteins showed a significant difference between the sham (0 Gy) and 0.3 Gy irradiated group (6 proteins up-regulated and 12 proteins down-regulated) and 17 proteins between the sham (0 Gy) and 1 Gy irradiated group (9 proteins up-regulated and 8 down-regulated). Four hours after irradiation, 16 proteins were differentially expressed between the sham irradiated and 0.3 Gy treated group (5 proteins up-regulated and 11 proteins downregulated). Relatively high dose of 1 Gy showed modulation of 13 proteins (5 proteins upregulated and 8 proteins down regulated) after 4 hours. There were 15 proteins that were observed both at the early time point of 1-hour and the late time point of 4-hour. Important among these were, proteins involved in cytoskeletal organization like Actin, Plastin-2, Vinculin, PDZ and LIM domain protein, WD repeat containing protein and the chaperone proteins like HSP 90-alpha and Protein disulfide-isomerase A3. Proteins like thiol specific antioxidant peroxiredoxin-6 (indicating increased levels of ROS and oxidative stress) showed dose specific expression while proteins like Ras-related Rap-1b-like protein (involved in cell survival) were observed with both 0.3 Gy and 1 Gy. During the study, human peripheral blood

  8. Novel application of stem cell-derived neurons to evaluate the time- and dose-dependent progression of excitotoxic injury.

    Directory of Open Access Journals (Sweden)

    Ian M Gut

    Full Text Available Glutamate receptor (GluR-mediated neurotoxicity is implicated in a variety of disorders ranging from ischemia to neural degeneration. Under conditions of elevated glutamate, the excessive activation of GluRs causes internalization of pathologic levels of Ca(2+, culminating in bioenergetic failure, organelle degradation, and cell death. Efforts to characterize cellular and molecular aspects of excitotoxicity and conduct therapeutic screening for pharmacologic inhibitors of excitogenic progression have been hindered by limitations associated with primary neuron culture. To address this, we evaluated glutamate-induced neurotoxicity in highly enriched glutamatergic neurons (ESNs derived from murine embryonic stem cells. As of 18 days in vitro (DIV 18, ESNs were synaptically coupled, exhibited spontaneous network activity with neurotypic mEPSCs and expressed NMDARs and AMPARs with physiological current:voltage behaviors. Addition of 0.78-200 μM glutamate evoked reproducible time- and dose-dependent metabolic failure in 6 h, with a calculated EC50 value of 0.44 μM at 24 h. Using a combination of cell viability assays and electrophysiology, we determined that glutamate-induced toxicity was specifically mediated by NMDARs and could be inhibited by addition of NMDAR antagonists, increased extracellular Mg(2+ or substitution of Ba(2+ for Ca(2+. Glutamate treatment evoked neurite fragmentation and focal swelling by both immunocytochemistry and scanning electron microscopy. Presentation of morphological markers of cell death was dose-dependent, with 0.78-200 μM glutamate resulting in apoptosis and 3000 μM glutamate generating a mixture of necrosis and apoptosis. Addition of neuroprotective small molecules reduced glutamate-induced neurotoxicity in a dose-dependent fashion. These data indicate that ESNs replicate many of the excitogenic mechanisms observed in primary neuron culture, offering a moderate-throughput model of excitotoxicity that combines the

  9. Different Dose-Dependent Modes of Action of C-Type Natriuretic Peptide on Pseudomonas aeruginosa Biofilm Formation

    Directory of Open Access Journals (Sweden)

    Florie Desriac

    2018-04-01

    Full Text Available We have previously shown that the C-type Natriuretic Peptide (CNP, a peptide produced by lungs, is able to impact Pseudomonas aeruginosa physiology. In the present work, the effect of CNP at different concentrations on P. aeruginosa biofilm formation was studied and the mechanisms of action of this human hormone on P. aeruginosa were deciphered. CNP was shown to inhibit dynamic biofilm formation in a dose-dependent manner without affecting the bacterial growth at any tested concentrations. The most effective concentrations were 1 and 0.1 µM. At 0.1 µM, the biofilm formation inhibition was fully dependent on the CNP sensor protein AmiC, whereas it was only partially AmiC-dependent at 1 µM, revealing the existence of a second AmiC-independent mode of action of CNP on P. aeruginosa. At 1 µM, CNP reduced both P. aeruginosa adhesion on glass and di-rhamnolipid production and also increased the bacterial membrane fluidity. The various effects of CNP at 1 µM and 0.1 µM on P. aeruginosa shown here should have major consequences to design drugs for biofilm treatment or prevention.

  10. Dose-dependent effects of lesogaberan on reflux measures in patients with refractory gastroesophageal reflux disease: a randomized, placebo-controlled study.

    Science.gov (United States)

    Miner, Philip B; Silberg, Debra G; Ruth, Magnus; Miller, Frank; Pandolfino, John

    2014-11-18

    The γ-aminobutyric acid type B-receptor agonist lesogaberan (AZD3355) has been developed for use in patients with gastroesophageal reflux disease (GERD) symptoms despite proton pump inhibitor (PPI) therapy (partial responders). This study aimed to explore the dose-response effect of lesogaberan on reflux episodes in partial responders. In this randomized, single-centre, double-blind, crossover, placebo-controlled study, partial responders taking optimised PPI therapy were given 30, 90, 120 and 240 mg doses of lesogaberan. Each dose was given twice (12 h apart) during a 24-h period, during which impedance-pH measurements were taken. Twenty-five patients were included in the efficacy analysis and 27 in the safety analysis. The effect of lesogaberan on the mean number of reflux episodes was dose-dependent, and all doses significantly reduced the mean number of reflux episodes relative to placebo. Lesogaberan also dose-dependently reduced the mean number of acid reflux episodes (except the 30 mg dose) and weakly acid reflux episodes (all doses) significantly, relative to placebo. Regardless of dose, lesogaberan had a similar effect on the percentage of time with esophageal pH < 4 [mean reduction: 68.5% (30 mg), 54.2% (90 mg), 65.9% (120 mg), 72.1% (240 mg); p < 0.05 except 90 mg dose]. No adverse events led to discontinuation and no serious adverse events occurred during active treatment. Lesogaberan inhibited reflux in a dose-dependent manner in partial responders taking optimised PPI therapy, and these effects were significant versus placebo. All lesogaberan doses were well tolerated and were not associated with clinically relevant adverse events. ClinicalTrials.gov identifier: NCT01043185.

  11. Dose-dependent utilisation of casein-linked lysinoalanine, N(epsilon)-fructoselysine and N(epsilon)-carboxymethyllysine in rats.

    Science.gov (United States)

    Somoza, Veronika; Wenzel, Elisabeth; Weiss, Carola; Clawin-Rädecker, Ingrid; Grübel, Nadine; Erbersdobler, Helmut F

    2006-09-01

    During the heat treatment of protein-containing foods, the amino acid lysine is most prone to undergo chemical reactions in the course of amino acid cross-linking or Maillard reactions. Among the reaction products formed, lysinoalanine (LAL), N(epsilon)-fructoselysine (FL) and N(epsilon)-carboxymethyllysine (CML) are those which serve as sensitive markers for the heat treatment applied. From a nutritional perspective, these compounds are ingested with the diet in considerable amounts but information about their metabolic transit and putative in vivo effects is scarce. In the present study, casein-linked LAL, FL and CML were administered to rats in two different doses for 10 days. Quantitation of LAL, FL and CML in plasma, tissue and faeces samples revealed that the kidneys are the predominant sites of accumulation and excretion. The maximum percent of dietary LAL, FL and CML excreted in the urine was 5.6, 5.2 and 29%, whereas the respective recoveries in the kidneys were 0.02, 26 and 1.4%. The plasma and tissue analyses revealed that the endogenous load of either compound is increased by its dietary intake. But the dose-dependent utilisation of dietary protein-linked LAL, FL and CML in rats has been demonstrated for the first time to vary substantially from each other.

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

    Science.gov (United States)

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

    2013-08-01

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

  13. Variation in U.V. primary fluorescence-intensity of vital cells depending on 60Co γ-radiation dose

    International Nuclear Information System (INIS)

    Merkle, K.

    1978-01-01

    Using impulse-cytofluorophotometry in the ultra-violet spectral region it has been shown on vital, unstained Ehrlich ascites tumour cells that the primary fluorescence intensity of this tumour was on day 11 after transplantation 20 per cent higher than on day 8. Storage of the vital cells for 25 min at 20 0 C had no effect on this result. When the cells were exposed to 60 Co γ-radiation on day 6, a new stable fluorescence level was established after 20 hours. Measurements of the primary fluorescence intensity depending on dose have shown a significant rise starting from 75 rad at 48 hours after irradiation. The fluorescence intensity rose by 42.5 per cent of the control value at 3000 rad, but only by 31.5 per cent on exposure to 4000 rad. (author)

  14. Dose-Dependent Change in Elimination Kinetics of Ethanol due to Shift of Dominant Metabolizing Enzyme from ADH 1 (Class I to ADH 3 (Class III in Mouse

    Directory of Open Access Journals (Sweden)

    Takeshi Haseba

    2012-01-01

    Full Text Available ADH 1 and ADH 3 are major two ADH isozymes in the liver, which participate in systemic alcohol metabolism, mainly distributing in parenchymal and in sinusoidal endothelial cells of the liver, respectively. We investigated how these two ADHs contribute to the elimination kinetics of blood ethanol by administering ethanol to mice at various doses, and by measuring liver ADH activity and liver contents of both ADHs. The normalized AUC (AUC/dose showed a concave increase with an increase in ethanol dose, inversely correlating with β. CLT (dose/AUC linearly correlated with liver ADH activity and also with both the ADH-1 and -3 contents (mg/kg B.W.. When ADH-1 activity was calculated by multiplying ADH-1 content by its Vmax⁡/mg (4.0 and normalized by the ratio of liver ADH activity of each ethanol dose to that of the control, the theoretical ADH-1 activity decreased dose-dependently, correlating with β. On the other hand, the theoretical ADH-3 activity, which was calculated by subtracting ADH-1 activity from liver ADH activity and normalized, increased dose-dependently, correlating with the normalized AUC. These results suggested that the elimination kinetics of blood ethanol in mice was dose-dependently changed, accompanied by a shift of the dominant metabolizing enzyme from ADH 1 to ADH 3.

  15. Whole body exposure of mice to secondhand smoke induces dose-dependent and persistent promutagenic DNA adducts in the lung

    International Nuclear Information System (INIS)

    Kim, Sang-In; Arlt, Volker M.; Yoon, Jae-In; Cole, Kathleen J.; Pfeifer, Gerd P.; Phillips, David H.; Besaratinia, Ahmad

    2011-01-01

    Secondhand smoke (SHS) exposure is a known risk factor for lung cancer in lifelong nonsmokers. However, the underlying mechanism of action of SHS in lung carcinogenesis remains elusive. We have investigated, using the 32 P-postlabeling assay, the genotoxic potential of SHS in vivo by determining the formation and kinetics of repair of DNA adducts in the lungs of mice exposed whole body to SHS for 2 or 4 months (5 h/day, 5 days/week), and an ensuing one-month recovery period. We demonstrate that exposure of mice to SHS elicits a significant genotoxic response as reflected by the elevation of DNA adduct levels in the lungs of SHS-exposed animals. The increases in DNA adduct levels in the lungs of SHS-exposed mice are dose-dependent as they are related to the intensity and duration of SHS exposure. After one month of recovery in clean air, the levels of lung DNA adducts in the mice exposed for 4 months remain significantly higher than those in the mice exposed for 2 months (P < 0.0005), levels in both groups being significantly elevated relative to controls (P < 0.00001). Our experimental findings accord with the epidemiological data showing that exposure to smoke-derived carcinogens is a risk factor for lung cancer; not only does the magnitude of risk depend upon carcinogen dose, but it also becomes more irreversible with prolonged exposure. The confirmation of epidemiologic data by our experimental findings is of significance because it strengthens the case for the etiologic involvement of SHS in nonsmokers' lung cancer. Identifying the etiologic factors involved in the pathogenesis of lung cancer can help define future strategies for prevention, early detection, and treatment of this highly lethal malignancy.

  16. Brassinolide Increases Potato Root Growth In Vitro in a Dose-Dependent Way and Alleviates Salinity Stress

    Directory of Open Access Journals (Sweden)

    Yueqing Hu

    2016-01-01

    Full Text Available Brassinosteroids (BRs are steroidal phytohormones that regulate various physiological processes, such as root development and stress tolerance. In the present study, we showed that brassinolide (BL affects potato root in vitro growth in a dose-dependent manner. Low BL concentrations (0.1 and 0.01 μg/L promoted root elongation and lateral root development, whereas high BL concentrations (1–100 μg/L inhibited root elongation. There was a significant (P<0.05 positive correlation between root activity and BL concentrations within a range from 0.01 to 100 μg/L, with the peak activity of 8.238 mg TTC·g−1 FW·h−1 at a BL concentration of 100 μg/L. Furthermore, plants treated with 50 μg/L BL showed enhanced salt stress tolerance through in vitro growth. Under this scenario, BL treatment enhanced the proline content and antioxidant enzymes’ (superoxide dismutase, peroxidase, and catalase activity and reduced malondialdehyde content in potato shoots. Application of BL maintain K+ and Na+ homeostasis by improving tissue K+/Na+ ratio. Therefore, we suggested that the effects of BL on root development from stem fragments explants as well as on primary root development are dose-dependent and that BL application alleviates salt stress on potato by improving root activity, root/shoot ratio, and antioxidative capacity in shoots and maintaining K+/Na+ homeostasis in potato shoots and roots.

  17. Feeding blueberry diets to young rats dose-dependently inhibits bone resorption through suppression of RANKL in stromal cells.

    Directory of Open Access Journals (Sweden)

    Jian Zhang

    Full Text Available Previous studies have demonstrated that weanling rats fed AIN-93G semi-purified diets supplemented with 10% whole blueberry (BB powder for two weeks beginning on postnatal day 21 (PND21 significantly increased bone formation at PND35. However, the minimal level of dietary BB needed to produce these effects is, as yet, unknown. The current study examined the effects of three different levels of BB diet supplementation (1, 3, and 5% for 35 days beginning on PND25 on bone quality, and osteoclastic bone resorption in female rats. Peripheral quantitative CT scan (pQCT of tibia, demonstrated that bone mineral density (BMD and content (BMC were dose-dependently increased in BB-fed rats compared to controls (P<0.05. Significantly increased bone mass after feeding 5% BB extracts was also observed in a TEN (total enteral nutrition rat model in which daily caloric and food intake was precisely controlled. Expression of RANKL (receptor activator of nuclear factor-κB ligand a protein essential for osteoclast formation was dose-dependently decreased in the femur of BB animals. In addition, expression of PPARγ (peroxisome proliferator-activated receptor γ which regulates bone marrow adipogenesis was suppressed in BB diet rats compared to non-BB diet controls. Finally, a set of in vitro cell cultures revealed that the inhibitory effect of BB diet rat serum on RANKL expression was more profound in mesenchymal stromal cells compared to its effect on mature osteoblasts, pre-adipocytes and osteocytes. These results suggest that inhibition of bone resorption may contribute to increased bone mass during early development after BB consumption.

  18. Critical dose threshold for TL dose response non-linearity: Dependence on the method of analysis: It’s not only the data

    International Nuclear Information System (INIS)

    Datz, H.; Horowitz, Y.S.; Oster, L.; Margaliot, M.

    2011-01-01

    It is demonstrated that the method of data analysis, i.e., the method of the phenomenological/theoretical interpretation of dose response data, can greatly influence the estimation of the onset of deviation from dose response linearity of the high temperature thermoluminescence in LiF:Mg,Ti (TLD-100).

  19. Extent of radiosensitization by the PARP inhibitor olaparib depends on its dose, the radiation dose and the integrity of the homologous recombination pathway of tumor cells

    NARCIS (Netherlands)

    Verhagen, C.V.M.; Haan, R. den; Hageman, F.; Oostendorp, T.P.; Carli, A.L.; O'Connor, M.J.; Jonkers, J.; Verheij, M.; Brekel, M.W. van den; Vens, C.

    2015-01-01

    BACKGROUND AND PURPOSE: The PARP inhibitor olaparib is currently tested in clinical phase 1 trials to define safe dose levels in combination with RT. However, certain clinically relevant insights are still lacking. Here we test, while comparing to single agent activity, the olaparib dose and genetic

  20. Extent of radiosensitization by the PARP inhibitor olaparib depends on its dose, the radiation dose and the integrity of the homologous recombination pathway of tumor cells

    NARCIS (Netherlands)

    Verhagen, C.V.M.; de Haan, R.; Hageman, F.; Oostendorp, T.P.D.; Carli, A.L.E.; O'Connor, M.J.; Jonkers, J.; Verheij, M.; van den Brekel, M.W.; Vens, C.

    2015-01-01

    Background and purpose The PARP inhibitor olaparib is currently tested in clinical phase 1 trials to define safe dose levels in combination with RT. However, certain clinically relevant insights are still lacking. Here we test, while comparing to single agent activity, the olaparib dose and genetic

  1. Dose-response relationships between exercise intensity, cravings, and inhibitory control in methamphetamine dependence: An ERPs study.

    Science.gov (United States)

    Wang, Dongshi; Zhou, Chenglin; Zhao, Min; Wu, Xueping; Chang, Yu-Kai

    2016-04-01

    The present study integrated behavioral and neuroelectric approaches for determining the dose-response relationships between exercise intensity and methamphetamine (MA) craving and between exercise intensity and inhibitory control in individuals with MA dependence. Ninety-two individuals with MA dependence were randomly assigned to an exercise group (light, moderate, or vigorous intensity) or to a reading control group. The participants then completed a craving self-report at four time points: before exercise, during exercise, immediately after exercise, and 50 min after exercise. Event-related potentials were also recorded while the participants completed a standard Go/NoGo task and an MA-related Go/NoGo task approximately 20 min after exercise cessation. The reduction in self-reported MA craving scores of the moderate and vigorous intensity groups was greater than that of the light intensity and control groups during acute exercise as well as immediately and 50 min following exercise termination. Additionally, an inverted-U-shaped relationship between exercise intensity and inhibitory control was generally observed for the behavioral and neuroelectric indices, with the moderate intensity group exhibiting shorter Go reaction times, increased NoGo accuracy, and larger NoGo-N2 amplitudes. Acute exercise may provide benefits for MA-associated craving and inhibitory control in MA-dependent individuals, as revealed by behavioral and neuroelectric measures. Moderate-intensity exercise may be associated with more positive effects, providing preliminary evidence for the establishment of an exercise prescription regarding intensity for MA dependence. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. TH-C-19A-03: Characterization of the Dose Per Pulse Dependence of Various Detectors Used in Quality Assurance of FFF Treatment Plans

    Energy Technology Data Exchange (ETDEWEB)

    Karan, T [Stronach Regional Cancer Center, Newmarket, ON (Canada); Viel, F; Atwal, P; Gete, E; Camborde, M; Horwood, R; Strgar, V; Duzenli, C [British Columbia Cancer Agency, Vancouver, BC (Canada)

    2014-06-15

    Purpose: To present the dose per pulse dependence of various QA devices under Flattening Filter Free (FFF) conditions. Methods: Air and liquid filled ion chamber arrays, diode arrays, radiochromic film and optically stimulated luminescence detectors were investigated. All detectors were irradiated under similar conditions of varying dose per pulse on a TrueBeam linac. Dose per pulse was controlled by varying SSD from 70 to 160 cm providing a range from ~0.5 to ~3 mGy per pulse. MU rates of up to 2400 MU/min for 10X FFF and 1400 MU/min for the 6X FFF beam were used. Beam pulses were counted using the Profiler™ diode array and pulse timing was confirmed by examining linac node files. Delivered doses were calculated with the Eclipse™ treatment planning system. Results: The detectors show a range of behaviors depending on the detector type, as expected. Diode arrays show up to 4% change in sensitivity (sensitivity increases with increasing dose per pulse) over the range tested. Air and liquid ion chambers arrays show a change in sensitivity of up to 3% (air) and 6% (liquid) (sensitivity decreases with increasing dose per pulse) while film and OSLD do not demonstrate a dependence on dose per pulse. Conclusion: Dependence of detector response on dose per pulse varies considerably depending on detector design. Interplay between dose per pulse and MU rate also exists for some detectors. Due diligence is required to characterize detector response prior to implementation of a QA protocol for FFF treatment delivery. During VMAT delivery, the MU rate may also vary dramatically within a treatment fraction. We intend to further investigate the implications of this for VMAT FFF patient specific quality assurance. T Karan and F Viel have received partial funding through the Varian Research program.

  3. TH-C-19A-03: Characterization of the Dose Per Pulse Dependence of Various Detectors Used in Quality Assurance of FFF Treatment Plans

    International Nuclear Information System (INIS)

    Karan, T; Viel, F; Atwal, P; Gete, E; Camborde, M; Horwood, R; Strgar, V; Duzenli, C

    2014-01-01

    Purpose: To present the dose per pulse dependence of various QA devices under Flattening Filter Free (FFF) conditions. Methods: Air and liquid filled ion chamber arrays, diode arrays, radiochromic film and optically stimulated luminescence detectors were investigated. All detectors were irradiated under similar conditions of varying dose per pulse on a TrueBeam linac. Dose per pulse was controlled by varying SSD from 70 to 160 cm providing a range from ~0.5 to ~3 mGy per pulse. MU rates of up to 2400 MU/min for 10X FFF and 1400 MU/min for the 6X FFF beam were used. Beam pulses were counted using the Profiler™ diode array and pulse timing was confirmed by examining linac node files. Delivered doses were calculated with the Eclipse™ treatment planning system. Results: The detectors show a range of behaviors depending on the detector type, as expected. Diode arrays show up to 4% change in sensitivity (sensitivity increases with increasing dose per pulse) over the range tested. Air and liquid ion chambers arrays show a change in sensitivity of up to 3% (air) and 6% (liquid) (sensitivity decreases with increasing dose per pulse) while film and OSLD do not demonstrate a dependence on dose per pulse. Conclusion: Dependence of detector response on dose per pulse varies considerably depending on detector design. Interplay between dose per pulse and MU rate also exists for some detectors. Due diligence is required to characterize detector response prior to implementation of a QA protocol for FFF treatment delivery. During VMAT delivery, the MU rate may also vary dramatically within a treatment fraction. We intend to further investigate the implications of this for VMAT FFF patient specific quality assurance. T Karan and F Viel have received partial funding through the Varian Research program

  4. Dose-dependent effects of Asparagus adscendens root (AARR) extract on the anabolic, reproductive, and sexual behavioral activity in rats.

    Science.gov (United States)

    Bansode, Falgun Wanganuji; Arya, Kamal Ram; Singh, Rama Kant; Narender, T

    2015-02-01

    Asparagus adscendens Roxb (Liliaceae) has a promising role in modulation of various disorders such as leucorrhea, diarrhea, dysentery, diabetes, senile pruritus, asthma, fatigue antifilarial, antifungal, spermatorrhea, and sexual debility/seminal weakness. To investigate dose-dependent effects of Asparagus adscendens root (AARR) extract on anabolic, reproductive, and sexual behavioral activities with a view to emphasize the pharmacological basis. Rats were divided into five groups: Group I (control), Groups II-IV (AARR treated, 100, 200, and 300 mg/kg body weight, respectively, orally for 30 d) and Group V (standard control treated with sildenafil citrate, 5 mg/kg body weight). On day 31, copulatory and potency tests were carried out and an autopsy was done to study the reproductive function, namely, organ weights, spermatogenesis, daily sperm production rate (DSP), and epididymal sperm counts (ESC). AARR extract (200 and 300 mg/kg doses) caused a significant increase in body (p < 0.02 and p < 0.001) and testes (p < 0.01 and p < 0.001, control versus treated) weights. Reproductive activity showed significant a increase in testicular tubular diameter (p < 0.005-0.001), the number of round/elongated spermatids (p < 0.02-0.001), DSP, and ESC (p < 0.05-0.001). The sexual behavioral parameters including mounting/intromission frequency (13.0 ± 0.32/11.8 ± 0.37 and 18.2 ± 2.12/14.8 ± 1.15 versus 11.2 ± 0.66/8.2 ± 1.16), ejaculation latency (187.4 ± 1.91 and 191.4 ± 1.72 versus 180.0 ± 3.47), and penile erections (13.5 ± 0.3 and 14.5 ± 0.5 versus 8.5 ± 0.2) showed a significant increase at 200 and 300 mg/kg doses (ED50 300 mg/kg), but less than a standard control. In contrast, 100 mg/kg dose caused an increase (p < 0.005) in mounting latency only. These results indicate increased anabolic, reproductive, and sexual activities by AARR treatment. Thus, the data provide

  5. Paradoxical dopaminergic drug effects in extraversion: Dose- and time-dependent effects of Sulpiride on EEG theta activity

    Directory of Open Access Journals (Sweden)

    Mira-Lynn eChavanon

    2013-04-01

    Full Text Available Dopaminergic drugs frequently produce paradoxical effects depending on baseline performance levels, genotype or personality traits. The present study for the first time aimed to specify the mechanisms underlying such opposite effects using the following recently reported scenario as an example: Depending on the personality trait agentic extraversion (aE; i.e. assertiveness, dominance, ambition, positive emotionality the selective dopamine D2 receptor antagonist sulpiride (200 mg had opposite effects on resting posterior versus anterior theta activity in the electroencephalogram (EEG. In order to better describe these opposite pharmaco-EEG effects and to generate hypotheses regarding the underlying mechanisms, we measured the EEG intermittently over five hours in 80 healthy male volunteers extremely high or low in aE who had received either placebo or one of three doses of sulpiride (50 mg, 200 mg, or 400 mg. The findings suggest a model postulating stronger pre- versus postsynaptic subreceptor effects in high aE individuals compared to low aE individuals. Future studies may now systematically apply the model to other examples of paradoxical dopaminergic drug effects and examine the molecular basis of individual differences in pre- versus postsynaptic dopamine D2 subreceptor sensitivities and densities.

  6. Local application of SCH 39166 reversibly and dose-dependently decreases acetylcholine release in the rat striatum.

    Science.gov (United States)

    Acquas, E; Di Chiara, G

    1999-11-03

    The effect of local application by reverse dialysis of the dopamine D(1) receptor antagonist (-)-trans-6,7,7a,8,9, 13b-exahydro-3-chloro-2-hydroxy-N-methyl-5H-benzo-[d]-nap hto-[2, 1b]-azepine hydrochloride (SCH 39166) on acetylcholine release was studied in awake, freely moving rats implanted with concentric microdialysis probes in the dorsal striatum. In these experiments, the reversible acetylcholine esterase inhibitor, neostigmine, was added to the perfusion solution at two different concentrations, 0.01 and 0.1 microM. SCH 39166 (1, 5 and 10 microM), in the presence of 0.01 microM neostigmine, reversibly decreased striatal acetylcholine release (1 microM SCH 39166 by 8+/-4%; 5 microM SCH 39166 by 24+/-5%; 10 microM SCH 39166 by 27+/-7%, from basal). Similarly, SCH 39166, applied in the presence of a higher neostigmine concentration (0.1 microM), decreased striatal acetylcholine release by 14+/-4% at 1 microM, by 28+/-8% at 5 microM and by 30+/-5% at 10 microM, in a dose-dependent and time-dependent manner. These results are consistent with the existence of a facilitatory tone of dopamine on striatal acetylcholine transmission mediated by dopamine D(1) receptors located on striatal cholinergic interneurons.

  7. Dose-Dependent Cytotoxic Effects of Boldine in HepG-2 Cells—Telomerase Inhibition and Apoptosis Induction

    Directory of Open Access Journals (Sweden)

    Sakineh Kazemi Noureini

    2015-02-01

    Full Text Available Plant metabolites are valuable sources of novel therapeutic compounds. In an anti-telomerase screening study of plant secondary metabolites, the aporphine alkaloid boldine (1,10-dimethoxy-2,9-dihydroxyaporphine exhibited a dose and time dependent cytotoxicity against hepatocarcinoma HepG-2 cells. Here we focus on the modes and mechanisms of the growth-limiting effects of this compound. Telomerase activity and expression level of some related genes were estimated by real-time PCR. Modes of cell death also were examined by microscopic inspection, staining methods and by evaluating the expression level of some critically relevant genes. The growth inhibition was correlated with down-regulation of the catalytic subunit of telomerase (hTERT gene (p < 0.01 and the corresponding reduction of telomerase activity in sub-cytotoxic concentrations of boldine (p < 0.002. However, various modes of cell death were stimulated, depending on the concentration of boldine. Very low concentrations of boldine over a few passages resulted in an accumulation of senescent cells so that HepG-2 cells lost their immortality. Moreover, boldine induced apoptosis concomitantly with increasing the expression of bax/bcl2 (p < 0.02 and p21 (p < 0.01 genes. Boldine might thus be an interesting candidate as a potential natural compound that suppresses telomerase activity in non-toxic concentrations.

  8. Dose-dependent increases in flow-mediated dilation following acute cocoa ingestion in healthy older adults

    Science.gov (United States)

    Feehan, Robert P.; Kunselman, Allen R.; Preston, Amy G.; Miller, Debra L.; Lott, Mary E. J.

    2011-01-01

    An inverse relation exists between intake of flavonoid-rich foods, such as cocoa, and cardiovascular-related mortality. Favorable effects of flavonoids on the endothelium may underlie these associations. We performed a randomized, double-blind, placebo-controlled study to test the hypothesis that acute cocoa ingestion dose dependently increases endothelium-dependent vasodilation, as measured by an increase in brachial artery flow-mediated dilation (FMD), in healthy older adults. Measurements were obtained before (preingestion) and after (1- and 2-h postingestion) ingestion of 0 (placebo), 2, 5, 13, and 26 g of cocoa in 23 adults (63 ± 2 yr old, mean ± SE). Changes in brachial artery FMD 1- and 2-h postingestion compared with preingestion were used to determine the effects of cocoa. FMD was unchanged 1 (Δ−0.3 ± 0.2%)- and 2-h (Δ0.1 ± 0.1%) after placebo (0 g cocoa). In contrast, FMD increased both 1-h postingestion (2 g cocoa Δ0.0 ± 0.2%, 5 g cocoa Δ0.8 ± 0.3%, 13 g cocoa Δ1.0 ± 0.3%, and 26 g cocoa Δ1.6 ± 0.3%: P FMD 1- and 2-h postingestion (r = 0.44–0.48; both P FMD in healthy older humans. These responses may help to explain associations between flavonoid intake and cardiovascular-related mortality in humans. PMID:21903881

  9. Dose dependence of tensoresistance for the symmetrical orientation of the deformation axis relatively to all isoenergetic ellipsoids in γ-irradiated (60Co n-Si crystals

    Directory of Open Access Journals (Sweden)

    G.P. Gaidar

    2018-03-01

    Full Text Available The dose dependence of tensoresistance X /0, which was measured at the symmetrical orientation of the deformation axis (compression relatively to all isoenergetic ellipsoids both in the initial and in -irradiated samples, was investigated in n-Si crystals. It has been shown that changing the irradiation doses is accompanied by not only quantitative but also qualitative changes in the functional dependence X /0 = f (Х. Features of tensoresistance in n-Si irradiated samples were found depending on three crystallographic directions, along which the samples were cut out and the mechanical stress Х was applied.

  10. Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells

    International Nuclear Information System (INIS)

    Lambert, Carine B.; Spire, Catherine; Claude, Nancy; Guillouzo, Andre

    2009-01-01

    Phenobarbital (PB) induces or represses a wide spectrum of genes in rodent liver. Much less is known about its effects in human liver. We used pangenomic cDNA microarrays to analyze concentration- and time-dependent gene expression profile changes induced by PB in the well-differentiated human HepaRG cell line. Changes in gene expression profiles clustered at specific concentration ranges and treatment times. The number of correctly annotated genes significantly modulated by at least three different PB concentration ranges (spanning 0.5 to 3.2 mM) at 20 h exposure amounted to 77 and 128 genes (p ≤ 0.01) at 2- and 1.8-fold filter changes, respectively. At low concentrations (0.5 and 1 mM), PB-responsive genes included the well-recognized CAR- and PXR-dependent responsive cytochromes P450 (CYP2B6, CYP3A4), sulfotransferase 2A1 and plasma transporters (ABCB1, ABCC2), as well as a number of genes critically involved in various metabolic pathways, including lipid (CYP4A11, CYP4F3), vitamin D (CYP24A1) and bile (CYP7A1 and CYP8B1) metabolism. At concentrations of 3.2 mM or higher after 20 h, and especially 48 h, increased cytotoxic effects were associated with disregulation of numerous genes related to oxidative stress, DNA repair and apoptosis. Primary human hepatocyte cultures were also exposed to 1 and 3.2 mM PB for 20 h and the changes were comparable to those found in HepaRG cells treated under the same conditions. Taken altogether, our data provide further evidence that HepaRG cells closely resemble primary human hepatocytes and provide new information on the effects of PB in human liver. These data also emphasize the importance of investigating dose- and time-dependent effects of chemicals when using toxicogenomic approaches

  11. HDL and CER-001 Inverse-Dose Dependent Inhibition of Atherosclerotic Plaque Formation in apoE-/- Mice: Evidence of ABCA1 Down-Regulation.

    Science.gov (United States)

    Tardy, Claudine; Goffinet, Marine; Boubekeur, Nadia; Cholez, Guy; Ackermann, Rose; Sy, Gavin; Keyserling, Constance; Lalwani, Narendra; Paolini, John F; Dasseux, Jean-Louis; Barbaras, Ronald; Baron, Rudi

    2015-01-01

    CER-001 is a novel engineered HDL-mimetic comprised of recombinant human apoA-I and charged phospholipids that was designed to mimic the beneficial properties of nascent pre-ß HDL. In this study, we have evaluated the dose-dependent regulation of ABCA1 expression in vitro and in vivo in the presence of CER-001 and native HDL (HDL3). CER-001 induced cholesterol efflux from J774 macrophages in a dose-dependent manner similar to natural HDL. A strong down-regulation of the ATP-binding cassette A1 (ABCA1) transporter mRNA (- 50%) as well as the ABCA1 membrane protein expression (- 50%) was observed at higher doses of CER-001 and HDL3 compared to non-lipidated apoA-I. In vivo, in an apoE-/- mouse "flow cessation model," in which the left carotid artery was ligatured to induce local inflammation, the inhibition of atherosclerotic plaque burden progression in response to a dose-range of every-other-day CER-001 or HDL in the presence of a high-fat diet for two weeks was assessed. We observed a U-shaped dose-response curve: inhibition of the plaque total cholesterol content increased with increasing doses of CER-001 or HDL3 up to a maximum inhibition (- 51%) at 5 mg/kg; however, as the dose was increased above this threshold, a progressively less pronounced inhibition of progression was observed, reaching a complete absence of inhibition of progression at doses of 20 mg/kg and over. ABCA1 protein expression in the same atherosclerotic plaque was decreased by-45% and-68% at 50 mg/kg for CER-001 and HDL respectively. Conversely, a-12% and 0% decrease in ABCA1 protein expression was observed at the 5 mg/kg dose for CER-001 and HDL respectively. These data demonstrate that high doses of HDL and CER-001 are less effective at slowing progression of atherosclerotic plaque in apoE-/- mice compared to lower doses, following a U-shaped dose-response curve. A potential mechanism for this phenomenon is supported by the observation that high doses of HDL and CER-001 induce a rapid and

  12. Dose-dependent transitions in Nrf2-mediated adaptive response and related stress responses to hypochlorous acid in mouse macrophages

    International Nuclear Information System (INIS)

    Woods, Courtney G.; Fu Jingqi; Xue Peng; Hou Yongyong; Pluta, Linda J.; Yang Longlong; Zhang Qiang; Thomas, Russell S.; Andersen, Melvin E.; Pi Jingbo

    2009-01-01

    Hypochlorous acid (HOCl) is potentially an important source of cellular oxidative stress. Human HOCl exposure can occur from chlorine gas inhalation or from endogenous sources of HOCl, such as respiratory burst by phagocytes. Transcription factor Nrf2 is a key regulator of cellular redox status and serves as a primary source of defense against oxidative stress. We recently demonstrated that HOCl activates Nrf2-mediated antioxidant response in cultured mouse macrophages in a biphasic manner. In an effort to determine whether Nrf2 pathways overlap with other stress pathways, gene expression profiling was performed in RAW 264.7 macrophages exposed to HOCl using whole genome mouse microarrays. Benchmark dose (BMD) analysis on gene expression data revealed that Nrf2-mediated antioxidant response and protein ubiquitination were the most sensitive biological pathways that were activated in response to low concentrations of HOCl (< 0.35 mM). Genes involved in chromatin architecture maintenance and DNA-dependent transcription were also sensitive to very low doses. Moderate concentrations of HOCl (0.35 to 1.4 mM) caused maximal activation of the Nrf2 pathway and innate immune response genes, such as IL-1β, IL-6, IL-10 and chemokines. At even higher concentrations of HOCl (2.8 to 3.5 mM) there was a loss of Nrf2-target gene expression with increased expression of numerous heat shock and histone cluster genes, AP-1-family genes, cFos and Fra1 and DNA damage-inducible Gadd45 genes. These findings confirm an Nrf2-centric mechanism of action of HOCl in mouse macrophages and provide evidence of interactions between Nrf2, inflammatory, and other stress pathways.

  13. Proposed mechanistic description of dose-dependent BDE-47 urinary elimination in mice using a physiologically based pharmacokinetic model

    Energy Technology Data Exchange (ETDEWEB)

    Emond, Claude, E-mail: claude.emond@umontreal.ca [BioSimulation Consulting Inc., Newark, DE (United States); Departments of Environmental and Occupational Health, Medicine Faculty, University of Montreal, Montreal, Quebec (Canada); Sanders, J. Michael, E-mail: sander10@mail.nih.gov [National Cancer Institute, Research Triangle Park, NC (United States); Wikoff, Daniele, E-mail: dwikoff@toxstrategies.com [ToxStrategies, Austin, TX (United States); Birnbaum, Linda S., E-mail: birnbaumls@niehs.nih.gov [National Cancer Institute, Research Triangle Park, NC (United States)

    2013-12-01

    Polybrominated diphenyl ethers (PBDEs) have been used in a wide variety of consumer applications as additive flame retardants. In North America, scientists have noted continuing increases in the levels of PBDE congeners measured in human serum. Some recent studies have found that PBDEs are associated with adverse health effects in humans, in experimental animals, and wildlife. This laboratory previously demonstrated that urinary elimination of 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) is saturable at high doses in mice; however, this dose-dependent urinary elimination has not been observed in adult rats or immature mice. Thus, the primary objective of this study was to examine the mechanism of urinary elimination of BDE-47 in adult mice using a physiologically based pharmacokinetic (PBPK) model. To support this objective, additional laboratory data were collected to evaluate the predictions of the PBPK model using novel information from adult multi-drug resistance 1a/b knockout mice. Using the PBPK model, the roles of mouse major urinary protein (a blood protein carrier) and P-glycoprotein (an apical membrane transporter in proximal tubule cells in the kidneys, brain, intestines, and liver) were investigated in BDE-47 elimination. The resulting model and new data supported the major role of m-MUP in excretion of BDE-47 in the urine of adult mice, and a lesser role of P-gp as a transporter of BDE-47 in mice. This work expands the knowledge of BDE-47 kinetics between species and provides information for determining the relevancy of these data for human risk assessment purposes. - Highlights: • We report the first study on PBPK model on flame retardant in mice for BDE-47. • We examine mechanism of urinary elimination of BDE-47 in mice using a PBPK model. • We investigated roles of m-MUP and P-gp as transporters in urinary elimination.

  14. Dose-dependent effects of the clinical anesthetic isoflurane on Octopus vulgaris: a contribution to cephalopod welfare.

    Science.gov (United States)

    Polese, Gianluca; Winlow, William; Di Cosmo, Anna

    2014-12-01

    Recent progress in animal welfare legislation relating to invertebrates has provoked interest in methods for the anesthesia of cephalopods, for which different approaches to anesthesia have been tried but in most cases without truly anesthetizing the animals. For example, several workers have used muscle relaxants or hypothermia as forms of "anesthesia." Several inhalational anesthetics are known to act in a dose-dependent manner on the great pond snail Lymnaea stagnalis, a pulmonate mollusk. Here we report, for the first time, on the effects of clinical doses of the well-known inhalational clinical anesthetic isoflurane on the behavioral responses of the common octopus Octopus vulgaris. In each experiment, isoflurane was equilibrated into a well-aerated seawater bath containing a single adult O. vulgaris. Using a web camera, we recorded each animal's response to touch stimuli eliciting withdrawal of the arms and siphon and observed changes in the respiratory rate and the chromatophore pattern over time (before, during, and after application of the anesthetic). We found that different animals of the same size responded with similar behavioral changes as the isoflurane concentration was gradually increased. After gradual application of 2% isoflurane for a maximum of 5 min (at which time all the responses indicated deep anesthesia), the animals recovered within 45-60 min in fresh aerated seawater. Based on previous findings in gastropods, we believe that the process of anesthesia induced by isoflurane is similar to that previously observed in Lymnaea. In this study we showed that isoflurane is a good, reversible anesthetic for O. vulgaris, and we developed a method for its use.

  15. Camphor-Crataegus berry extract combination dose-dependently reduces tilt induced fall in blood pressure in orthostatic hypotension.

    Science.gov (United States)

    Belz, G G; Butzer, R; Gaus, W; Loew, D

    2002-10-01

    In order to test the efficacy of a combination of natural D-camphor and an extract of fresh crataegus berries (Korodin Herz-Kreislauf-Tropfen) on orthostatic hypotension, two similar, controlled, randomized studies were carried out in a balanced crossover design in 24 patients each with orthostatic dysregulation. The camphor-crataegus berry combination (CCC) was orally administered as a single regimen in 3 different dosages of 5 drops, 20 drops and 80 drops; a placebo with 20 drops of a 60% alcoholic solution served as control. Orthostatic hypotension was assessed with the tilt table test before and after medication. Source data of both studies were pooled and meta-analytically evaluated for all 48 patients. CCC drops decreased the orthostatic fall in blood pressure versus placebo, as almost uniformly established at all times by mean arterial pressure and diastolic blood pressure. Mean arterial pressure demonstrated the very fast onset of action by a clearly dose-dependent statistically significant effect even after 1-minute orthostasis. Increase of mean arterial pressure as compared to the orthostasis test before medication was on average 4.5 mmHg. CCC affected diastolic blood pressure after 1 minute of orthostasis in all dosages as compared to placebo. A statistically significant effect of the highest dose of 80 drops on diastolic blood pressure could be demonstrated after 1-, 3-, and 5-minute orthostasis. The hemodynamic findings of a stabilizing effect on arterial pressure in orthostasis corroborate the long-term medical experience with CCC and justify the indication orthostatic hypotension.

  16. Delivery of adjuvant sequential dose-dense FEC-Doc to patients with breast cancer is feasible, but dose reductions and toxicity are dependent on treatment sequence.

    Science.gov (United States)

    Wildiers, H; Dirix, L; Neven, P; Prové, A; Clement, P; Squifflet, P; Amant, F; Skacel, T; Paridaens, R

    2009-03-01

    This study prospectively investigates the impact of dose densification and altering sequence of fluorouracil, epirubicin and cyclophosphamide [FEC(100)] and docetaxel [Doc] on dose delivery and tolerability of adjuvant chemotherapy in breast cancer patients. 117 patients with high-risk primary operable breast cancer were randomized (1:1:2:2) to conventional (three cycles of 3-weekly FEC(100) then three cycles of 3-weekly Doc 100 mg/m(2) or reverse sequence) or dose-dense (dd) treatment (four 10- to 11-day cycles of FEC(75) then four 2-weekly cycles of Doc 75 mg/m(2), or the reverse). In the dd arms, pegfilgrastim was given on day 2 of each cycle, but only as secondary prophylaxis in conventional arms. The primary endpoint was the proportion of patients completing intended cycles at relative dose intensity >or=85% and this was achieved by 95% of patients in each group except for the ddDoc-->FEC group (90%). Dose intensity in the dd arms increased by 48% for FEC and 11% for docetaxel, compared with the conventional arms (both P Doc dose reductions were more frequent with dd treatment and when Doc was given after FEC. Grade 3-4 neutropenia was significantly more frequent with conventional treatment, while fatigue and hand-foot syndrome were numerically more common with dd treatment, particularly when Doc was given after FEC. Discussion Delivery of adjuvant sequential ddFEC and Doc is feasible with growth factor support, and chemotherapy sequence appeared to affect delivery of target doses and toxicity.

  17. Influence of energy dependence GafChromic XR-RV3 movies to the extent of skin dose

    International Nuclear Information System (INIS)

    Martinez Gomez, L. C.; Gilarranz Moreno, R.; Rot San Juan, M. J.; Delgado Rodriguez, J. M.; Adaimi Hernandez, P.; Milanes Gaillet, A.

    2013-01-01

    In this work we have evaluated uncertainties by comparing the calculated dose with films from a calibration reference with dose measurements ionization with chamber using beams in clinical conditions. (Author)

  18. Growth hormone therapy for children born small for gestational age: height gain is less dose dependent over the long term than over the short term.

    Science.gov (United States)

    de Zegher, Francis; Hokken-Koelega, Anita

    2005-04-01

    Approximately 3% of children are born small for gestational age (SGA), and approximately 10% of SGA children maintain a small body size throughout childhood and often into adult life. Among short SGA children, growth hormone (GH) therapy increases short-term growth in a dose-dependent manner; experience with long-term therapy is limited. To delineate the dose dependency of long-term height gain among short SGA children receiving GH therapy. We performed an epianalysis of the first adult height data for SGA children (n = 28) enrolled in 3 randomized trials comparing the growth-promoting efficacy of 2 continuous GH regimens (33 or 67 microg/kg per day for approximately 10 years, starting at approximately 5 years of age); in addition, we performed a meta-analysis of the adult height results published previously and those presented here. Epianalysis outcomes (n = 28) suggested that adult height increased more with a higher-dose regimen than with a lower-dose regimen. In the meta-analysis (n = 82), the higher-dose regimen was found to elicit a long-term height gain superior to that achieved with the lower-dose regimen by a mean of 0.4 SD (approximately 1 inch). Children who were shorter at the start of therapy experienced more long-term height gain. These findings confirm GH therapy as an effective and safe approach to reduce the adult height deficit that short SGA children otherwise face. In addition, the first meta-analysis indicated that height gain is less dose dependent over the long term than over the short term, at least within the dose range explored to date. For SGA children whose stature is not extremely short, current data support the use of a GH dose of approximately 33 microg/kg per day from start to adult height, particularly if treatment starts at a young age; shorter children (for example, height below -3 SD) might benefit from an approach in which short-term catch-up growth is achieved with a higher dose (> or =50 microg/kg per day) and long-term growth

  19. A swinging seesaw as a novel model mechanism for time-dependent hormesis under dose-dependent stimulatory and inhibitory effects: A case study on the toxicity of antibacterial chemicals to Aliivibrio fischeri.

    Science.gov (United States)

    Sun, Haoyu; Calabrese, Edward J; Zheng, Min; Wang, Dali; Pan, Yongzheng; Lin, Zhifen; Liu, Ying

    2018-08-01

    Hormesis occurs frequently in broadly ranging biological areas (e.g. plant biology, microbiology, biogerontology), toxicology, pharmacology and medicine. While numerous mechanisms (e.g. receptor and pathway mediated pathway responses) account for stimulatory and inhibitory features of hormetic dose responses, the vast majority emphasizes the inclusion of many doses but only one timepoint or use of a single optimized dose that is assessed over a broad range of timepoints. In this paper, a toxicity study was designed using a large number of properly spaced doses with responses determined over a large number of timepoints, which could help us reveal the underlying mechanism of hormesis. We present the results of a dose-time-response study on hormesis using five antibacterial chemicals on the bioluminescence of Aliivibrio fischeri, measuring expression of protein mRNA based on quorum sensing, simulating bioluminescent reaction and analyzing toxic actions of test chemicals. The findings show dose-time-dependent responses conforming to the hormetic dose-response model, while revealing unique response dynamics between agent induced stimulatory and inhibitory effects within bacterial growth phase dynamics. These dynamic dose-time features reveal a type of biological seesaw model that integrates stimulatory and inhibitory responses within unique growth phase, dose and time features, which has faultlessly explained the time-dependent hormetic phenomenon induced by five antibacterial chemicals (characterized by low-dose stimulation and high-dose inhibition). This study offers advances in understanding cellular dynamics, the biological integration of diverse and opposing responses and their role in evolutionary adaptive strategies to chemicals, which can provide new insight into the mechanistic investigation of hormesis. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Argon inhalation attenuates retinal apoptosis after ischemia/reperfusion injury in a time- and dose-dependent manner in rats.

    Directory of Open Access Journals (Sweden)

    Felix Ulbrich

    Full Text Available Retinal ischemia and reperfusion injuries (IRI permanently affect neuronal tissue and function by apoptosis and inflammation due to the limited regenerative potential of neurons. Recently, evidence emerged that the noble gas Argon exerts protective properties, while lacking any detrimental or adverse effects. We hypothesized that Argon inhalation after IRI would exert antiapoptotic effects in the retina, thereby protecting retinal ganglion cells (RGC of the rat's eye.IRI was performed on the left eyes of rats (n = 8 with or without inhaled Argon postconditioning (25, 50 and 75 Vol% for 1 hour immediately or delayed after ischemia (i.e. 1.5 and 3 hours. Retinal tissue was harvested after 24 hours to analyze mRNA and protein expression of Bcl-2, Bax and Caspase-3, NF-κB. Densities of fluorogold-prelabeled RGCs were analyzed 7 days after injury in whole-mounts. Histological tissue samples were prepared for immunohistochemistry and blood was analyzed regarding systemic effects of Argon or IRI. Statistics were performed using One-Way ANOVA.IRI induced RGC loss was reduced by Argon 75 Vol% inhalation and was dose-dependently attenuated by lower concentrations, or by delayed Argon inhalation (1504±300 vs. 2761±257; p<0.001. Moreover, Argon inhibited Bax and Bcl-2 mRNA expression significantly (Bax: 1.64±0.30 vs. 0.78±0.29 and Bcl-2: 2.07±0.29 vs. 0.99±0.22; both p<0.01, as well as caspase-3 cleavage (1.91±0.46 vs. 1.05±0.36; p<0.001. Expression of NF-κB was attenuated significantly. Immunohistochemistry revealed an affection of Müller cells and astrocytes. In addition, IRI induced leukocytosis was reduced significantly after Argon inhalation at 75 Vol%.Immediate and delayed Argon postconditioning protects IRI induced apoptotic loss of RGC in a time- and dose-dependent manner, possibly mediated by the inhibition of NF-κB. Further studies need to evaluate Argon's possible role as a therapeutic option.

  1. Different dose-dependent effects of hydrogen sulfide on ischemia-reperfusion induced acute kidney injury in rats

    Directory of Open Access Journals (Sweden)

    Fateme Azizi

    2017-12-01

    Conclusion: Our study demonstrates that different doses of Sodium hydrosulfide (NaHS can play diverse role in renal ischemia reperfusion injury. However, NaHS in the low-doses could protect the kidney from the RIR injury, in a higher dose NaHS exaggerated the renal function by increases plasma creatinine and BUN. Therefore, determining of the therapeutic doses of NaHS may be important in the protection of kidney from the RIR injury.

  2. Basic investigations on the performance of a normoxic polymer gel with tetrakis-hydroxy-methyl-phosphonium chloride as an oxygen scavenger: Reproducibility, accuracy, stability, and dose rate dependence

    International Nuclear Information System (INIS)

    Bayreder, Christian; Georg, Dietmar; Moser, Ewald; Berg, Andreas

    2006-01-01

    Magnetic resonance (MR)-based polymer gel dosimetry using normoxic polymer gels, represents a new dosimetric method specially suited for high-resolution three-dimensional dosimetric problems. The aim of this study was to investigate the dose response with regard to stability, accuracy, reproducibility, and the dose rate dependence. Tetrakis-hydroxy-methyl-phosphonium chloride (THPC) is used as an oxygen scavenger, and methacrylic acid as a monomer. Accuracy, reproducibility, and dose resolution were determined for MR protocols at low spatial resolution (typical for clinical scanners), medium, and microimaging-resolution protocols at three different dose levels. The dose-response stability and preirradiation-induced variations in R2, related to the time interval between preparation and irradiation of the polymer gel, were investigated. Also postirradiation stability of the polymer gel was considered. These experiments were performed using a 60 Co beam (E=1.2 MV) in a water phantom. Moreover, we investigated the dose rate dependence in the low, medium, and saturation dose region of the normoxic polymer gel using a linear accelerator at photon energy of 25 MV. MR scanning was performed on a 3 T whole body scanner (MEDSPEC 30/80, BRUKER BIOSPIN, Ettlingen, Germany) using several coils and different gradient systems adapted to the acquired spatial resolution investigated. For T2-parameter selective imaging and determination of the relaxation rate R2=1/T2, a multiple spin echo sequence with 20 equidistant echoes was used. With regard to preirradiation induced variations R2 increases significantly with the increasing time interval between the polymer gel preparation and irradiation. Only a slight increase in R2 can be observed for varying the postirradiation-time solely. The dose reproducibility at voxel volumes of about 1.4x1.4x2 mm 3 is better than 2%. The accuracy strongly depends on the calibration curve. THPC represents a very effective oxygen scavenger in

  3. SHOEBOX Modulates Root Meristem Size in Rice through Dose-Dependent Effects of Gibberellins on Cell Elongation and Proliferation.

    Science.gov (United States)

    Li, Jintao; Zhao, Yu; Chu, Huangwei; Wang, Likai; Fu, Yanru; Liu, Ping; Upadhyaya, Narayana; Chen, Chunli; Mou, Tongmin; Feng, Yuqi; Kumar, Prakash; Xu, Jian

    2015-08-01

    Little is known about how the size of meristem cells is regulated and whether it participates in the control of meristem size in plants. Here, we report our findings on shoebox (shb), a mild gibberellin (GA) deficient rice mutant that has a short root meristem size. Quantitative analysis of cortical cell length and number indicates that shb has shorter, rather than fewer, cells in the root meristem until around the fifth day after sowing, from which the number of cortical cells is also reduced. These defects can be either corrected by exogenous application of bioactive GA or induced in wild-type roots by a dose-dependent inhibitory effect of paclobutrazol on GA biosynthesis, suggesting that GA deficiency is the primary cause of shb mutant phenotypes. SHB encodes an AP2/ERF transcription factor that directly activates transcription of the GA biosynthesis gene KS1. Thus, root meristem size in rice is modulated by SHB-mediated GA biosynthesis that regulates the elongation and proliferation of meristem cells in a developmental stage-specific manner.

  4. SHOEBOX Modulates Root Meristem Size in Rice through Dose-Dependent Effects of Gibberellins on Cell Elongation and Proliferation.

    Directory of Open Access Journals (Sweden)

    Jintao Li

    2015-08-01

    Full Text Available Little is known about how the size of meristem cells is regulated and whether it participates in the control of meristem size in plants. Here, we report our findings on shoebox (shb, a mild gibberellin (GA deficient rice mutant that has a short root meristem size. Quantitative analysis of cortical cell length and number indicates that shb has shorter, rather than fewer, cells in the root meristem until around the fifth day after sowing, from which the number of cortical cells is also reduced. These defects can be either corrected by exogenous application of bioactive GA or induced in wild-type roots by a dose-dependent inhibitory effect of paclobutrazol on GA biosynthesis, suggesting that GA deficiency is the primary cause of shb mutant phenotypes. SHB encodes an AP2/ERF transcription factor that directly activates transcription of the GA biosynthesis gene KS1. Thus, root meristem size in rice is modulated by SHB-mediated GA biosynthesis that regulates the elongation and proliferation of meristem cells in a developmental stage-specific manner.

  5. Cholecalciferol attenuates perseverative behavior associated with developmental alcohol exposure in rats in a dose-dependent manner.

    Science.gov (United States)

    Idrus, N M; Happer, J P; Thomas, J D

    2013-07-01

    Alcohol is a known teratogen that is estimated to affect 2-5% of the births in the U.S. Prenatal alcohol exposure can produce physical features such as facial dysmorphology, physiological alterations such as cell loss in the central nervous system (CNS), and behavioral changes that include hyperactivity, cognitive deficits, and motor dysfunction. The range of effects associated with prenatal alcohol exposure is referred to as fetal alcohol spectrum disorders (FASD). Despite preventative measures, some women continue to drink while pregnant. Therefore, identifying interventions that reduce the severity of FASD is critical. This study investigated one such potential intervention, vitamin D3, a nutrient that exerts neuroprotective properties. The present study determined whether cholecalciferol, a common vitamin D3 nutritional supplement, could serve as a means of mitigating alcohol-related learning deficits. Using a rat model of FASD, cholecalciferol was given before, during, and after 3rd trimester equivalent alcohol exposure. Three weeks after cholecalciferol treatment, subjects were tested on a serial spatial discrimination reversal learning task. Animals exposed to ethanol committed significantly more errors compared to controls. Cholecalciferol treatment reduced perseverative behavior that is associated with developmental alcohol exposure in a dose-dependent manner. These data have important implications for the treatment of FASD and suggest that cholecalciferol may reduce some aspects of FASD. This article is part of a Special Issue entitled 'Vitamin D Workshop'. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Dose-dependency and reversibility of radiation-induced injury in cardiac explant-derived cells of mice

    Science.gov (United States)

    Luo, Lan; Yan, Chen; Urata, Yoshishige; Hasan, Al Shaimaa; Goto, Shinji; Guo, Chang-Ying; Zhang, Shouhua; Li, Tao-Sheng

    2017-01-01

    We evaluated the dose-dependency and reversibility of radiation-induced injury in cardiac explant-derived cells (CDCs), a mixed cell population grown from heart tissues. Adult C57BL/6 mice were exposed to 0, 10, 50 and 250 mGy γ-rays for 7 days and atrial tissues were collected for experiments 24 hours after last exposure. The number of CDCs was significantly decreased by daily exposure to over 250 mGy. Interestingly, daily exposure to over 50 mGy significantly decreased the c-kit expression and telomerase activity, increased 53BP1 foci in the nuclei of CDCs. However, CD90 expression and growth factors production in CDCs were not significantly changed even after daily exposure to 250 mGy. We further evaluated the reversibility of radiation-induced injury in CDCs at 1 week and 3 weeks after a single exposure to 3 Gy γ-rays. The number and growth factors production of CDCs were soon recovered at 1 week. However, the increased expression of CD90 were retained at 1 week, but recovered at 3 weeks. Moreover, the decreased expression of c-kit, impaired telomerase activity, and increased 53BP1 foci were poorly recovered even at 3 weeks. These data may help us to find the most sensitive and reliable bio-parameter(s) for evaluating radiation-induced injury in CDCs. PMID:28098222

  7. Dose-Dependent Antimicrobial Activity of Silver Nanoparticles on Polycaprolactone Fibers against Gram-Positive and Gram-Negative Bacteria

    Directory of Open Access Journals (Sweden)

    Erick Pazos-Ortiz

    2017-01-01

    Full Text Available The adhesion ability and adaptability of bacteria, coupled with constant use of the same bactericides, have made the increase in the diversity of treatments against infections necessary. Nanotechnology has played an important role in the search for new ways to prevent and treat infections, including the use of metallic nanoparticles with antibacterial properties. In this study, we worked on the design of a composite of silver nanoparticles (AgNPS embedded in poly-epsilon-caprolactone nanofibers and evaluated its antimicrobial properties against various Gram-positive and Gram-negative microorganisms associated with drug-resistant infections. Polycaprolactone-silver composites (PCL-AgNPs were prepared in two steps. The first step consisted in the reduction in situ of Ag+ ions using N,N-dimethylformamide (DMF in tetrahydrofuran (THF solution, and the second step involved the simple addition of polycaprolactone before electrospinning process. Antibacterial activity of PCL-AgNPs nanofibers against E. coli, S. mutans, K. pneumoniae, S. aureus, P. aeruginosa, and B. subtilis was evaluated. Results showed sensibility of E. coli, K. pneumoniae, S. aureus, and P. aeruginosa, but not for B. subtilis and S. mutans. This antimicrobial activity of PCL-AgNPs showed significant positive correlations associated with the dose-dependent effect. The antibacterial property of the PCL/Ag nanofibers might have high potential medical applications in drug-resistant infections.

  8. Indoor visible mold and mold odor are associated with new-onset childhood wheeze in a dose-dependent manner.

    Science.gov (United States)

    Shorter, Caroline; Crane, Julian; Pierse, Nevil; Barnes, Phillipa; Kang, Janice; Wickens, Kristin; Douwes, Jeroen; Stanley, Thorsten; Täubel, Martin; Hyvärinen, Anne; Howden-Chapman, Philippa

    2018-01-01

    Evidence is accumulating that indoor dampness and mold are associated with the development of asthma. The underlying mechanisms remain unknown. New Zealand has high rates of both asthma and indoor mold and is ideally placed to investigate this. We conducted an incident case-control study involving 150 children with new-onset wheeze, aged between 1 and 7 years, each matched to two control children with no history of wheezing. Each participant's home was assessed for moisture damage, condensation, and mold growth by researchers, an independent building assessor and parents. Repeated measures of temperature and humidity were made, and electrostatic dust cloths were used to collect airborne microbes. Cloths were analyzed using qPCR. Children were skin prick tested for aeroallergens to establish atopy. Strong positive associations were found between observations of visible mold and new-onset wheezing in children (adjusted odds ratios ranged between 1.30 and 3.56; P ≤ .05). Visible mold and mold odor were consistently associated with new-onset wheezing in a dose-dependent manner. Measurements of qPCR microbial levels, temperature, and humidity were not associated with new-onset wheezing. The association between mold and new-onset wheeze was not modified by atopic status, suggesting a non-allergic association. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. He-Ne laser irradiation affects proliferation of cultured rat Schwann cells in a dose-dependent manner

    International Nuclear Information System (INIS)

    Breugel, H.H.F.I. van; Bar, P.R.

    1993-01-01

    Schwann cell proliferation is considered an essential part of Wallerian degeneration after nerve damage. Laminin, an important component of the extracellular matrix and produced by Schwann cells, provides a preferred substrate for outgrowing axons. To study whether low energy (He-Ne) laser irradiation may exert a positive effect on nerve regeneration through an effect on Schwann cells, its effect was evaluated in vitro. Schwann cells were isolated from sciatic nerves of 4-5-day old Wistar rats and cultures on 96-multiwell plates. The cells were irradiated by a He-Ne laser beam. At three consecutive days, starting either at day 5 or day 8, cells were irradiated each day for 0.5, 1, 2, 5 or 10 min. Both cell number and laminin production were determined for each irradiation condition within one experiment. Schwann cells that were irradiated from day 8 on were hardly affected by laser irradiation. However, the proliferation of cells that were irradiated starting on day 5 was significantly increased after 1, 2 and 5 min of daily irradiation, compared to non-irradiated control cultures. The lamin production per cell of these Schwann cells was not significantly altered. From these results we conclude that He-Ne laser irradiation can modulate proliferation of rat Schwann cells in vitro in a dose-dependent manner. (Author)

  10. Host manipulation by the orange leafhopper Cicadulina bipunctata: gall induction on distant leaves by dose-dependent stimulation

    Science.gov (United States)

    Matsukura, Keiichiro; Matsumura, Masaya; Tokuda, Makoto

    2009-09-01

    The evolution of the gall-inducing ability in insects and the adaptive significance of the galling habit have been addressed by many studies. Cicadulina bipunctata, the maize orange leafhopper, is an ideal study organism for evaluating these topics because it can be mass-reared and it feeds on model plants such as rice ( Oryza sativa) and maize ( Zea mays). To reveal differences between gall inductions by C. bipunctata and other gall inducers, we conducted four experiments concerning (a) the relationship between the feeding site and gall-induction sites of C. bipunctata on maize, (b) the effects of leafhopper sex and density, (c) the effects of length of infestation on gall induction, and (d) the effects of continuous infestation. C. bipunctata did not induce galls on the leaves where it fed but induced galls on other leaves situated at more distal positions. The degree of gall induction was significantly correlated with infestation density and length. These results indicate that C. bipunctata induces galls in a dose-dependent manner on leaves distant from feeding sites, probably by injecting chemical(s) to the plant during feeding. We suggest that insect galls are induced by a chemical stimulus injected by gall inducers during feeding into the hosts.

  11. Cell nanomechanics and focal adhesions are regulated by retinol and conjugated linoleic acid in a dose-dependent manner

    International Nuclear Information System (INIS)

    Silberberg, Yaron R; Horton, Michael A; Pelling, Andrew E; Yakubov, Gleb E

    2009-01-01

    Retinol and conjugated linoleic acid (CLA) have previously been shown to have an important role in gene expression and various cellular processes, including differentiation, proliferation and cell death. In this study we have investigated the effect of retinol and CLA, both individually and in combination, on the intracellular cytoskeleton, focal adhesions (FAs) and the nanomechanical properties of 3T3 fibroblasts. We observed a dose-dependent decrease in the formation of FAs following treatment with either compound, which was directly correlated to an increase in cell height (>30%) and a decrease in the measured Young's modulus (∼28%). Furthermore, treatments with both compounds demonstrated an increased effect and led to a reduction of>70% in the average number of FAs per cell and a decrease of >50% in average cell stiffness. These data reveal that retinol and CLA disrupt FA formation, leading to an increase in cell height and a significant decrease in stiffness. These results may broaden our understanding of the interplay between cell nanomechanics and cellular contact with the external microenvironment, and help to shed light on the important role of retinoids and CLA in health and disease.

  12. Study of positional dependence of dose to bladder, pelvic wall and rectal points in High-Dose-Rate Brachytherapy in cervical cancer patients

    International Nuclear Information System (INIS)

    Talluri, Anil Kumar; Alluri, Krishnam Raju; Gudipudi, Deleep Kumar; Ahamed, Shabbir; Sresty, Madhusudhana M.; Reddy, Aparna Yarrama

    2013-01-01

    The objective of the study is to examine the variation in doses to, Bladder, pelvic wall and Rectal Points when a patient is simulated in Supine (S Position) and Lithotomy M shaped positions (LM Position), respectively as part of Intracavitary Brachytherapy in Cervical Cancer patients. Patients (n = 19) were simulated and orthogonal images were taken in S Position and LM Positions on a physical simulator. Digital orthogonal X-ray images were transferred to Brachyvision Treatment Planning System via Dicom to generate treatment plans. Radio opaque dye of 7 ml was injected into the Foley bulb for identification and digitization of International Commission on Radiological Units and Measurements (ICRU) Bladder point. Pelvic side wall points were marked in accordance with ICRU 38 recommendations. A Rectal tube containing dummy source marker wire was used to identify Rectal Point. Students' t-test was used to analyze the results. Doses in LM Position were lower and statistically significant when compared to S Position for ICRU Bladder Point, pelvic walls and Rectal Point. It was observed that movement of applicator could be the reason for the variations in doses between the two positions. Bladder, pelvic wall and rectal points systematically registered lower doses in LM Position as compared to S Position. (author)

  13. SU-F-T-113: Inherent Functional Dependence of Spinal Cord Doses of Variable Irradiated Volumes in Spine SBRT

    Energy Technology Data Exchange (ETDEWEB)

    Ma, L; Braunstein, S; Chiu, J [University of California San Francisco, San Francisco, CA (United States); Sahgal, A [Sunnybrook Health Sciences Center, University of Toronto, Toronto, Ontario (Canada)

    2016-06-15

    Purpose: Spinal cord tolerance for SBRT has been recommended for the maximum point dose level or at irradiated volumes such as 0.35 mL or 10% of contoured volumes. In this study, we investigated an inherent functional relationship that associates these dose surrogates for irradiated spinal cord volumes of up to 3.0 mL. Methods: A hidden variable termed as Effective Dose Radius (EDR) was formulated based on a dose fall-off model to correlate dose at irradiated spinal cord volumes ranging from 0 mL (point maximum) to 3.0 mL. A cohort of 15 spine SBRT cases was randomly selected to derive an EDR-parameterized formula. The mean prescription dose for the studied cases was 21.0±8.0 Gy (range, 10–40Gy) delivered in 3±1 fractions with target volumes of 39.1 ± 70.6 mL. Linear regression and variance analysis were performed for the fitting parameters of variable EDR values. Results: No direct correlation was found between the dose at maximum point and doses at variable spinal cord volumes. For example, Pearson R{sup 2} = 0.643 and R{sup 2}= 0.491 were obtained when correlating the point maximum dose with the spinal cord dose at 1 mL and 3 mL, respectively. However, near perfect correlation (R{sup 2} ≥0.99) was obtained when corresponding parameterized EDRs. Specifically, Pearson R{sup 2}= 0.996 and R{sup 2} = 0.990 were obtained when correlating EDR (maximum point dose) with EDR (dose at 1 mL) and EDR(dose at 3 mL), respectively. As a result, high confidence level look-up tables were established to correlate spinal cord doses at the maximum point to any finite irradiated volumes. Conclusion: An inherent functional relationship was demonstrated for spine SBRT. Such a relationship unifies dose surrogates at variable cord volumes and proves that a single dose surrogate (e.g. point maximum dose) is mathematically sufficient in constraining the overall spinal cord dose tolerance for SBRT.

  14. An international pooled analysis for obtaining a benchmark dose for environmental lead exposure in children

    DEFF Research Database (Denmark)

    Budtz-Jørgensen, Esben; Bellinger, David; Lanphear, Bruce

    2013-01-01

    Lead is a recognized neurotoxicant, but estimating effects at the lowest measurable levels is difficult. An international pooled analysis of data from seven cohort studies reported an inverse and supra-linear relationship between blood lead concentrations and IQ scores in children. The lack...... of a clear threshold presents a challenge to the identification of an acceptable level of exposure. The benchmark dose (BMD) is defined as the dose that leads to a specific known loss. As an alternative to elusive thresholds, the BMD is being used increasingly by regulatory authorities. Using the pooled data...... yielding lower confidence limits (BMDLs) of about 0.1-1.0 μ g/dL for the dose leading to a loss of one IQ point. We conclude that current allowable blood lead concentrations need to be lowered and further prevention efforts are needed to protect children from lead toxicity....

  15. DNA adducts and liver DNA replication in rats during chronic exposure to N-nitrosodimethylamine (NDMA) and their relationships to the dose-dependence of NDMA hepatocarcinogenesis.

    Science.gov (United States)

    Souliotis, Vassilis L; Henneman, John R; Reed, Carl D; Chhabra, Saranjit K; Diwan, Bhalchandra A; Anderson, Lucy M; Kyrtopoulos, Soterios A

    2002-03-20

    Exposure of rats to the hepatocarcinogen N-nitrosodimethylamine (NDMA) (0.2-2.64 ppm in the drinking water) for up to 180 days resulted in rapid accumulation of N7- and O6-methylguanine in liver and white blood cell DNA, maximum adduct levels being reached within 1-7 days, depending on the dose. The levels of both adducts remained constant up to treatment day 28, subsequently declining slowly to about 40% of maximal levels for the liver and 60% for white blood cells by day 180. In order to elucidate the role of DNA replication in NDMA hepatocarcinogenesis, changes in liver cell labeling index (LI) were also measured on treatment days 21, 120 and 180. Although the time- and dose-dependence of the observed effects were complex, a clear trend towards increased rates of hepatocyte LI, as indicated by BrdU incorporation, with increasing NDMA doses was evident, particularly above 1 ppm, a concentration above which NDMA hepatocarcinogenicity is known to increase sharply. In contrast, no increase in Kupffer cell DNA replication was found at any of the doses employed, in accordance with the low susceptibility of these cells to NDMA-induced carcinogenesis. No significant increase in the occurrence of necrotic or apoptotic cells was noted under the treatment conditions employed. These results suggest that, in addition to the accumulation of DNA damage, alterations in hepatocyte DNA replication during the chronic NDMA exposure may influence the dose-dependence of its carcinogenic efficacy.

  16. Current Smoking Dose-Dependently Associated with Decreased β-Cell Function in Chinese Men without Diabetes

    Directory of Open Access Journals (Sweden)

    Chun Wang

    2015-01-01

    Full Text Available The aim of this study was to evaluate the associations between chronic smoking and insulin resistance and β-cell function in Chinese men without diabetes. A total of 1,568 participants were recruited by multistage sampling. Using homeostatic model assessment (HOMA, geometric means of insulin resistance (HOMA-IR and β-cell function (HOMA-β with 95% confidence interval (CI were calculated by general linear model. Odds ratios (ORs with 95% CI were estimated to evaluate the associations between smoking status and insulin resistance and β-cell deficiency under a logistic regression model. Current smokers had higher levels of 2 h glucose (6.66 versus 6.48 mmol/L for oral glucose tolerance test and lower levels of fasting insulin (5.68 versus 6.03 mU/L than never smokers. The adjusted means for HOMA-β (% were 54.86 in current smokers and 58.81 in never smokers (P=0.0257. Current smoking was associated with β-cell deficiency (OR 1.29, 95% CI 1.01–1.64 compared to never smoking. The β-cell function gradually decreased with increasing smoking intensity (Ptrend=0.0026, and the differences were statistically significant when the pack-year of smoking was 20 or above. No association was observed between smoking status and HOMA-IR. Our study suggested that chronic smoking may dose-dependently suppress insulin secretion in Chinese men.

  17. Respiratory function in healthy ever-smokers is impaired by smoking habits in a dose-dependent manner.

    Science.gov (United States)

    Osanai, Shinobu; Ogasa, Toshiyuki; Sumitomo, Kazuhiro; Hasebe, Naoyuki

    2018-01-01

    There is limited information about the respiratory function of ever-smokers without lung disorders. We sought to assess the effects of smoking habits on respiratory function in subjects without lung disorders. Subjects were recruited from among patients without any evidence of respiratory disorders who visited rural primary care clinics. Each participant was asked to answer a questionnaire that included questions smoking history. Their forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were measured. We analyzed 802 subjects (364 men and 438 women). The means of the lambda-mu-sigma method derived z-score of FEV1 (zFEV1) both in current-smokers and ex-smokers were lower than that in never-smokers. The mean zFEV1 in the ever-smokers with more than 30 pack-years of smoking history were lower than that in the ever-smokers with less smoking history. Univariate analysis showed that there were significant negative correlations between pack-years and zFEV1 both in the ex-smokers and current-smokers. There was no significant correlation between the duration of smoking cessation and zFEV1 in the ex-smokers. Our data suggests that respiratory function in healthy ever-smokers is decreased based on smoking habits in a dose-dependent manner. Even after a long period of smoking cessation, the decreased respiratory function seems to be maintained in ex-smokers. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

  18. The Dose-Dependent Effects of Vascular Risk Factors on Dynamic Compensatory Neural Processes in Mild Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Haifeng Chen

    2018-05-01

    Full Text Available Background/Objectives: Mild cognitive impairment (MCI has been associated with risk for Alzheimer's Disease (AD. Previous investigations have suggested that vascular risk factors (VRFs were associated with cognitive decline and AD pathogenesis, and the intervention of VRFs may be a possible way to prevent dementia. However, in MCI, little is known about the potential impacts of VRFs on neural networks and their neural substrates, which may be a neuroimaging biomarker of the disease progression.Methods: 128 elderly Han Chinese participants (67 MCI subjects and 61 matched normal elderly with or without VRFs (hypertension, diabetes mellitus, hypercholesterolemia, smoking and alcohol drinking underwent the resting-state functional magnetic resonance imaging (fMRI and neuropsychological tests. We obtained the default mode network (DMN to identify alterations in MCI with the varying number of the VRF and analyzed the significant correlation with behavioral performance.Results: The effects of VRF on the DMN were primarily in bilateral dorsolateral prefrontal cortex (DLPFC (i.e., middle frontal gyrus. Normal elderly showed the gradually increased functional activity of DLPFC, while a fluctuant activation of DLPFC was displayed in MCI with the growing number of the VRF. Interestingly, the left DLPFC further displayed significantly dynamic correlation with executive function as the variation of VRF loading. Initial level of compensation was observed in normal aging and none-vascular risk factor (NVRF MCI, while these compensatory neural processes were suppressed in One-VRF MCI and were subsequently re-aroused in Over-One-VRF MCI.Conclusions: These findings suggested that the dose-dependent effects of VRF on DLPFC were highlighted in MCI, and the dynamic compensatory neural processes that fluctuated along with variations of VRF loading could be key role in the progression of MCI.

  19. Dose-dependent protective effect of coffee, tea, and smoking in Parkinson's disease: a study in ethnic Chinese.

    Science.gov (United States)

    Tan, E-K; Tan, C; Fook-Chong, S M C; Lum, S Y; Chai, A; Chung, H; Shen, H; Zhao, Y; Teoh, M L; Yih, Y; Pavanni, R; Chandran, V R; Wong, M C

    2003-12-15

    Few studies have examined the relationship of coffee and tea in Parkinson's disease (PD). The potential protective effect of coffee intake and risk of PD has not been studied in a Chinese population. There is a high prevalence of caffeine takers among Chinese in our population. We undertook a case control study to examine the relationship between coffee and tea drinking, cigarette smoking, and other enviromental factors and risk of PD among ethnic Chinese in our population. 300 PD and 500 population controls were initially screened. Two hundred case control pairs matched for age, gender, and race were finally included in the analysis. Univariate analysis revealed significant association of PD with coffee drinking (pcoffee drunk (OR 0.787, 95%CI 0.664-0.932, p=0.006), amount of tea drunk (OR 0.724, 95%CI 0.559-0.937, p=0.014), number of cigarettes smoked (OR 0.384, 95%CI 0.204-0.722, p=0.003), history of heavy metal and toxin exposure (OR 11.837, 95%CI 1.075-130.366, p=0.044), and heart disease (OR 5.518, 95%CI 1.377-22.116, p=0.016) to be significant factors associated with PD. One unit of coffee and tea (3 cups/day for 10 years) would lead to a 22% and 28% risk reduction of PD. One unit of cigarette smoke (3 packs/day for 10 years) reduced the risk of PD by 62%. We demonstrated a dose-dependent protective effect of PD in coffee and tea drinkers and smokers in an ethnic Chinese population. A history of exposure to heavy metals increased the risk of PD, supporting the multifactorial etiologies of the disease.

  20. Inhibition of the iNOS pathway in inflammatory macrophages by low-dose X-irradiation in vitro. Is there a time dependence?

    International Nuclear Information System (INIS)

    Hildebrandt, G.; Loppnow, G.; Jahns, J.; Hindemith, M.; Kamprad, F.; Anderegg, U.; Saalbach, A.

    2003-01-01

    Background: Low radiation doses (≤ 1.25 Gy), if applied 6 h before or after stimulation, are known to inhibit the inducible nitric oxide synthase (iNOS) pathway in inflammatory macrophages in vitro. We therefore investigated the time dependence and the underlying molecular mechanism of this effect, since it may be involved in the clinically observed anti-inflammatory and analgesic efficacy of low-dose radiotherapy. Material and Methods: Metabolic activity, nitric oxide (NO) production, iNOS- and hemoxygenase 1-(HO-1-)protein and -mRNA expression by macrophages in vitro after stimulation with LPS/IFN-γ (0.1 μg ml -1 /100 U ml -1 ) were investigated. Irradiation was performed at 6, 4, 2 h before and 0, 2, 4, 6 h after stimulation with doses ranging from 0.3 to 10 Gy. For each group, three independent experiments were performed over a period of 30 h with sampling intervals of 3 h. Results: In stimulated macrophages, metabolic activity was not affected by radiation doses up to 10 Gy. A dose-dependent modulation of the cumulative NO production was observed with significant inhibition by low radiation doses (≤ 1.25 Gy) and return to control level and even higher concentrations by higher doses (≥ 5 Gy). The degree of inhibition did not show any significant time dependence within the experimental time window used. The iNOS-mRNA expression 3-18 h following stimulation and subsequent irradiation was not affected by doses ≤ 1.25 Gy. The iNOS-protein expression 6-24 h following stimulation and subsequent irradiation was reduced by doses ≤ 1.25 Gy. By contrast, neither HO-1-protein nor HO-1-mRNA expression at the same time points was influenced by these low doses. Conclusion: The inhibitory interference of low radiation doses with the iNOS pathway in inflammatory macrophages appears to be based on radiation effects on the translational and posttranslational control mechanisms of iNOS activity. However, contrary to our working hypothesis this is not related to

  1. Pharmacokinetics and pharmacodynamics of high doses of pharmaceutically prepared heroin, by intravenous or by inhalation route in opioid-dependent patients

    NARCIS (Netherlands)

    Rook, Elisabeth J.; van Ree, Jan M.; van den Brink, Wim; Hillebrand, Michel J. X.; Huitema, Alwin D. R.; Hendriks, Vincent M.; Beijnen, Jos H.

    2006-01-01

    A pharmacokinetic-pharmacodynamic study was performed in opioid-dependent patients in the Netherlands, who were currently treated with high doses of pharmaceutically prepared heroin on medical prescription. Besides intravenous heroin, heroin was prescribed for inhalation by "chasing the dragon"

  2. Dose-dependent inhibition of CYP1A2, CYP2C19 and CYP2D6 by citalopram, fluoxetine, fluvoxamine and paroxetine

    DEFF Research Database (Denmark)

    Jeppesen, U; Gram, L F; Vistisen, K

    1996-01-01

    OBJECTIVE: The purpose of this pharmacokinetic study was to investigate the dose-dependent inhibition of model substrates for CYP2D6, CYP2C19 and CYP1A2 by four marketed selective serotonin reuptake inhibitors (SSRIs): citalopram, fluoxetine, fluvoxamine and paroxetine. METHODS: The study...

  3. 2,3-Butanedione monoxime facilitates successful resuscitation in a dose-dependent fashion in a pig model of cardiac arrest.

    Science.gov (United States)

    Lee, Byung Kook; Kim, Mu Jin; Jeung, Kyung Woon; Choi, Sung Soo; Park, Sang Wook; Yun, Seong Woo; Lee, Sung Min; Lee, Dong Hun; Min, Yong Il

    2016-06-01

    Ischemic contracture compromises the hemodynamic effectiveness of cardiopulmonary resuscitation (CPR) and resuscitability from cardiac arrest. In a pig model of cardiac arrest, 2,3-butanedione monoxime (BDM) attenuated ischemic contracture. We investigated the effects of different doses of BDM to determine whether increasing the dose of BDM could improve the hemodynamic effectiveness of CPR further, thus ultimately improving resuscitability. After 16minutes of untreated ventricular fibrillation and 8minutes of basic life support, 36 pigs were divided randomly into 3 groups that received 50mg/kg (low-dose group) of BDM, 100mg/kg (high-dose group) of BDM, or an equivalent volume of saline (control group) during advanced cardiovascular life support. During advanced cardiovascular life support, the control group showed an increase in left ventricular (LV) wall thickness and a decrease in LV chamber area. In contrast, the BDM-treated groups showed a decrease in the LV wall thickness and an increase in the LV chamber area in a dose-dependent fashion. Mixed-model analyses of the LV wall thickness and LV chamber area revealed significant group effects and group-time interactions. Central venous oxygen saturation at 3minutes after the drug administration was 21.6% (18.4-31.9), 39.2% (28.8-53.7), and 54.0% (47.5-69.4) in the control, low-dose, and high-dose groups, respectively (Pfashion. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Sun-Induced Changes in Stratum Corneum Function Are Gender and Dose Dependent in a Chinese Population

    Science.gov (United States)

    Liu, Z.; Fluhr, J.W.; Song, S.P.; Sun, Z.; Wang, H.; Shi, Y.J.; Elias, P.M.; Man, M.-Q.

    2010-01-01

    Previous studies have demonstrated that UVB radiation changes the epidermal permeability barrier and stratum corneum (SC) hydration. It is well known that sun exposure causes erythema, sunburn and melanoma. However, whether daily sun exposure alters SC integrity and epidermal permeability barrier function is largely unknown, especially in Chinese subjects. In the present study, we assess the SC integrity, SC hydration and epidermal permeability barrier function following various doses of sun exposure. A total of 258 subjects (124 males and 134 females) aged 18–50 years were enrolled. A multifunctional skin physiology monitor (Courage & Khazaka MPA5) was used to measure SC hydration and transepidermal water loss (TEWL) on the forearms. In males, basal TEWL was higher with higher doses of sun exposure than with lower doses and control, whereas in females, basal TEWL was higher with lower doses of sun exposure than with higher doses and control. In the group with higher doses of sun exposure, TEWL in females was significantly lower than that in males. The barrier recovery was faster in females than in males in both control and lower-dose groups. In both males and females, barrier recovery was delayed with higher doses of sun exposure. In males, sun exposure did not alter SC hydration, while in females SC hydration was lower with lower doses of sun exposure as compared with control and higher doses of sun exposure. These results demonstrated that sun-induced changes in SC function and SC hydration vary with gender and the extent of sun exposure. PMID:20571289

  5. Dose-dependent effects of theta burst rTMS on cortical excitability and resting-state connectivity of the human motor system.

    Science.gov (United States)

    Nettekoven, Charlotte; Volz, Lukas J; Kutscha, Martha; Pool, Eva-Maria; Rehme, Anne K; Eickhoff, Simon B; Fink, Gereon R; Grefkes, Christian

    2014-05-14

    Theta burst stimulation (TBS), a specific protocol of repetitive transcranial magnetic stimulation (rTMS), induces changes in cortical excitability that last beyond stimulation. TBS-induced aftereffects, however, vary between subjects, and the mechanisms underlying these aftereffects to date remain poorly understood. Therefore, the purpose of this study was to investigate whether increasing the number of pulses of intermittent TBS (iTBS) (1) increases cortical excitability as measured by motor-evoked potentials (MEPs) and (2) alters functional connectivity measured using resting-state fMRI, in a dose-dependent manner. Sixteen healthy, human subjects received three serially applied iTBS blocks of 600 pulses over the primary motor cortex (M1 stimulation) and the parieto-occipital vertex (sham stimulation) to test for dose-dependent iTBS effects on cortical excitability and functional connectivity (four sessions in total). iTBS over M1 increased MEP amplitudes compared with sham stimulation after each stimulation block. Although the increase in MEP amplitudes did not differ between the first and second block of M1 stimulation, we observed a significant increase after three blocks (1800 pulses). Furthermore, iTBS enhanced resting-state functional connectivity between the stimulated M1 and premotor regions in both hemispheres. Functional connectivity between M1 and ipsilateral dorsal premotor cortex further increased dose-dependently after 1800 pulses of iTBS over M1. However, no correlation between changes in MEP amplitudes and functional connectivity was detected. In summary, our data show that increasing the number of iTBS stimulation blocks results in dose-dependent effects at the local level (cortical excitability) as well as at a systems level (functional connectivity) with a dose-dependent enhancement of dorsal premotor cortex-M1 connectivity. Copyright © 2014 the authors 0270-6474/14/346849-11$15.00/0.

  6. Key enzymes of gluconeogenesis are dose-dependently reduced in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-treated rats

    Energy Technology Data Exchange (ETDEWEB)

    Weber, L.W.D.; Rozman, K. (Kansas Univ., Kansas City, KS (USA). Dept. of Pharmacology, Toxicology and Therapeutics Gesellschaft fuer Strahlen- und Umweltforschung mbH Muenchen (GSF), Neuherberg (Germany, F.R.). Inst. fuer Toxikologie); Lebofsky, M. (Kansas Univ., Kansas City, KS (USA). Dept. of Pharmacology, Toxicology and Therapeutics); Greim, H. (Gesellschaft fuer Strahlen- und Umweltforschung mbH Muenchen (GSF), Neuherberg (Germany, F.R.). Inst. fuer Toxikologie)

    1991-02-01

    Male Sprague-Dawley rats (240-245 g) were dosed ip with 5, 15, 25, or 125 {mu}g/kg -,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in corn oil. Ad libitum-fed and pair-fed controls received vehicle (4 ml/kg) alone. Two or 8 days after dosing five rats of each group were sacrificed, their livers removed and assayed for the activities of three gluconeogenic enzymes, (phosphoenol-pyruvate carboxykinase (PEPCK; EC 4.1.1.32), pyruvate carboxylase (PC; EC 6.4.1.1.), and glucose-6-phosphatase (G-6-Pase, EC 3.1.3.9)), and one glycolytic enzyme (pyruvate kinase (PK; EC 2.7.1.40)) by established procedures. The activity of PK was not affected by TCDD at either time point. The activity of G-6-Phase tended to be decreased in TCDD-treated animals, as compared to pair-fed controls, but the decrease was variable without an apparent dose-response. The activity of PEPCK was significantly decreased 2 days after dosing, but a clear dose-response was apparent only at the 8-day time point. Maximum loss of activity at the highest dose was 56% below pair-fed control levels. PC activity was slightly decreased 2 days after TCDD treatment and displayed statistically significant, dose-dependent reduction by 8 days after dosing with a 49% loss of enzyme activity after the highest dose. It is concluded that inhibition of gluconeogenesis by TCDD previously demonstrated in vivo is probably due to decreased activities of PEPCK and PC. The data also support the prevailing view that PEPCK and PC are rate-determining enzymes in gluconeogenesis. (orig.).

  7. Dependence of the rate of DNA synthesis in x-irradiated HeLa S3 cells on dose and time after exposure

    International Nuclear Information System (INIS)

    Tolmach, L.J.; Jones, R.W.

    1977-01-01

    After irradiation of randomly dividing cultures of HeLa S3 cells with 220-kV x rays, the rate of DNA synthesis, measured by pulsed incorporation of labeled thymidine, falls nearly exponentially with time (t/sub 1/2/ approximately 1.3 hr), in a dose-independent fashion. The fall is less rapid than that observed after addition of inhibitors of protein synthesis. With doses up to 8 krad, the rate reaches a minimum and begins to increase after 1-3 hr, the minima occurring at lower values and at slightly later times with increasing dose. The increase appears to be roughly linear for about 6 hr, with the slope an inverse function of dose in the range 1-8 krad. About 7-9 hr after the completion of irradiation, the rate again falls, although no more than 10 percent of the cells die sooner than 14 hr after irradiation with 8 krad (and later with smaller doses). Fluorodeoxyuridine-mediated delay in expression of the depression, described previously for doses up to 1 krad, occurs also at higher doses. During the period when the rate per culture rises, the rate in the individual cells, measured autoradiographically, appears to increase also, i.e., the rise presumably does not merely reflect populational shifts. The initial descending portion of the rate curve can be at least partially separated from the ascending portion by administering the total dose in suitably spaced fractions. If interpreted in terms of the model that attributes the initial depression in rate of synthesis to a temporary absence of replicon initiation, the results indicate that initiation is halted by an x-ray dose smaller than 1 krad; that it begins again after a dose-dependent delay amounting to about 0.7 hr after 1 krad and 1.5 hr after 7 krad; and that once begun, the rate of synthesis increases in a dose-dependent fashion. The second depression might derive from synchronization and/or from the imminence of cell death

  8. Dose-dependent effect of alpha-lactalbumin in combination with two different doses of glucose on the plasma Trp/LNAA ratio

    NARCIS (Netherlands)

    Markus, C.R.; Klöpping-Ketelaars, W.I.; Pasman, W.; Klarenbeek, B.; Berg, H. van den

    2000-01-01

    A deficient brain serotonin function has been demonstrated in psychiatric disorders and increases in brain serotonin ameliorate emotional and behavioural abnormalities found in depression. The uptake of the serotonin precursor tryptophan into the brain is dependent on nutrients that influence the

  9. [Dose-Response Dependences for Frequency of RET/PTC Gene Rearrangements in Papillary Thyroid Carcinoma after Irradiation. Simple Pooling Analysis of Molecular Epidemiological Data].

    Science.gov (United States)

    Koterov, A N; Ushenkova, L N; Biryukov, A P

    2016-01-01

    On the basis of all possible publications on the theme included in the previously formed base of sources on molecular epidemiology of RET/PTC rearrangements in thyroid papillary carcinoma a pooled analysis ("simple pooling data") on determination of the dose-effect dependences for RET/PTC frequency in radiogenic carcinomas of various irradiated groups was performed. (They are groups subjected to radiotherapeutic exposure, residents near the Chernobyl nuclear power plant (CNPP) and victims of nuclear bombing). The tendency to Pearson linear correlation (r = 0.746; p = 0.148) between the frequency of RET/PTC and the estimated dose on thyroid in the regions affected by the CNPP accident was revealed. But this tendency was recognized to be random owing to abnormally low values of the indicator for the most contaminated Gomel region. The method tentatively called "case-control" showed reliable differences in thyroid dose values for carcinomas with RET/PTC and without those. The versatility of changes was found: the lack of RET/PTC for radiotherapeutic impacts was associated with higher doses, whereas in case of the CNPP accident and for nuclear bombing victims it was the opposite. Probably, in the first case the "cellular cleaning" phenomenon after exposure to very high doses took place. Search of direct Pearson correlations between average/median thyroid doses on groups and RET/PTC frequency in carcinomas of these groups showed a high reliability for the dose-effect dependences- at the continuous dose scale (for RET/PTC in total and RET/PTC1 respectively: r = 0.830; p = 0.002 and r = 0.906; p = 0.0003); while there was no significant correlation received for RET/PTC3. When using the weighting least square regression analysis (proceeding from the number of carcinomas in samples), the specified regularities remained. Attempts to influence the strength of correlation by exception ofthe data of all the samples connected with the accident on the CNPP did not significantly

  10. Graves' disease and radioiodine therapy. Is success of ablation dependent on the achieved dose above 200 Gy?

    Energy Technology Data Exchange (ETDEWEB)

    Kobe, C.; Eschner, W.; Sudbrock, F.; Weber, I.; Marx, K.; Dietlein, M.; Schicha, H. [Dept. of Nuclear Medicine, Univ. of Cologne (Germany)

    2008-07-01

    Aim: this study was performed to determine the results of ablative radioiodine therapy (RIT) when the achieved dose in the thyroid was above 200 Gy and to characterize predictive factors for treatment outcome. Patients, methods: a total of 571 consecutive patients were observed for 12 months between July 2001 and June 2004. Inclusion criteria were a confirmed diagnosis Groves' disease, compensation of hyperthyroidism and withdrawal of antithyroid drugs two days before preliminary radioiodine-testing and RIT. The intended dose was 250 Gy and the therapeutically achieved dose was calculated from serial uptake measurements. The end-point measure was thyroid function 12 months after RIT; success was defined as elimination of hyperthyroidism. The relation between success rate and the achieved dose, thyroid volume, age and sex of patients, TSH- and TRAb-values and presence of ophthalmopathy was analysed. Results: relief from hyperthyroidism was achieved in 96% of patients who received more than 200 Gy, even for thyroid volumes >40 ml. The success of ablative RIT was not influenced by age or sex of patients, or by TSH- or TRAb values or concomitant ophthalmopathy. The mean achieved dose in the thyroid was 298 Gy with a standard deviation of 74.6 Gy. Conclusion: to achieve a dose of over 200 Gy with the above standard deviation, we recommend calculating on intended dose of 250 Gy and using a dosimetric approach with early and late uptake values in the radioiodine test, to allow early therapeutic intervention should the posttherapeutic thyroid dose fall unexpectedly below 200 Gy. (orig.)

  11. An endocrine disruptor, bisphenol A, affects development in the protochordate Ciona intestinalis: Hatching rates and swimming behavior alter in a dose-dependent manner

    International Nuclear Information System (INIS)

    Matsushima, Ayami; Ryan, Kerrianne; Shimohigashi, Yasuyuki; Meinertzhagen, Ian A.

    2013-01-01

    Bisphenol A (BPA) is widely used industrially to produce polycarbonate plastics and epoxy resins. Numerous studies document the harmful effects caused by low-dose BPA exposure especially on nervous systems and behavior in experimental animals such as mice and rats. Here, we exposed embryos of a model chordate, Ciona intestinalis, to seawater containing BPA to evaluate adverse effects on embryonic development and on the swimming behavior of subsequent larvae. Ciona is ideal because its larva develops rapidly and has few cells. The rate of larval hatching decreased in a dose-dependent manner with exposures to BPA above 3 μM; swimming behavior was also affected in larvae emerging from embryos exposed to 1 μM BPA. Adverse effects were most severe on fertilized eggs exposed to BPA within 7 h post-fertilization. Ciona shares twelve nuclear receptors with mammals, and BPA is proposed to disturb the physiological functions of one or more of these. - Highlights: ► Embryos of Ciona intestinalis were exposed to BPA to evaluate its developmental effects. ► The rate of larval hatching decreased in a dose-dependent manner. ► Swimming behavior was affected in larvae that emerge from embryos exposed to 1 μM BPA. ► Our findings will support a new strategy to analyze the developmental effects induced by BPA. - Exposure of fertilized Ciona embryos to BPA decreased their hatch rate in a dose-dependent manner and led to abnormal larval swimming behavior.

  12. An analysis of uncertainty and of dependence on season of year of ingestion population dose arising from design basis accidents in advanced thermal reactors

    International Nuclear Information System (INIS)

    Nair, S.; Ponting, A.C.

    1985-03-01

    The results of a detailed study of ingestion collective dose from five limiting PWR design basis releases are presented, the PWR being chosen as being typical of an advanced thermal reactor for which source terms are readily available. The ingestion collective dose was calculated for a range of wind direction/weather scenarios for releases from a typical U.K. rural and a U.K. semi-urban site and scenarios identified where the ingestion pathway was of potential significance. The dependence of the ingestion collective dose for these cases on the season of year when the release occurs was investigated. An analysis was carried out of the uncertainty in the ''worst case'' ingestion calculations arising from uncertainties in foodchain input parameters. An efficient but comprehensive set of dynamic foodchain computer models was produced and the literature surveyed to produce probability distribution functions (PDF's) for all relevant independent input data items. These were used to produce output PDF's for food contamination levels and for ingestion collective dose from the five releases. Finally, the study has highlighted several areas central to ingestion collective dose assessments where the available data are inadequate. This led to the formulation of a set of future research requirements which will need to be met both to obtain a better fundamental understanding of foodchain transfer and to reduce uncertainties in ingestion collective dose assessments. (author)

  13. Lemna minor plants chronically exposed to ionising radiation: RNA-seq analysis indicates a dose rate dependent shift from acclimation to survival strategies.

    Science.gov (United States)

    Van Hoeck, Arne; Horemans, Nele; Nauts, Robin; Van Hees, May; Vandenhove, Hildegarde; Blust, Ronny

    2017-04-01

    Ecotoxicological research provides knowledge on ionising radiation-induced responses in different plant species. However, the sparse data currently available are mainly extracted from acute exposure treatments. To provide a better understanding of environmental exposure scenarios, the response to stress in plants must be followed in more natural relevant chronic conditions. We previously showed morphological and biochemical responses in Lemna minor plants continuously exposed for 7days in a dose-rate dependent manner. In this study responses on molecular (gene expression) and physiological (photosynthetic) level are evaluated in L. minor plants exposed to ionising radiation. To enable this, we examined the gene expression profiles of irradiated L. minor plants by using an RNA-seq approach. The gene expression data reveal indications that L. minor plants exposed at lower dose rates, can tolerate the exposure by triggering acclimation responses. In contrast, at the highest dose rate tested, a high number of genes related to antioxidative defense systems, DNA repair and cell cycle were differentially expressed suggesting that only high dose rates of ionising radiation drive L. minor plants into survival strategies. Notably, the photosynthetic process seems to be unaffected in L. minor plants among the tested dose rates. This study, supported by our earlier work, clearly indicates that plants shift from acclimation responses towards survival responses at increasing dose rates of ionising radiation. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Editorial: dose-dependent ZnO particle-induced acute phase response in humans warrants re-evaluation of occupational exposure limits for metal oxides

    DEFF Research Database (Denmark)

    Vogel, Ulla Birgitte; Cassee, Flemming R.

    2018-01-01

    in autonomic imbalance and particle-induced pulmonary inflammation and acute phase response.The acute phase response is the systemic response to acute and chronic inflammatory states caused by for example bacterial infection, virus infection, trauma and infarction. It is characterized by differential...... studies and SAA has been causally related to the formation of plaques in the aorta in animal studies.In a recent paper in Particle and Fibre Toxicology, Christian Monse et al. provide evidence that inhalation of ZnO nanoparticles induces dose-dependent acute phase response in humans at dose levels well...

  15. The environmental chemical tributyltin chloride (TBT) shows both estrogenic and adipogenic activities in mice which might depend on the exposure dose

    International Nuclear Information System (INIS)

    Penza, M.; Jeremic, M.; Marrazzo, E.; Maggi, A.; Ciana, P.; Rando, G.; Grigolato, P.G.; Di Lorenzo, D.

    2011-01-01

    Exposure during early development to chemicals with hormonal action may be associated with weight gain during adulthood because of altered body homeostasis. It is known that organotins affect adipose mass when exposure occurs during fetal development, although no knowledge of effects are available for exposures after birth. Here we show that the environmental organotin tributyltin chloride (TBT) exerts adipogenic action when peripubertal and sexually mature mice are exposed to the chemical. The duration and extent of these effects depend on the sex and on the dose of the compound, and the effects are relevant at doses close to the estimated human intake (0.5 μg/kg). At higher doses (50-500 μg/kg), TBT also activated estrogen receptors (ERs) in adipose cells in vitro and in vivo, based on results from acute and longitudinal studies in ERE/luciferase reporter mice. In 3T3-L1 cells (which have no ERs), transiently transfected with the ERE-dependent reporter plus or minus ERα or ERβ, TBT (in a dose range of 1-100 nM) directly targets each ER subtype in a receptor-specific manner through a direct mechanism mediated by ERα in undifferentiated preadipocytic cells and by ERβ in differentiating adipocytes. The ER antagonist ICI-182,780 inhibits this effect. In summary, the results of this work suggest that TBT is adipogenic at all ages and in both sexes and that it might be an ER activator in fat cells. These findings might help to resolve the apparent paradox of an adipogenic chemical being also an estrogen receptor activator by showing that the two apparently opposite actions are separated by the different doses to which the organism is exposed. - Research highlights: → The environmental organotin tributyltin chloride shows dose-dependent estrogenic and adipogenic activities in mice. → The duration and extent of these effects depend on the sex and the dose of the compound. → The estrogenic and adipogenic effects of TBT occur at doses closed to the estimated

  16. Volume and dose rate dependent (MDR-LDR Ir-192 afterloading interstitial brachytherapy) treatment optimisation, for squamouscell carcinoma of the lip

    International Nuclear Information System (INIS)

    Stas, Nathalie; Goncalves, Julieta; Pinho, Eliana; Trigo, Lurdes; Fernandes, Tome; Vieira, Elio

    1996-01-01

    Introduction: From 1/1/90 to 1/1/95, 53 patients with squamouscell carcinoma of the lip were treated by MDR or LDR Ir-192 afterloading interstitital brachytherapy. We compare the oncological and aesthetical results and sequelae depending on the volume and the dose rate. Material and methods: 53 patients, 41 men and 12 women, median age = 66y; 48 primary tumors (T1 = 26; T2 = 16; T3 = 6; N0 = 47; N1 = 1; M0 = 48) and 5 recurrencies; squamouscell carcinoma (grade 1 =45, g2 =6, g3 =2); clinical extension: buccal comissure=3, check =2, muscular =15, skin =7, lower and upper lip =1. Before radiotherapy, 28 biopsies and 25 excisional surgeries (19 with positive margins, 6 with negative margins) were performed. Brachytherapy was performed alone (dose 60-75 Gy BD85%) or as a boost (dose 10-30 Gy BD85%) associated with external beam (dose 46-50 Gy). MDR or LDR microselectron's afterloading was done after a computerised dosimetry (Paris System): treatment mean time = 30, 98 hours; mean volume = 10,2 cc (T1-T2 8, 61cc); Ir - 192 activity = range 0,7 - 4,792 mCi/cm; reference dose rate 45,6 - 290, 1 cGy/h. Results: 46 patients are alive without cancer, 1 died without responding, 6 died from non oncological diseases; 8 patients had recurrences (5 local, 3 nodal) but are alive. Mean follow-up 30,83 months (range 3-60m), mean DFS = 22,49 m (range 5-57m). Acute secondary effects: 30 radioepithelyties (grade 1 = 7, g2=23, g3=14), and 39 radiomucitis (g1=3; g2=23; g3=13); mean time for complete healing = 21, 66 days. Sequelae: moderate sclerosis of the skin =11, skin retraction = 1, hyperpigmentation2, depigmentation= 10, edema= 6, gingivitis= 7. Aesthetical results: good32; moderate= 18; bad= 2, very bad= 1 (uncontrolled tumor). Conclusions: The sequelae and aesthetical results are closely dependent on the treated volume and the dose rate, less dependent on the total dose, and independent on the Iridium activity. Complete healing time does not influence the late aesthetical results

  17. Achieving consistent image quality and overall radiation dose reduction for coronary CT angiography with body mass index-dependent tube voltage and tube current selection

    International Nuclear Information System (INIS)

    Wang, G.; Gao, J.; Zhao, S.; Sun, X.; Chen, X.; Cui, X.

    2014-01-01

    Aim: To develop a quantitative body mass index (BMI)-dependent tube voltage and tube current selection method for obtaining consistent image quality and overall dose reduction in computed tomography coronary angiography (CTCA). Methods and materials: The images of 190 consecutive patients (group A) who underwent CTCA with fixed protocols (100 kV/193 mAs for 100 patients with a BMI of <27 and 120 kV/175 mAs for 90 patients with a BMI of >27) were retrospectively analysed and reconstructed with an adaptive statistical iterative reconstruction (ASIR) algorithm at 50% blending. Image noise was measured and the relationship to BMI was studied to establish BMI-dependent tube current for obtaining CTCA images with user-specified image noise. One hundred additional cardiac patients (group B) were examined using prospective triggering with the BMI-dependent tube voltage/current. CTCA image-quality score, image noise, and effective dose from groups B and C (subgroup of A of 100 patients examined with prospective triggering only) were obtained and compared. Results: There was a linear relationship between image noise and BMI in group A. Using a BMI-dependent tube current in group B, an average CTCA image noise of 27.7 HU (target 28 HU) and 31.7 HU (target 33 HU) was obtained for the subgroups of patients with BMIs of >27 and of <27, respectively, and was independent of patient BMI. There was no difference between image-quality scores between groups B and C (4.52 versus 4.60, p > 0.05). The average effective dose for group B (2.56 mSv) was 42% lower than group C (4.38 mSv; p < 0.01). Conclusion: BMI-dependent tube voltage/current selection in CTCA provides an individualized protocol that generates consistent image quality and helps to reduce overall patient radiation dose. - Highlights: • BMI-dependent kVp and mA selection method may be established in CCTA. • BMI-dependent kVp and mA enables consistent CCTA image quality. • Overall dose reduction of 40% can

  18. Dose- dependent ameliorative effects of quercetin and l-Carnitine against atrazine- induced reproductive toxicity in adult male Albino rats.

    Science.gov (United States)

    Abdel Aziz, Rabie L; Abdel-Wahab, Ahmed; Abo El-Ela, Fatma I; Hassan, Nour El-Houda Y; El-Nahass, El-Shaymaa; Ibrahim, Marwa A; Khalil, Abdel-Tawab A Y

    2018-06-01

    This study aimed to determine the protective effects of co-administration of Quercetin (QT) or l-Carnitine (LC) against the oxidative stress induced by Atrazine (ATZ) in the reproductive system of intact male Albino rats. 36 rats were divided equally into 6 groups. Rats in the control negative "CNT" group received 1.5 ml distilled water for 21 days. All rats in the other groups received ATZ (120 mg/kg bw) through gavage. Groups 3 and 4 were co-administered with either low or high dose of QT (10 "ATZLQT" and 50 "ATZHQT" mg/kg bw, respectively). Groups 5 and 6 were co-administered with either low or high dose of LC (200 "ATZLLC" and 400 "ATZHLC" mg/kg bw, respectively). At the end of the experiment, animals were sacrificed and all samples were collected. ATZ significantly increased serum level of malondialdehyde (MDA) and decreased total antioxidant capacity (TAC). Also, ATZ increased significantly the sperm cell abnormalities and reduced both testicular IgA and serum testosterone levels. Testicular DNA laddering % and CYP17A1 mRNA expression were significantly reduced in ATZ group. Interestingly, co-administration with low dose QT or different doses of LC succeeded to counteract the negative toxic effects of ATZ on serum oxidative stress indicators, serum testosterone levels, testicular IgA level and improved testicular CYP17A1 mRNA expression. In conclusion, QT in low dose and LC in both low and high doses exerted a significant protective action against the reproductive toxicity of ATZ, while higher dose of QT failed induce immune-stimulant effect against ATZ in adult male Albino rats. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  19. Lack of dose dependent kinetics of methyl salicylate-2-O-β-D-lactoside in rhesus monkeys after oral administration.

    Science.gov (United States)

    He, Yangyang; Yan, Yu; Zhang, Tiantai; Ma, Yinzhong; Zhang, Wen; Wu, Ping; Song, Junke; Wang, Shuang; Du, Guanhua

    2015-04-22

    Methyl salicylate-2-O-β-d-lactoside (MSL) is one of the main active components isolated from Gaultheria yunnanensis, which is a traditional Chinese medicine used to treat arthritis and various aches and pains. Pharmacological researches showed that MSL had various effective activities in both in vivo and in vitro experiments. However, the pharmacokinetics features and oral bioavailability of MSL in primates were not studied up to now. To study the pharmacokinetics of different doses of MSL in rhesus monkeys and investigate the absolute bioavailability of MSL after oral administration. Male and female rhesus monkeys were either orally administrated with MSL 200, 400 and 800 mg/kg or received an intravenous dose of 20mg/kg randomly. The levels of MSL and salicylic acid (SA) in plasma were simultaneous measured by a simple, sensitive and reproducible high performance liquid chromatography method. Mean peak plasma concentration values for groups treated with 200, 400 and 800 mg/kg doses ranged from 48.79 to 171.83 μg/mL after single-dose oral administration of MSL, and mean area under the concentration-time curve values ranged from 195.16 to 1107.76 μg/mL h. Poor linearity of the kinetics of SA after oral administration of MSL was observed in the regression analysis of the Cmax-dose plot (r(2)=0.812), CL-dose plot (r(2)=0.225) and AUC(0-t)-dose plot (r(2)=0.938). Absolute bioavailability of MSL was assessed to be 118.89 ± 57.50, 213.54 ± 58.98 and 168.72 ± 76.58%, respectively. Bioavailability of MSL after oral administration in rhesus monkeys was measured for the first time. Pharmacokinetics parameters did not appear to be dose proportional among the three oral doses of treatments, and MSL showed an apparent absolute bioavailability in excess of 100% in rhesus monkeys based on the present study. In addition, a rapid, sensitive and reliable HPLC method was established and demonstrated for the research of traditional Chinese medicine in this study. Copyright

  20. Dose-response study of caffeine effects on cerebral functional activity with a specific focus on dependence.

    Science.gov (United States)

    Nehlig, A; Boyet, S

    2000-03-06

    Caffeine is a behavioral stimulant consumed on a worldwide basis. The question of whether caffeine is addictive has been debated for over a decade. Caffeine acts as a mild positive reinforcer but is not consistently self-administered in humans or animals. With [14C]2-deoxyglucose autoradiography, we studied the effects of increasing doses of caffeine on cerebral glucose utilization in rats. At 1 mg/kg, caffeine activated the caudate nucleus mediating locomotion, and the raphe nuclei and locus coeruleus involved with mood and sleep. After 2.5 and 5 mg/kg caffeine, metabolic activation spread to other components of the nigrostriatal dopaminergic system, the thalamus, ventral tegmental area and amygdala. The functional activation of the shell of the nucleus accumbens, an area involved in addiction and reward, was only induced by the highest dose of caffeine, 10 mg/kg. At this dose, the activation of the shell of the nucleus accumbens occurred together with that of the core of the nucleus accumbens and of most other brain regions. These data correlate well with the known sensitivity of locomotion, mood and sleep to low doses of caffeine. They also show that low doses of caffeine which reflect the usual human level of consumption fail to activate reward circuits in the brain and thus provide functional evidence of the very low addictive potential of caffeine.

  1. Dose-dependent adsorptive capacity of activated charcoal for gastrointestinal decontamination of a simulated paracetamol overdose in human volunteers

    DEFF Research Database (Denmark)

    Gude, Anne-Bolette Jill; Hoegberg, Lotte Christine Groth; Riis Angelo, Helle

    2010-01-01

    The amount of activated charcoal needed to treat drug overdoses has arbitrarily been set at a charcoal-drug ratio of 10:1. Recent in vitro studies have shown a larger adsorptive capacity for activated charcoal when used in a model of paracetamol overdose. In the present study, we investigated...... whether this reserve capacity exists in vivo. This is clinically relevant in cases of large overdoses or if the full standard dose of 50 g activated charcoal cannot be administered. We performed a randomized, cross-over study (n = 16). One hour after a standard breakfast, 50 mg/kg paracetamol...... was administered, followed 1 hr later by an activated charcoal-Water slurry containing 50 (control), 25 or 5 g activated charcoal. The areas under the serum concentration-time curve (AUC) for paracetamol were used to estimate the efficacy of each activated charcoal dose. The AUC of the 25-g dose was found...

  2. Risk group dependence of dose-response for biopsy outcome after three-dimensional conformal radiation therapy of prostate cancer

    International Nuclear Information System (INIS)

    Levegruen, Sabine; Jackson, Andrew; Zelefsky, Michael J.; Venkatraman, Ennapadam S.; Skwarchuk, Mark W.; Schlegel, Wolfgang; Fuks, Zvi; Leibel, Steven A.; Ling, C. Clifton

    2002-01-01

    Background and purpose: We fit phenomenological tumor control probability (TCP) models to biopsy outcome after three-dimensional conformal radiation therapy (3D-CRT) of prostate cancer patients to quantify the local dose-response of prostate cancer. Materials and methods: We analyzed the outcome after photon beam 3D-CRT of 103 patients with stage T1c-T3 prostate cancer treated at Memorial Sloan-Kettering Cancer Center (MSKCC) (prescribed target doses between 64.8 and 81 Gy) who had a prostate biopsy performed ≥2.5 years after end of treatment. A univariate logistic regression model based on D mean (mean dose in the planning target volume of each patient) was fit to the whole data set and separately to subgroups characterized by low and high values of tumor-related prognostic factors T-stage ( 6), and pre-treatment prostate-specific antigen (PSA) (≤10 ng/ml vs. >10 ng/ml). In addition, we evaluated five different classifications of the patients into three risk groups, based on all possible combinations of two or three prognostic factors, and fit bivariate logistic regression models with D mean and the risk group category to all patients. Dose-response curves were characterized by TCD 50 , the dose to control 50% of the tumors, and γ 50 , the normalized slope of the dose-response curve at TCD 50 . Results: D mean correlates significantly with biopsy outcome in all patient subgroups and larger values of TCD 50 are observed for patients with unfavorable compared to favorable prognostic factors. For example, TCD 50 for high T-stage patients is 7 Gy higher than for low T-stage patients. For all evaluated risk group definitions, D mean and the risk group category are independent predictors of biopsy outcome in bivariate analysis. The fit values of TCD 50 show a clear separation of 9-10.6 Gy between low and high risk patients. The corresponding dose-response curves are steeper (γ 50 =3.4-5.2) than those obtained when all patients are analyzed together (γ 50 =2

  3. [Could it be a little less? Let the dose of thiopental in euthanasia depend on the body weight].

    Science.gov (United States)

    Sprij, Bram

    2010-01-01

    The Dutch 'euthanasia and assisted suicide' practice guideline advises using 2000 mg thiopental to induce coma, followed by a muscle relaxant to cause death by respiratory paralysis. However, when a doctor administers such a high dose of thiopental as a bolus injection to a cachectic patient, there is a high likelihood of immediate death and other side effects, which can be distressing for the family. Doctors who administered less than 2000 mg have been reprimanded for not working according to current standards. Arguments are given concerning in which circumstances it is reasonable to use the advised dose of 2000 mg of thiopental and when to use less thiopental to induce coma by direct intravenous injection. The author suggests that it may be better to adjust the dose of thiopental according to the body weight of the patient. The current practice guideline needs revision.

  4. Dose-response model of murine typhus (Rickettsia typhi: time post inoculation and host age dependency analysis

    Directory of Open Access Journals (Sweden)

    Tamrakar Sushil B

    2012-03-01

    Full Text Available Abstract Background Rickettsia typhi (R. mooseri is the causative agent of murine typhus. It is one of the most widely distributed flea-borne diseases with a relatively mild febrile initial illness with six to 14 days of incubation period. The bacterium is gram negative and an obligate intracellular pathogen. The disease is transmitted to humans and vertebrate host through fleabites or via contact with infected feces. This paper develops dose-response models of different routes of exposure for typhus in rodents. Methods Data from published articles were analyzed using parametric dose-response relationship models. Dose-response relationships were fit to data using the method of maximum likelihood estimation (MLE. Results Dose-response models quantifying the effects of different ages of rats and time post inoculation in BALB/c mice were analyzed in the study. Both the adult rats (inoculated intradermally and newborn rats (inoculated subcutaneously were best fit by exponential models and both distributions could be described by a single dose-response relationship. The BALB/C mice inoculated subcutaneously were best fit by Beta-Poisson models. The time post inoculation analysis showed that there was a definite time and response relationship existed in this case. Conclusions Intradermally or subcutaneously inoculated rats (adult and newborn models suggest that less than 1 plaque-forming unit (PFU (1.33 to 0.38 in 95% confidence limits of the pathogen is enough to seroconvert 50% of the exposed population on average. For the BALB/c mouse time post inoculation model, an average dose of 0.28 plaque-forming units (PFU (0.75 to 0.11 in 95% confidence limits will seroconvert 50% of the exposed mice.

  5. Dose-dependent efficacy of the Vitex agnus castus extract Ze 440 in patients suffering from premenstrual syndrome.

    Science.gov (United States)

    Schellenberg, Ruediger; Zimmermann, Christian; Drewe, Jürgen; Hoexter, Godehard; Zahner, Catherine

    2012-11-15

    Preparations of Vitex agnus castus L. (VAC) have been shown to be effective to treat irregular menstrual cycles, cyclical mastalgia and symptoms of the premenstrual syndrome (PMS). However, the dose-effect relationship for the treatment of PMS has not yet been established. This study aimed to investigate the clinical effects of three different doses of the VAC extract Ze 440 in comparison to placebo in patients suffering from PMS. In a multicenter, double-blind, placebo-controlled, parallel-group study, 162 female patients with PMS (18-45 years) were randomized to either placebo or different doses of Ze 440 (8, 20 and 30 mg) over three menstrual cycles. PMS symptoms' severity was assessed by patients using visual analog scales (VAS) for the symptoms irritability, mood alteration, anger, headache, bloating and breast fullness. Each of the treatments was well tolerated. Improvement in the total symptom score (TSS) in the 20mg group was significantly higher than in the placebo and 8 mg treatment group. The higher dose of 30 mg, on the other hand, did not significantly decrease symptom severity compared to the 20mg treatment, providing a rational for the usage of 20mg. Corresponding results were observed with the single PMS symptom scores. This study demonstrated that the VAC extract Ze 440 was effective in relieving symptoms of PMS, when applied in a dose of 20mg. Therefore, for patients suffering from PMS, 20mg Ze 440 should be the preferred daily dose. Copyright © 2012 Elsevier GmbH. All rights reserved.

  6. Analyzing the dose-dependence of the Saccharomyces cerevisiae global transcriptional response to methyl methanesulfonate and ionizing radiation.

    Science.gov (United States)

    Benton, Michael G; Somasundaram, Swetha; Glasner, Jeremy D; Palecek, Sean P

    2006-12-01

    One of the most crucial tasks for a cell to ensure its long term survival is preserving the integrity of its genetic heritage via maintenance of DNA structure and sequence. While the DNA damage response in the yeast Saccharomyces cerevisiae, a model eukaryotic organism, has been extensively studied, much remains to be elucidated about how the organism senses and responds to different types and doses of DNA damage. We have measured the global transcriptional response of S. cerevisiae to multiple doses of two representative DNA damaging agents, methyl methanesulfonate (MMS) and gamma radiation. Hierarchical clustering of genes with a statistically significant change in transcription illustrated the differences in the cellular responses to MMS and gamma radiation. Overall, MMS produced a larger transcriptional response than gamma radiation, and many of the genes modulated in response to MMS are involved in protein and translational regulation. Several clusters of coregulated genes whose responses varied with DNA damaging agent dose were identified. Perhaps the most interesting cluster contained four genes exhibiting biphasic induction in response to MMS dose. All of the genes (DUN1, RNR2, RNR4, and HUG1) are involved in the Mec1p kinase pathway known to respond to MMS, presumably due to stalled DNA replication forks. The biphasic responses of these genes suggest that the pathway is induced at lower levels as MMS dose increases. The genes in this cluster with a threefold or greater transcriptional response to gamma radiation all showed an increased induction with increasing gamma radiation dosage. Analyzing genome-wide transcriptional changes to multiple doses of external stresses enabled the identification of cellular responses that are modulated by magnitude of the stress, providing insights into how a cell deals with genotoxicity.

  7. Iodine-131 dose dependent gene expression in thyroid cancers and corresponding normal tissues following the Chernobyl accident.

    Directory of Open Access Journals (Sweden)

    Michael Abend

    Full Text Available The strong and consistent relationship between irradiation at a young age and subsequent thyroid cancer provides an excellent model for studying radiation carcinogenesis in humans. We thus evaluated differential gene expression in thyroid tissue in relation to iodine-131 (I-131 doses received from the Chernobyl accident. Sixty three of 104 papillary thyroid cancers diagnosed between 1998 and 2008 in the Ukrainian-American cohort with individual I-131 thyroid dose estimates had paired RNA specimens from fresh frozen tumor (T and normal (N tissue provided by the Chernobyl Tissue Bank and satisfied quality control criteria. We first hybridized 32 randomly allocated RNA specimen pairs (T/N on 64 whole genome microarrays (Agilent, 4×44 K. Associations of differential gene expression (log(2(T/N with dose were assessed using Kruskall-Wallis and trend tests in linear mixed regression models. While none of the genes withstood correction for the false discovery rate, we selected 75 genes with a priori evidence or P kruskall/P trend <0.0005 for validation by qRT-PCR on the remaining 31 RNA specimen pairs (T/N. The qRT-PCR data were analyzed using linear mixed regression models that included radiation dose as a categorical or ordinal variable. Eleven of 75 qRT-PCR assayed genes (ACVR2A, AJAP1, CA12, CDK12, FAM38A, GALNT7, LMO3, MTA1, SLC19A1, SLC43A3, ZNF493 were confirmed to have a statistically significant differential dose-expression relationship. Our study is among the first to provide direct human data on long term differential gene expression in relation to individual I-131 doses and to identify a set of genes potentially important in radiation carcinogenesis.

  8. Analyzing the dose-dependence of the Saccharomyces cerevisiae global transcriptional response to methyl methanesulfonate and ionizing radiation

    Directory of Open Access Journals (Sweden)

    Glasner Jeremy D

    2006-12-01

    Full Text Available Abstract Background One of the most crucial tasks for a cell to ensure its long term survival is preserving the integrity of its genetic heritage via maintenance of DNA structure and sequence. While the DNA damage response in the yeast Saccharomyces cerevisiae, a model eukaryotic organism, has been extensively studied, much remains to be elucidated about how the organism senses and responds to different types and doses of DNA damage. We have measured the global transcriptional response of S. cerevisiae to multiple doses of two representative DNA damaging agents, methyl methanesulfonate (MMS and gamma radiation. Results Hierarchical clustering of genes with a statistically significant change in transcription illustrated the differences in the cellular responses to MMS and gamma radiation. Overall, MMS produced a larger transcriptional response than gamma radiation, and many of the genes modulated in response to MMS are involved in protein and translational regulation. Several clusters of coregulated genes whose responses varied with DNA damaging agent dose were identified. Perhaps the most interesting cluster contained four genes exhibiting biphasic induction in response to MMS dose. All of the genes (DUN1, RNR2, RNR4, and HUG1 are involved in the Mec1p kinase pathway known to respond to MMS, presumably due to stalled DNA replication forks. The biphasic responses of these genes suggest that the pathway is induced at lower levels as MMS dose increases. The genes in this cluster with a threefold or greater transcriptional response to gamma radiation all showed an increased induction with increasing gamma radiation dosage. Conclusion Analyzing genome-wide transcriptional changes to multiple doses of external stresses enabled the identification of cellular responses that are modulated by magnitude of the stress, providing insights into how a cell deals with genotoxicity.

  9. Specific dose-dependent damage of Lieberkuehn crypts promoted by large doses of type 2 ribosome-inactivating protein nigrin b intravenous injection to mice

    International Nuclear Information System (INIS)

    Gayoso, M.J.; Munoz, R.; Arias, Y.; Villar, R.; Rojo, M.A.; Jimenez, P.; Ferreras, J.M.; Aranguez, I.; Girbes, T.

    2005-01-01

    Nigrin b is a non-toxic type 2 ribosome-inactivating protein as active as ricin at ribosomal level but 10 5 and 5 x 10 3 times less toxic for animal cell cultures and mice, respectively, than ricin. The purpose of the present study was to analyze the effects of intravenous injection of large amounts of nigrin b to the mouse. Injection through the tail vein of 16 mg/kg body weight killed all mice studied before 2 days. Analysis of several major tissues by light microscopy did not reveal gross nigrin b-promoted changes, except in the intestines which appeared highly damaged. As a consequence of the injury, the villi and crypt structures of the small intestine disappeared, leading to profuse bleeding and death. In contrast, intravenous injection of 5 mg/kg body weight was not lethal to mice but did trigger reversible toxic effects. In both cases, lethal and sub-lethal doses, the target of nigrin b appeared to be the highly proliferating stem cells of the intestinal crypts, which had undergone apoptotic changes. In contrast to nigrin b, the injection of 3 μg/kg of ricin kills all mice in 5 days but does not trigger apoptosis in the crypts. Therefore, the effect seen with sub-lethal nigrin b concentrations seems to be specific. Nigrin b killed COLO 320 human colon adenocarcinoma cells with an IC 50 of 3.1 x 10 -8 M and the effect was parallel to the extent of DNA fragmentation of these cells. Accordingly, despite the low general toxicity exerted by nigrin b as compared with ricin, intravenous injection of large amounts of nigrin b is able to kill mouse intestinal stem cells without threatening the lives of the animals, thereby opening a door for its use for the targeting of intestinal stem cells

  10. Transient impairment of hippocampus-dependent learning and memory in relatively low-dose of acute radiation syndrome is associated with inhibition of hippocampal neurogenesis

    International Nuclear Information System (INIS)

    Kim, Joong-Sun; Lee, Hae-June; Kim, Jong-Choon

    2008-01-01

    Neurogenesis in the adult hippocampus, which occurs constitutively, is vulnerable to ionizing radiation. In the relatively low-dose exposure of acute radiation syndrome (ARS), the change in the adult hippocampal function is poorly understood. This study analyzed the changes in apoptotic cell death and neurogenesis in the DGs of hippocampi from adult ICR mice with single whole-body gamma-irradiation using the TdT-mediated dUTP-biotin nick end-labeling (TUNEL) method and immunohistochemical markers of neurogenesis, Ki-67 and doublecortin (DCX). In addition, the hippocampus-dependent learning and memory tasks after single whole-body gamma-irradiation were examined in order to evaluate the hippocampus-related behavioral dysfunction in the relatively low-dose exposure of ARS. The number of TUNEL-positive apoptotic nuclei in the dentate gyrus (DG) was increased 6-12 h after acute gamma-irradiation (a single dose of 0.5 to 4 Gy). In contrast, the number of Ki-67- and DCX-positive cells began to decrease significantly 6 h postirradiation, reaching its lowest level 24 h after irradiation. The level of Ki-67 and DCX immunoreactivity decreased in a dose-dependent manner within the range of irradiation applied (0-4 Gy). In passive avoidance and object recognition memory test, the mice trained 1 day after acute irradiation (2 Gy) showed significant memory deficits, compared with the sham controls. In conclusion, the pattern of the hippocampus-dependent memory dysfunction is consistent with the change in neurogenesis after acute irradiation. It is suggested that a relatively low dose of ARS in adult ICR mice is sufficiently detrimental to interrupt the functioning of the hippocampus, including learning and memory, possibly through the inhibition of neurogenesis. (author)

  11. Effect of low doses of ionizing radiation on the thymus-dependent humoral immune response and the polyclonal activation of B-lymphocytes

    International Nuclear Information System (INIS)

    Sharetskij, A.N.; Surinov, B.P.; Abramova, M.R.

    2000-01-01

    The results of studies on the effect of the low-dose (10 cGy with the dose rate of 1cGy/min) γ-radiation on the indices of the mice system and local immune response are presented. The sheep erythrocytes were used as a thymus-dependent antigen. It is shown that the total irradiation with the above dose rate induced the increase in the primary thymus-dependent humoral immune response on the sheep erythrocytes and polyclonal activation of the B-lymphocytes. The sharp oppression of the antibody formation was observed in the immune response dynamics after the phase of the radiation-induced elevation. The injection of hydroquinone right after the irradiation resulted in elimination of the radiation stimulation of the polyclonal response of the B-cells. The essential decrease in the immunoantilogarithmic radiation effect took place in the animals treated with thymogen. The possible negative consequences of the low-dose ionizing radiation impact on the body immune system are discussed [ru

  12. Radiation-induced strand-breaks and DNA-protein crosslinks depend predominantly on the dose, oxygen concentration and repair time

    International Nuclear Information System (INIS)

    Wheeler, K.T.; Miyagi, Y.; Zhang, H.

    1995-01-01

    It has been known for many years that the DNA damage produced by ionizing radiation depends upon the oxygen concentration around the DNA. For example, the number of DNA strand-breaks (SBs) formed per unit dose decreases at low oxygen concentrations, and the number of DNA-protein crosslinks formed per unit dose increases at low oxygen concentrations. If radiation-induced SBs and DPCs are to be useful for detecting and/or quantifying hypoxic cells in solid tumors, the formation of these lesions must depend predominantly on the oxygen concentration around the DNA. All other physical, biological, and physiological factors must either be controllable or have little influence on the assay used to measure these lesions. This paper is a summary of the authors' recent experiments to determine if the radiation-induced SBs and DPCs measured by alkaline elution may be used to estimate the hypoxic fraction or fractional hypoxic volume of solid tumors

  13. Milnacipran affects mouse impulsive, aggressive, and depressive-like behaviors in a distinct dose-dependent manner.

    Science.gov (United States)

    Tsutsui-Kimura, Iku; Ohmura, Yu; Yoshida, Takayuki; Yoshioka, Mitsuhiro

    2017-07-01

    Serotonin/noradrenaline reuptake inhibitors (SNRIs) are widely used for the treatment for major depressive disorder, but these drugs induce several side effects including increased aggression and impulsivity, which are risk factors for substance abuse, criminal involvement, and suicide. To address this issue, milnacipran (0, 3, 10, or 30 mg/kg), an SNRI and antidepressant, was intraperitoneally administered to mice prior to the 3-choice serial reaction time task, resident-intruder test, and forced swimming test to measure impulsive, aggressive, and depressive-like behaviors, respectively. A milnacipran dose of 10 mg/kg suppressed all behaviors, which was accompanied by increased dopamine and serotonin levels in the medial prefrontal cortex (mPFC) but not in the nucleus accumbens (NAc). Although the most effective dose for depressive-like behavior was 30 mg/kg, the highest dose increased aggressive behavior and unaffected impulsive behavior. Increased dopamine levels in the NAc could be responsible for the effects. In addition, the mice basal impulsivity was negatively correlated with the latency to the first agonistic behavior. Thus, the optimal dose range of milnacipran is narrower than previously thought. Finding drugs that increase serotonin and dopamine levels in the mPFC without affecting dopamine levels in the NAc is a potential strategy for developing novel antidepressants. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  14. Milnacipran affects mouse impulsive, aggressive, and depressive-like behaviors in a distinct dose-dependent manner

    Directory of Open Access Journals (Sweden)

    Iku Tsutsui-Kimura

    2017-07-01

    Full Text Available Serotonin/noradrenaline reuptake inhibitors (SNRIs are widely used for the treatment for major depressive disorder, but these drugs induce several side effects including increased aggression and impulsivity, which are risk factors for substance abuse, criminal involvement, and suicide. To address this issue, milnacipran (0, 3, 10, or 30 mg/kg, an SNRI and antidepressant, was intraperitoneally administered to mice prior to the 3-choice serial reaction time task, resident–intruder test, and forced swimming test to measure impulsive, aggressive, and depressive-like behaviors, respectively. A milnacipran dose of 10 mg/kg suppressed all behaviors, which was accompanied by increased dopamine and serotonin levels in the medial prefrontal cortex (mPFC but not in the nucleus accumbens (NAc. Although the most effective dose for depressive-like behavior was 30 mg/kg, the highest dose increased aggressive behavior and unaffected impulsive behavior. Increased dopamine levels in the NAc could be responsible for the effects. In addition, the mice basal impulsivity was negatively correlated with the latency to the first agonistic behavior. Thus, the optimal dose range of milnacipran is narrower than previously thought. Finding drugs that increase serotonin and dopamine levels in the mPFC without affecting dopamine levels in the NAc is a potential strategy for developing novel antidepressants.

  15. Dose-dependent risk of malformations with antiepileptic drugs: an analysis of data from the EURAP epilepsy and pregnancy registry

    DEFF Research Database (Denmark)

    Tomson, Torbjörn; Battino, Dina; Bonizzoni, Erminio

    2011-01-01

    Prenatal exposure to antiepileptic drugs is associated with a greater risk of major congenital malformations, but there is inadequate information on the comparative teratogenicity of individual antiepileptic drugs and the association with dose. We aimed to establish the risks of major congenital ...

  16. Dose-dependent changes in renal 1H-/23Na MRI after adjuvant radiochemotherapy for gastric cancer

    International Nuclear Information System (INIS)

    Haneder, Stefan; Budjan, Johannes Michael; Schoenberg, Stefan Oswald; Konstandin, Simon; Schad, Lothar Rudi; Hofheinz, Ralf Dieter; Gramlich, Veronika; Wenz, Frederik; Lohr, Frank; Boda-Heggemann, Judit

    2015-01-01

    Combined radiochemotherapy (RCT) for gastric cancer with three-dimensional conformal radiotherapy (3D-CRT) results in ablative doses to the upper left kidney, while image-guided intensity-modulated radiotherapy (IG-IMRT) allows kidney sparing despite improved target coverage. Renal function in long-term gastric cancer survivors was evaluated with 3T functional magnetic resonance imaging (MRI) including diffusion-weighted imaging (DWI) and 23 Na imaging. Five healthy volunteers and 13 patients after radiotherapy were included: 11 x IG-IMRT; 1 x 3D-CRT; 1 x ''positive control'' with stereotactic body radiotherapy (SBRT) of a metastasis between the spleen/left kidney. Radiation doses were documented for the upper/middle/lower kidney subvolumes. Late toxicity was evaluated based on CTC criteria, questionnaire, and creatinine values. Morphological sequences, DWI images, and 23 Na images were acquired using a 1 H/ 23 Na-tuned body-coil before/after intravenous water load (WL). Statistics for [ 23 Na] (concentration) and apparent diffusion coefficient (ADC) values were calculated for upper/middle/lower renal subvolumes. Corticomedullary [ 23 Na] gradients and [ 23 Na] differences after WL were determined. No major morphological alteration was detected in any patient. Minor scars were observed in the cranial subvolume of the left kidney of the 3D-CRT and the whole kidney of the control SBRT patient. All participants presented a corticomedullary [ 23 Na] gradient. After WL, a significant physiological [ 23 Na] gradient decrease (p < 0.001) was observed in all HV and IG-IMRT patients. In the cranial left kidney of the 3D-CRT patient and the positive control SBRT patient, the decrease was nonsignificant (p = 0.01, p = 0.02). ADC values were altered nonsignificantly in all renal subvolumes (all participants). Renal subvolumes with doses ≥ 35 Gy showed a reduced change of the [ 23 Na] gradient after WL (p = 0.043). No participants showed clinical renal

  17. Novel Application of Stem Cell-Derived Neurons to Evaluate the Time-and Dose-Dependent Progression of Excitotoxic Injury

    Science.gov (United States)

    2013-05-14

    3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE Novel Application of Stem Cell -Derived Neurons to Evaluate the Time- and Dose-Dependent 5a...01.10.RC.021). 14. ABSTRACT See reprint. 15. SUBJECT TERMS Mouse stem cell -derived neurons, NMDA receptor, AMPA receptor, Neurotoxicity, Apoptosis...area code) 410-436-8044 Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 Novel Application of Stem Cell -Derived Neurons to Evaluate the

  18. Dose-dependent testosterone sensitivity of the steroidal passport and GC-C-IRMS analysis in relation to the UGT2B17 deletion polymorphism.

    Science.gov (United States)

    Strahm, Emmanuel; Mullen, Jenny E; Gårevik, Nina; Ericsson, Magnus; Schulze, Jenny J; Rane, Anders; Ekström, Lena

    2015-01-01

    The newly implemented Steroid Module of the Athlete Biological Passport has improved doping tests for steroids. A biomarker included in this passport is the urinary testosterone glucuronide to epitestosterone glucuronide (T/E) ratio, a ratio greatly affected by a deletion polymorphism in UGT2B17. Suspect urine doping tests are further analyzed with gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) to determine the origin of the androgen. In this study, we investigated the sensitivity of the steroidal module and the IRMS analysis, in subjects administered with three doses of testosterone enanthate (500, 250, and 125 mg), in relation to the UGT2B17 polymorphism. All subjects carrying the UGT2B17 enzyme reached the traditionally used threshold, a T/E ratio of 4, after all three administered doses, whereas none of the subjects devoid of this enzyme reached a T/E of 4. On the other hand, using the athlete biological passport and IRMS analysis, all three doses could be detected to a high degree of sensitivity. The concentrations of all steroids included in the steroidal module were dose dependently increased, except for epitestosterone which decreased independent of dose. The decrease in epitestosterone was significantly associated with circulatory levels of testosterone post dose (rs =0.60 and p=0.007). In conclusion, these results demonstrate that administration of a single dose of 125-500 mg testosterone enanthate could be detected using the athlete biological passport, together with IRMS. Since IRMS is sensitive to testosterone doping independent of UGT2B17 genotype, also very small changes in the steroidal passport should be investigated with IRMS. Copyright © 2015 John Wiley & Sons, Ltd.

  19. Experimental determination of the photon-energy dependent dose-to-water response of TLD600 and TLD700 (LiF:Mg,Ti) thermoluminescence detectors

    Energy Technology Data Exchange (ETDEWEB)

    Schwahofer, Andrea [Vivantes Clinic Neukoelln, Berlin (Germany). Dept. of Radiation Therapy; German Cancer Research Center, Heidelberg (Germany). Medical Physics in Radiation Therapy; Feist, Harald [Munich Univ. (Germany). Dept. of Radiation Therapy; Georg, Holger [PTW Freiburg (Germany). Calibration Lab.; Haering, Peter; Schlegel, Wolfgang [German Cancer Research Center, Heidelberg (Germany). Medical Physics in Radiation Therapy

    2017-05-01

    The aim of this study has been the experimental determination of the energy dependent dose-to-water response of TLD600 and TLD700 thermoluminescent detectors (Harshaw) in X-ray beams with mean photon energies from about 20 to 200 keV in comparison with {sup 60}Co gamma rays and 6 MV X-rays. Experiments were carried out in collaboration with the German secondary standard laboratory PTW Freiburg. The energy dependent relative responses of TLD600 and TLD700 thermoluminescence detectors were determined at radiation qualities between 30 kV{sub p} and 280 kV{sub p}. The overall uncertainty of the measured values was characterized by standard deviations varying from 1.2 to 3%. The present results agree with previous studies on the energy dependent dose-to-water response of TLD100. As an application example, the results were used to measure doses associated with X-ray imaging in image-guided radiotherapy.

  20. Bright-light intervention induces a dose-dependent increase in striatal response to risk in healthy volunteers

    DEFF Research Database (Denmark)

    Macoveanu, Julian; Fisher, Patrick M; Madsen, Martin K

    2016-01-01

    Bright-light interventions have successfully been used to reduce depression symptoms in patients with seasonal affective disorder, a depressive disorder most frequently occurring during seasons with reduced daylight availability. Yet, little is known about how light exposure impacts human brain...... function, for instance on risk taking, a process affected in depressive disorders. Here we examined the modulatory effects of bright-light exposure on brain activity during a risk-taking task. Thirty-two healthy male volunteers living in the greater Copenhagen area received 3weeks of bright......-light intervention during the winter season. Adopting a double-blinded dose-response design, bright-light was applied for 30minutes continuously every morning. The individual dose varied between 100 and 11.000lx. Whole-brain functional MRI was performed before and after bright-light intervention to probe how...

  1. Cumulative dose 60Co gamma irradiation effects on AlGaN/GaN Schottky diodes and its area dependence

    Science.gov (United States)

    Sharma, Chandan; Laishram, Robert; Rawal, Dipendra Singh; Vinayak, Seema; Singh, Rajendra

    2018-04-01

    Cumulative dose gamma radiation effects on current-voltage characteristics of GaN Schottky diodes have been investigated. The different area diodes have been fabricated on AlGaN/GaN high electron mobility transistor (HEMT) epi-layer structure grown over SiC substrate and irradiated with a dose up to the order of 104 Gray (Gy). Post irradiation characterization shows a shift in the turn-on voltage and improvement in reverse leakage current. Other calculated parameters include Schottky barrier height, ideality factor and reverse saturation current. Schottky barrier height has been decreased whereas reverse saturation current shows an increase in the value post irradiation with improvement in the ideality factor. Transfer length measurement (TLM) characterization shows an improvement in the contact resistance. Finally, diodes with larger area have more variation in the calculated parameters due to the induced local heating effect.

  2. SU-E-T-647: Quality Assurance of VMAT by Gamma Analysis Dependence On Low-Dose Threshold

    Energy Technology Data Exchange (ETDEWEB)

    Song, J; Kim, M; Lee, S; Lee, M; Suh, T [Department of Biomedical Engineering, Reasearch Institute of Biomedical Engineering, The Catholic University of Korea, Seoul (Korea, Republic of); Park, S [Department of Biomedical Engineering, Reasearch Institute of Biomedical Engineering, The Catholic University of Korea, Seoul (Korea, Republic of); Department of Radiation Oncology, Uijeongbu St. Mary’s Hospital, Gyeonggi-do (Korea, Republic of)

    2015-06-15

    Purpose: The AAPM TG-119 instructed institutions to use low-dose threshold (LDT) of 10% or a ROI determined by the jaw when they collected gamma analysis QA data of planar dose distribution. Also, based on a survey by Nelms and Simon, more than 70% of institutions use a LDT between 0% and 10% for gamma analysis. However, there are no clinical data to quantitatively demonstrate the impact of the LDT on the gamma index. Therefore, we performed a gamma analysis with LDTs of 0% to 15% according to both global and local normalization and different acceptance criteria: 3%/3 mm, 2%/2 mm, and 1%/1 mm. Methods: A total of 30 treatment plans—10 head and neck, 10 brain, and 10 prostate cancer cases—were randomly selected from the Varian Eclipse TPS, retrospectively. For the gamma analysis, a predicted portal image was acquired through a portal dose calculation algorithm in the Eclipse TPS, and a measured portal image was obtained using a Varian Clinac iX and an EPID. Then, the gamma analysis was performed using the Portal Dosimetry software. Results: For the global normalization, the gamma passing rate (%GP) decreased as the LDT increased, and all cases of low-dose thresholds exhibited a %GP above 95% for both the 3%/3 mm and 2%/2 mm criteria. However, for local normalization, the %GP increased as LDT increased. The gamma passing rate with LDT of 10% increased by 6.86%, 9.22% and 6.14% compared with the 0% in the case of the head and neck, brain and prostate for 3%/3 mm criteria, respectively. Conclusion: Applying the LDT in the global normalization does not have critical impact to judge patient-specific QA results. However, LDT for the local normalization should be carefully selected because applying the LDT could affect the average of the %GP to increase rapidly.

  3. SU-E-T-647: Quality Assurance of VMAT by Gamma Analysis Dependence On Low-Dose Threshold

    International Nuclear Information System (INIS)

    Song, J; Kim, M; Lee, S; Lee, M; Suh, T; Park, S

    2015-01-01

    Purpose: The AAPM TG-119 instructed institutions to use low-dose threshold (LDT) of 10% or a ROI determined by the jaw when they collected gamma analysis QA data of planar dose distribution. Also, based on a survey by Nelms and Simon, more than 70% of institutions use a LDT between 0% and 10% for gamma analysis. However, there are no clinical data to quantitatively demonstrate the impact of the LDT on the gamma index. Therefore, we performed a gamma analysis with LDTs of 0% to 15% according to both global and local normalization and different acceptance criteria: 3%/3 mm, 2%/2 mm, and 1%/1 mm. Methods: A total of 30 treatment plans—10 head and neck, 10 brain, and 10 prostate cancer cases—were randomly selected from the Varian Eclipse TPS, retrospectively. For the gamma analysis, a predicted portal image was acquired through a portal dose calculation algorithm in the Eclipse TPS, and a measured portal image was obtained using a Varian Clinac iX and an EPID. Then, the gamma analysis was performed using the Portal Dosimetry software. Results: For the global normalization, the gamma passing rate (%GP) decreased as the LDT increased, and all cases of low-dose thresholds exhibited a %GP above 95% for both the 3%/3 mm and 2%/2 mm criteria. However, for local normalization, the %GP increased as LDT increased. The gamma passing rate with LDT of 10% increased by 6.86%, 9.22% and 6.14% compared with the 0% in the case of the head and neck, brain and prostate for 3%/3 mm criteria, respectively. Conclusion: Applying the LDT in the global normalization does not have critical impact to judge patient-specific QA results. However, LDT for the local normalization should be carefully selected because applying the LDT could affect the average of the %GP to increase rapidly

  4. Aspartame and the hippocampus: Revealing a bi-directional, dose/time-dependent behavioural and morphological shift in mice.

    Science.gov (United States)

    Onaolapo, Adejoke Y; Onaolapo, Olakunle J; Nwoha, Polycarp U

    2017-03-01

    Changes, in behaviour, oxidative markers of stress and hippocampal morphology were evaluated following aspartame administration. Mice, (20-22g each) were given vehicle (10ml/kg) or aspartame (20, 40, 80 and 160mg/kg) daily for 28days. They were tested in the Y-maze, radial-arm maze and elevated plus-maze (EPM) after the first and last dose of vehicle or aspartame; and then sacrificed. Hippocampal slices were analysed for aspartic acid, nitric oxide (NO) and superoxide dismutase (SOD); and processed for general histology and neuritic plaques. Glial fibrillary-acid protein (GFAP) expression and neuron-specific enolase (NSE) activities were determined. Radial-arm maze scores increased significantly after acute administration at 80 and 160mg/kg. Repeated administration at 20 and 40mg/kg (Y-maze) and at 40mg/kg (radial-arm maze) was also associated with increased scores, however, performance decreased at higher doses. EPM tests revealed anxiogenic responses following both acute and repeated administration. Significant increase in SOD and NO activities were observed at 40, 80 and 160mg/kg. Neuron counts reduced at higher doses of aspartame. At 40, 80 and 160mg/kg, fewer GFAP-reactive astrocytes were observed in the cornus ammonis, but increased GFAP-reactivity was observed in the dentate gyrus subgranular zone. NSE-positive neurons were readily identifiable within the dentate gyrus at the lower doses of aspartame; but at 160mg/kg, there was marked neuron loss and reduction in NSE-positive neurons. Oral aspartame significantly altered behaviour, anti-oxidant status and morphology of the hippocampus in mice; also, it may probably trigger hippocampal adult neurogenesis. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Biological effective dose evaluation in gynaecological brachytherapy: LDR and HDR treatments, dependence on radiobiological parameters, and treatment optimisation.

    Science.gov (United States)

    Bianchi, C; Botta, F; Conte, L; Vanoli, P; Cerizza, L

    2008-10-01

    This study was undertaken to compare the biological efficacy of different high-dose-rate (HDR) and low-dose-rate (LDR) treatments of gynaecological lesions, to identify the causes of possible nonuniformity and to optimise treatment through customised calculation. The study considered 110 patients treated between 2001 and 2006 with external beam radiation therapy and/or brachytherapy with either LDR (afterloader Selectron, (137)Cs) or HDR (afterloader microSelectron Classic, (192)Ir). The treatments were compared in terms of biologically effective dose (BED) to the tumour and to the rectum (linear-quadratic model) by using statistical tests for comparisons between independent samples. The difference between the two treatments was statistically significant in one case only. However, within each technique, we identified considerable nonuniformity in therapeutic efficacy due to differences in fractionation schemes and overall treatment time. To solve this problem, we created a Microsoft Excel spreadsheet allowing calculation of the optimal treatment for each patient: best efficacy (BED(tumour)) without exceeding toxicity threshold (BED(rectum)). The efficacy of a treatment may vary as a result of several factors. Customised radiobiological evaluation is a useful adjunct to clinical evaluation in planning equivalent treatments that satisfy all dosimetric constraints.

  6. Study of intrinsic energy dependence of α-alanine and dose intercomparison with ESR and ISE techniques

    International Nuclear Information System (INIS)

    Laere, K. van; Bartolotta, A.; Callens, F.

    1993-01-01

    The intrinsic energy behavior of the radiation chemical yields G(R ·) and G(NH 3 ) which determine the dose response for the alanine/ESR and alanine/Ion-Selective Electrode (ISE) system, is an important characteristic for the consistent use in different radiation environments. Therefore, the response of ISS and Gent α-alanine dosimeters in the dose range 0.1 to 700 kGy was examined with 60 Co, bremsstrahlung and electron beam radiation. Bremsstrahlung beams with end point energy between 5 and 12 MeV and electron beams with mean energy at the effective point of measurement between 4 and 25 MeV were used. Analysis of the 60 Co calibration results shows that there are no significant differences in dose determination between the two laboratories. The statistical evaluation of 41 sets of independent series of measurements has shown no significant variation with beam energy. The results also confirm good consistency between ISE and ESR measurements. (author)

  7. The environmental chemical tributyltin chloride (TBT) shows both estrogenic and adipogenic activities in mice which might depend on the exposure dose.

    Science.gov (United States)

    Penza, M; Jeremic, M; Marrazzo, E; Maggi, A; Ciana, P; Rando, G; Grigolato, P G; Di Lorenzo, D

    2011-08-15

    Exposure during early development to chemicals with hormonal action may be associated with weight gain during adulthood because of altered body homeostasis. It is known that organotins affect adipose mass when exposure occurs during fetal development, although no knowledge of effects are available for exposures after birth. Here we show that the environmental organotin tributyltin chloride (TBT) exerts adipogenic action when peripubertal and sexually mature mice are exposed to the chemical. The duration and extent of these effects depend on the sex and on the dose of the compound, and the effects are relevant at doses close to the estimated human intake (0.5μg/kg). At higher doses (50-500μg/kg), TBT also activated estrogen receptors (ERs) in adipose cells in vitro and in vivo, based on results from acute and longitudinal studies in ERE/luciferase reporter mice. In 3T3-L1 cells (which have no ERs), transiently transfected with the ERE-dependent reporter plus or minus ERα or ERβ, TBT (in a dose range of 1-100nM) directly targets each ER subtype in a receptor-specific manner through a direct mechanism mediated by ERα in undifferentiated preadipocytic cells and by ERβ in differentiating adipocytes. The ER antagonist ICI-182,780 inhibits this effect. In summary, the results of this work suggest that TBT is adipogenic at all ages and in both sexes and that it might be an ER activator in fat cells. These findings might help to resolve the apparent paradox of an adipogenic chemical being also an estrogen receptor activator by showing that the two apparently opposite actions are separated by the different doses to which the organism is exposed. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Dose-dependent effects of fish oil on cardio-metabolic biomarkers in healthy middle-aged and elderly Chinese people: a double-blind randomized controlled trial.

    Science.gov (United States)

    Song, Jia; Hu, Manjiang; Li, Cheng; Yang, Bo; Ding, Qing; Wang, Chunhong; Mao, Limei

    2018-06-20

    n-3PUFA consumption has been widely accepted as a nutritional strategy for the secondary prevention of cardiovascular events in patients at high risk of cardiovascular disease (CVD), but little is known about the dose-response relationship between dietary n-3PUFA and serum biomarkers associated with cardiovascular health in the general population. The present study involved a 12-week double-blind, randomized controlled trial to explore the effects of fish oil with different doses (0.31, 0.62 and 1.24 g d-1 of EPA and DHA) on serum fatty acids and cardio-metabolic biomarkers including adiponectin, inflammatory markers, lipid profiles and fasting glucose in healthy middle-aged and elderly Chinese people. 240 volunteers met our inclusion criteria. A total of 39 subjects dropped out and 201 finally completed the intervention. No significant differences in baseline characteristics and daily intakes of dietary nutrients were detected among all groups. After a 12-week intervention, fish oil dose-dependently enhanced serum EPA, DHA, n-3PUFA and adiponectin (except for 0.31 g d-1), but decreased serum n-6/n-3PUFA, TG and fasting glucose. Changes in the above indicators from the baseline to week 12 in fish oil groups significantly differed from those in the control. Meanwhile, all the doses of EPA and DHA led to decreases in serum CRP; only 1.24 g d-1 led to an increase in HDL-C with a concurrent decrease in TC/HDL-C even though these changes were not significantly different among all groups. All the findings suggested that fish oil dose-dependently regulated serum PUFA and cardio-metabolic biomarkers including adiponectin, CRP, lipid profiles and fasting glucose in healthy middle-aged and elderly Chinese people who consumed insufficient dietary n-3PUFA, and the most desirable changes were observed for 1.24 g d-1.

  9. Spatial dependence and origin of the ambient dose due to neutron activation processes in linear accelerators; Dependencia espacial y origen de la dosis ambiental debeda a procesos de activacion neutronica en aceleradores lineales

    Energy Technology Data Exchange (ETDEWEB)

    Ruiz Egea, E.; Sanchez Carrascal, M.; Torres Pozas, S.; Monja Ray, P. de la; Perez Molina, J. L.; Madan Rodriguez, C.; Luque Japon, L.; Morera Molina, A.; Hernandez Perez, A.; Barquero Bravo, Y.; Morengo Pedagna, I.; Oliva Gordillo, M. C.; Martin Olivar, R.

    2011-07-01

    In order to try to determine the high dose in the bunker of a Linear Accelerator clinical use trying to measure the spatial dependence of the same from the isocenter to gateway to the board cheeking to establish the origin of it. This dose measurements performed with an ionization chamber at different locations inside the bunker after an irradiation of 400 Monitor Units verifying the dose rate per minute for an hour, and accumulating the dose received during that period of time.

  10. Left ventricular wall stress and sarcoplasmic reticulum Ca(2+)-ATPase gene expression in renal hypertensive rats: dose-dependent effects of ACE inhibition and AT1-receptor blockade.

    Science.gov (United States)

    Zierhut, W; Studer, R; Laurent, D; Kästner, S; Allegrini, P; Whitebread, S; Cumin, F; Baum, H P; de Gasparo, M; Drexler, H

    1996-05-01

    Cardiac hypertrophy is associated with altered Ca2+ handling and may predispose to the development of LV dysfunction and cardiac failure. At the cellular level, the re-expression of ANF represents a well-established marker of myocyte hypertrophy while the decreased expression of the sarcoplasmatic reticulum (SR) Ca(2+)-ATPase is thought o play a crucial role in the alterations of Ca2+ handling and LV function. We assessed the dose-dependent effect of chronic ACE inhibition or AT1 receptor blockade on cardiac function in relation to the cardiac expression of the SR Ca(2+)-ATPase and ANF. Renal hypertensive rats (2K-1C) were treated for 12 weeks with three different doses of the ACE inhibitor benazepril, the AT1-receptor antagonist valsartan (each drug 0.3, 3, and 10 mg/kg per day i.p.) or placebo. LV dimensions, hypertrophy and wall stress were determined in vivo by magnetic resonance imaging and the gene expressions of ANF and SR Ca(2+)-ATPase were quantified by Northern blot. Low doses of both drugs did not affect blood pressure, hypertrophy, systolic wall stress and the ANF and SR Ca(2+)-ATPase gene expression. High doses of each drug reduced systolic blood pressure, wall stress, and LV hypertrophy to a similar extent and to values comparable to normotensive, age-matched rats. In addition, high dose treatment reduced LV end-systolic and end-diastolic volume as compared to untreated 2K-1C animals and normalized the mRNA levels of both ANF and SR Ca(2+)-ATPase (as compared to normotensive animals). We conclude that in this model, high doses of ACE inhibition and AT1-receptor blockade are necessary to normalize systolic blood pressure, LV hypertrophy and systolic LV wall stress which, in turn, is associated with restoration of a normal cardiac phenotype with respect to SR Ca(2+)-ATPase and ANF and normalization of cardiac function.

  11. Intravenous infusion of docosahexaenoic acid increases serum concentrations in a dose-dependent manner and increases seizure latency in the maximal PTZ model.

    Science.gov (United States)

    Trépanier, Marc-Olivier; Kwong, Kei-Man; Domenichiello, Anthony F; Chen, Chuck T; Bazinet, Richard P; Burnham, W M

    2015-09-01

    Docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid (n-3 PUFA) that has been shown to raise seizure thresholds in the maximal pentylenetetrazole model following acute subcutaneous (s.c.) administration in rats. Following s.c. administration, however, the dose-response relationship for DHA has shown an inverted U-pattern. The purposes of the present experiment were as follows: (1) to determine the pattern of serum unesterified concentrations resulting from the intravenous (i.v.) infusions of various doses of DHA, (2) to determine the time course of these concentrations following the discontinuation of the infusions, and (3) to determine whether seizure protection in the maximal PTZ model would correlate with serum unesterified DHA levels. Animals received 5-minute i.v. infusions of saline or 25, 50, 100, or 200mg/kg of DHA via a cannula inserted into one of the tail veins. Blood was collected during and after the infusions by means of a second cannula inserted into the other tail vein (Experiment 1). A separate group of animals received saline or 12.5-, 25-, 50-, 100-, or 200 mg/kg DHA i.v. via a cannula inserted into one of the tail veins and were then seizure-tested in the maximal PTZ model either during infusion or after the discontinuation of the infusions. Slow infusions of DHA increased serum unesterified DHA concentrations in a dose-dependent manner, with the 200-mg/kg dose increasing the concentration approximately 260-fold compared with saline-infused animals. Following discontinuation of the infusions, serum concentrations rapidly dropped toward baseline, with half-lives of approximately 40 and 11s for the 25-mg/kg dose and 100-mg/kg dose, respectively. In the seizure-tested animals, DHA significantly increased latency to seizure onset in a dose-dependent manner. Following the discontinuation of infusion, seizure latency rapidly decreased toward baseline. Overall, our study suggests that i.v. infusion of unesterified DHA results in

  12. Drug- not carrier-dependent haematological and biochemical changes in a repeated dose study of cyclosporine encapsulated polyester nano- and micro-particles: Size does not matter

    International Nuclear Information System (INIS)

    Venkatpurwar, V.P.; Rhodes, S.; Oien, K.A.; Elliott, M.A.; Tekwe, C.D.; Jørgensen, H.G.; Kumar, M.N.V. Ravi

    2015-01-01

    Highlights: • The particulate delivery allows an increase in dose range without accrual of toxicities. • The altered haematological and biochemical changes are drug, but not particle dependent. • PLGA nano/microparticles are safe on subacute peroral dosing over 28 days. • Nano-toxicology, drug needs to be considered. - Abstract: Biodegradable nanoparticles are being considered more often as drug carriers to address pharmacokinetic/pharmacodynamic issues, yet nano-product safety has not been systematically proven. In this study, haematological, biochemical and histological parameters were examined on 28 day daily dosing of rats with nano- or micro-particle encapsulated cyclosporine (CsA) to confirm if any changes observed were drug or carrier dependent. CsA encapsulated poly(lactide-co-glycolide) [PLGA] nano- (nCsA) and micro-particles (mCsA) were prepared by emulsion techniques. CsA (15, 30, 45 mg/kg) were administered by oral gavage to Sprague Dawley (SD) rats over 28 days. Haematological and biochemical metrics were followed with tissue histology performed on sacrifice. Whether presented as nCsA or mCsA, 45 mg/kg dose caused significant loss of body weight and lowered food consumption compared to untreated control. Across the doses, both nCsA and mCsA produce significant decreases in lymphocyte numbers compared to controls, commensurate with the proprietary product, Neoral ® 15. Dosing with nCsA showed higher serum drug levels than mCsA presumably owing to the smaller particle size facilitating absorption. The treatment had no noticeable effects on inflammatory/oxidative stress markers or antioxidant enzyme levels, except an increase in ceruloplasmin (CP) levels for high dose nCsA/mCsA group. Further, only subtle, sub-lethal changes were observed in histology of nCsA/mCsA treated rat organs. Blank (drug-free) particles did not induce changes in the parameters studied. Therefore, it is extremely important that the encapsulated drug in the nano-products is

  13. Immunological low-dose radiation modulates the pediatric medulloblastoma antigens and enhances antibody-dependent cellular cytotoxicity.

    Science.gov (United States)

    Das, Arabinda; McDonald, Daniel; Lowe, Stephen; Bredlau, Amy-Lee; Vanek, Kenneth; Patel, Sunil J; Cheshier, Samuel; Eskandari, Ramin

    2017-03-01

    Immunotherapy can be an effective treatment for pediatric medulloblastoma (MB) patients. However, major subpopulations do not respond to immunotherapy, due to the lack of antigenic mutations or the immune-evasive properties of MB cells. Clinical observations suggest that radiation therapy (RT) may expand the therapeutic reach of immunotherapy. The aim of the present investigation is to study the effect of low-dose X-ray radiation (LDXR, 1 Gy) on the functional immunological responses of MB cells (DAOY, D283, and D341). Induction of MB cell death was examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Production of reactive oxygen species (ROS) was measured by fluorescent probes. Changes in the expression of  human leukocyte antigen (HLA) molecules and caspase-3 activities during treatment were analyzed using Western blotting and caspase-3 assay. Western blot analysis demonstrated that LDXR upregulated the expression of HLA class I and HLA II molecules by more than 20% compared with control and high-dose (12 Gy) groups in vitro. Several of these HLA subtypes, such as MAGE C1, CD137, and ICAM-1, have demonstrated upregulation. In addition, LDXR increases ROS production in association with phosphorylation of NF-κB and cell surface expression of mAb target molecules (HER2 and VEGF). These data suggest that a combined LDXR and mAb therapy can create a synergistic effect in vitro. These results suggest that LDXR modulates HLA molecules, leading