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,

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.

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

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.

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.

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

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

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

Radiation dose in cardiac SPECT/CT: An estimation of SSDE and effective dose

International Nuclear Information System (INIS)

Abdollahi, Hamid; Shiri, Isaac; Salimi, Yazdan; Sarebani, Maghsoud; Mehdinia, Reza; Deevband, Mohammad Reza; Mahdavi, Seied Rabi; Sohrabi, Ahmad; Bitarafan-Rajabi, Ahmad

2016-01-01

Aims: The dose levels for Computed Tomography (CT) localization and attenuation correction of Single Photon Emission Computed Tomography (SPECT) are limited and reported as Volume Computed Tomography Dose Index (CTDIvol) and Dose-Length Product (DLP). This work presents CT dose estimation from Cardiac SPECT/CT based on new American Association of Physicists in Medicine (AAPM) Size Specific Dose Estimation (SSDE) parameter, effective dose, organ doses and also emission dose from nuclear issue. Material and methods: Myocardial perfusion SPECT/CT for 509 patients was included in the study. SSDE, effective dose and organ dose were calculated using AAPM guideline and Impact-Dose software. Data were analyzed using R and SPSS statistical software. Spearman-Pearson correlation test and linear regression models were used for finding correlations and relationships among parameters. Results: The mean CTDIvol was 1.34 mGy ± 0.19 and the mean SSDE was 1.7 mGy ± 0.16. The mean ± SD of effective dose from emission, CT and total dose were 11.5 ± 1.4, 0.49 ± 0.11 and 12.67 ± 1.73 (mSv) respectively. The mean ± SD of effective dose from emission, CT and total dose were 11.5 ± 1.4, 0.49 ± 0.11 and 12.67 ± 1.73 (mSv) respectively. The spearman test showed that correlation between body size and organ doses is significant except thyroid and red bone marrow. CTDIvol was strongly dependent on patient size, but SSDE was not. Emission dose was strongly dependent on patient weight, but its dependency was lower to effective diameter. Conclusion: The dose parameters including CTDIvol, DLP, SSDE, effective dose values reported here are very low and below the reference level. This data suggest that appropriate CT acquisition parameters in SPECT/CT localization and attenuation correction are very beneficial for patients and lowering cancer risks.

Radiation dose in cardiac SPECT/CT: An estimation of SSDE and effective dose

Energy Technology Data Exchange (ETDEWEB)

Abdollahi, Hamid, E-mail: Hamid_rbp@yahoo.com [Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Shiri, Isaac [Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Salimi, Yazdan [Biomedical Engineering and Medical Physics Department, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran (Iran, Islamic Republic of); Sarebani, Maghsoud; Mehdinia, Reza [Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Deevband, Mohammad Reza [Biomedical Engineering and Medical Physics Department, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran (Iran, Islamic Republic of); Mahdavi, Seied Rabi [Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Radiation Biology Research Center, Iran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Sohrabi, Ahmad [Department of Biostatistics, School of Public Health, Iran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Bitarafan-Rajabi, Ahmad, E-mail: bitarafan@hotmail.com [Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Department of Nuclear Medicine, Rajaei Cardiovascular, Medical and Research Center, Iran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

2016-12-15

Aims: The dose levels for Computed Tomography (CT) localization and attenuation correction of Single Photon Emission Computed Tomography (SPECT) are limited and reported as Volume Computed Tomography Dose Index (CTDIvol) and Dose-Length Product (DLP). This work presents CT dose estimation from Cardiac SPECT/CT based on new American Association of Physicists in Medicine (AAPM) Size Specific Dose Estimation (SSDE) parameter, effective dose, organ doses and also emission dose from nuclear issue. Material and methods: Myocardial perfusion SPECT/CT for 509 patients was included in the study. SSDE, effective dose and organ dose were calculated using AAPM guideline and Impact-Dose software. Data were analyzed using R and SPSS statistical software. Spearman-Pearson correlation test and linear regression models were used for finding correlations and relationships among parameters. Results: The mean CTDIvol was 1.34 mGy ± 0.19 and the mean SSDE was 1.7 mGy ± 0.16. The mean ± SD of effective dose from emission, CT and total dose were 11.5 ± 1.4, 0.49 ± 0.11 and 12.67 ± 1.73 (mSv) respectively. The mean ± SD of effective dose from emission, CT and total dose were 11.5 ± 1.4, 0.49 ± 0.11 and 12.67 ± 1.73 (mSv) respectively. The spearman test showed that correlation between body size and organ doses is significant except thyroid and red bone marrow. CTDIvol was strongly dependent on patient size, but SSDE was not. Emission dose was strongly dependent on patient weight, but its dependency was lower to effective diameter. Conclusion: The dose parameters including CTDIvol, DLP, SSDE, effective dose values reported here are very low and below the reference level. This data suggest that appropriate CT acquisition parameters in SPECT/CT localization and attenuation correction are very beneficial for patients and lowering cancer risks.

TREATMENT OF STEROID DEPENDENT ASTHMATICS WITH LOW DOSES OF CYCLOSPORINE

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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.

Gamma dose rate effect on JFET transistors

International Nuclear Information System (INIS)

Assaf, J.

2011-04-01

The effect of Gamma dose rate on JFET transistors is presented. The irradiation was accomplished at the following available dose rates: 1, 2.38, 5, 10 , 17 and 19 kGy/h at a constant dose of 600 kGy. A non proportional relationship between the noise and dose rate in the medium range (between 2.38 and 5 kGy/h) was observed. While in the low and high ranges, the noise was proportional to the dose rate as the case of the dose effect. This may be explained as follows: the obtained result is considered as the yield of a competition between many reactions and events which are dependent on the dose rate. At a given values of that events parameters, a proportional or a non proportional dose rate effects are generated. No dependence effects between the dose rate and thermal annealing recovery after irradiation was observed . (author)

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

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)

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.

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

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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.

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.)

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.

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

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

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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.

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.

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

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).

Determination of organ doses and effective doses in radiooncology

International Nuclear Information System (INIS)

Roth, J.; Martinez, A.E.

2007-01-01

Background and Purpose: With an increasing chance of success in radiooncology, it is necessary to estimate the risk from radiation scatter to areas outside the target volume. The cancer risk from a radiation treatment can be estimated from the organ doses, allowing a somewhat limited effective dose to be estimated and compared. Material and Methods: The doses of the radiation-sensitive organs outside the target volume can be estimated with the aid of the PC program PERIDOSE developed by van der Giessen. The effective doses are determined according to the concept of ICRP, whereby the target volume and the associated organs related to it are not taken into consideration. Results: Organ doses outside the target volume are generally < 1% of the dose in the target volume. In some cases, however, they can be as high as 3%. The effective doses during radiotherapy are between 60 and 900 mSv, depending upon the specific target volume, the applied treatment technique, and the given dose in the ICRU point. Conclusion: For the estimation of the radiation risk, organ doses in radiooncology can be calculated with the aid of the PC program PERIDOSE. While evaluating the radiation risk after ICRP, for the calculation of the effective dose, the advanced age of many patients has to be considered to prevent that, e.g., the high gonad doses do not overestimate the effective dose. (orig.)

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.

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.

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.

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)

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

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

We can do better than effective dose for estimating or comparing low-dose radiation risks

International Nuclear Information System (INIS)

Brenner, D.J.

2012-01-01

The effective dose concept was designed to compare the generic risks of exposure to different radiation fields. More commonly these days, it is used to estimate or compare radiation-induced cancer risks. For various reasons, effective dose represents flawed science: for instance, the tissue-specific weighting factors used to calculate effective dose are a subjective mix of different endpoints; and the marked and differing age and gender dependencies for different health detriment endpoints are not taken into account. This paper suggests that effective dose could be replaced with a new quantity, ‘effective risk’, which, like effective dose, is a weighted sum of equivalent doses to different tissues. Unlike effective dose, where the tissue-dependent weighting factors are a set of generic, subjective committee-defined numbers, the weighting factors for effective risk are simply evaluated tissue-specific lifetime cancer risks per unit equivalent dose. Effective risk, which has the potential to be age and gender specific if desired, would perform the same comparative role as effective dose, be just as easy to estimate, be less prone to misuse, be more directly understandable, and would be based on solid science. An added major advantage is that it gives the users some feel for the actual numerical values of the radiation risks they are trying to control.

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

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.

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.

Neuroprotective effect of interleukin-6 regulation of voltage-gated Na+ channels of cortical neurons is time- and dose-dependent

Directory of Open Access Journals (Sweden)

Wei Xia

2015-01-01

Full Text Available Interleukin-6 has been shown to be involved in nerve injury and nerve regeneration, but the effects of long-term administration of high concentrations of interleukin-6 on neurons in the central nervous system is poorly understood. This study investigated the effects of 24 hour exposure of interleukin-6 on cortical neurons at various concentrations (0.1, 1, 5 and 10 ng/mL and the effects of 10 ng/mL interleukin-6 exposure to cortical neurons for various durations (2, 4, 8, 24 and 48 hours by studying voltage-gated Na + channels using a patch-clamp technique. Voltage-clamp recording results demonstrated that interleukin-6 suppressed Na + currents through its receptor in a time- and dose-dependent manner, but did not alter voltage-dependent activation and inactivation. Current-clamp recording results were consistent with voltage-clamp recording results. Interleukin-6 reduced the action potential amplitude of cortical neurons, but did not change the action potential threshold. The regulation of voltage-gated Na + channels in rat cortical neurons by interleukin-6 is time- and dose-dependent.

Dose and Dose-Rate Effectiveness Factor (DDREF); Der Dosis- und Dosisleistungs-Effektivitaetsfaktor (DDREF)

Energy Technology Data Exchange (ETDEWEB)

Breckow, Joachim [Fachhochschule Giessen-Friedberg, Giessen (Germany). Inst. fuer Medizinische Physik und Strahlenschutz

2016-08-01

For practical radiation protection purposes it is supposed that stochastic radiation effects a determined by a proportional dose relation (LNT). Radiobiological and radiation epidemiological studies indicated that in the low dose range a dependence on dose rates might exist. This would trigger an overestimation of radiation risks based on the LNT model. OCRP had recommended a concept to combine all effects in a single factor DDREF (dose and dose-Rate effectiveness factor). There is still too low information on cellular mechanisms of low dose irradiation including possible repair and other processes. The Strahlenschutzkommission cannot identify a sufficient scientific justification for DDREF and recommends an adaption to the actual state of science.

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

Bayesian estimation of dose rate effectiveness

International Nuclear Information System (INIS)

Arnish, J.J.; Groer, P.G.

2000-01-01

A Bayesian statistical method was used to quantify the effectiveness of high dose rate 137 Cs gamma radiation at inducing fatal mammary tumours and increasing the overall mortality rate in BALB/c female mice. The Bayesian approach considers both the temporal and dose dependence of radiation carcinogenesis and total mortality. This paper provides the first direct estimation of dose rate effectiveness using Bayesian statistics. This statistical approach provides a quantitative description of the uncertainty of the factor characterising the dose rate in terms of a probability density function. The results show that a fixed dose from 137 Cs gamma radiation delivered at a high dose rate is more effective at inducing fatal mammary tumours and increasing the overall mortality rate in BALB/c female mice than the same dose delivered at a low dose rate. (author)

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.

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

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.

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....

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

Effects of proton radiation dose, dose rate and dose fractionation on hematopoietic cells in mice

International Nuclear Information System (INIS)

Ware, J.H.; Rusek, A.; Sanzari, J.; Avery, S.; Sayers, C.; Krigsfeld, G.; Nuth, M.; Wan, X.S.; Kennedy, A.R.

2010-01-01

The present study evaluated the acute effects of radiation dose, dose rate and fractionation as well as the energy of protons in hematopoietic cells of irradiated mice. The mice were irradiated with a single dose of 51.24 MeV protons at a dose of 2 Gy and a dose rate of 0.05-0.07 Gy/min or 1 GeV protons at doses of 0.1, 0.2, 0.5, 1, 1.5 and 2 Gy delivered in a single dose at dose rates of 0.05 or 0.5 Gy/min or in five daily dose fractions at a dose rate of 0.05 Gy/min. Sham-irradiated animals were used as controls. The results demonstrate a dose-dependent loss of white blood cells (WBCs) and lymphocytes by up to 61% and 72%, respectively, in mice irradiated with protons at doses up to 2 Gy. The results also demonstrate that the dose rate, fractionation pattern and energy of the proton radiation did not have significant effects on WBC and lymphocyte counts in the irradiated animals. These results suggest that the acute effects of proton radiation on WBC and lymphocyte counts are determined mainly by the radiation dose, with very little contribution from the dose rate (over the range of dose rates evaluated), fractionation and energy of the protons.

Effects of proton radiation dose, dose rate and dose fractionation on hematopoietic cells in mice.

Science.gov (United States)

Ware, J H; Sanzari, J; Avery, S; Sayers, C; Krigsfeld, G; Nuth, M; Wan, X S; Rusek, A; Kennedy, A R

2010-09-01

The present study evaluated the acute effects of radiation dose, dose rate and fractionation as well as the energy of protons in hematopoietic cells of irradiated mice. The mice were irradiated with a single dose of 51.24 MeV protons at a dose of 2 Gy and a dose rate of 0.05-0.07 Gy/min or 1 GeV protons at doses of 0.1, 0.2, 0.5, 1, 1.5 and 2 Gy delivered in a single dose at dose rates of 0.05 or 0.5 Gy/min or in five daily dose fractions at a dose rate of 0.05 Gy/min. Sham-irradiated animals were used as controls. The results demonstrate a dose-dependent loss of white blood cells (WBCs) and lymphocytes by up to 61% and 72%, respectively, in mice irradiated with protons at doses up to 2 Gy. The results also demonstrate that the dose rate, fractionation pattern and energy of the proton radiation did not have significant effects on WBC and lymphocyte counts in the irradiated animals. These results suggest that the acute effects of proton radiation on WBC and lymphocyte counts are determined mainly by the radiation dose, with very little contribution from the dose rate (over the range of dose rates evaluated), fractionation and energy of the protons.

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

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 ...

Dose and time-dependent effects of cyanide on thiosulfate sulfurtransferase, 3-mercaptopyruvate sulfurtransferase, and cystathionine λ-lyase activities.

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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.

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

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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.

Dose-dependent effects of an immune challenge at both ultimate and proximate levels in Drosophila melanogaster.

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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.

Low-dose effect on blood chromosomes

International Nuclear Information System (INIS)

Pohl-Rueling, J.

1992-01-01

Linear dose response relationships of biological effects at low doses are experimentally and theoretically disputed. Structural chromosome aberration rates at doses ranging from normal background exposures up to about 30 mGy/yr in vivo and up to 50 mGy in vitro were investigated by the author and other scientists. Results are comparable and dose effect curves reveal following shapes; within the normal burden and up to 2-10 mGy/yr in vivo rates they increase sharply to about 3-6 times the lowest values; subsequent doses either from natural, occupational or accidental exposures up to about 30 mGy/yr yield either constant aberration rates, assuming a plateau, or perhaps even a decrease. In vitro experiments show comparable results up to 50 mGy. Other biological effects seem to have similar dose dependencies. The non-linearity of low-dose effects can be explained by induction of repair enzymes at certain damage to the DNA. This hypothesis is sustained experimentally and theoretically by several papers in literature. (author). 14 refs., 5 figs

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

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)

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...

Cocaine and Pavlovian fear conditioning: dose-effect analysis.

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Wood, Suzanne C; Fay, Jonathan; Sage, Jennifer R; Anagnostaras, Stephan G

2007-01-25

Emerging evidence suggests that cocaine and other drugs of abuse can interfere with many aspects of cognitive functioning. The authors examined the effects of 0.1-15mg/kg of cocaine on Pavlovian contextual and cued fear conditioning in mice. As expected, pre-training cocaine dose-dependently produced hyperactivity and disrupted freezing. Surprisingly, when the mice were tested off-drug later, the group pre-treated with a moderate dose of cocaine (15mg/kg) displayed significantly less contextual and cued memory, compared to saline control animals. Conversely, mice pre-treated with a very low dose of cocaine (0.1mg/kg) showed significantly enhanced fear memory for both context and tone, compared to controls. These results were not due to cocaine's anesthetic effects, as shock reactivity was unaffected by cocaine. The data suggest that despite cocaine's reputation as a performance-enhancing and anxiogenic drug, this effect is seen only at very low doses, whereas a moderate dose disrupts hippocampus and amygdala-dependent fear conditioning.

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)

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

The effects of steroids during sepsis depend on dose and severity of illness: an updated meta-analysis

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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

Biological Effects of Low-Dose Exposure

CERN Document Server

Komochkov, M M

2000-01-01

On the basis of the two-protection reaction model an analysis of stochastic radiobiological effects of low-dose exposure of different biological objects has been carried out. The stochastic effects are the results published in the last decade: epidemiological studies of human cancer mortality, the yield of thymocyte apoptosis of mice and different types of chromosomal aberrations. The results of the analysis show that as dependent upon the nature of biological object, spontanous effect, exposure conditions and radiation type one or another form dose - effect relationship is realized: downwards concave, near to linear and upwards concave with the effect of hormesis included. This result testifies to the incomplete conformity of studied effects of 1990 ICRP recomendations based on the linear no-threshold hypothesis about dose - effect relationship. Because of this the methodology of radiation risk estimation recomended by ICRP needs more precisian and such quantity as collective dose ought to be classified into...

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)

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

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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.

Mathematical model for evaluation of dose-rate effect on biological responses to low dose γ-radiation

International Nuclear Information System (INIS)

Ogata, H.; Kawakami, Y.; Magae, J.

2003-01-01

Full text: To evaluate quantitative dose-response relationship on the biological response to radiation, it is necessary to consider a model including cumulative dose, dose-rate and irradiation time. In this study, we measured micronucleus formation and [ 3 H] thymidine uptake in human cells as indices of biological response to gamma radiation, and analyzed mathematically and statistically the data for quantitative evaluation of radiation risk at low dose/low dose-rate. Effective dose (ED x ) was mathematically estimated by fitting a general function of logistic model to the dose-response relationship. Assuming that biological response depends on not only cumulative dose but also dose-rate and irradiation time, a multiple logistic function was applied to express the relationship of the three variables. Moreover, to estimate the effect of radiation at very low dose, we proposed a modified exponential model. From the results of fitting curves to the inhibition of [ 3 H] thymidine uptake and micronucleus formation, it was obvious that ED 50 in proportion of inhibition of [ 3 H] thymidine uptake increased with longer irradiation time. As for the micronuclei, ED 30 also increased with longer irradiation times. These results suggest that the biological response depends on not only total dose but also irradiation time. The estimated response surface using the three variables showed that the biological response declined sharply when the dose-rate was less than 0.01 Gy/h. These results suggest that the response does not depend on total cumulative dose at very low dose-rates. Further, to investigate the effect of dose-rate within a wider range, we analyzed the relationship between ED x and dose-rate. Fitted curves indicated that ED x increased sharply when dose-rate was less than 10 -2 Gy/h. The increase of ED x signifies the decline of the response or the risk and suggests that the risk approaches to 0 at infinitely low dose-rate

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

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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.

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

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

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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.

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

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.

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

Dose and dose rate effects on coherent-to-incoherent transition of precipitates upon irradiation

Institute of Scientific and Technical Information of China (English)

LI Zhengchao

2006-01-01

A typical precipitation hardened alloy, Cu-Co dilute alloy was selected to study the precipitation behavior and irradiation effect on precipitates. It is found that the principal effect of ion irradiation on the coherent precipitates is loss of coherency, and TEM cross-section observations show that the fraction of the incoherent precipitates is dependent on dose but not on dose rate during heavy ion irradiation.

Testing Dose-Dependent Effects of the Nectar Alkaloid Anabasine on Trypanosome Parasite Loads in Adult Bumble Bees.

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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.

Testing Dose-Dependent Effects of the Nectar Alkaloid Anabasine on Trypanosome Parasite Loads in Adult Bumble Bees.

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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.

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

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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.

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

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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.

Effective dose equivalents from external radiation due to Chernobyl accident

International Nuclear Information System (INIS)

Erkin, V.G.; Debedev, O.V.; Balonov, M.I.; Parkhomenko, V.I.

1992-01-01

Summarized data on measurements of individual dose of external γ-sources in 1987-1990 of population of western areas of Bryansk region were presented. Type of distribution of effective dose equivalent, its significance for various professional and social groups of population depending on the type of the house was discussed. Dependences connecting surface soil activity in the populated locality with average dose of external radiation sources were presented. Tendency of dose variation in 1987-1990 was shown

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

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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.

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

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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.

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

Dose rate effect models for biological reaction to ionizing radiation in human cell lines

International Nuclear Information System (INIS)

Magae, Junji; Ogata, Hiromitsu

2008-01-01

Full text: Because of biological responses to ionizing radiation are dependent on irradiation time or dose rate as well as dose, simultaneous inclusion of dose and dose rate is required to evaluate the risk of long term irradiation at low dose rates. We previously published a novel statistical model for dose rate effect, modified exponential (MOE) model, which predicts irradiation time-dependent biological response to low dose rate ionizing radiation, by analyzing micronucleus formation and growth inhibition in a human osteosarcoma cell line, exposed to wide range of doses and dose rates of gamma-rays. MOE model demonstrates that logarithm of median effective dose exponentially increases in low dose rates, and thus suggests that the risk approaches to zero at infinitely low dose rate. In this paper, we extend the analysis in various kinds of human cell lines exposed to ionizing radiation for more than a year. We measured micronucleus formation and [ 3 H]thymidine uptake in human cell lines including an osteosarcoma, a DNA-dependent protein kinase-deficient glioma, a SV40-transformed fibroblast derived from an ataxia telangiectasia patient, a normal fibroblast, and leukemia cell lines. Cells were exposed to gamma-rays in irradiation room bearing 50,000 Ci of cobalt-60. After the irradiation, they were cultured for 24 h in the presence of cytochalasin B to block cytokinesis, and cytoplasm and nucleus were stained with DAPI and prospidium iodide. The number of binuclear cells bearing a micronucleus was counted under a fluorescence microscope. For proliferation inhibition, cells were cultured for 48 h after the irradiation and [ 3 H] thymidine was pulsed for 4 h before harvesting. We statistically analyzed the data for quantitative evaluation of radiation risk. While dose and dose rate relationship cultured within one month followed MOE model in cell lines holding wild-type DNA repair system, dose rate effect was greatly impaired in DNA repair-deficient cell lines

A model for homeopathic remedy effects: low dose nanoparticles, allostatic cross-adaptation, and time-dependent sensitization in a complex adaptive system

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Bell Iris R

2012-10-01

Full Text Available Abstract Background This paper proposes a novel model for homeopathic remedy action on living systems. Research indicates that homeopathic remedies (a contain measurable source and silica nanoparticles heterogeneously dispersed in colloidal solution; (b act by modulating biological function of the allostatic stress response network (c evoke biphasic actions on living systems via organism-dependent adaptive and endogenously amplified effects; (d improve systemic resilience. Discussion The proposed active components of homeopathic remedies are nanoparticles of source substance in water-based colloidal solution, not bulk-form drugs. Nanoparticles have unique biological and physico-chemical properties, including increased catalytic reactivity, protein and DNA adsorption, bioavailability, dose-sparing, electromagnetic, and quantum effects different from bulk-form materials. Trituration and/or liquid succussions during classical remedy preparation create “top-down” nanostructures. Plants can biosynthesize remedy-templated silica nanostructures. Nanoparticles stimulate hormesis, a beneficial low-dose adaptive response. Homeopathic remedies prescribed in low doses spaced intermittently over time act as biological signals that stimulate the organism’s allostatic biological stress response network, evoking nonlinear modulatory, self-organizing change. Potential mechanisms include time-dependent sensitization (TDS, a type of adaptive plasticity/metaplasticity involving progressive amplification of host responses, which reverse direction and oscillate at physiological limits. To mobilize hormesis and TDS, the remedy must be appraised as a salient, but low level, novel threat, stressor, or homeostatic disruption for the whole organism. Silica nanoparticles adsorb remedy source and amplify effects. Properly-timed remedy dosing elicits disease-primed compensatory reversal in direction of maladaptive dynamics of the allostatic network, thus promoting

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

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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.

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

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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

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

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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.

Dose and dose rate effects of whole-body gamma-irradiation: II. Hematological variables and cytokines

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Gridley, D. S.; Pecaut, M. J.; Miller, G. M.; Moyers, M. F.; Nelson, G. A.

2001-01-01

The goal of part II of this study was to evaluate the effects of gamma-radiation on circulating blood cells, functional characteristics of splenocytes, and cytokine expression after whole-body irradiation at varying total doses and at low- and high-dose-rates (LDR, HDR). Young adult C57BL/6 mice (n = 75) were irradiated with either 1 cGy/min or 80 cGy/min photons from a 60Co source to cumulative doses of 0.5, 1.5, and 3.0 Gy. The animals were euthanized at 4 days post-exposure for in vitro assays. Significant dose- (but not dose-rate-) dependent decreases were observed in erythrocyte and blood leukocyte counts, hemoglobin, hematocrit, lipopolysaccharide (LPS)-induced 3H-thymidine incorporation, and interleukin-2 (IL-2) secretion by activated spleen cells when compared to sham-irradiated controls (p < 0.05). Basal proliferation of leukocytes in the blood and spleen increased significantly with increasing dose (p < 0.05). Significant dose rate effects were observed only in thrombocyte counts. Plasma levels of transforming growth factor-beta 1 (TGF-beta 1) and splenocyte secretion of tumor necrosis factor-alpha (TNF-alpha) were not affected by either the dose or dose rate of radiation. The data demonstrate that the responses of blood and spleen were largely dependent upon the total dose of radiation employed and that an 80-fold difference in the dose rate was not a significant factor in the great majority of measurements.

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

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.

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

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.

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.)

Dose-dependent effects of atorvastatin on myocardial infarction

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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

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.

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.

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.

Proton dose distribution measurements using a MOSFET detector with a simple dose-weighted correction method for LET effects.

Science.gov (United States)

Kohno, Ryosuke; Hotta, Kenji; Matsuura, Taeko; Matsubara, Kana; Nishioka, Shie; Nishio, Teiji; Kawashima, Mitsuhiko; Ogino, Takashi

2011-04-04

We experimentally evaluated the proton beam dose reproducibility, sensitivity, angular dependence and depth-dose relationships for a new Metal Oxide Semiconductor Field Effect Transistor (MOSFET) detector. The detector was fabricated with a thinner oxide layer and was operated at high-bias voltages. In order to accurately measure dose distributions, we developed a practical method for correcting the MOSFET response to proton beams. The detector was tested by examining lateral dose profiles formed by protons passing through an L-shaped bolus. The dose reproducibility, angular dependence and depth-dose response were evaluated using a 190 MeV proton beam. Depth-output curves produced using the MOSFET detectors were compared with results obtained using an ionization chamber (IC). Since accurate measurements of proton dose distribution require correction for LET effects, we developed a simple dose-weighted correction method. The correction factors were determined as a function of proton penetration depth, or residual range. The residual proton range at each measurement point was calculated using the pencil beam algorithm. Lateral measurements in a phantom were obtained for pristine and SOBP beams. The reproducibility of the MOSFET detector was within 2%, and the angular dependence was less than 9%. The detector exhibited a good response at the Bragg peak (0.74 relative to the IC detector). For dose distributions resulting from protons passing through an L-shaped bolus, the corrected MOSFET dose agreed well with the IC results. Absolute proton dosimetry can be performed using MOSFET detectors to a precision of about 3% (1 sigma). A thinner oxide layer thickness improved the LET in proton dosimetry. By employing correction methods for LET dependence, it is possible to measure absolute proton dose using MOSFET detectors.

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.

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.

The biological effects of low doses of radiation: medical, biological and ecological aspects

International Nuclear Information System (INIS)

Gun-Aajav, T.; Ajnai, L.; Manlaijav, G.

2007-01-01

Full text: The results of recent studies show that low doses of radiation make many different structural and functional changes in a cell and these changes are preserved for a long time. This phenomenon is called as effects of low doses of radiation in biophysics, radiation biology and radiation medicine. The structural and functional changes depend on doses and this dependence has non-linear and bimodal behaviour. More detail, the radiation effect goes up and reaches its maximum (Low doses maximum) in low doses region, then it goes down and takes its stationary means (there is a negative effect in a few cases). With increases in doses and with further increases it goes up. It is established that low dose's maximum depends on physiological state of a biological object, radiation quality and dose rate. During the experiments another special date was established. This specialty is that many different physical and chemical factors are mutually connected and have synergetic behaviour. At present, researches are concentrating their attention on the following three directions: 1. Direct and indirect interaction of radiation's low doses: 2. Interpretation of its molecular mechanism, regulation of the positive effects and elaboration of ways o removing negative effects: 3. Application of the objective research results into practice. In conclusion the authors mention the current concepts on interpretation of low doses effect mechanism, forward their own views and emphasize the importance of considering low doses effects in researches of environmental radiation pollution, radiation medicine and radiation protection. (author)

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)

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.

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

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

Estimating effective doses to children from CT examinations

International Nuclear Information System (INIS)

Heron, J.C.L.

2000-01-01

Full text: Assessing doses to patients in diagnostic radiology is an integral part of implementing optimisation of radiation protection. Sources of normalised data are available for estimating doses to adults undergoing CT examinations, but for children this is not the case. This paper describes a simple method for estimating effective doses arising from paediatric CT examinations. First the effective dose to an adult is calculated, having anatomically matched the scanned regions of the child and the adult and also matched the irradiation conditions. A conversion factor is then applied to the adult effective dose, based on the region of the body being scanned - head, upper or lower trunk. This conversion factor is the child-to-adult ratio of the ratios of effective dose per entrance air kerma (in the absence of the patient) at the FAD. The values of these conversion factors were calculated by deriving effective dose per entrance air kerma at the FAD for new-born, 1, 5, 10, 15 and adult phantoms using four projections (AP, PA, left and right laterals) over a range of beam qualities and FADs.The program PCXMC was used for this purpose. Results to date suggest that the conversion factors to give effective doses for children undergoing CT examinations of the upper trunk are approximately 1.3, 1.2, 1.15, 1.1 and 1.05 for ages 0, 1, 5, 10 and 15 years respectively; CT of the lower trunk - 1.4, 1.3, 1.2, 1.2, 1.1; and CT of the head - 2.3, 2.0, 1.5, 1.3, 1.1. The dependence of these factors on beam quality (HVL from 4 to 10 mm Al) is less than 10%, with harder beams resulting in slightly smaller conversion factors. Dependence on FAD is also less than 10%. Major sources of uncertainties in the conversion factors include matching anatomical regions across the phantoms, and the presence of beam divergence in the z-direction when deriving the factors. The method described provides a simple means of estimating effective doses arising from paediatric CT examinations with

Effects of low doses of ionizing radiation

International Nuclear Information System (INIS)

Masse, R.

2006-01-01

Several groups of human have been irradiated by accidental or medical exposure, if no gene defect has been associated to these exposures, some radioinduced cancers interesting several organs are observed among persons exposed over 100 to 200 mSv delivered at high dose rate. Numerous steps are now identified between the initial energy deposit in tissue and the aberrations of cell that lead to tumors but the sequence of events and the specific character of some of them are the subject of controversy. The stake of this controversy is the risk assessment. From the hypothesis called linear relationship without threshold is developed an approach that leads to predict cancers at any tiny dose without real scientific foundation. The nature and the intensity of biological effects depend on the quantity of energy absorbed in tissue and the modality of its distribution in space and time. The probability to reach a target (a gene) associated to the cancerating of tissue is directly proportional to the dose without any other threshold than the quantity of energy necessary to the effect, its probability of effect can be a more complex function and depends on the quality of the damage produced as well as the ability of the cell to repair the damage. These two parameters are influenced by the concentration of initial injuries in the target so by the quality of radiation and by the dose rate. The mechanisms of defence explain the low efficiency of radiation as carcinogen and then the linearity of effects in the area of low doses is certainly the least defensible scientific hypothesis for the prediction of the risks. (N.C.)

Organ or tissue doses, effective dose and collective effective dose from X-ray diagnosis, in Japan

International Nuclear Information System (INIS)

Murayama, Takashi; Nishizawa, Kanae; Noda, Yutaka; Kumamoto, Yoshikazu; Iwai, Kazuo.

1996-01-01

Effective doses and collective effective doses from X-ray diagnostic examinations were calculated on the basis of the frequency of examinations estimated by a nationwide survey and the organ or tissue doses experimentally determined. The average organ or tissue doses were determined with thermoluminescence dosimeters put at various sites of organs or tissues in an adult and a child phantom. Effective doses (effective dose equivalents) were calculated as the sum of the weighted equivalent doses in all the organs or tissues of the body. As the examples of results, the effective doses per radiographic examination were approximately 7 mGy for male, and 9 mGy for female angiocardiography, and about 3 mGy for barium meal. Annual collective effective dose from X-ray diagnostic examinations in 1986 were about 104 x 10 3 person Sv from radiography and 118 x 10 3 person Sv from fluoroscopy, with the total of 222 x 10 3 person Sv. (author)

Dose and dose rate effects of whole-body gamma-irradiation: II. Hematological variables and cytokines

Science.gov (United States)

Gridley, D. S.; Pecaut, M. J.; Miller, G. M.; Moyers, M. F.; Nelson, G. A.

2001-01-01

The goal of part II of this study was to evaluate the effects of gamma-radiation on circulating blood cells, functional characteristics of splenocytes, and cytokine expression after whole-body irradiation at varying total doses and at low- and high-dose-rates (LDR, HDR). Young adult C57BL/6 mice (n = 75) were irradiated with either 1 cGy/min or 80 cGy/min photons from a 60Co source to cumulative doses of 0.5, 1.5, and 3.0 Gy. The animals were euthanized at 4 days post-exposure for in vitro assays. Significant dose- (but not dose-rate-) dependent decreases were observed in erythrocyte and blood leukocyte counts, hemoglobin, hematocrit, lipopolysaccharide (LPS)-induced 3H-thymidine incorporation, and interleukin-2 (IL-2) secretion by activated spleen cells when compared to sham-irradiated controls (p factor-beta 1 (TGF-beta 1) and splenocyte secretion of tumor necrosis factor-alpha (TNF-alpha) were not affected by either the dose or dose rate of radiation. The data demonstrate that the responses of blood and spleen were largely dependent upon the total dose of radiation employed and that an 80-fold difference in the dose rate was not a significant factor in the great majority of measurements.

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

Estimation and comparison of effective dose (E) in standard chest CT by organ dose measurements and dose-length-product methods and assessment of the influence of CT tube potential (energy dependency) on effective dose in a dual-source CT

International Nuclear Information System (INIS)

Paul, Jijo; Banckwitz, Rosemarie; Krauss, Bernhard; Vogl, Thomas J.; Maentele, Werner; Bauer, Ralf W.

2012-01-01

Highlights: ► The dual-energy protocol delivers the lowest effective dose of the investigated protocols for standard chest CT examinations, thus enabling functional imaging (like dual-energy perfusion) and can produce weighted images without dose penalty. ► The high-pitch protocol goes along with a 16% increase in dose compared to the standard 120 kV protocol and thus should preferably be used in pediatric, acute care settings (e.g. pulmonary embolism, aortic dissection and the like) or restless patients. ► The difference in effective dose estimates between ICRP 60 and 103 is minimal. ► Tube potential definitely has an effect on estimates of effective dose. - Abstract: Purpose: To determine effective dose (E) during standard chest CT using an organ dose-based and a dose-length-product-based (DLP) approach for four different scan protocols including high-pitch and dual-energy in a dual-source CT scanner of the second generation. Materials and methods: Organ doses were measured with thermo luminescence dosimeters (TLD) in an anthropomorphic male adult phantom. Further, DLP-based dose estimates were performed by using the standard 0.014 mSv/mGycm conversion coefficient k. Examinations were performed on a dual-source CT system (Somatom Definition Flash, Siemens). Four scan protocols were investigated: (1) single-source 120 kV, (2) single-source 100 kV, (3) high-pitch 120 kV, and (4) dual-energy with 100/Sn140 kV with equivalent CTDIvol and no automated tube current modulation. E was then determined following recommendations of ICRP publication 103 and 60 and specific k values were derived. Results: DLP-based estimates differed by 4.5–16.56% and 5.2–15.8% relatively to ICRP 60 and 103, respectively. The derived k factors calculated from TLD measurements were 0.0148, 0.015, 0.0166, and 0.0148 for protocol 1, 2, 3 and 4, respectively. Effective dose estimations by ICRP 103 and 60 for single-energy and dual-energy protocols show a difference of less than 0.04 m

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

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.

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.

Assessment of organ equivalent doses and effective doses from diagnostic X-ray examinations

International Nuclear Information System (INIS)

Park, Sang Hyun

2003-02-01

The MIRD-type adult male, female and age 10 phantoms were constructed to evaluate organ equivalent dose and effective dose of patient due to typical diagnostic X-ray examination. These phantoms were constructed with external and internal dimensions of Korean. The X-ray energy spectra were generated with SPEC78. MCNP4B ,the general-purposed Monte Carlo code, was used. Information of chest PA , chest LAT, and abdomen AP diagnostic X-ray procedures was collected on the protocol of domestic hospitals. The results showed that patients pick up approximate 0.02 to 0.18 mSv of effective dose from a single chest PA examination, and 0.01 to 0.19 mSv from a chest LAT examination depending on the ages. From an abdomen AP examination, patients pick up 0.17 to 1.40 mSv of effective dose. Exposure time, organ depth from the entrance surface and X-ray beam field coverage considerably affect the resulting doses. Deviation among medical institutions is somewhat high, and this indicated that medical institutions should interchange their information and the need of education for medical staff. The methodology and the established system can be applied, with some expansion, to dose assessment for other medical procedures accompanying radiation exposure of patients like nuclear medicine or therapeutic radiology

Effects of low doses of ionizing radiation; Effets des faibles doses de rayonnements ionisants

Energy Technology Data Exchange (ETDEWEB)

Masse, R. [Office de Protection contre les Rayonnements Ionisants, 78 - le Vesinet (France)

2006-07-01

Several groups of human have been irradiated by accidental or medical exposure, if no gene defect has been associated to these exposures, some radioinduced cancers interesting several organs are observed among persons exposed over 100 to 200 mSv delivered at high dose rate. Numerous steps are now identified between the initial energy deposit in tissue and the aberrations of cell that lead to tumors but the sequence of events and the specific character of some of them are the subject of controversy. The stake of this controversy is the risk assessment. From the hypothesis called linear relationship without threshold is developed an approach that leads to predict cancers at any tiny dose without real scientific foundation. The nature and the intensity of biological effects depend on the quantity of energy absorbed in tissue and the modality of its distribution in space and time. The probability to reach a target (a gene) associated to the cancerating of tissue is directly proportional to the dose without any other threshold than the quantity of energy necessary to the effect, its probability of effect can be a more complex function and depends on the quality of the damage produced as well as the ability of the cell to repair the damage. These two parameters are influenced by the concentration of initial injuries in the target so by the quality of radiation and by the dose rate. The mechanisms of defence explain the low efficiency of radiation as carcinogen and then the linearity of effects in the area of low doses is certainly the least defensible scientific hypothesis for the prediction of the risks. (N.C.)

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).

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)

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)

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

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

Dose-dependent effect of silver nanoparticles (AgNPs on fertility and survival of Drosophila: An in-vivo study.

Directory of Open Access Journals (Sweden)

Akanksha Raj

Full Text Available Silver nanoparticles (AgNPs containing consumer products have been proliferating in the market due to its unique antimicrobial property, however, lack of in-depth knowledge about their potential effect on human health in a longer run is of great concern. Therefore, we investigated dose-dependent in vivo effect of AgNPs using Drosophila as a model system. Drosophila, a genetically tractable organism with distinct developmental stages, short life cycle and significant homology with human serves as an ideal organism to study nanomaterial-mediated toxicity. Our studies suggest that ingestion of AgNPs in Drosophila during adult stage for short and long duration significantly affects egg laying capability along with impaired growth of ovary. Additionally, dietary intake of AgNPs from larval stage has more deleterious effects that result in reduced survival, longevity, ovary size and egg laying capability at a further lower dosage. Interestingly, the trans-generational effect of AgNPs was also observed without feeding progeny with AgNPs, thereby suggesting its impact from previous generation. Our results strongly imply that higher doses of AgNPs and its administration early during development is detrimental to the reproductive health and survival of Drosophila that follows in generations to come without feeding them to AgNPs.

Sub-therapeutic doses of fluvastatin and valsartan are more effective than therapeutic doses in providing beneficial cardiovascular pleiotropic effects in rats: A proof of concept study.

Science.gov (United States)

Janić, Miodrag; Lunder, Mojca; France Štiglic, Alenka; Jerin, Aleš; Skitek, Milan; Černe, Darko; Marc, Janja; Drevenšek, Gorazd; Šabovič, Mišo

2017-12-01

Statins and sartans can, in therapeutic doses, induce pleiotropic cardiovascular effects. Similar has recently been shown also for sub-therapeutic doses. We thus explored and compared the cardiovascular pleiotropic efficacy of sub-therapeutic vs. therapeutic doses. Wistar rats were randomly divided into 7 groups receiving fluvastatin, valsartan and their combination in sub-therapeutic and therapeutic doses, or saline. After 6weeks, the animals were euthanised, their hearts and thoracic aortas isolated, and blood samples taken. Endothelium-dependent relaxation of the thoracic aortae and ischaemic-reperfusion injury of the isolated hearts were assessed along with the related serum parameters and genes expression. Fluvastatin and valsartan alone or in combination were significantly more effective in sub-therapeutic than therapeutic doses. The sub-therapeutic combination greatly increased thoracic aorta endothelium-dependent relaxation and maximally protected the isolated hearts against ischaemia-reperfusion injury and was thus most effective. Beneficial effects were accompanied by increased levels of nitric oxide (NO) and decreased levels of asymmetric dimethylarginine (ADMA) in the serum (again prominently induced by the sub-therapeutic combination). Furthermore, nitric oxide synthase 3 (NOS3) and endothelin receptor type A (EDNRA) genes expression increased, but only in both combination groups and without significant differences between them. In the therapeutic dose groups, fluvastatin and valsartan decreased cholesterol values and systolic blood pressure. Sub-therapeutic doses of fluvastatin and valsartan are more effective in expressing cardiovascular pleiotropic effects than therapeutic doses of fluvastatin and/or valsartan. These results could be of significant clinical relevance. Copyright © 2017 Elsevier Inc. All rights reserved.

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

Radiobiological modelling of dose-gradient effects in low dose rate, high dose rate and pulsed brachytherapy

International Nuclear Information System (INIS)

Armpilia, C; Dale, R G; Sandilos, P; Vlachos, L

2006-01-01

This paper presents a generalization of a previously published methodology which quantified the radiobiological consequences of dose-gradient effects in brachytherapy applications. The methodology uses the linear-quadratic (LQ) formulation to identify an equivalent biologically effective dose (BED eq ) which, if applied uniformly to a specified tissue volume, would produce the same net cell survival as that achieved by a given non-uniform brachytherapy application. Multiplying factors (MFs), which enable the equivalent BED for an enclosed volume to be estimated from the BED calculated at the dose reference surface, have been calculated and tabulated for both spherical and cylindrical geometries. The main types of brachytherapy (high dose rate (HDR), low dose rate (LDR) and pulsed (PB)) have been examined for a range of radiobiological parameters/dimensions. Equivalent BEDs are consistently higher than the BEDs calculated at the reference surface by an amount which depends on the treatment prescription (magnitude of the prescribed dose) at the reference point. MFs are closely related to the numerical BED values, irrespective of how the original BED was attained (e.g., via HDR, LDR or PB). Thus, an average MF can be used for a given prescribed BED as it will be largely independent of the assumed radiobiological parameters (radiosensitivity and α/β) and standardized look-up tables may be applicable to all types of brachytherapy treatment. This analysis opens the way to more systematic approaches for correlating physical and biological effects in several types of brachytherapy and for the improved quantitative assessment and ranking of clinical treatments which involve a brachytherapy component

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)

Dose rate effect on material aging due to radiation. [Gamma radiation

Energy Technology Data Exchange (ETDEWEB)

Okamoto, Shin-ichi (Radiation Center of Osaka Prefecture, Sakai (Japan)); Hayakawa, Chikara; Takeya, Chikashi

1982-12-01

Although many reports have been presented on the radiation aging of the organic materials for electric cables, those have been based on the experiments carried out at high dose rate near 1 x 10/sup 6/ rad/h, assuming that aging effect depends on only radiation dose. Therefore, to investigate the aging behaviour in low dose rate range is an important subject to predict their practical life time. In this report, the results of having investigated the aging behaviour of six types of materials are described, (polyethylene for general insulation purpose, chemically cross-linked polyethylene, fire-retardant chemically cross-linked polyethylene, fire-retardant ethylene-propylene rubber, fire-retardant chloro-sulfonated polyethylene for sheaths, and fire-retardant, low hydrochloric acid, special heat-resistant vinyl for insulation purpose or chloroclean). They were irradiated with /sup 60/Co ..gamma..-ray at the dose from 5 x 10/sup 3/ to 1 x 10/sup 6/ rad/h, and their deterioration was tested for the items of elongation, tensile strength, resistivity, dielectric tangent and gel fraction. The aging mechanism and dose rate effect were also considered. The dose rate effect appeared or did not appear depending on the types of materials and also their properties. The materials that showed the dose rate effect included the typical ones whose characteristics degraded with the decreasing dose rate, and the peculiar ones whose deterioration of characteristics did not appear constantly. Aging mechanism may vary in the case of high dose rate and low dose rate. Also, if the life time at respective dose rate in relatively higher dose rate region is clarified, the life time in low dose rate region may possibly be predicted.

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

Estimation of effective dose for children in interventional cardiology

Directory of Open Access Journals (Sweden)

S. S. Sarycheva

2017-01-01

Full Text Available This study is devoted to the estimation of effective dose for children undergoing interventional cardiology examinations. The conversion coefficients (CC from directly measured dose area product (DAP value to effective dose (ED were calculated within the approved effective dose assessment methodology (Guidelines 2.6.1. 2944-11. The CC, Ed K , [mSv / (Gy • cm2] for newborn infants and children of 1, 5, 10 and 15 years old (main(range were calculated as 2.5 (1.8-3.2; 1.1 (0.8-1.3; 0.6 (0.4-0.7; 0.4 (0.3-0.5; and 0,22 (0,18-0,30 respectively. A special Finnish computer program PCXMC 2.0 was used for calculating the dose CC. The series of calculations were made for different values of the physical and geometrical parameters based on their real-existing range of values. The value of CC from DAP to ED were calculated for all pediatric age groups. This work included 153 pediatric interventional studies carried out in two hospitals of the city of St. Petersburg for the period of one year from the summer of 2015. The dose CC dependency from the patient’s age and parameters of the examinations were under the study. The dependence from the beam quality (filtration and tube voltage and age of the patient were found. The younger is the patient, stronger is the filtration and higher is the voltage, the higher is the CC value. The CC in the younger (newborn and older (15 years age groups are different by the factor of 10. It was shown that the changes of the geometric parameters (in the scope of their real existing range have small effect on the value of the effective dose, not exceed 30-50% allowable for radiation protection purpose. The real values of effective doses of children undergoing cardiac interventions were estimated. In severe cases, the values of ED can reach several tens of mSv.

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)

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.

Dose reconstruction in deforming lung anatomy: Dose grid size effects and clinical implications

International Nuclear Information System (INIS)

Rosu, Mihaela; Chetty, Indrin J.; Balter, James M.; Kessler, Marc L.; McShan, Daniel L.; Ten Haken, Randall K.

2005-01-01

In this study we investigated the accumulation of dose to a deforming anatomy (such as lung) based on voxel tracking and by using time weighting factors derived from a breathing probability distribution function (p.d.f.). A mutual information registration scheme (using thin-plate spline warping) provided a transformation that allows the tracking of points between exhale and inhale treatment planning datasets (and/or intermediate state scans). The dose distributions were computed at the same resolution on each dataset using the Dose Planning Method (DPM) Monte Carlo code. Two accumulation/interpolation approaches were assessed. The first maps exhale dose grid points onto the inhale scan, estimates the doses at the 'tracked' locations by trilinear interpolation and scores the accumulated doses (via the p.d.f.) on the original exhale data set. In the second approach, the 'volume' associated with each exhale dose grid point (exhale dose voxel) is first subdivided into octants, the center of each octant is mapped to locations on the inhale dose grid and doses are estimated by trilinear interpolation. The octant doses are then averaged to form the inhale voxel dose and scored at the original exhale dose grid point location. Differences between the interpolation schemes are voxel size and tissue density dependent, but in general appear primarily only in regions with steep dose gradients (e.g., penumbra). Their magnitude (small regions of few percent differences) is less than the alterations in dose due to positional and shape changes from breathing in the first place. Thus, for sufficiently small dose grid point spacing, and relative to organ motion and deformation, differences due solely to the interpolation are unlikely to result in clinically significant differences to volume-based evaluation metrics such as mean lung dose (MLD) and tumor equivalent uniform dose (gEUD). The overall effects of deformation vary among patients. They depend on the tumor location, field

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

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.

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.

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

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

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

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.

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

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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.

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

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)

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.

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.

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

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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.

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)

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)

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.

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

Study of total ionization dose effects in electronic devices

International Nuclear Information System (INIS)

Nidhin, T.S.; Bhattacharyya, Anindya; Gour, Aditya; Behera, R.P.; Jayanthi, T.

2018-01-01

Radiation effects in electronic devices are a major challenge in the dependable application developments of nuclear power plant instrumentation and control systems. The main radiation effects are total ionization dose (TID) effects, displacement damage dose (DDD) effects and single event effects (SEE). In this study, we are concentrating on TID effects in electronic devices. The focus of the study is mainly on SRAM based field programmable gate arrays (FPGA) along with that the devices of our interest are voltage regulators, flash memory and optocoupler. The experiments are conducted by exposing the devices to gamma radiation in power off condition and the degradation in the performances are analysed

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)

Estimation and comparison of effective dose (E) in standard chest CT by organ dose measurements and dose-length-product methods and assessment of the influence of CT tube potential (energy dependency) on effective dose in a dual-source CT.

Science.gov (United States)

Paul, Jijo; Banckwitz, Rosemarie; Krauss, Bernhard; Vogl, Thomas J; Maentele, Werner; Bauer, Ralf W

2012-04-01

To determine effective dose (E) during standard chest CT using an organ dose-based and a dose-length-product-based (DLP) approach for four different scan protocols including high-pitch and dual-energy in a dual-source CT scanner of the second generation. Organ doses were measured with thermo luminescence dosimeters (TLD) in an anthropomorphic male adult phantom. Further, DLP-based dose estimates were performed by using the standard 0.014mSv/mGycm conversion coefficient k. Examinations were performed on a dual-source CT system (Somatom Definition Flash, Siemens). Four scan protocols were investigated: (1) single-source 120kV, (2) single-source 100kV, (3) high-pitch 120kV, and (4) dual-energy with 100/Sn140kV with equivalent CTDIvol and no automated tube current modulation. E was then determined following recommendations of ICRP publication 103 and 60 and specific k values were derived. DLP-based estimates differed by 4.5-16.56% and 5.2-15.8% relatively to ICRP 60 and 103, respectively. The derived k factors calculated from TLD measurements were 0.0148, 0.015, 0.0166, and 0.0148 for protocol 1, 2, 3 and 4, respectively. Effective dose estimations by ICRP 103 and 60 for single-energy and dual-energy protocols show a difference of less than 0.04mSv. Estimates of E based on DLP work equally well for single-energy, high-pitch and dual-energy CT examinations. The tube potential definitely affects effective dose in a substantial way. Effective dose estimations by ICRP 103 and 60 for both single-energy and dual-energy examinations differ not more than 0.04mSv. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

COCAINE AND PAVLOVIAN FEAR CONDITIONING: DOSE-EFFECT ANALYSIS

OpenAIRE

Wood, Suzanne C.; Fay, Jonathon; Sage, Jennifer R.; Anagnostaras, Stephan G.

2006-01-01

Emerging evidence suggests that cocaine and other drugs of abuse can interfere with many aspects of cognitive functioning. The authors examined the effects of 0.1 – 15 mg/kg of cocaine on Pavlovian contextual and cued fear conditioning in mice. As expected, pre-training cocaine dose-dependently produced hyperactivity and disrupted freezing. Surprisingly, when the mice were tested off-drug later, the group pre-treated with a moderate dose of cocaine (15 mg/kg) displayed significantly less cont...

The MLC tongue-and-groove effect on IMRT dose distributions

Energy Technology Data Exchange (ETDEWEB)

Deng Jun [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305 (United States). E-mail: jun@reyes.stanford.edu; Pawlicki, Todd; Chen Yan; Li Jinsheng; Jiang, Steve B.; Ma, C.-M. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305 (United States)

2001-04-01

We have investigated the tongue-and-groove effect on the IMRT dose distributions for a Varian MLC. We have compared the dose distributions calculated using the intensity maps with and without the tongue-and-groove effect. Our results showed that, for one intensity-modulated treatment field, the maximum tongue-and-groove effect could be up to 10% of the maximum dose in the dose distributions. For an IMRT treatment with multiple gantry angles ({>=} 5), the difference between the dose distributions with and without the tongue-and-groove effect was hardly visible, less than 1.6% for the two typical clinical cases studied. After considering the patient setup errors, the dose distributions were smoothed with reduced and insignificant differences between plans with and without the tongue-and-groove effect. Therefore, for a multiple-field IMRT plan ({>=} 5), the tongue-and-groove effect on the IMRT dose distributions will be generally clinically insignificant due to the smearing effect of individual fields. The tongue-and-groove effect on an IMRT plan with small number of fields (<5) will vary depending on the number of fields in a plan (coplanar or non-coplanar), the MLC leaf sequences and the patient setup uncertainty, and may be significant (>5% of maximum dose) in some cases, especially when the patient setup uncertainty is small ({<=} 2 mm). (author)

Plutonium dose-effect relationship

International Nuclear Information System (INIS)

Matsuoka, Osamu

1976-01-01

Dose in internal exposure to Pu was investigated, and dose-effect relationship was discussed. Dose-effect relationship in internal exposure was investigated by means of two methods, which were relationship between dose and its effect (relationship between μ Ci/Kg and its effect), and exposure dose and its effects (rad-effect), and merits and demerits of two methods were mentioned. Problems in a indication method such as mean dose were discussed with respect to the dose in skeleton, the liver and the lung. Pu-induced osteosarcoma in mice rats, and beagles was described, and differences in its induction between animals were discussed. Pulmonary neoplasma induced by 239 PuO 2 inhalation in beagles was reported, and description was made as to differences in induction of lung cancer between animals when Pu was inhaled and was taken into the lung. A theoretical and experimental study of a extrapolation of the results of the animal experiment using Pu to human cases is necessary. (Serizawa, K.)

Development of Real-Time Measurement of Effective Dose for High Dose Rate Neutron Fields

CERN Document Server

Braby, L A; Reece, W D

2003-01-01

Studies of the effects of low doses of ionizing radiation require sources of radiation which are well characterized in terms of the dose and the quality of the radiation. One of the best measures of the quality of neutron irradiation is the dose mean lineal energy. At very low dose rates this can be determined by measuring individual energy deposition events, and calculating the dose mean of the event size. However, at the dose rates that are normally required for biology experiments, the individual events can not be separated by radiation detectors. However, the total energy deposited in a specified time interval can be measured. This total energy has a random variation which depends on the size of the individual events, so the dose mean lineal energy can be calculated from the variance of repeated measurements of the energy deposited in a fixed time. We have developed a specialized charge integration circuit for the measurement of the charge produced in a small ion chamber in typical neutron irradiation exp...

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

Dose and dose rate effects of whole-body gamma-irradiation: I. Lymphocytes and lymphoid organs

Science.gov (United States)

Pecaut, M. J.; Nelson, G. A.; Gridley, D. S.

2001-01-01

The major goal of part I of this study was to compare varying doses and dose rates of whole-body gamma-radiation on lymphoid cells and organs. C57BL/6 mice (n = 75) were exposed to 0, 0.5, 1.5, and 3.0 Gy gamma-rays (60Co) at 1 cGy/min (low-dose rate, LDR) and 80 cGy/min (high-dose rate, HDR) and euthanized 4 days later. A significant dose-dependent loss of spleen mass was observed with both LDR and HDR irradiation; for the thymus this was true only with HDR. Decreasing leukocyte and lymphocyte numbers occurred with increasing dose in blood and spleen at both dose rates. The numbers (not percentages) of CD3+ T lymphocytes decreased in the blood in a dose-dependent manner at both HDR and LDR. Splenic T cell counts decreased with dose only in HDR groups; percentages increased with dose at both dose rates. Dose-dependent decreases occurred in CD4+ T helper and CD8+ T cytotoxic cell counts at HDR and LDR. In the blood the percentages of CD4+ cells increased with increasing dose at both dose rates, whereas in the spleen the counts decreased only in the HDR groups. The percentages of the CD8+ population remained stable in both blood and spleen. CD19+ B cell counts and percentages in both compartments declined markedly with increasing HDR and LDR radiation. NK1.1+ natural killer cell numbers and proportions remained relatively stable. Overall, these data indicate that the observed changes were highly dependent on the dose, but not dose rate, and that cells in the spleen are more affected by dose rate than those in blood. The results also suggest that the response of lymphocytes in different body compartments may be variable.

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.

The relationships between radiation doses and their effects

International Nuclear Information System (INIS)

Beau, P.G.; Nenot, J.C.

1982-01-01

Dose-effect relationships have been developed both for the biological effects studied by Radiobiology and the long-term pathological effects (malignant diseases) studied by Radiation Protection. The former approach chiefly considers the primary biological injuries at the cellular level, and the relationship between the dependent variable characteristic of the effect and the dose -an independent variable- has an explanatory meaning. The parameters associated to the independent variable have a biophysical signification and fit into a model of the action of ionizing radiations. In the latter approach, the relationship is pragmatic and the previous parameters are just the results of a curve-fitting procedure realized on experimental or human data. The biophysical models have led to a general formulation associating a linear term to a quadratic term both of them weighted by an exponential term describing cellular killing at the highest doses. To a certain extent the curves obtained for leukemias, bronchopulmonary and breast cancers prove the validity of the pragmatic model [fr

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).

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.

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.

Effective doses received by air crew of airlines registered in the Czech and Slovak Republics

International Nuclear Information System (INIS)

Kubancak, Jan; Orcikova, H.; Kovar, I.

2013-01-01

The results of effective dose monitoring for airlines registered in the Czech Republic since 1999 and in Slovakia since 2011 are presented. The recommended effective dose limits were apparently exceeded in over 75% Czech crew members. The dependence of the effective doses on the heliocentric potential was also examined. (orig.)

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

Normal tissue dose-effect models in biological dose optimisation

International Nuclear Information System (INIS)

Alber, M.

2008-01-01

Sophisticated radiotherapy techniques like intensity modulated radiotherapy with photons and protons rely on numerical dose optimisation. The evaluation of normal tissue dose distributions that deviate significantly from the common clinical routine and also the mathematical expression of desirable properties of a dose distribution is difficult. In essence, a dose evaluation model for normal tissues has to express the tissue specific volume effect. A formalism of local dose effect measures is presented, which can be applied to serial and parallel responding tissues as well as target volumes and physical dose penalties. These models allow a transparent description of the volume effect and an efficient control over the optimum dose distribution. They can be linked to normal tissue complication probability models and the equivalent uniform dose concept. In clinical applications, they provide a means to standardize normal tissue doses in the face of inevitable anatomical differences between patients and a vastly increased freedom to shape the dose, without being overly limiting like sets of dose-volume constraints. (orig.)

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

Dose-dependent effect of 17 beta-estradiol determined by growth curves and flow cytometric DNA analysis of a human breast carcinoma (T61) grown in nude mice

DEFF Research Database (Denmark)

Brünner, N; Spang-Thomsen, M; Vindeløv, L

1985-01-01

fraction of polyploid cells. The results suggest that estradiol induces a dose-dependent cell killing effect in the T61 human breast carcinoma. The correlation between the treatment-induced growth delay and the effect on the cell cycle distribution indicates that the changes in the cell cycle...

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

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.

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

Dose-rate and humidity effects upon the gamma-radiation response of nylon-based radiachromic film dosimeters

International Nuclear Information System (INIS)

Gehringer, P.; Eschweiler, H.; Proksch, E.

1979-10-01

At dose-rates typical for 60 Co gamma irradiation sources, the radiation response of hexahydroxyethyl pararosaniline cyanide/ 50μm nylon radiachromic films is dependent upon dose-rate as well as upon the moisture content of the films, or the relative humidity of the surrounding atmosphere, respectively. Under equilibrium moisture conditions, the response measured at 606 nm 24 hours after end of irradiation shows its highest dose-rate dependence at about 32 % r.h. A decrease in dose-rate from 2.8 to 0.039 Gy.s -1 results in a decrease in response by 17%. At higher humidities, the sensitivity of the film as well as the rate dependence decreases and at 86% r.h. no discernible dose-rate effect could be found. At lower humidities than 32% a flat maximum in response follows. At nominal 0% r.h. a second absorption band at 412 nm appears which is converted completely to an additional 606 nm absorption by exposure to a humid atmosphere. After that procedure the resultant response is somewhat lower than but shows almost the same dose-rate dependence as at 32% r.h. or else to eliminate the dose-rate effect by an extrapolation procedure based on the fact that the rate dependence vanishes at zero dose. (author)

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.

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.

Dose-dependent effects on sphingoid bases and cytokines in chickens fed diets prepared with fusarium verticillioides culture material containing fumonisins.

Science.gov (United States)

Grenier, Bertrand; Schwartz-Zimmermann, Heidi E; Caha, Sylvia; Moll, Wulf Dieter; Schatzmayr, Gerd; Applegate, Todd J

2015-04-13

In chickens, the effect of mycotoxins, especially fumonisins (FB), in the gastrointestinal tract (GIT) is not well documented. Thus, this study in broiler chicks determined the effects of consuming diets prepared with Fusarium verticillioides culture material containing FB on intestinal gene expression and on the sphinganine (Sa)/sphingosine (So) ratio (Sa/So; a biomarker of FB effect due to disruption of sphingolipid metabolism). Male broilers were assigned to 6 diets (6 cages/diet; 6 birds/cage) from hatch to 20 days containing 0.4, 5.6, 11.3, 17.5, 47.8, or 104.8 mg FB/kg diet. Exposure to FB altered the Sa/So ratio in all tissues analyzed, albeit to varying extents. Linear dose-responses were observed in the kidney, jejunum and cecum. The liver and the ileum were very sensitive and data fit a cubic and quadratic polynomial model, respectively. Gene expression in the small intestine revealed low but significant upregulations of cytokines involved in the pro-inflammatory, Th1/Th17 and Treg responses, especially at 10 days of age. Interestingly, the cecal tonsils exhibited a biphasic response. Unlike the sphingolipid analysis, the effects seen on gene expression were not dose dependent, even showing more effects when birds were exposed to 11.3 mg FB/kg. In conclusion, this is the first report on the disruption of the sphingolipid metabolism by FB in the GIT of poultry. Further studies are needed to reach conclusions on the biological meaning of the immunomodulation observed in the GIT, but the susceptibility of chickens to intestinal pathogens when exposed to FB, at doses lower than those that would cause overt clinical symptoms, should be addressed.

Dose-Dependent Effects on Sphingoid Bases and Cytokines in Chickens Fed Diets Prepared with Fusarium Verticillioides Culture Material Containing Fumonisins

Directory of Open Access Journals (Sweden)

Bertrand Grenier

2015-04-01

Full Text Available In chickens, the effect of mycotoxins, especially fumonisins (FB, in the gastrointestinal tract (GIT is not well documented. Thus, this study in broiler chicks determined the effects of consuming diets prepared with Fusarium verticillioides culture material containing FB on intestinal gene expression and on the sphinganine (Sa/sphingosine (So ratio (Sa/So; a biomarker of FB effect due to disruption of sphingolipid metabolism. Male broilers were assigned to 6 diets (6 cages/diet; 6 birds/cage from hatch to 20 days containing 0.4, 5.6, 11.3, 17.5, 47.8, or 104.8 mg FB/kg diet. Exposure to FB altered the Sa/So ratio in all tissues analyzed, albeit to varying extents. Linear dose-responses were observed in the kidney, jejunum and cecum. The liver and the ileum were very sensitive and data fit a cubic and quadratic polynomial model, respectively. Gene expression in the small intestine revealed low but significant upregulations of cytokines involved in the pro-inflammatory, Th1/Th17 and Treg responses, especially at 10 days of age. Interestingly, the cecal tonsils exhibited a biphasic response. Unlike the sphingolipid analysis, the effects seen on gene expression were not dose dependent, even showing more effects when birds were exposed to 11.3 mg FB/kg. In conclusion, this is the first report on the disruption of the sphingolipid metabolism by FB in the GIT of poultry. Further studies are needed to reach conclusions on the biological meaning of the immunomodulation observed in the GIT, but the susceptibility of chickens to intestinal pathogens when exposed to FB, at doses lower than those that would cause overt clinical symptoms, should be addressed.

Medical irradiation and the use of the ''effective dose equivalent'' concept

International Nuclear Information System (INIS)

Persson, B.R.R.

1980-01-01

The aim of this paper is to demonstrate the use of the effective dose for all kinds of medical irradiation. In order to estimate the 'somatic effective dose' the weighting factors recommended by ICRP 26 have been separated into those for somatic effects and for genetic effects. Calculation of the effective dose in diagnostic radiology procedures must consider the various technical parameters which determine the absorbed dose in the various organs, i.e. beam quality, typical entrance dose and the number of films of each view. Knowledge about these parameters is not always well established and therefore the effective dose estimates are very uncertain. The average dose absorbed by various organs in the case of administration of radionuclides to the body depends to a much higher degree on biological parameters than in the case of external irradiation. In contrast to the variability and lack of reliability of biological data, the physical methods for internal dose calculation are quite elaborate. However, these methods have to be extended to involve the target dose from the radioactivity distributed within the remaining parts of the body. An attempt was made to estimate the somatic effective dose for the most common diagnostic X-ray and nuclear medicine procedures. This would make it possible to compare the risk of X-ray and nuclear medicine techniques on a more equitable basis. The collective effective dose from medical irradiation is estimated for various countries on the basis of reported statistical data. (H.K.)

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.

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

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

Alternate day treatment and late effects: The concept of an effective dose per fraction

International Nuclear Information System (INIS)

Courdi, A.; Hery, M.; Gabillat, J.M.

1990-01-01

Although most institutions treat all fields each day, some radiotherapists continue to adopt an alternate day schedule. The resulting daily variations of the dose per fraction in laterally located targets have been analyzed using the linear-quadratic model. Patients with breast carcinoma treated with definitive radiotherapy in 1974-1975 with one field a day were studied. An effective dose per fraction was derived, with a value higher than the average dose per fraction received by the reference point. The greater the fluctuations between the doses per fraction on successive days, the higher the effective dose per fraction. The corresponding cell survival due to alternate treatment as compared to survival with daily treatment depends on the alpha/beta ratio. For a late effect with low alpha/beta ratio, an alternate treatment may lead to almost 10-fold increase in cell kill in these lateral targets such as those responsible for subcutaneous sclerosis as compared to daily treatment of all fields with the same total dose. Taking the average effective dose per fraction in our series, the increase in cell kill was 4-fold. Acute effects would suffer less damage due to alternate treatment because of a high alpha/beta ratio. Treatment on an alternate schedule should be restricted to palliative radiotherapy

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.

Decreasing Irradiated Rat Lung Volume Changes Dose-Limiting Toxicity From Early to Late Effects

Energy Technology Data Exchange (ETDEWEB)

Veen, Sonja J. van der; Faber, Hette; Ghobadi, Ghazaleh [Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Brandenburg, Sytze [KVI Center for Advanced Radiation Research, University of Groningen, Groningen (Netherlands); Langendijk, Johannes A. [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Coppes, Robert P. [Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Luijk, Peter van, E-mail: p.van.luijk@umcg.nl [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands)

2016-01-01

Purpose: Technological developments in radiation therapy result in smaller irradiated volumes of normal tissue. Because the risk of radiation therapy-induced toxicity generally depends on irradiated volume, changing volume could change the dose-limiting toxicity of a treatment. Recently, in our rat model, we found that early radiation-induced lung dysfunction (RILD) was closely related to irradiated volume dependent vascular remodeling besides inflammation. The exact relationship between early and late RILD is still unknown. Therefore, in this preclinical study we investigated the dose-volume relationship of late RILD, assessed its dependence on early and late pathologies and studied if decreasing irradiated volume changed the dose-limiting toxicity. Methods and Materials: A volume of 25%, 32%, 50%, 63%, 88%, or 100% of the rat lung was irradiated using protons. Until 26 weeks after irradiation, respiratory rates were measured. Macrovascular remodeling, pulmonary inflammation, and fibrosis were assessed at 26 weeks after irradiation. For all endpoints dose-volume response curves were made. These results were compared to our previously published early lung effects. Results: Early vascular remodeling and inflammation correlated significantly with early RILD. Late RILD correlated with inflammation and fibrosis, but not with vascular remodeling. In contrast to the early effects, late vascular remodeling, inflammation and fibrosis showed a primarily dose but not volume dependence. Comparison of respiratory rate increases early and late after irradiation for the different dose-distributions indicated that with decreasing irradiated volumes, the dose-limiting toxicity changed from early to late RILD. Conclusions: In our rat model, different pathologies underlie early and late RILD with different dose-volume dependencies. Consequently, the dose-limiting toxicity changed from early to late dysfunction when the irradiated volume was reduced. In patients, early and late

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

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.

Effects of low priming dose irradiation on cell cycle arrest of HepG2 cells caused by high dose irradiation

International Nuclear Information System (INIS)

Xia Jingguang; Jin Xiaodong; Chinese Academy of Sciences, Beijing; Li Wenjian; Wang Jufang; Guo Chuanling; Gao Qingxiang

2005-01-01

Human hepatoma cells hepG2 were irradiated twice by 60 Co γ-rays with a priming dose of 5 cGy and a higher dose of 3 Gy performed 4h or 8h after the low dose irradiation. Effects of the priming dose irradiation on cell cycle arrest caused by high dose were examined with flow cytometry. Cells in G 2 /M phase accumulated temporarily after the 5 cGy irradiation, and proliferation of tumor cells was promoted significantly by the low dose irradiation. After the 3 Gy irradiation, G 2 phase arrest occurred, and S phase delayed temporally. In comparison with 3 kGy irradiation only, the priming dose delivered 4h prior to the high dose irradiation facilitated accumulation of hepG2 cells in G 2 /M phase, whereas the priming dose delivered 8h prior to the high dose irradiation helped the cells to overcome G 2 arrest. It was concluded that effects of the priming dose treatment on cell cycle arrest caused by high dose irradiation were dependent on time interval between the two irradiations. (authors)

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.

An efficient dose-compensation method for proximity effect correction

International Nuclear Information System (INIS)

Wang Ying; Han Weihua; Yang Xiang; Zhang Yang; Yang Fuhua; Zhang Renping

2010-01-01

A novel simple dose-compensation method is developed for proximity effect correction in electron-beam lithography. The sizes of exposed patterns depend on dose factors while other exposure parameters (including accelerate voltage, resist thickness, exposing step size, substrate material, and so on) remain constant. This method is based on two reasonable assumptions in the evaluation of the compensated dose factor: one is that the relation between dose factors and circle-diameters is linear in the range under consideration; the other is that the compensated dose factor is only affected by the nearest neighbors for simplicity. Four-layer-hexagon photonic crystal structures were fabricated as test patterns to demonstrate this method. Compared to the uncorrected structures, the homogeneity of the corrected hole-size in photonic crystal structures was clearly improved. (semiconductor technology)

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

Effective dose estimation to patients and staff during urethrography procedures

International Nuclear Information System (INIS)

Sulieman, A.; Barakat, H.; Alkhorayef, M.; Babikir, E.; Dalton, A.; Bradley, D.

2015-10-01

Medical-related radiation is the largest source of controllable radiation exposure to humans and it accounts for more than 95% of radiation exposure from man-made sources. Few data were available worldwide regarding patient and staff dose during urological ascending urethrography (ASU) procedure. The purposes of this study are to measure patient and staff entrance surface air kerma dose (ESAK) during ASU procedure and evaluate the effective doses. A total of 243 patients and 145 staff (Urologist) were examined in three Hospitals in Khartoum state. ESAKs were measured for patient and staff using thermoluminescent detectors (TLDs). Effective doses (E) were calculated using published conversion factors and methods recommended by the national Radiological Protection Board (NRPB). The mean ESAK dose for patients and staff dose were 7.79±6.7 mGy and 0.161±0.30 mGy per procedures respectively. The mean and range of the effective dose was 1.21 mSv per procedure. The radiation dose in this study is comparable with previous studies except Hospital C. It is obvious that high patient and staff exposure is due to the lack of experience and protective equipment s. Interventional procedures remain operator dependent; therefore continuous training is crucial. (Author)

Effective dose estimation to patients and staff during urethrography procedures

Energy Technology Data Exchange (ETDEWEB)

Sulieman, A. [Prince Sattam bin Abdulaziz University, College of Applied Medical Sciences, Radiology and Medical Imaging Department, P. O- Box 422, Alkharj 11942 (Saudi Arabia); Barakat, H. [Neelain University, College of Science and Technology, Medical Physics Department, Khartoum (Sudan); Alkhorayef, M.; Babikir, E. [King Saud University, College of Applied Sciences, Radiological Sciences Department, P. O. Box 10219, Riyadh 11433 (Saudi Arabia); Dalton, A.; Bradley, D. [University of Surrey, Centre for Nuclear and Radiation Physics, Department of Physics, Surrey, GU2 7XH Guildford (United Kingdom)

2015-10-15

Medical-related radiation is the largest source of controllable radiation exposure to humans and it accounts for more than 95% of radiation exposure from man-made sources. Few data were available worldwide regarding patient and staff dose during urological ascending urethrography (ASU) procedure. The purposes of this study are to measure patient and staff entrance surface air kerma dose (ESAK) during ASU procedure and evaluate the effective doses. A total of 243 patients and 145 staff (Urologist) were examined in three Hospitals in Khartoum state. ESAKs were measured for patient and staff using thermoluminescent detectors (TLDs). Effective doses (E) were calculated using published conversion factors and methods recommended by the national Radiological Protection Board (NRPB). The mean ESAK dose for patients and staff dose were 7.79±6.7 mGy and 0.161±0.30 mGy per procedures respectively. The mean and range of the effective dose was 1.21 mSv per procedure. The radiation dose in this study is comparable with previous studies except Hospital C. It is obvious that high patient and staff exposure is due to the lack of experience and protective equipment s. Interventional procedures remain operator dependent; therefore continuous training is crucial. (Author)

Building shielding effects on radiation doses from routine radionuclide releases

International Nuclear Information System (INIS)

Kocher, D.C.

1977-01-01

In calculating population doses from the release of radionuclides to the atmosphere, it is usually assumed that man spends all of his time outdoors standing on a smooth infinite plane. Realistically, however, man spends most of the time indoors, so that substantial reductions in radiation doses may result compared with the usual estimates. Calculational models were developed to study the effects of building structures on radiation doses from routine releases of radionuclides to the atmosphere. Both internal dose from inhaled radionuclides and external photon dose from airborne and surface-deposited radionuclides are considered. The effect of building structures is described quantitatively by a dose reduction factor, which is the ratio of the dose inside a structure to the corresponding dose with no structure present. The internal dose from inhaled radionuclides is proportional to the radionuclide concentration in the air. Assuming that the outdoor airborne concentration is constant with time, the time-dependence of the indoor airborne concentration in terms of the structure air ventilation rate, the deposition velocities for radionuclides on the inside floor, walls, and ceiling, and the radioactive decay constant, were calculated

Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions

Energy Technology Data Exchange (ETDEWEB)

Zeng Chuan; Giantsoudi, Drosoula; Grassberger, Clemens; Goldberg, Saveli; Niemierko, Andrzej; Paganetti, Harald; Efstathiou, Jason A.; Trofimov, Alexei [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114 (United States)

2013-05-15

control probability (TCP) and normal tissue complication probability (NTCP). To assess potential local RBE variations, LET distributions were calculated with Monte Carlo, and compared for different plans. The results were assessed in terms of their sensitivity to uncertainties in model parameters and delivery. Results: IFD courses included equal number of fractions boosting either hemisphere, thus, the combined physical dose was close to uniform throughout the prostate. However, for the entire course, the prostate EUD in IFD was higher than in conventional FTP by up to 14%, corresponding to the estimated increase in TCP to 96% from 88%. The extent of gain depended on the mixing factor, i.e., relative weights used to combine FTP and STP spot weights. Increased weighting of STP typically yielded a higher target EUD, but also led to increased sensitivity of dose to variations in the proton's range. Rectal and bladder EUD were same or lower (per normalization), and the NTCP for both remained below 1%. The LET distributions in IFD also depended strongly on the mixing weights: plans using higher weight of STP spots yielded higher LET, indicating a potentially higher local RBE. Conclusions: In proton therapy delivered by pencil beam scanning, improved therapeutic outcome can potentially be expected with delivery of IFD distributions, while administering the prescribed quasi-uniform dose to the target over the entire course. The biological effectiveness of IFD may be further enhanced by optimizing the LET distributions. IFD distributions are characterized by a dose gradient located in proximity of the prostate's midplane, thus, the fidelity of delivery would depend crucially on the precision with which the proton range could be controlled.

Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions

International Nuclear Information System (INIS)

Zeng Chuan; Giantsoudi, Drosoula; Grassberger, Clemens; Goldberg, Saveli; Niemierko, Andrzej; Paganetti, Harald; Efstathiou, Jason A.; Trofimov, Alexei

2013-01-01

control probability (TCP) and normal tissue complication probability (NTCP). To assess potential local RBE variations, LET distributions were calculated with Monte Carlo, and compared for different plans. The results were assessed in terms of their sensitivity to uncertainties in model parameters and delivery. Results: IFD courses included equal number of fractions boosting either hemisphere, thus, the combined physical dose was close to uniform throughout the prostate. However, for the entire course, the prostate EUD in IFD was higher than in conventional FTP by up to 14%, corresponding to the estimated increase in TCP to 96% from 88%. The extent of gain depended on the mixing factor, i.e., relative weights used to combine FTP and STP spot weights. Increased weighting of STP typically yielded a higher target EUD, but also led to increased sensitivity of dose to variations in the proton's range. Rectal and bladder EUD were same or lower (per normalization), and the NTCP for both remained below 1%. The LET distributions in IFD also depended strongly on the mixing weights: plans using higher weight of STP spots yielded higher LET, indicating a potentially higher local RBE. Conclusions: In proton therapy delivered by pencil beam scanning, improved therapeutic outcome can potentially be expected with delivery of IFD distributions, while administering the prescribed quasi-uniform dose to the target over the entire course. The biological effectiveness of IFD may be further enhanced by optimizing the LET distributions. IFD distributions are characterized by a dose gradient located in proximity of the prostate's midplane, thus, the fidelity of delivery would depend crucially on the precision with which the proton range could be controlled.

Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions.

Science.gov (United States)

Zeng, Chuan; Giantsoudi, Drosoula; Grassberger, Clemens; Goldberg, Saveli; Niemierko, Andrzej; Paganetti, Harald; Efstathiou, Jason A; Trofimov, Alexei

2013-05-01

(TCP) and normal tissue complication probability (NTCP). To assess potential local RBE variations, LET distributions were calculated with Monte Carlo, and compared for different plans. The results were assessed in terms of their sensitivity to uncertainties in model parameters and delivery. IFD courses included equal number of fractions boosting either hemisphere, thus, the combined physical dose was close to uniform throughout the prostate. However, for the entire course, the prostate EUD in IFD was higher than in conventional FTP by up to 14%, corresponding to the estimated increase in TCP to 96% from 88%. The extent of gain depended on the mixing factor, i.e., relative weights used to combine FTP and STP spot weights. Increased weighting of STP typically yielded a higher target EUD, but also led to increased sensitivity of dose to variations in the proton's range. Rectal and bladder EUD were same or lower (per normalization), and the NTCP for both remained below 1%. The LET distributions in IFD also depended strongly on the mixing weights: plans using higher weight of STP spots yielded higher LET, indicating a potentially higher local RBE. In proton therapy delivered by pencil beam scanning, improved therapeutic outcome can potentially be expected with delivery of IFD distributions, while administering the prescribed quasi-uniform dose to the target over the entire course. The biological effectiveness of IFD may be further enhanced by optimizing the LET distributions. IFD distributions are characterized by a dose gradient located in proximity of the prostate's midplane, thus, the fidelity of delivery would depend crucially on the precision with which the proton range could be controlled.

Health effect of low dose/low dose rate radiation

International Nuclear Information System (INIS)

Kodama, Seiji

2012-01-01

The clarified and non-clarified scientific knowledge is discussed to consider the cause of confusion of explanation of the title subject. The low dose is defined roughly lower than 200 mGy and low dose rate, 0.05 mGy/min. The health effect is evaluated from 2 aspects of clinical symptom/radiation hazard protection. In the clinical aspect, the effect is classified in physical (early and late) and genetic ones, and is classified in stochastic (no threshold value, TV) and deterministic (with TV) ones from the radioprotection aspect. Although the absence of TV in the carcinogenic and genetic effects has not been proved, ICRP employs the stochastic standpoint from the safety aspect for radioprotection. The lowest human TV known now is 100 mGy, meaning that human deterministic effect would not be generated below this dose. Genetic deterministic effect can be observable only in animal experiments. These facts suggest that the practical risk of exposure to <100 mGy in human is the carcinogenesis. The relationship between carcinogenic risk in A-bomb survivors and their exposed dose are found fitted to the linear no TV model, but the epidemiologic data, because of restriction of subject number analyzed, do not always mean that the model is applicable even below the dose <100 mGy. This would be one of confusing causes in explanation: no carcinogenic risk at <100 mGy or risk linear to dose even at <100 mGy, neither of which is scientifically conclusive at present. Also mentioned is the scarce risk of cancer in residents living in the high background radiation regions in the world in comparison with that in the A-bomb survivors exposed to the chronic or acute low dose/dose rate. Molecular events are explained for the low-dose radiation-induced DNA damage and its repair, gene mutation and chromosome aberration, hypothesis of carcinogenesis by mutation, and non-targeting effect of radiation (bystander effect and gene instability). Further researches to elucidate the low dose

Multilevel mechanisms of stimulatory effect of low dose radiation on immunity

International Nuclear Information System (INIS)

Shu-Zeng Liu

1992-01-01

Attention is paid to the effects of low level ionizing radiation on humans. The conference is devoted to low dose radiation and defense mechanisms of the body. Due to the importance of the immune system in body resistance, special attention has been given to host defense mechanisms following exposure to different doses of ionizing radiation. The immune system has long been known to be highly sensitive to moderate to high doses of ionizing radiation with immuno-depression as one of the most important causes of death in acute radiation syndrome. However, the dose-effect relationship of immune functions has been found to be quite different in the low dose range, especially with doses within 0.1 Gy. With doses above 0.5 Gy most immunologic parameters show a dose dependent depression. With doses between 0.1-0.5 Gy there may be no definite changes in immune functions. Doses within 0.1 Gy, given in single or chronic exposures, have been found to stimulate many immune responses. (author). 16 refs., 2 figs., 7 tabs

Effect of dose and dose rate of gamma radiation on catalytic activity of catalase

International Nuclear Information System (INIS)

Vaclav Cuba; Tereza Pavelkova; Viliam Mucka

2010-01-01

Catalytic activity of gamma irradiated catalase from bovine liver was studied for hydrogen peroxide decomposition at constant temperature and pressure. The measurement was performed at temperatures 27, 32, 37, 42 and 47 deg C. Solutions containing 1 and 0.01 g dm -3 of catalase in phosphate buffer were used for the study. Repeatability of both sample preparation and kinetics measurement was experimentally verified. Rate constants of the reaction were determined for all temperatures and the activation energy was evaluated from Arrhenius plot. Gamma irradiation was performed using 60 Co radionuclide source Gammacell 220 at two different dose rates 5.5 and 70 Gy h -1 , with doses ranging from 10 to 1000 Gy. The observed reaction of irradiated and non-irradiated catalase with hydrogen peroxide is of the first order. Irradiation significantly decreases catalytic activity of catalase, but the activation energy does not depend markedly on the dose. The effect of irradiation is more significant at higher dose rate. (author)

The radiosensitizing effect of doranidazole on human colorectal cancer cells exposed to high doses of irradiation

International Nuclear Information System (INIS)

Zhang, Li; Gong, Aimin; Ji, Jun; Wu, Yuanyuan; Zhu, Xiaoyu; Lv, Suqing; Lv, Hongzhu; Sun, Xizhuo

2007-01-01

This paper investigates the effects of a new radiosensitizer, doranidazole, and enhancing irradiation on colorectal cancer cells. The radiosensitizing effect of doranidazole was determined using colony formation and propidium iodide (PI) assays to measure cell growth inhibition and the cell killing effect of human colorectal cancer cell lines exposed to high doses of γ-ray irradiation under hypoxic conditions in vitro. Fluorescence staining and cell migration assays were also used to assess the radiosensitizing effect. Cell proliferation evaluated by clonogenic survival curves was significantly inhibited by 5 mmol/L doranidazole, particularly at doses ranging from 10 to 30 Gy of irradiation. The radiosensitizing effect of doranidazole on colorectal cancer cells occurs in a time- and dose-dependent manner. Doranidazole also inhibited the mobility of cell invasion and migration. Doranidazole can enhance the killing effect and the cell growth inhibition of colorectal cancer after high-dose irradiation in a time and dose-dependent manner

LDR brachytherapy: can low dose rate hypersensitivity from the "inverse" dose rate effect cause excessive cell killing to peripherial connective tissues and organs?

Science.gov (United States)

Leonard, B E; Lucas, A C

2009-02-01

Examined here are the possible effects of the "inverse" dose rate effect (IDRE) on low dose rate (LDR) brachytherapy. The hyper-radiosensitivity and induced radioresistance (HRS/IRR) effect benefits cell killing in radiotherapy, and IDRE and HRS/IRR seem to be generated from the same radioprotective mechanisms. We have computed the IDRE excess cell killing experienced in LDR brachytherapy using permanent seed implants. We conclude, firstly, that IDRE is a dose rate-dependent manifestation of HRS/IRR. Secondly, the presence of HRS/IRR or IDRE in a cell species or tissue must be determined by direct dose-response measurements. Thirdly, a reasonable estimate is that 50-80% of human adjoining connective and organ tissues experience IDRE from permanent implanted LDR brachytherapy. If IDRE occurs for tissues at point A for cervical cancer, the excess cell killing will be about a factor of 3.5-4.0 if the initial dose rate is 50-70 cGy h(-1). It is greater for adjacent tissues at lower dose rates and higher for lower initial dose rates at point A. Finally, higher post-treatment complications are observed in LDR brachytherapy, often for unknown reasons. Some of these are probably a result of IDRE excess cell killing. Measurements of IDRE need be performed for connective and adjacent organ tissues, i.e. bladder, rectum, urinary tract and small bowels. The measured dose rate-dependent dose responses should extended to tissues and organs remain above IDRE thresholds).

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....

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.

Pediatric Obesity: Pharmacokinetic Alterations and Effects on Antimicrobial Dosing.

Science.gov (United States)

Natale, Stephanie; Bradley, John; Nguyen, William Huy; Tran, Tri; Ny, Pamela; La, Kirsten; Vivian, Eva; Le, Jennifer

2017-03-01

Limited data exist for appropriate drug dosing in obese children. This comprehensive review summarizes pharmacokinetic (PK) alterations that occur with age and obesity, and these effects on antimicrobial dosing. A thorough comparison of different measures of body weight and specific antimicrobial agents including cefazolin, cefepime, ceftazidime, daptomycin, doripenem, gentamicin, linezolid, meropenem, piperacillin-tazobactam, tobramycin, vancomycin, and voriconazole is presented. PubMed (1966-July 2015) and Cochrane Library searches were performed using these key terms: children, pharmacokinetic, obesity, overweight, body mass index, ideal body weight, lean body weight, body composition, and specific antimicrobial drugs. PK studies in obese children and, if necessary, data from adult studies were summarized. Knowledge of PK alterations stemming from physiologic changes that occur with age from the neonate to adolescent, as well as those that result from increased body fat, become an essential first step toward optimizing drug dosing in obese children. Excessive amounts of adipose tissue contribute significantly to body size, total body water content, and organ size and function that may modify drug distribution and clearance. PK studies that evaluated antimicrobial dosing primarily used total (or actual) body weight (TBW) for loading doses and TBW or adjusted body weight for maintenance doses, depending on the drugs' properties and dosing units. PK studies in obese children are imperative to elucidate drug distribution, clearance, and, consequently, the dose required for effective therapy in these children. Future studies should evaluate the effects of both age and obesity on drug dosing because the incidence of obesity is increasing in pediatric patients. © 2017 Pharmacotherapy Publications, Inc.

Dose-rate effects on gamma-induced genetic injury in rat spermatogonia

International Nuclear Information System (INIS)

Vyglenov, A.

1990-01-01

Data for correlation between the reciprocal translocations (RT) yield in rat germ cells and the doses of 0.5 - 3.0 Gy are presented. A 60 Co source has been used with dose rates of 0.25, 8 x 10 -2 and 7 x 10 -3 Gy/min. The results from the cytogenetic analysis made 6 months after irradiation have shown an increase of the yield with the increase of the dose, which can be described as a linear unthreshold dependence. The dose rate effect is expressed in decrease of mutation frequency. The comparison with earlier author's data from similar experiments for acute irradiation allows to determine the RBE of gamma irradiation at the three dose rates investigated as 0.6, 0.2 and 0.1 respectively. The reported results are connected with the problem of variety specificity of the dose rate effect. 2 figs., 2 tabs., 15 refs

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

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

Low doses effects

International Nuclear Information System (INIS)

Tubiana, M.

1997-01-01

In this article is asked the question about a possible carcinogens effect of low dose irradiation. With epidemiological data, knowledge about the carcinogenesis, the professor Tubiana explains that in spite of experiments made on thousand or hundred of thousands animals it has not been possible to bring to the fore a carcinogens effect for low doses and then it is not reasonable to believe and let the population believe that low dose irradiation could lead to an increase of neoplasms and from this point of view any hardening of radiation protection standards could in fact, increase anguish about ionizing radiations. (N.C.)

Effects of emitter junction and passive base region on low dose rate effect in bipolar devices

International Nuclear Information System (INIS)

Pershenkov, V.S.; Cherepko, S.V.; Maslov, V.B.; Belyakov, V.V.; Sogoyan, A.V.; Ulimov, N.; Emelianov, V.V.

1999-01-01

Low dose rate effect in bipolar devices consists in the increase of peripheral surface recombination current with dose rate decrease. This is due to the more rapid positive oxide charge and interface trap density build-up as the dose rate becomes lower. High dose rate elevated temperature irradiation is proposed for simulation if the low dose rate effect. In the present we tried to separate the effect of radiation-induced charge in the thick passivation oxide over the emitter junction and passive base regions of npn bipolar transistor. Its goal is to improve bipolar device design for use in space environments and nuclear installations. Three experiments were made during this work. 1. Experiment on radiation-induced charge neutralization (RICN) effect under elevated temperature was performed to show transistor degradation dependence on emitter-base bias. 2. High dose rate elevated and room temperature irradiation of bipolar transistors were performed to separate effects of emitter-junction and passive base regions. 3. Pre- and post- irradiation hydrogen ambient storage was used to investigate its effect on radiation-induced charge build-up over the passive base region. All experiments were performed with npn and pnp transistors. (authors)

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

Effective dose equivalent

International Nuclear Information System (INIS)

Huyskens, C.J.; Passchier, W.F.

1988-01-01

The effective dose equivalent is a quantity which is used in the daily practice of radiation protection as well as in the radiation hygienic rules as measure for the health risks. In this contribution it is worked out upon which assumptions this quantity is based and in which cases the effective dose equivalent can be used more or less well. (H.W.)

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.)

MCNP Code in Assessment of Variations of Effective Dose with Torso Adipose Tissue Thickness

International Nuclear Information System (INIS)

Massoud, E.

2005-01-01

The effective dose is the unite used in the field of radiation protection. It is a well defined doubly weighted uantity involving both physical and biological variables. Several factors may induce variation in the effective dose in different individuals of similar exposure data. One of these factors is the variation of adipose tissue thickness in different exposed individuals. This study essentially concenrs the assessment of the possible variation in the effective dose due to variation in the thickness of adipose tissue. The study was done using MCNP4b code to perform mathematical model of the human body depending on that given to the reference man developed by International Commission of Radiological Protection (ICRP), and calculate the effective dose with different thicknessess of adipose tissues. The study includes a comprehensive appraisal of the Monte Cario simulation, the Medical Internal Radiation Dose (MIRD) model for the human body, and the various mathematical considerations involved in the radiation dose calculations for the various pertinent parts of the human body. The radiation energies considered were 80 KeV, 300 KeV and I MeV, applying two exposure positions; anteroposterior (AP), postero-anterior (PA) with different adipose tissue thickness. This study is a theoretical approach based on detailed mathematical calculations of great precision that deals with all considerations involved in the mechanisms of radiation energy absorption in biological system depending on the variation in the densities of the particular in biological system depending on the variation in the densities of the particular tissues. The results obtained indicate that maximum decrease in effective dose occures with the lowest energy at 5cm adipose tissues thickeness for both AP and PA exposure positions. The results obtained were compared to similar work previsouly done using MCNP4 b showing very good agreement

Study on the estimation of probabilistic effective dose. Committed effective dose from intake of marine products using Oceanic General Circulation Model

International Nuclear Information System (INIS)

Nakano, Masanao

2007-01-01

The worldwide environmental protection is required by the public. A long-term environmental assessment from nuclear fuel cycle facilities to the aquatic environment also becomes more important to utilize nuclear energy more efficiently. Evaluation of long-term risk including not only in Japan but also in neighboring countries is considered to be necessary in order to develop nuclear power industry. The author successfully simulated the distribution of radionuclides in seawater and seabed sediment produced by atmospheric nuclear tests using LAMER (Long-term Assessment ModEl for Radioactivity in the oceans). A part of the LAMER calculated the advection- diffusion-scavenging processes for radionuclides in the oceans and the Japan Sea in cooperate with Oceanic General Circulation Model (OGCM) and was validated. The author is challenging to calculate probabilistic effective dose suggested by ICRP from intake of marine products due to atmospheric nuclear tests using the Monte Carlo method in the other part of LAMER. Depending on the deviation of each parameter, the 95th percentile of the probabilistic effective dose was calculated about half of the 95th percentile of the deterministic effective dose in proforma calculation. The probabilistic assessment gives realistic value for the dose assessment of a nuclear fuel cycle facility. (author)

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.

Consideration of the ICRP 2006 revised tissue weighting factors on age-dependent values of the effective dose for external photons

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Lee, Choonsik; Lee, Choonik; Han, Eun Young; Bolch, Wesley E.

2007-01-01

The effective dose recommended by the International Commission on Radiological Protection (ICRP) is the sum of organ equivalent doses weighted by corresponding tissue weighting factors, wT. ICRP is in the process of revising its 1990 recommendations on the effective dose where new values of organs and tissue weighting factors have been proposed and published in draft form for consultation by the radiological protection community. In its 5 June 2006 draft recommendations, new organs and tissues have been introduced in the effective dose which do not exist within the 1987 Oak Ridge National Laboratory (ORNL) phantom series (e.g., salivary glands). Recently, the investigators at University of Florida have updated the series of ORNL phantoms by implementing new organ models and adopting organ-specific elemental composition and densities. In this study, the effective dose changes caused by the transition from the current recommendation of ICRP Publication 60 to the 2006 draft recommendations were investigated for external photon irradiation across the range of ICRP reference ages (newborn, 1-year, 5-year, 10-year, 15-year and adult) and for six idealized irradiation geometries: anterior-posterior (AP), posterior-anterior (PA), left-lateral (LLAT), right-lateral (RLAT), rotational (ROT) and isotropic (ISO). Organ-absorbed doses were calculated by implementing the revised ORNL phantoms in the Monte Carlo radiation transport code, MCNPX2.5, after which effective doses were calculated under the 1990 and draft 2006 evaluation schemes of the ICRP. Effective doses calculated under the 2006 draft scheme were slightly higher than estimated under ICRP Publication 60 methods for all irradiation geometries exclusive of the AP geometry where an opposite trend was observed. The effective doses of the adult phantom were more greatly affected by the change in tissue weighting factors than that seen within the paediatric members of the phantom series. Additionally, dose conversion

The effects of glucocorticoids on the inhibition of emotional information: A dose-response study.

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Taylor, Véronique A; Ellenbogen, Mark A; Washburn, Dustin; Joober, Ridha

2011-01-01

There is evidence that cortisol influences cognitive and affective processes such as selective attention and memory for emotional events, yet the effects of glucocorticoids on attentional inhibition in humans remain unknown. Consequently, this double-blind study examined dose-dependent effects of exogenous glucocorticoids on the inhibition of emotional information. Sixty-three university students (14 male, 49 female) ingested either a placebo pill or hydrocortisone (10mg or 40mg), and completed a negative priming task assessing the inhibition of pictures depicting angry, sad, and happy faces. The 10mg, but not the 40mg hydrocortisone dose elicited increased inhibition for angry faces relative to placebo. Thus, moderate glucocorticoid elevations may have adaptive effects on emotional information processing, whereas high glucocorticoid elevations appear to attenuate this effect, consistent with the view that there are dose-dependent effects of glucocorticoids on cognition. Copyright © 2010 Elsevier B.V. All rights reserved.

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

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.

Effective dose to radon considering people's activities

International Nuclear Information System (INIS)

Shimo, M.; Seki, K.; Kikuchi, I.

1992-01-01

The tidal volume was estimated for evaluating the effective dose due to radon concentration in the atmosphere. In this study regional population was separated to vocation and non-vocation. The occupancy time and the breathing rate for both vocation and non-vocation groups were estimated, and the annual tidal volume for both groups were calculated. Human actions were separated to 18 activities in the process for estimating the breathing rate. It was clear that the breathing rate depended on human activity and that the human activity changed with its age, so the breathing rate varied with age. Finally the effective doses due to radon and radon progeny indoors and outdoors were evaluated. The maximum annual effective dose was estimated to be 1.2 mSv, minimum 0.2 mSv, and mean 0.51 mSv for vocation. For non-vocation, the male maximum value 0.43 mSv was obtained at the 16 age and the minimum 0.12 mSv at the 70 age, whereas female maximum 0.26 mSv was obtained at the 12 age and the minimum 0.11 mSv at the 70 age. In addition in this study objective areas are Aichi, Gifu, and Mie prefectures for vocation and only Aichi prefecture for non-vocation. (author)

Radiobiological aspects of continuous low dose-rate irradiation and fractionated high dose-rate irradiation

International Nuclear Information System (INIS)

Turesson, I.

1990-01-01

The biological effects of continuous low dose-rate irradiation and fractionated high dose-rate irradiation in interstitial and intracavitary radiotherapy and total body irradiation are discussed in terms of dose-rate fractionation sensitivity for various tissues. A scaling between dose-rate and fraction size was established for acute and late normal-tissue effects which can serve as a guideline for local treatment in the range of dose rates between 0.02 and 0.005 Gy/min and fraction sizes between 8.5 and 2.5 Gy. This is valid provided cell-cycle progression and proliferation can be ignored. Assuming that the acute and late tissue responses are characterized by α/β values of about 10 and 3 Gy and a mono-exponential repair half-time of about 3 h, the same total doses given with either of the two methods are approximately equivalent. The equivalence for acute and late non-hemopoietic normal tissue damage is 0.02 Gy/min and 8.5 Gy per fraction; 0.01 Gy/min and 5.5 Gy per fraction; and 0.005 Gy/min and 2.5Gy per fraction. A very low dose rate, below 0.005 Gy/min, is thus necessary to simulate high dose-rate radiotherapy with fraction sizes of about 2Gy. The scaling factor is, however, dependent on the repair half-time of the tissue. A review of published data on dose-rate effects for normal tissue response showed a significantly stronger dose-rate dependence for late than for acute effects below 0.02 Gy/min. There was no significant difference in dose-rate dependence between various acute non-hemopoietic effects or between various late effects. The consistent dose-rate dependence, which justifies the use of a general scaling factor between fraction size and dose rate, contrasts with the wide range of values for repair half-time calculated for various normal-tissue effects. This indicates that the model currently used for repair kinetics is not satisfactory. There are also few experimental data in the clinical dose-rate range, below 0.02 Gy/min. It is therefore

The dose-rate effect

International Nuclear Information System (INIS)

Steel, G.G.

1989-01-01

This paper presents calculations that illustrate two conclusions; for any particular cell type there will be a critical radius at which tumor control breaks down, and the radius at which this occurs is strongly dependent upon the low-dose-rate radiosensitivity of the cells

Uncertainties in effective dose estimates of adult CT head scans: The effect of head size

International Nuclear Information System (INIS)

Gregory, Kent J.; Bibbo, Giovanni; Pattison, John E.

2009-01-01

Purpose: This study is an extension of a previous study where the uncertainties in effective dose estimates from adult CT head scans were calculated using four CT effective dose estimation methods, three of which were computer programs (CT-EXPO, CTDOSIMETRY, and IMPACTDOSE) and one that involved the dose length product (DLP). However, that study did not include the uncertainty contribution due to variations in head sizes. Methods: The uncertainties due to head size variations were estimated by first using the computer program data to calculate doses to small and large heads. These doses were then compared with doses calculated for the phantom heads used by the computer programs. An uncertainty was then assigned based on the difference between the small and large head doses and the doses of the phantom heads. Results: The uncertainties due to head size variations alone were found to be between 4% and 26% depending on the method used and the patient gender. When these uncertainties were included with the results of the previous study, the overall uncertainties in effective dose estimates (stated at the 95% confidence interval) were 20%-31% (CT-EXPO), 15%-30% (CTDOSIMETRY), 20%-36% (IMPACTDOSE), and 31%-40% (DLP). Conclusions: For the computer programs, the lower overall uncertainties were still achieved when measured values of CT dose index were used rather than tabulated values. For DLP dose estimates, head size variations made the largest (for males) and second largest (for females) contributions to effective dose uncertainty. An improvement in the uncertainty of the DLP method dose estimates will be achieved if head size variation can be taken into account.

Uncertainties in effective dose estimates of adult CT head scans: The effect of head size

Energy Technology Data Exchange (ETDEWEB)

Gregory, Kent J.; Bibbo, Giovanni; Pattison, John E. [Department of Medical Physics, Royal Adelaide Hospital, Adelaide, South Australia 5000 (Australia) and School of Electrical and Information Engineering (Applied Physics), University of South Australia, Mawson Lakes, South Australia 5095 (Australia); Division of Medical Imaging, Women' s and Children' s Hospital, North Adelaide, South Australia 5006 (Australia) and School of Electrical and Information Engineering (Applied Physics), University of South Australia, Mawson Lakes, South Australia 5095 (Australia); School of Electrical and Information Engineering (Applied Physics), University of South Australia, Mawson Lakes, South Australia 5095 (Australia)

2009-09-15

Purpose: This study is an extension of a previous study where the uncertainties in effective dose estimates from adult CT head scans were calculated using four CT effective dose estimation methods, three of which were computer programs (CT-EXPO, CTDOSIMETRY, and IMPACTDOSE) and one that involved the dose length product (DLP). However, that study did not include the uncertainty contribution due to variations in head sizes. Methods: The uncertainties due to head size variations were estimated by first using the computer program data to calculate doses to small and large heads. These doses were then compared with doses calculated for the phantom heads used by the computer programs. An uncertainty was then assigned based on the difference between the small and large head doses and the doses of the phantom heads. Results: The uncertainties due to head size variations alone were found to be between 4% and 26% depending on the method used and the patient gender. When these uncertainties were included with the results of the previous study, the overall uncertainties in effective dose estimates (stated at the 95% confidence interval) were 20%-31% (CT-EXPO), 15%-30% (CTDOSIMETRY), 20%-36% (IMPACTDOSE), and 31%-40% (DLP). Conclusions: For the computer programs, the lower overall uncertainties were still achieved when measured values of CT dose index were used rather than tabulated values. For DLP dose estimates, head size variations made the largest (for males) and second largest (for females) contributions to effective dose uncertainty. An improvement in the uncertainty of the DLP method dose estimates will be achieved if head size variation can be taken into account.

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)

SU-F-T-661: Dependence of Gold Nano Particles Cluster Morphology On Dose Enhancement of Photon Radiation Therapy Apply for Radiation Biology Effect

Energy Technology Data Exchange (ETDEWEB)

Ahn, S [Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University (Korea, Republic of); Chung, K; Han, Y; Park, H [Samsung Medical Center, Sungkyunkwan University School of Medicine radiation oncology (Korea, Republic of)

2016-06-15

Purpose: Injected gold nano particles (GNPs) to a body for dose enhancement are known to form in the tumorcell cluster morphology. We investigated the dependence of dose enhancement on the morphology characteristic with an approximated morphology model by using Monte Carlo simulations. Methods: For MC simulation, TOPAS version 2.0P-03 was used. GNP cluster morphology was approximated as a body center cubic(BCC) model by placing 8 GNPs at the corner and one at the center of cube with length from 2.59 µm to 0.25 µm located in a 4 µm length water filled cube phantom. 4 µm length square shaped beams of poly-energetic 50, 260 kVp photons were irradiated to the water filled cube phantom with 100 nm diameter GNPs in it. Dose enhancement ratio(DER) was computed as a function of distance from the surface of the GNP at the cube center for 18 cubes geometries. For scoring particles, 10 nm width of concentric shell shaped detector was constructed up to 100 nm from the center. Total dose in a sphere of 100 nm radius of detector were normalized to 2.59 µm length cube morphology. To verified biological effect of BCC model applied to cell survival curve fitting. Results: DER increase as the distance of the GNPs reduces. DER was largest for 0.25 µm length cube. Dependence of GNP distance DER increment was 1.73, 1.60 for 50 kVp, 260 kVp photons, respectively. Also, Using BCC model applied to cell survival curve was well prediction. Conclusion: DER with GNPs was larger when they are closely packed in the phantom. Therefore, better therapeutic effects can be expected with close-packed GNPs. This research was supported by the NRF funded by the Ministry of Science, ICT & Future Planning (2012M3A9B6055201 and 2012R1A1A2042414), Samsung Medical Center grant[GFO1130081].

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.

The dose effects of short-term dronabinol (oral THC) maintenance in daily cannabis users.

Science.gov (United States)

Vandrey, Ryan; Stitzer, Maxine L; Mintzer, Miriam Z; Huestis, Marilyn A; Murray, Jeannie A; Lee, Dayong

2013-02-01

Prior studies have separately examined the effects of dronabinol (oral THC) on cannabis withdrawal, cognitive performance, and the acute effects of smoked cannabis. A single study examining these clinically relevant domains would benefit the continued evaluation of dronabinol as a potential medication for the treatment of cannabis use disorders. Thirteen daily cannabis smokers completed a within-subject crossover study and received 0, 30, 60 and 120mg dronabinol per day for 5 consecutive days. Vital signs and subjective ratings of cannabis withdrawal, craving and sleep were obtained daily; outcomes under active dose conditions were compared to those obtained under placebo dosing. On the 5th day of medication maintenance, participants completed a comprehensive cognitive performance battery and then smoked five puffs of cannabis for subjective effects evaluation. Each dronabinol maintenance period occurred in a counterbalanced order and was separated by 9 days of ad libitum cannabis use. Dronabinol dose-dependently attenuated cannabis withdrawal and resulted in few adverse side effects or decrements in cognitive performance. Surprisingly, dronabinol did not alter the subjective effects of smoked cannabis, but cannabis-induced increases in heart rate were attenuated by the 60 and 120mg doses. Dronabinol's ability to dose-dependently suppress cannabis withdrawal may be therapeutically beneficial to individuals trying to stop cannabis use. The absence of gross cognitive impairment or side effects in this study supports safety of doses up to 120mg/day. Continued evaluation of dronabinol in targeted clinical studies of cannabis treatment, using an expanded range of doses, is warranted. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

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.

Low doses effects and gamma radiations low dose rates

International Nuclear Information System (INIS)

Averbeck, D.

1999-01-01

This expose wishes for bringing some definitions and base facts relative to the problematics of low doses effects and low dose rates effects. It shows some already used methods and some actual experimental approaches by focusing on the effects of ionizing radiations with a low linear energy transfer. (N.C.)

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

Effective dose range for dental cone beam computed tomography scanners

International Nuclear Information System (INIS)

Pauwels, Ruben; Beinsberger, Jilke; Collaert, Bruno; Theodorakou, Chrysoula; Rogers, Jessica; Walker, Anne; Cockmartin, Lesley; Bosmans, Hilde; Jacobs, Reinhilde; Bogaerts, Ria; Horner, Keith

2012-01-01

Objective: To estimate the absorbed organ dose and effective dose for a wide range of cone beam computed tomography scanners, using different exposure protocols and geometries. Materials and methods: Two Alderson Radiation Therapy anthropomorphic phantoms were loaded with LiF detectors (TLD-100 and TLD-100H) which were evenly distributed throughout the head and neck, covering all radiosensitive organs. Measurements were performed on 14 CBCT devices: 3D Accuitomo 170, Galileos Comfort, i-CAT Next Generation, Iluma Elite, Kodak 9000 3D, Kodak 9500, NewTom VG, NewTom VGi, Pax-Uni3D, Picasso Trio, ProMax 3D, Scanora 3D, SkyView, Veraviewepocs 3D. Effective dose was calculated using the ICRP 103 (2007) tissue weighting factors. Results: Effective dose ranged between 19 and 368 μSv. The largest contributions to the effective dose were from the remainder tissues (37%), salivary glands (24%), and thyroid gland (21%). For all organs, there was a wide range of measured values apparent, due to differences in exposure factors, diameter and height of the primary beam, and positioning of the beam relative to the radiosensitive organs. Conclusions: The effective dose for different CBCT devices showed a 20-fold range. The results show that a distinction is needed between small-, medium-, and large-field CBCT scanners and protocols, as they are applied to different indication groups, the dose received being strongly related to field size. Furthermore, the dose should always be considered relative to technical and diagnostic image quality, seeing that image quality requirements also differ for patient groups. The results from the current study indicate that the optimisation of dose should be performed by an appropriate selection of exposure parameters and field size, depending on the diagnostic requirements.

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

Calculation of the effective environmental dose rate for ESR and luminescence dating

International Nuclear Information System (INIS)

Brennan, B.J.

2001-01-01

The determination of the age of a sample using luminescence and ESR dating techniques requires knowledge of the sample's average effective environmental dose rate due to natural radiation sources (alpha, beta, gamma, and cosmic), and age estimates can never be more accurate than the estimate of this dose rate. The estimation process is often complicated by spatial and temporal inhomogeneities in the distribution of natural radiation sources. This paper discusses applications of radiation physics in modelling the effects of these inhomogeneities to ensure accurate estimation of the average dose rate for the sample. For natural alpha, beta, and gamma sources, 'dose point kernels' are employed in calculations using an assumed model for the spatial and temporal dependence of source concentrations. These three types of radiation have rather different penetration properties, with their typical effective ranges being multiples of 10 micrometre, 1 mm, and 100 mm respectively. For each type of radiation, applications are discussed where spatial inhomogeneity in the distribution of sources around and in a sample has a serious effect on the average dose rate to the sample. In some cases, (e.g. gamma dose estimation in 'lumpy' environments) lack of detailed knowledge precludes accurate modelling of the site for a particular sample, but useful statistical information can still be obtained. Temporal variation of radioactive source concentrations is usually coupled with spatial effects and can arise from processes such as parent-daughter disequilibrium, uptake or leaching of sources, or variation in burial depth or water saturation. Again, calculations based non a known or assumed history can be employed to obtain a time-averaged dose rate for a sample. The accuracy with which these calculations can reflect the true environmental dose rate is limited principally by the reliability of the model assumed, which in turn depends on the state of knowledge of the site and its history

Calculation of the effective dose from natural radioactivity sources in soil using MCNP code

International Nuclear Information System (INIS)

Krstic, D.; Nikezic, D.

2008-01-01

Full text: Effective dose delivered by photon emitted from natural radioactivity in soil was calculated in this report. Calculations have been done for the most common natural radionuclides in soil as 238 U, 232 Th series and 40 K. A ORNL age-dependent phantom and the Monte Carlo transport code MCNP-4B were employed to calculate the energy deposited in all organs of phantom.The effective dose was calculated according to ICRP74 recommendations. Conversion coefficients of effective dose per air kerma were determined. Results obtained here were compared with other authors

Dose-Dependent Effects of the Cimicifuga racemosa Extract Ze 450 in the Treatment of Climacteric Complaints: A Randomized, Placebo-Controlled Study

Directory of Open Access Journals (Sweden)

Ruediger Schellenberg

2012-01-01

Full Text Available Extracts from Cimicifuga racemosa (CR, synonym Actaea racemosa have shown efficacy in trials in women with menopausal symptoms. Yet, dose dependency remains unclear. Therefore, 180 female outpatients with climacteric complaints were treated for 12 weeks in a randomized, double-blind, placebo-controlled, 3-armed trial (CR extract Ze 450 in 6.5 mg or 13.0 mg, or placebo. Primary outcome was the difference in menopausal symptoms (vasomotor, psychological, and somatic, assessed by the Kupperman Menopausal Index between baseline and week 12. Secondary efficacy variables were patients’ self-assessments of general quality of life (QoL, responder rates, and safety. Compared to placebo, patients receiving Ze 450 showed a significant reduction in the severity of menopausal symptoms in a dose-dependent manner from baseline to endpoint (mean absolute differences 17.0 (95% CI 14.65–19.35 score points, P<0.0001 for 13.0 mg; mean absolute differences 8.47 (95% CI 5.55–11.39 score points, P=0.0003 for 6.5 mg. QoL and responder rates corresponded with the main endpoint. Changes in menopausal symptoms and QoL were inversely correlated. Reported adverse events and clinical laboratory testing did not raise safety concerns. The CR extract Ze 450 is an effective and well-tolerated nonhormonal alternative to hormone treatment for symptom relief in menopausal women.

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)

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.

Radiation absorbed dose estimates for [1-carbon-11]-glucose in adults: The effects of hyperinsulinemia

International Nuclear Information System (INIS)

Powers, W.J.

1996-01-01

As preparation for studies of blood-brain glucose transport in diabetes mellitus, radiation absorbed dose estimates from intravenous administration of [1- 11 C]-glucose for 24 internal organs, lens, blood and total body were calculated for three physiologic conditions: euinsulinemic euglycemia, hyperinsulinemic euglycemia and hyperinsulinemic hyperglycemia. Cumulated activities in blood, insulin-independent and insulin-dependent compartments were calculated from blood time-activity curves in normal human volunteers and macaques. Apportionment of cumulated activity to individual organs in insulin-dependent and insulin-independent compartments was based on previously published data. Absorbed doses were calculated with the computer program MIRDOSE 3 for the 70-kg adult phantom. S for blood was calculated separately. The heart wall, lungs and spleen were the organs receiving the highest dose. The effect of hyperinsulinemia was demonstrated by the increase in adsorbed dose to the muscle, heart and blood with a decrease to other internal organs. This effect was more pronounced during hyperinsulinemic hyperglycemia. Hyperinsulinemia produced a decrease in effective dose due to the decrease in cumulated activity in organs with specified weighting factors greater than 0.05. The effective dose per study for [1- 11 C]-glucose is comparable to that reported for 2-deoxy-[2- 18 F]-glucose. 43 refs., 1 fig., 4 tabs

Adult head CT scans: the uncertainties of effective dose estimates

International Nuclear Information System (INIS)

Gregory, Kent J.; Bibbo, Giovanni; Pattison, John E.

2008-01-01

Full Text: CT scanning is a high dose imaging modality. Effective dose estimates from CT scans can provide important information to patients and medical professionals. For example, medical practitioners can use the dose to estimate the risk to the patient, and judge whether this risk is outweighed by the benefits of the CT examination, while radiographers can gauge the effect of different scanning protocols on the patient effective dose, and take this into consideration when establishing routine scan settings. Dose estimates also form an important part of epidemiological studies examining the health effects of medical radiation exposures on the wider population. Medical physicists have been devoting significant effort towards estimating patient radiation doses from diagnostic CT scans for some years. The question arises: How accurate are these effective dose estimates? The need for a greater understanding and improvement of the uncertainties in CT dose estimates is now gaining recognition as an important issue (BEIR VII 2006). This study is an attempt to analyse and quantify the uncertainty components relating to effective dose estimates from adult head CT examinations that are calculated with four commonly used methods. The dose estimation methods analysed are the Nagel method, the ImpaCT method, the Wellhoefer method and the Dose-Length Product (DLP) method. The analysis of the uncertainties was performed in accordance with the International Standards Organisation's Guide to the Expression of Uncertainty in Measurement as discussed in Gregory et al (Australas. Phys. Eng. Sci. Med., 28: 131-139, 2005). The uncertainty components vary, depending on the method used to derive the effective dose estimate. Uncertainty components in this study include the statistical and other errors from Monte Carlo simulations, uncertainties in the CT settings and positions of patients in the CT gantry, calibration errors from pencil ionization chambers, the variations in the organ

Effective doses in paediatric radiology

International Nuclear Information System (INIS)

Iacob, Olga; Diaconescu, Cornelia; Roca, Antoaneta

2001-01-01

Because of their longer life expectancy, the risk of late manifestations of detrimental radiation effects is greater in children than in adults and, consequently, paediatric radiology gives ground for more concern regarding radiation protection than radiology of adults. The purpose of our study is to assess in terms of effective doses the magnitude of paediatric patient exposure during conventional X-ray examinations, selected for their high frequency or their relatively high doses to the patient. Effective doses have been derived from measurements of dose-area product (DAP) carried out on over 900 patients undergoing X-ray examinations, in five paediatric units. The conversion coefficients for estimating effective doses are those calculated by the NRPB using Monte-Carlo technique on a series of 5 mathematical phantoms representing 0, 1, 5, 10 and 15 year old children. The annual frequency of X-ray examinations necessary for collective dose calculation are those reported in our last national study on medical exposure, conducted in 1995. The annual effective doses from all medical examinations for the average paediatric patient are as follows: 1.05 mSv for 0 year old, 0.98 mSv for 1 year old, 0.53 mSv for 5 year old, 0.65 mSv for 10 year old and 0.70 mSv for 15 year old. The resulting annual collective effective dose was evaluated at 625 man Sv with the largest contribution of pelvis and hip examinations (34%). The annual collective effective associated with paediatric radiology in Romania represent 5% of the annual value resulting from all diagnostic radiology. Examination of the chest is by far the most frequent procedure for children, accounting for about 60 per cent of all annually performed X-ray conventional examinations. Knowledge of real level of patient dose is an essential component of quality assurance programs in paediatric radiology. (authors)

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.

Effect of stress at dosing on organophosphate and heavy metal toxicity

International Nuclear Information System (INIS)

Jortner, Bernard S.

2008-01-01

This paper reviews recent studies assessing the effect of well-defined, severe, transient stress at dosing on two classical models of toxicity. These are the acute (anticholinesterase) toxicity seen following exposure to the organophosphate insecticide chlorpyrifos, and the nephrotoxicity elicited by the heavy metal depleted uranium, in rats. Stress was induced by periods of restraint and forced swimming in days to weeks preceding toxicant exposure. Forced swimming was far more stressful, as measured by marked, if transient, elevation of plasma corticosterone. This form of stress was administered immediately prior to administration of chlorpyrifos or depleted uranium. Chlorpyrifos (single 60 mg/kg subcutaneously) elicited marked inhibition of brain acetylcholinesterase 4-day post-dosing. Depleted uranium (single intramuscular doses of 0.1, 0.3 or 1.0 mg/kg uranium) elicited dose-dependent increase in kidney concentration of the metal, with associated injury to proximal tubular epithelium and increases in serum blood urea nitrogen and creatinine during the 30-day post-dosing period. Stress at dosing had no effect on these toxicologic endpoints

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

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.

Low doses effects of ionizing radiation on Saccharomyces cerevisiae

International Nuclear Information System (INIS)

Durand, J.; Broock, M. van; Gillette, V.H.

2000-01-01

The exposure of living cells to low doses of ionizing radiation induce in response the activation of cellular protection mechanisms against subsequent larger doses of radiation. This cellular adaptive response may vary depending on radiation intensity and time of exposure, and also on the testing probes used whether they were mammalian cells, yeast, bacteria and other organisms or cell types. The mechanisms involved are the genome activation, followed by DNA repair enzymes synthesis. Due to the prompt cell response, the cell cycle can be delayed, and the secondary detoxification of free radicals and/or activation of membrane bound receptors may proceed. All these phenomena are submitted to intense scientific research nowadays, and their elucidation will depend on the complexity of the organism under study. In the present work, the effects of low doses of ionizing radiation (gamma rays) over a suspension of the yeast Saccharomyces cerevisiae (Baker's yeast) was studied, mainly in respect to survival rate and radio-adaptive response. At first, the yeast surviving curve was assessed towards increasing doses, and an estimation of Lethal Dose 50 (LD50) was made. The irradiation tests were performed at LINAC (electrons Linear Accelerator) where electron energy reached approximately 2.65 MeV, and gamma-radiation was produced for bremsstrahlung process over an aluminium screen target. A series of experiments of conditioning doses was performed and an increment surviving fraction was observed when the dose was 2.3 Gy and a interval time between this and a higher dose (challenging dose) of 27 Gy was 90 minutes. A value of 58 ± 4 Gy was estimated for LD50, at a dose rate of 0.44 ± 0.03 Gy/min These quantities must be optimized. Besides data obtained over yeast survival, an unusual increasing amount of tiny yeast colonies appeared on the agar plates after incubation, and this number increased as increasing the time exposure. Preliminary results indicate these colonies as

Validation of effective half-life of tritium and computation of dose at Madras Atomic Power Station

International Nuclear Information System (INIS)

Moolya, L.L.; Kannan, R.K.; Sreekumaran Nair, B.; Mohandas, P.G.; Rajan, R.

2001-01-01

In Pressurised Heavy Water Reactors (PHWRs) tritium is produced by the activation of deuterium present in the moderator and coolant system. Hence, the inventory of tritium in PHWR is high and it contributes about 20 percent of the Station Dose. Tritium enters body by inhalation, ingestion and skin absorption. Dose received by an individual depends on its elimination rate from the body and hence the effective half-life. It is found that the effective half-life varies from person to person. The effective half-life also depends on the weather condition. The variation of effective half-life is taken care of in dose estimation by average method. However, in case of dose calculation for single uptake cases, there is a need to take fixed effective half-life. ICRP has taken the effective half-life as 10 days. The effective half-life is taken as 6 days in Indian conditions based on the studies conducted earlier in MAPS and elsewhere. Now with available data for about 16 years a fresh study was conducted to validate the effective half-life. This paper gives the study of effective half-life of tritium and its variation during different seasons of the year in MAPS. This paper also gives methods used for computing dose due to tritium. (author)

Energy imparted-based estimates of the effect of z overscanning on adult and pediatric patient effective doses from multi-slice computed tomography

International Nuclear Information System (INIS)

Theocharopoulos, Nicholas; Damilakis, John; Perisinakis, Kostas; Gourtsoyiannis, Nicholas

2007-01-01

In the present study effective dose values normalized to computed tomography dose index measured free in air were calculated for adult, newborn, 1, 5, 10 and 15 year old patients regarding scans of the head, chest, abdomen, pelvis, abdomen and pelvis, and trunk, using the energy imparted method. The effect of z overscanning on patient doses was accounted for, and normalized doses are provided for varying beam collimation, pitch and reconstruction slice width values. The contribution of overscanning depends on patient age, anatomic region imaged, acquisition and reconstruction settings. For a head scan it constitutes 15% of the adult effective dose and 24% of the effective dose to a newborn but for an abdomen scan it may be as high as 58% for a newborn and 31% for an adult. The ratios of normalized pediatric doses relative to that for adults for helical scans depend not only on age but also on acquisition and reconstruction parameters, because of variations in the relative distance between the primary beam and the radiosensitive tissues/organs of the body. Regarding scans of the trunk, pediatric doses are up to a factor of 2.5 times higher compared to adult doses (abdominal scans), whereas for scans of the head up to a factor of 1.5. Increasing the pitch value of helical scans while maintaining the same effective mAs setting, and hence noise levels, leads to an increase in patient doses which depends on age, body region, scan and reconstruction parameters. The % difference between doses at pitch 1.5 and pitch 1 is more pronounced in the abdominal region (14% increase for adults) and in young patients (31% in a newborn and 18% in a 10 year old patient) and it is minimal in head scans (4% increase in newborns and 1% in adults). If multiple body regions are to be imaged, doses to adults can be reduced by up to 15% and 36% to children by performing single long-range scans. Scanning adult patients at 100 kVp instead of 120 kVp, results in a 32% reduction in effective

Effects of trapped proton flux anisotropy on dose rates in low Earth orbit

International Nuclear Information System (INIS)

Badhwar, G.D.; Kushin, V.V.; Akatov, Yu A.; Myltseva, V.A.

1999-01-01

Trapped protons in the South Atlantic Anomaly (SAA) have a rather narrow pitch angle distribution and exhibit east-west anisotropy. In low Earth orbits, the E-W effect results in different amounts of radiation dose received by different sections of the spacecraft. This effect is best studied on missions in which the spacecraft flies in a fixed orientation. The magnitude of the effect depends on the particle energy and altitude through the SAA. In this paper, we describe a clear example of this effect from measurements of radiation dose rates and linear energy transfer spectra made on Space Shuttle flight STS-94 (28.5 deg. inclination x 296 km altitude). The ratio of dose rates from the two directions at this location in the mid-deck was 2.7. As expected from model calculations, the spectra from the two directions are different, that is the ratio is energy dependent. The data can be used to distinguish the anisotropy models. The flight carried an active tissue equivalent proportional counter (TEPC), and passive thermoluminscent detectors (TLDs), and two types of nuclear emulsions. Using nuclear emulsions, charged particles and secondary neutron energy spectra were measured. The combined galactic cosmic radiation+trapped charged particle lineal energy spectra measured by the TEPC and the linear energy transfer spectrum measured by nuclear emulsions are in good agreement. The charged particle absorbed dose rates varied from 112 to 175 μGy/day, and dose equivalent rates from 264.3 to 413 μSv/day. Neutrons in the 1-10 MeV contributed a dose rate of 3.7 μGy/day and dose equivalent rate of 30.8 μSv/day, respectively

Effects of trapped proton flux anisotropy on dose rates in low Earth orbit.

Science.gov (United States)

Badhwar, G D; Kushin, V V; Akatov YuA; Myltseva, V A

1999-06-01

Trapped protons in the South Atlantic Anomaly (SAA) have a rather narrow pitch angle distribution and exhibit east-west anisotropy. In low Earth orbits, the E-W effect results in different amounts of radiation dose received by different sections of the spacecraft. This effect is best studied on missions in which the spacecraft flies in a fixed orientation. The magnitude of the effect depends on the particle energy and altitude through the SAA. In this paper, we describe a clear example of this effect from measurements of radiation dose rates and linear energy transfer spectra made on Space Shuttle flight STS-94 (28.5 degree inclination x 296 km altitude). The ratio of dose rates from the two directions at this location in the mid-deck was 2.7. As expected from model calculations, the spectra from the two directions are different, that is the ratio is energy dependent. The data can be used to distinguish the anisotropy models. The flight carried an active tissue equivalent proportional counter (TEPC), and passive thermoluminscent detectors (TLDs), and two types of nuclear emulsions. Using nuclear emulsions, charged particles and secondary neutron energy spectra were measured. The combined galactic cosmic radiation+trapped charged particle lineal energy spectra measured by the TEPC and the linear energy transfer spectrum measured by nuclear emulsions are in good agreement. The charged particle absorbed dose rates varied from 112 to 175 microGy/day, and dose equivalent rates from 264.3 to 413 microSv/day. Neutrons in the 1-10 MeV contributed a dose rate of 3.7 microGy/day and dose equivalent rate of 30.8 microSv/day, respectively.

Effects of irradiation source and dose level on quality characteristics of processed meat products

Science.gov (United States)

Ham, Youn-Kyung; Kim, Hyun-Wook; Hwang, Ko-Eun; Song, Dong-Heon; Kim, Yong-Jae; Choi, Yun-Sang; Song, Beom-Seok; Park, Jong-Heum; Kim, Cheon-Jei

2017-01-01

The effect of irradiation source (gamma-ray, electron-beam, and X-ray) and dose levels on the physicochemical, organoleptic and microbial properties of cooked beef patties and pork sausages was studied, during 10 days of storage at 30±1 °C. The processed meat products were irradiated at 0, 2.5, 5, 7.5, and 10 kGy by three different irradiation sources. The pH of cooked beef patties and pork sausages was unaffected by irradiation sources or their doses. The redness of beef patties linearly decreased with increasing dose level (Pchanges in overall acceptability were observed for pork sausages regardless of irradiation source (P>0.05), while gamma-ray irradiated beef patties showed significantly decreased overall acceptability in a dose-dependent manner (Poxidation of samples was accelerated by irradiation depending on irradiation sources and dose levels during storage at 30 °C. E-beam reduced total aerobic bacteria of beef patties more effectively, while gamma-ray considerably decreased microbes in pork sausages as irradiation dose increased. The results of this study indicate that quality attributes of meat products, in particular color, lipid oxidation, and microbial properties are significantly influenced by the irradiation sources.

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.

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

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

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.

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

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

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.

Self-reported smoking effects and comparative value between cigarettes and high dose e-cigarettes in nicotine-dependent cigarette smokers.

Science.gov (United States)

McPherson, Sterling; Howell, Donelle; Lewis, Jennifer; Barbosa-Leiker, Celestina; Bertotti Metoyer, Patrick; Roll, John

2016-04-01

The objective of this experiment was to evaluate the comparative value of cigarettes versus high dose e-cigarettes among nicotine-dependent cigarette smokers when compared with money or use of their usual cigarette brand. The experiment used a within-subject design with four sessions. After baseline assessment, participants attended two 15-min unrestricted smoking sessions: one cigarette smoking session and one e-cigarette smoking session. Participants then attended two multiple-choice procedure (MCP) sessions: a session comparing cigarettes and money and a session comparing e-cigarettes and money. Participants (n=27) had used cigarettes regularly, had never used e-cigarettes, and were not currently attempting to quit smoking. The sample consisted primarily of males (72%), with a mean age of 34 years. When given the opportunity to choose between smoking a cigarette or an e-cigarette, participants chose the cigarette 73.9% of the time. Findings from the MCP demonstrated that after the first e-cigarette exposure sessions, the crossover value for cigarettes ($3.45) was significantly higher compared with the crossover value for e-cigarettes ($2.73). The higher participant preference, self-reported smoking effects, and higher MCP crossover points indicate that cigarettes have a higher comparative value than high dose e-cigarettes among e-cigarette naive smokers.

In vitro and in vivo effects of low dose HTO contamination modulated by dose rate

International Nuclear Information System (INIS)

Petcu, I.; Savu, D.; Moisoi, N.; Koeteles, G.J.

1997-01-01

The experiment performed in vitro intended to examine whether an adaptive response could be elicited on lymphocytes by low-level contamination of whole blood with tritiated water and if the modification of the dose rate has any influence on it. Lymphocytes pre-exposed to 3 HOH (0.2 - 6.6 MBq/ml) and subsequently irradiated with I Gy γ-rays showed micronuclei frequency significantly lower (40% - 45%) than the expected member (sum of the yields induced by 3 HOH and γ-rays separately). The degree of the radioresistance induced by HTO pre-treatments became higher with decreasing dose-rate for a rather similar total adapting dose. In vivo, the aim of the study was to investigate if different dose rates are inducing modulation of the lipid peroxidation level and of the thymidine uptake in different tissues of animals contaminated by HTO ingestion. The total doses varied between 5 and 20 cGy and were delivered as chronic (100 days) or acute contamination (5 days). It was observed that only doses about 20 cGy caused a dose-rate dependent increase of the lipid peroxidation level in the tissues of small intestine, kidney and spleen. Both chronic and acute contamination did produce reduced incorporation of thymidine in the cells of bone marrow. The most effective decrease of thymidine uptake was induced by the acute contamination in the lower dose domain (approx. 5 cGy). Our hypothesis is that in this dose domain the modification of thymidine uptake could be due to changes at the level of membrane transport. (author)

Effects of Chronic Low-Dose Radiation on Human Neural Progenitor Cells

Science.gov (United States)

Katsura, Mari; Cyou-Nakamine, Hiromasa; Zen, Qin; Zen, Yang; Nansai, Hiroko; Amagasa, Shota; Kanki, Yasuharu; Inoue, Tsuyoshi; Kaneki, Kiyomi; Taguchi, Akashi; Kobayashi, Mika; Kaji, Toshiyuki; Kodama, Tatsuhiko; Miyagawa, Kiyoshi; Wada, Youichiro; Akimitsu, Nobuyoshi; Sone, Hideko

2016-01-01

The effects of chronic low-dose radiation on human health have not been well established. Recent studies have revealed that neural progenitor cells are present not only in the fetal brain but also in the adult brain. Since immature cells are generally more radiosensitive, here we investigated the effects of chronic low-dose radiation on cultured human neural progenitor cells (hNPCs) derived from embryonic stem cells. Radiation at low doses of 31, 124 and 496 mGy per 72 h was administered to hNPCs. The effects were estimated by gene expression profiling with microarray analysis as well as morphological analysis. Gene expression was dose-dependently changed by radiation. By thirty-one mGy of radiation, inflammatory pathways involving interferon signaling and cell junctions were altered. DNA repair and cell adhesion molecules were affected by 124 mGy of radiation while DNA synthesis, apoptosis, metabolism, and neural differentiation were all affected by 496 mGy of radiation. These in vitro results suggest that 496 mGy radiation affects the development of neuronal progenitor cells while altered gene expression was observed at a radiation dose lower than 100 mGy. This study would contribute to the elucidation of the clinical and subclinical phenotypes of impaired neuronal development induced by chronic low-dose radiation.

Effects of dose, dose-rate and fraction on radiation-induced breast and lung cancers

International Nuclear Information System (INIS)

Howe, G.R.

1992-01-01

Recent results from a large Canadian epidemiologic cohort study of low-LET radiation and cancer will be described. This is a study of 64,172 tuberculosis patients first treated in Canada between 1930 and 1952, of whom many received substantial doses to breast and lung tissue from repeated chest fluoroscopies. The mortality of the cohort between 1950 and 1987 has been determined by computerized record linkage to the National Mortality Data Base. There is a strong positive association between radiation and breast cancer risk among the females in the cohort, but in contrast very little evidence of any increased risk in lung cancer. The results of this and other studies suggest that the effect of dose-rate and/or fractionation on cancer risk may will differ depending upon the particular cancer being considered. (author)

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.

Inverse dose-rate-effects on the expressions of extra-cellular matrix-related genes in low-dose-rate γ-ray irradiated murine cells

International Nuclear Information System (INIS)

Sugihara, Takashi; Tanaka, Kimio; Oghiso, Yoichi; Murano, Hayato

2008-01-01

Based on the results of previous microarray analyses of murine NIH3T3/PG13Luc cells irradiated with continuous low-dose-rate (LDR) γ-ray or end-high-dose-rate-irradiations (end-HDR) at the end of the LDR-irradiation period, the inverse dose-rate-effects on gene expression levels were observed. To compare differences of the effects between LDR-irradiation and HDR-irradiation, HDR-irradiations at 2 different times, one (ini-HDR) at the same time at the start of LDR-irradiation and the other (end-HDR), were performed. The up-regulated genes were classified into two types, in which one was up-regulated in LDR-, ini-HDR-, and end-HDR irradiation such as Cdkn1a and Ccng1, which were reported as p53-dependent genes, and the other was up-regulated in LDR- and ini-HDR irradiations such as pro-collagen TypeIa2/Colla2, TenascinC/Tnc, and Fibulin5/Fbln5, which were reported as extra-cellular matrix-related (ECM) genes. The time dependent gene expression patterns in LDR-irradiation were also classified into two types, in which one was an early response such as in Cdkn1a and Ccng1 and the other was a delayed response such as the ECM genes which have no linearity to total dose. The protein expression pattern of Cdkn1a increased dose dependently in LDR- and end-HDR-irradiations, but those of p53Ser15/18 and MDM2 in LDR-irradiations were different from end-HDR-irradiations. Furthermore, the gene expression levels of the ECM genes in embryonic fibroblasts from p53-deficient mice were not increased by LDR- and end-HDR-irradiation, so the delayed expressions of the ECM genes seem to be regulated by p53. Consequently, the inverse dose-rate-effects on the expression levels of the ECM genes in LDR- and end-HDR-irradiations may be explained from different time responses by p53 status. (author)

Development of Real-Time Measurement of Effective Dose for High Dose Rate Neutron Fields

International Nuclear Information System (INIS)

Braby, L. A.; Reece, W. D.; Hsu, W. H.

2003-01-01

Studies of the effects of low doses of ionizing radiation require sources of radiation which are well characterized in terms of the dose and the quality of the radiation. One of the best measures of the quality of neutron irradiation is the dose mean lineal energy. At very low dose rates this can be determined by measuring individual energy deposition events, and calculating the dose mean of the event size. However, at the dose rates that are normally required for biology experiments, the individual events can not be separated by radiation detectors. However, the total energy deposited in a specified time interval can be measured. This total energy has a random variation which depends on the size of the individual events, so the dose mean lineal energy can be calculated from the variance of repeated measurements of the energy deposited in a fixed time. We have developed a specialized charge integration circuit for the measurement of the charge produced in a small ion chamber in typical neutron irradiation experiments. We have also developed 4.3 mm diameter ion chambers with both tissue equivalent and carbon walls for the purpose of measuring dose mean lineal energy due to all radiations and due to all radiations except neutrons, respectively. By adjusting the gas pressure in the ion chamber, it can be made to simulate tissue volumes from a few nanometers to a few millimeters in diameter. The charge is integrated for 0.1 seconds, and the resulting pulse height is recorded by a multi channel analyzer. The system has been used in a variety of photon and neutron radiation fields, and measured values of dose and dose mean lineal energy are consistent with values extrapolated from measurements made by other techniques at much lower dose rates. It is expected that this technique will prove to be much more reliable than extrapolations from measurements made at low dose rates because these low dose rate exposures generally do not accurately reproduce the attenuation and

Dose-dependent social-cognitive effects of intranasal oxytocin delivered with novel Breath Powered device in adults with autism spectrum disorder: a randomized placebo-controlled double-blind crossover trial.

Science.gov (United States)

Quintana, D S; Westlye, L T; Hope, S; Nærland, T; Elvsåshagen, T; Dørum, E; Rustan, Ø; Valstad, M; Rezvaya, L; Lishaugen, H; Stensønes, E; Yaqub, S; Smerud, K T; Mahmoud, R A; Djupesland, P G; Andreassen, O A

2017-05-23

The neuropeptide oxytocin has shown promise as a treatment for symptoms of autism spectrum disorders (ASD). However, clinical research progress has been hampered by a poor understanding of oxytocin's dose-response and sub-optimal intranasal delivery methods. We examined two doses of oxytocin delivered using a novel Breath Powered intranasal delivery device designed to improve direct nose-to-brain activity in a double-blind, crossover, randomized, placebo-controlled trial. In a randomized sequence of single-dose sessions, 17 male adults with ASD received 8 international units (IU) oxytocin, 24IU oxytocin or placebo followed by four social-cognitive tasks. We observed an omnibus main effect of treatment on the primary outcome measure of overt emotion salience as measured by emotional ratings of faces (η 2 =0.18). Compared to placebo, 8IU treatment increased overt emotion salience (P=0.02, d=0.63). There was no statistically significant increase after 24IU treatment (P=0.12, d=0.4). The effects after 8IU oxytocin were observed despite no significant increase in peripheral blood plasma oxytocin concentrations. We found no significant effects for reading the mind in the eyes task performance or secondary outcome social-cognitive tasks (emotional dot probe and face-morphing). To our knowledge, this is the first trial to assess the dose-dependent effects of a single oxytocin administration in autism, with results indicating that a low dose of oxytocin can significantly modulate overt emotion salience despite minimal systemic exposure.

Dose-dependent analysis of acute medical effects of mixed neutron-gamma radiation from selected severe 235U or 239Pu criticality accidents in USSR, United States, and Argentina.

Science.gov (United States)

Barabanova, Tatyana; Wiley, Albert L; Bushmanov, Andrey

2012-04-01

Eight of the most severe cases of acute radiation disease (ARS) known to have occurred in humans (as the result of criticality accidents) had survival times less than 120 h (herein defined as "early death"). These accidents were analyzed and are discussed with respect to the specific accident scenarios and the resulting accident-specific, mixed neutron-gamma radiation clinical dose distributions. This analysis concludes that the cardiovascular system appears to be the most critical organ system failure for causing "early death" following approximate total body, mixed gamma-neutron radiation doses greater than 40-50 Gy. The clinical data also suggest that there was definite chest dose dependence in the resulting survival times for these eight workers, who unfortunately suffered profound radiation injury and unusual clinical effects from such high dose radiation exposures. In addition, "toxemic syndrome" is correlated with the irradiation of large volumes of soft tissues. Doses to the hands or legs greater than 80-100 Gy or radiation lung injury also play significant but secondary roles in causing "early death" in accidents delivering chest doses greater than 50 Gy.

Epidemiological methods for assessing dose-response and dose-effect relationships

DEFF Research Database (Denmark)

Kjellström, Tord; Grandjean, Philippe

2007-01-01

Selected Molecular Mechanisms of Metal Toxicity and Carcinogenicity General Considerations of Dose-Effect and Dose-Response Relationships Interactions in Metal Toxicology Epidemiological Methods for Assessing Dose-Response and Dose-Effect Relationships Essential Metals: Assessing Risks from Deficiency......Description Handbook of the Toxicology of Metals is the standard reference work for physicians, toxicologists and engineers in the field of environmental and occupational health. This new edition is a comprehensive review of the effects on biological systems from metallic elements...... access to a broad range of basic toxicological data and also gives a general introduction to the toxicology of metallic compounds. Audience Toxicologists, physicians, and engineers in the fields of environmental and occupational health as well as libraries in these disciplines. Will also be a useful...

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.

[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

[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.

Evaluation of effective dose from CT scans for overweight and obese adult patients using the VirtualDose software

International Nuclear Information System (INIS)

Liang, Baohui; Gao, Yiming; Chen, Zhi; Xu, X. George

2017-01-01

This paper evaluates effective dose (ED) of overweight and obese patients who undergo body computed tomography (CT) examinations. ED calculations were based on tissue weight factors in the International Commission on Radiological Protection Publication 103 (ICRP 103). ED per unit dose length product (DLP) are reported as a function of the tube voltage, body mass index (BMI) of patient. The VirtualDose software was used to calculate ED for male and female obese phantoms representing normal weight, overweight, obese 1, obese 2 and obese 3 patients. Five anatomic regions (chest, abdomen, pelvis, abdomen/pelvis and chest/abdomen/pelvis) were investigated for each phantom. The conversion factors were computed from the DLP, and then compared with data previously reported by other groups. It was observed that tube voltage and BMI are the major factors that influence conversion factors of obese patients, and that ED computed using ICRP 103 tissue weight factors were 24% higher for a CT chest examination and 21% lower for a CT pelvis examination than the ED using ICRP 60 factors. For body CT scans, increasing the tube voltage from 80 to 140 kVp would increase the conversion factors by as much as 19-54% depending on the patient's BMI. Conversion factor of female patients was ∼7% higher than the factors of male patients. DLP and conversion factors were used to estimate ED, where conversion factors depended on tube voltage, sex, BMI and tissue weight factors. With increasing number of obese individuals, using size-dependence conversion factors will improve accuracy, in estimating patient radiation dose. (authors)

Cytogenetic effects of low-dose radiation

International Nuclear Information System (INIS)

Metalli, P.

1983-01-01

The effects of ionizing radiation on chromosomes have been known for several decades and dose-effect relationships are also fairly well established in the mid- and high-dose and dose-rate range for chromosomes of mammalian cells. In the range of low doses and dose rates of different types of radiation few data are available for direct analysis of the dose-effect relationships, and extrapolation from high to low doses is still the unavoidable approach in many cases of interest for risk assessment. A review is presented of the data actually available and of the attempts that have been made to obtain possible generalizations. Attention is focused on some specific chromosomal anomalies experimentally induced by radiation (such as reciprocal translocations and aneuploidies in germinal cells) and on their relevance for the human situation. (author)

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.

Radiation Dose Effects into LCO in Technical Specification by Iodine in Hanul units 1,2

Energy Technology Data Exchange (ETDEWEB)

Lee, Hye Min; Lee, Seung Chan [KHNP Central Research Institute, Daejeon (Korea, Republic of)

2015-05-15

This study estimates the impact of the 1-th coolant system in NPP to the LCO (Limiting Condition of Operation) limits which is in the site boundary. Dose limit is merged into the effective dose from whole body and thyroid dose limits, that is possible to combine the two LCOs to a unified LCO. To estimate the limits, the radiation dose of one of the designed accidents should be chosen to check the radiation dose response. The selected accident is based on Seung Chan Lee's study at KHNP in 2011. Using the selected accident, Iodine dose effect is reviewed depending on the LCO limiting responsibility and the specific behavior. In order to evaluate the radiation dose effect in Technical Specification of Hanul 1,2, SGTR is selected for some sensitivity analysis. From the results, in Hanul site, the case of LOOP plus ADV plus GIS is the most severe case and the dose limit margin is about 110% in LCO.

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.

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.

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

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

Dose-rate effects on the bulk etch-rate of CR-39 track detector exposed to low-LET radiations

CERN Document Server

Yamauchi, T; Oda, K; Ikeda, T; Honda, Y; Tagawa, S

1999-01-01

The effect of gamma-rays and pulsed electrons has been investigated on the bulk etch rate of CR-39 detector at doses up to 100 kGy under various dose-rate between 0.0044 and 35.0 Gy/s. The bulk etch rate increased exponentially with the dose at every examined dose-rates. It was reveled to be strongly depend on the dose-rate: the bulk etch rate was decreased with increasing dose-rate at the same total dose. A primitive model was proposed to explain the dose-rate effect in which oxygen dissolved was assumed to dominate the damage formation process.

Drug-, dose- and sex-dependent effects of chronic fluoxetine, reboxetine and venlafaxine on open-field behavior and spatial memory in rats.

Science.gov (United States)

Gray, Vanessa C; Hughes, Robert N

2015-03-15

In an effort to address the need to include both sexes in studies of effects of the SSRI fluoxetine, the NRI reboxetine and the SNRI venlafaxine on anxiety-related behavior and memory along with the use of chronic drug administration, male and female PVG/c rats were fed diets containing two doses of each drug for 21 days. The rats' anxiety level was then assessed in an open field. Short-term spatial memory for a brightness change in a Y maze was also measured. While there was little evidence of anxiolytic effects of any of the drugs, both fluoxetine and, to a lesser extent, venlafaxine appeared to be mainly anxiogenic in their action depending on both dose and sex. Reboxetine was relatively ineffective in this respect. Ability to locate the Y-maze arm that had changed (from white to black) seemed to be impaired for male (but not female) rats by both fluoxetine and venlafaxine and, to a much lesser extent, by reboxetine. Given the relative ineffectiveness of reboxetine in either test, it is possible that the effects of the other two drugs on both anxiety and memory were mainly due to their serotonin reuptake inhibiting properties. The differences that occurred between males and females in responsiveness to all three drugs supported the long-held view that both sexes should be investigated in studies of this sort, especially in view of reports of sex differences in effects of clinically prescribed antidepressants. Copyright © 2014 Elsevier B.V. All rights reserved.

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

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.

Low-dose naloxone provides an abuse-deterrent effect to buprenorphine

Directory of Open Access Journals (Sweden)

Webster LR

2015-11-01

Full Text Available Lynn R Webster,1 Michael D Smith,1 Cemal Unal,2 Andrew Finn3 1PRA Health Sciences, Salt Lake City, UT, USA; 2Biometrical Solutions LLC, Raleigh, NC, USA; 3BioDelivery Sciences International, Inc., Raleigh, NC, USA Abstract: In developmental research, plasma buprenorphine concentrations comparable to a 2 mg buprenorphine–naloxone (BN sublingual tablet have been achieved with a 0.75 mg dose of BN buccal film, a small, bioerodible polymer film for application to mucosal membranes. This was a randomized, double-blind, placebo-controlled, single-dose, four-period crossover study in opioid-dependent subjects with chronic pain receiving >100 mg oral morphine equivalents daily who experienced withdrawal following a naloxone challenge dose. The objective of the study was to determine if intravenous (IV naloxone doses of 0.1 and 0.2 mg would produce a withdrawal response when coadministered with a 0.75 mg IV dose of buprenorphine. Fifteen subjects receiving 90–1,260 mg oral morphine equivalents per day enrolled and completed the study. Precipitated withdrawal occurred in 13% (2/15 of placebo-treated subjects and 47% (7/15 of buprenorphine-treated subjects. When combined with the 0.75 mg dose of buprenorphine, a 0.1 mg dose of naloxone increased the incidence of precipitated withdrawal to 60%, and a 0.2 mg dose of naloxone increased the incidence to 73%. By 15 minutes postdose, the mean change in Clinical Opioid Withdrawal Scale (COWS score from predose was 3.0 for placebo, 6.9 for buprenorphine, 9.8 for BN 0.1 mg, and 12.4 for BN 0.2 mg. The mean COWS score with each active treatment was significantly greater than placebo (P<0.001, and the mean COWS score for each of the naloxone-containing treatments was significantly greater than for buprenorphine alone (P<0.001. Naloxone doses as low as 0.1 mg added an abuse-deterrent effect to a 0.75 mg IV dose of buprenorphine. Keywords: opioid dependence, withdrawal symptoms, abuse-deterrent, buprenorphine

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.)

Study of the effect of dose-rate on radiation-induced damage to human erythrocytes

Energy Technology Data Exchange (ETDEWEB)

Krokosz, Anita [Department of Molecular Biophysics, University of Lodz, Banacha 12/16, Lodz (Poland)]. E-mail: krokosz@biol.uni.lodz.pl; Koziczak, Renata [Department of Molecular Biophysics, University of Lodz, Banacha 12/16, Lodz (Poland); Gonciarz, Marta [Department of Molecular Biophysics, University of Lodz, Banacha 12/16, Lodz (Poland); Szweda-Lewandowska, Zofia [Department of Molecular Biophysics, University of Lodz, Banacha 12/16, Lodz (Poland)

2006-01-15

Human erythrocytes suspended in an isotonic Na-phosphate buffer, pH 7.4 (hematocrit of 2%) were irradiated with {gamma}-rays at three dose-rates of 66.7, 36.7, 25 Gy min{sup -1} in order to investigate the influence of the dose-rate on radiation-induced membrane damage, hemoglobin oxidation and loss of reduced glutathione. The obtained results showed that such processes as erythrocyte hemolysis, lipid and protein destruction depend on the radiation dose-rate. The parameter values describing these processes showed an inverse dose-rate effect.

Study of the effect of dose-rate on radiation-induced damage to human erythrocytes

International Nuclear Information System (INIS)

Krokosz, Anita; Koziczak, Renata; Gonciarz, Marta; Szweda-Lewandowska, Zofia

2006-01-01

Human erythrocytes suspended in an isotonic Na-phosphate buffer, pH 7.4 (hematocrit of 2%) were irradiated with γ-rays at three dose-rates of 66.7, 36.7, 25 Gy min -1 in order to investigate the influence of the dose-rate on radiation-induced membrane damage, hemoglobin oxidation and loss of reduced glutathione. The obtained results showed that such processes as erythrocyte hemolysis, lipid and protein destruction depend on the radiation dose-rate. The parameter values describing these processes showed an inverse dose-rate effect

Dose and Spatial Effects in Long-Distance Radiation Signaling In Vivo: Implications for Abscopal Tumorigenesis

International Nuclear Information System (INIS)

Mancuso, Mariateresa; Giardullo, Paola; Leonardi, Simona; Pasquali, Emanuela; Casciati, Arianna; De Stefano, Ilaria; Tanori, Mirella; Pazzaglia, Simonetta; Saran, Anna

2013-01-01

Purpose: To investigate the dose and spatial dependence of abscopal radiation effects occurring in vivo in the mouse, along with their tumorigenic potential in the central nervous system (CNS) of a radiosensitive mouse model. Methods and Materials: Patched1 (Ptch1) +/− mice, carrying a germ-line heterozygous inactivating mutation in the Ptch1 gene and uniquely susceptible to radiation damage in neonatal cerebellum, were exposed directly to ionizing radiation (1, 2, or 3 Gy of x-rays) or treated in a variety of partial-body irradiation protocols, in which the animals' head was fully protected by suitable lead cylinders while the rest of the body was exposed to x-rays in full or in part. Apoptotic cell death was measured in directly irradiated and shielded cerebellum shortly after irradiation, and tumor development was monitored in lifetime groups. The same endpoints were measured using different shielding geometries in mice irradiated with 3 or 10 Gy of x-rays. Results: Although dose-dependent cell death was observed in off-target cerebellum for all doses and shielding conditions tested, a conspicuous lack of abscopal response for CNS tumorigenesis was evident at the lowest dose of 1 Gy. By changing the amount of exposed body volume, the shielding geometry could also significantly modulate tumorigenesis depending on dose. Conclusions: We conclude that interplay between radiation dose and exposed tissue volume plays a critical role in nontargeted effects occurring in mouse CNS under conditions relevant to humans. These findings may help understanding the mechanisms of long-range radiation signaling in harmful effects, including carcinogenesis, occurring in off-target tissues

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

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.

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.

Cancer risk of low dose/low dose rate radiation: a meta-analysis of cancer data of mammals exposed to low doses of radiation

International Nuclear Information System (INIS)

Ogata, Hiromitsu; Magae, Junji

2008-01-01

Full text: Linear No Threshold (LNT) model is a basic theory for radioprotection, but the adaptability of this hypothesis to biological responses at low doses or at low dose rates is not sufficiently investigated. Simultaneous consideration of the cumulative dose and the dose rate is necessary for evaluating the risk of long-term exposure to ionizing radiation at low dose. This study intends to examine several numerical relationships between doses and dose rates in biological responses to gamma radiation. Collected datasets on the relationship between dose and the incidence of cancer in mammals exposed to low doses of radiation were analysed using meta-regression models and modified exponential (MOE) model, which we previously published, that predicts irradiation time-dependent biological response at low dose rate ionizing radiation. Minimum doses of observable risk and effective doses with a variety of dose rates were calculated using parameters estimated by fitting meta-regression models to the data and compared them with other statistical models that find values corresponding to 'threshold limits'. By fitting a weighted regression model (fixed-effects meta-regression model) to the data on risk of all cancers, it was found that the log relative risk [log(RR)] increased as the total exposure dose increased. The intersection of this regression line with the x-axis denotes the minimum dose of observable risk. These estimated minimum doses and effective doses increased with decrease of dose rate. The goodness of fits of MOE-model depended on cancer types, but the total cancer risk is reduced when dose rates are very low. The results suggest that dose response curve for cancer risk is remarkably affected by dose rate and that dose rate effect changes as a function of dose rate. For scientific discussion on the low dose exposure risk and its uncertainty, the term 'threshold' should be statistically defined, and dose rate effects should be included in the risk

Effective dose and dose to crystalline lens during angiographic procedures

International Nuclear Information System (INIS)

Pages, J.

1998-01-01

The highest radiation doses levels received by radiologists are observed during interventional procedures. Doses to forehead and neck received by a radiologist executing angiographic examinations at the department of radiology at the academic hospital (AZ-VUB) have been measured for a group of 34 examinations. The doses to crystalline lens and the effective doses for a period of one year have been estimated. For the crystalline lens the maximum dose approaches the ICRP limit, that indicates the necessity for the radiologist to use leaded glasses. (N.C.)

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...

Problems following hippocampal irradiation in interventional radiologists - doses and potential effect:a Monte Carlo simulation

International Nuclear Information System (INIS)

Cumak, V.; Morgun, A.; Bakhanova, O.; Loganovs'kij, K.; Loganovs'ka, T.; Marazziti, D.

2015-01-01

This study aimed at investigating radiation exposure of hippocampus in interventional medical professionals irradiated in the operating room, and to compare doses in the hippocampus with the effective dose (protection quantity), as well as with the doses measured by individual dosimeter, in order to estimate probability of reaching levels of radiation induced cognitive and other neuropsychiatric alterations during their working career, through a Monte Carlo simulation. The results showed that cranial irradiation was very heterogeneous and depended on the projection: doses of left and right hippocampi may be different up to a factor of 2.5; under certain conditions, the dose of the left hippocampus may be twice the effective dose, estimated by conventional double dosimetry algorithm. The professional span doses of the irradiated hippocampus may overcome the threshold able to provoke possible cognitive and emotional-behavioral impairment. Therefore, in-depth studies of the effects of brain irradiation in occupationally exposed interventional medical personnel appear urgently needed and crucial

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.

Effect of uncertainty in nasal airway deposition of radioactive particles on effective dose

Energy Technology Data Exchange (ETDEWEB)

Guilmette, R.A.; Birchall, A.; Jarvis, N.S

1998-07-01

In the current ICRP human respiratory tract (RT) model (ICRP Publication 66), the deposition of particles in various regions of the RT during natural breathing is modelled by considering the RT as a series of filters, resulting in deposition probabilities for distal portions of the RT being dependent on those of the proximal segments. Thus, uncertainties in regional deposition in proximal segments of the RT are reflected or propagated in uncertainties in deposition in the distal segments of the lung. Experimental data on aerosol particle deposition have demonstrated significant variability in nasal airway (NA) deposition for different individuals studied. This report summarises the impact of introducing variability in NA deposition efficiency on the calculation of effective doses using the ICRP 66 model for selected radionuclides. The computer software LUDEP, modified for this purpose, was used to customise deposition patterns, and effective doses were calculated for several radionuclides ({sup 111}In, {sup 106}Ru, {sup 60}Co, {sup 210}Po, {sup 238}U and {sup 239}Pu) chosen to represent isotopes with various decay schemes and half-lives. The results indicated significant but particle-size-specific effects of assumed NA deposition efficiencies on the calculated effective doses, which varied typically by factors of five to six. The majority of the variability was associated with direct effects on deposition patterns, but in some cases, alterations of radiation dose distribution within the various target organs also contributed to the variability. These results provide a basis for evaluating uncertainties due to inter-individual differences in deposition patterns for radiation protection and risk analysis. (author)

Dose-rate effects in plateau-phase cultures of S3 HeLa and V79 cells

International Nuclear Information System (INIS)

Mitchell, J.B.; Bedford, J.S.; Bailey, S.M.

1979-01-01

Dose-rate effects on cell survival were studied for log-, fed plateau-, and unfed plateau-phase cultures of V79 and S3 HeLa cells. For log-phase cultures, repair, cell-cycle redistribution, and cell division during exposure can contribute to the overall dose-rate effect, but their relative contributions are difficult to determine. With plateau-phase cultures, the cell-cycle times are greatly lengthened, for those cells that are in cycle. Hence, the contribution to the overall dose-rate effect of cell-cycle redistribution and cell division during the exposure could be minimized using plateau-phase cultures. With respect to the acute dose-survival curves, there was a clear loss in effectiveness when the dose rate was lowered to 154 rad/hr for both fed and unfed plateau-phase HeLa and V79 cells. There was no further reduction in effectiveness per unit dose, however, when the dose rate was reduced to 55 rad/hr. Since there was virtually no cell division or cell-cycle redistribution, it may be that a limit to the repair-dependent dose-rate effect at 37 0 C has been reached at a dose rate of 154 rad/hr

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.

Reduced-Nicotine Cigarettes in Young Smokers: Impact of Nicotine Metabolism on Nicotine Dose Effects.

Science.gov (United States)

Faulkner, Paul; Ghahremani, Dara G; Tyndale, Rachel F; Cox, Chelsea M; Kazanjian, Ari S; Paterson, Neil; Lotfipour, Shahrdad; Hellemann, Gerhard S; Petersen, Nicole; Vigil, Celia; London, Edythe D

2017-07-01

The use of cigarettes delivering different nicotine doses allows evaluation of the contribution of nicotine to the smoking experience. We compared responses of 46 young adult smokers to research cigarettes, delivering 0.027, 0.110, 0.231, or 0.763 mg nicotine, and conventional cigarettes. On five separate days, craving, withdrawal, affect, and sustained attention were measured after overnight abstinence and again after smoking. Participants also rated each cigarette, and the nicotine metabolite ratio (NMR) was used to identify participants as normal or slow metabolizers. All cigarettes equally alleviated craving, withdrawal, and negative affect in the whole sample, but normal metabolizers reported greater reductions of craving and withdrawal than slow metabolizers, with dose-dependent effects. Only conventional cigarettes and, to a lesser degree, 0.763-mg nicotine research cigarettes increased sustained attention. Finally, there were no differences between ratings of lower-dose cigarettes, but the 0.763-mg cigarettes and (even more so) conventional cigarettes were rated more favorably than lower-dose cigarettes. The findings indicate that smoking-induced relief of craving and withdrawal reflects primarily non-nicotine effects in slow metabolizers, but depends on nicotine dose in normal metabolizers. By contrast, relief of withdrawal-related attentional deficits and cigarette ratings depend on nicotine dose regardless of metabolizer status. These findings have bearing on the use of reduced-nicotine cigarettes to facilitate smoking cessation and on policy regarding regulation of nicotine content in cigarettes. They suggest that normal and slow nicotine metabolizers would respond differently to nicotine reduction in cigarettes, but that irrespective of metabolizer status, reductions to <0.763 mg/cigarette may contribute to temporary attentional deficits.

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)

Laboratory measures of methylphenidate effects in cocaine-dependent patients receiving treatment.

Science.gov (United States)

Roache, J D; Grabowski, J; Schmitz, J M; Creson, D L; Rhoades, H M

2000-02-01

Two experiments examined the effects of methylphenidate in male and female patients enrolled in an outpatient treatment program for primary cocaine dependence. The first study was a component of a double-blind efficacy trial wherein 57 patients were first tested in a human laboratory for their initial responsiveness to medication. Patients were randomly assigned to receive either placebo or methylphenidate treatment and received their first dose in the human laboratory environment before continuing in outpatient treatment. Methylphenidate was given as a 20-mg sustained-release dose (twice daily) plus an additional 5-mg immediate-release dose combined with the morning dose. Methylphenidate increased heart rate and subjective ratings; however, the subjective effects were primarily of a "dysphoric" nature, and significant effects were limited to increases in anxiety, depression, and anger on the Profile of Mood States; shaky/jittery ratings on a visual analog scale; and dysphoria on the lysergic acid diethylamide (LSD) scale of the Addiction Research Center Inventory. Methylphenidate did not increase cocaine craving nor ratings suggesting abuse potential (i.e., Morphine-Benzedrine Group or drug-liking scores, etc.). None of the drug effects observed in the human laboratory was of clinical concern, and no subject was precluded from continuing in the outpatient study. After outpatient treatment completion, 12 patients were brought back into a second double-blind human laboratory study in which three doses (15, 30, and 60 mg) of immediate-release methylphenidate were administered in an ascending series preceded and followed by placebo. Methylphenidate produced dose-related increases in heart rate, subjective ratings of shaky/jittery, and LSD/dysphoria without significantly altering cocaine craving or stimulant euphoria ratings. These results suggest that stimulant substitution-type approaches to the treatment of cocaine dependence are not necessarily contraindicated

Immunomodulatory Properties and Molecular Effects in Inflammatory Diseases of Low-Dose X-Irradiation

International Nuclear Information System (INIS)

Rödel, Franz; Frey, Benjamin; Manda, Katrin; Hildebrandt, Guido; Hehlgans, Stephanie; Keilholz, Ludwig; Seegenschmiedt, M. Heinrich; Gaipl, Udo S.; Rödel, Claus

2012-01-01

Inflammatory diseases are the result of complex and pathologically unbalanced multicellular interactions. For decades, low-dose X-irradiation therapy (LD-RT) has been clinically documented to exert an anti-inflammatory effect on benign diseases and chronic degenerative disorders. By contrast, experimental studies to confirm the effectiveness and to reveal underlying cellular and molecular mechanisms are still at their early stages. During the last decade, however, the modulation of a multitude of immunological processes by LD-RT has been explored in vitro and in vivo. These include leukocyte/endothelial cell adhesion, adhesion molecule and cytokine/chemokine expression, apoptosis induction, and mononuclear/polymorphonuclear cell metabolism and activity. Interestingly, these mechanisms display comparable dose dependences and dose-effect relationships with a maximum effect in the range between 0.3 and 0.7 Gy, already empirically identified to be most effective in the clinical routine. This review summarizes data and models exploring the mechanisms underlying the immunomodulatory properties of LD-RT that may serve as a prerequisite for further systematic analyses to optimize low-dose irradiation procedures in future clinical practice.

Immunomodulatory Properties and Molecular Effects in Inflammatory Diseases of Low-Dose X-Irradiation

Energy Technology Data Exchange (ETDEWEB)

Rödel, Franz [Department of Radiotherapy and Oncology, University Hospital of Frankfurt, Johann Wolfgang-Goethe Universität, Frankfurt am Main (Germany); Frey, Benjamin [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen (Germany); Manda, Katrin; Hildebrandt, Guido [Department of Radiotherapy and Radiation Oncology, University of Rostock, Rostock (Germany); Hehlgans, Stephanie [Department of Radiotherapy and Oncology, University Hospital of Frankfurt, Johann Wolfgang-Goethe Universität, Frankfurt am Main (Germany); Keilholz, Ludwig [Department of Radiotherapy, Clinical Center Bayreuth, Bayreuth (Germany); Seegenschmiedt, M. Heinrich [Strahlenzentrum Hamburg Medizinisches Versorgungszentrum, Hamburg (Germany); Gaipl, Udo S. [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen (Germany); Rödel, Claus, E-mail: franz.roedel@kgu.de [Department of Radiotherapy and Oncology, University Hospital of Frankfurt, Johann Wolfgang-Goethe Universität, Frankfurt am Main (Germany)

2012-09-25

Inflammatory diseases are the result of complex and pathologically unbalanced multicellular interactions. For decades, low-dose X-irradiation therapy (LD-RT) has been clinically documented to exert an anti-inflammatory effect on benign diseases and chronic degenerative disorders. By contrast, experimental studies to confirm the effectiveness and to reveal underlying cellular and molecular mechanisms are still at their early stages. During the last decade, however, the modulation of a multitude of immunological processes by LD-RT has been explored in vitro and in vivo. These include leukocyte/endothelial cell adhesion, adhesion molecule and cytokine/chemokine expression, apoptosis induction, and mononuclear/polymorphonuclear cell metabolism and activity. Interestingly, these mechanisms display comparable dose dependences and dose-effect relationships with a maximum effect in the range between 0.3 and 0.7 Gy, already empirically identified to be most effective in the clinical routine. This review summarizes data and models exploring the mechanisms underlying the immunomodulatory properties of LD-RT that may serve as a prerequisite for further systematic analyses to optimize low-dose irradiation procedures in future clinical practice.

Dose-dependent acute effects of recombinant human TSH (rhTSH) on thyroid size and function. Comparison of 0.1, 0.3 and 0.9 mg of rhTSH

DEFF Research Database (Denmark)

Fast, Søren; Nielsen, Viveque Egsgaard; Bonnema, Steen Joop

2009-01-01

Context: Recombinant human TSH (rhTSH) is used to augment the effect of radioiodine therapy for nontoxic multinodular goitre. Reports of acute thyroid swelling and hyperthyroidism warrant safety studies evaluating whether these side-effects are dose-dependent. Objective: To determine the effects...... on thyroid size and function of various doses of rhTSH. Design: In nine healthy male volunteers the effect of placebo, 0.1, 0.3 and 0.9 mg of rhTSH was examined in a paired design including four consecutive study rounds. Main outcome measures: Were evaluated at baseline, 24h, 48h, 96h, 7 days and 28 days...... after rhTSH and included: Thyroid volume (TV) estimation by planimetric ultrasound, and thyroid function by serum TSH, freeT3, freeT4 and Tg levels. Results: Following placebo or 0.1 mg rhTSH the TV did not change significantly from baseline at any time. At 24 and 48 hours after administration of 0.3 mg...

Organ dose and effective dose with the EOS scanner in spine deformity surgery

DEFF Research Database (Denmark)

Heide Pedersen, Peter; Petersen, Asger Greval; Eiskjær, Søren Peter

2016-01-01

Organ dose and effective dose with the EOS scanner in spine deformity surgery. A study on anthropomorphic phantoms describing patient radiation exposure in full spine examinations. Authors: Peter Heide Pedersen, Asger Greval Petersen, Søren Peter Eiskjær. Background: Ionizing radiation potentially...... quality images while at the same time reducing radiation dose. At our institution we use the EOS for pre- and postoperative full spine examinations. Purpose: The purpose of the study is to make first time organ dose and effective dose evaluations with micro-dose settings in full spine examinations. Our...... hypothesis is that organ dose and effective doses can be reduced 5-10 times compared to standard settings, without too high image-quality trade off, resulting in a theoretical reduction of radiation induced cancer. Methods: Patient dosimetry is performed on anthropomorphic child phantoms, representing a 5...

Density Dependence and Growth Rate: Evolutionary Effects on Resistance Development to Bt (Bacillus thuringiensis).

Science.gov (United States)

Martinez, Jeannette C; Caprio, Michael A; Friedenberg, Nicholas A

2018-02-09

It has long been recognized that pest population dynamics can affect the durability of a pesticide, but dose remains the primary component of insect resistance management (IRM). For transgenic pesticidal traits such as Bt (Bacillus thuringiensis Berliner (Bacillales: Bacillaceae)), dose (measured as the mortality of susceptibles caused by a toxin) is a relatively fixed characteristic and often falls below the standard definition of high dose. Hence, it is important to understand how pest population dynamics modify durability and what targets they present for IRM. We used a deterministic model of a generic arthropod pest to examine how timing and strength of density dependence interacted with population growth rate and Bt mortality to affect time to resistance. As in previous studies, durability typically reached a minimum at intermediate doses. However, high population growth rates could eliminate benefits of high dose. The timing of density dependence had a more subtle effect. If density dependence operated simultaneously with Bt mortality, durability was insensitive to its strengths. However, if density dependence was driven by postselection densities, decreasing its strength could increase durability. The strength of density dependence could affect durability of both single traits and pyramids, but its influence depended on the timing of density dependence and size of the refuge. Our findings suggest the utility of a broader definition of high dose, one that incorporates population-dynamic context. That maximum growth rates and timing and strength of interactions causing density dependent mortality can all affect durability, also highlights the need for ecologically integrated approaches to IRM research. © The Author(s) 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Evaluation of organ doses and specific k effective dose of 64-slice CT thorax examination using an adult anthropomorphic phantom

International Nuclear Information System (INIS)

Hashim, S.; Karim, M.K.A.; Bakar, K.A.; Sabarudin, A.; Chin, A.W; Saripan, M.I.; Bradley, D.A.

2016-01-01

The magnitude of radiation dose in computed tomography (CT) depends on the scan acquisition parameters, investigated herein using an anthropomorphic phantom (RANDO®) and thermoluminescence dosimeters (TLD). Specific interest was in the organ doses resulting from CT thorax examination, the specific k coefficient for effective dose estimation for particular protocols also being determined. For measurement of doses representing five main organs (thyroid, lung, liver, esophagus and skin), TLD-100 (LiF:Mg, Ti) were inserted into selected holes in a phantom slab. Five CT thorax protocols were investigated, one routine (R1) and four that were modified protocols (R2 to R5). Organ doses were ranked from greatest to least, found to lie in the order: thyroid>skin>lung>liver>breast. The greatest dose, for thyroid at 25 mGy, was that in use of R1 while the lowest, at 8.8 mGy, was in breast tissue using R3. Effective dose (E) was estimated using three standard methods: the International Commission on Radiological Protection (ICRP)-103 recommendation (E103), the computational phantom CT-EXPO (E(CTEXPO)) method, and the dose-length product (DLP) based approach. E103 k factors were constant for all protocols, ~8% less than that of the universal k factor. Due to inconsistency in tube potential and pitch factor the k factors from CTEXPO were found to vary between 0.015 and 0.010 for protocols R3 and R5. With considerable variation between scan acquisition parameters and organ doses, optimization of practice is necessary in order to reduce patient organ dose. - Highlights: • Using TLD-100 dosimeters and a RANDO phantom 5 CT thorax protocol organ doses were assessed. • The specific k coefficient for effective dose estimation of protocols differed with approach. • Organ dose was observed to decrease in the order: thyroid>skin>lung>liver>breast. • E103 k factors were constant for all protocols, lower by ~8% compared to the universal k factor.

Effective dose in abdominal digital radiography: Patient factor

Energy Technology Data Exchange (ETDEWEB)

Jang, Ji Sung; Koo, Hyun Jung; Park, Jung Hoon; Cho, Young Chul; Do, Kyung Hyun [Dept. of Radiology, and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul(Korea, Republic of); Yang, Hyung Jin [Dept. of Medical Physics, Korea University, Seoul (Korea, Republic of)

2017-08-15

To identify independent patient factors associated with an increased radiation dose, and to evaluate the effect of patient position on the effective dose in abdominal digital radiography. We retrospectively evaluated the effective dose for abdominal digital radiography in 222 patients. The patients were divided into two groups based on the cut-off dose value of 0.311 mSv (the upper third quartile of dose distribution): group A (n = 166) and group B (n = 56). Through logistic regression, independent factors associated with a larger effective dose were identified. The effect of patient position on the effective dose was evaluated using a paired t-test. High body mass index (BMI) (≥ 23 kg/m2), presence of ascites, and spinal metallic instrumentation were significantly associated with a larger effective dose. Multivariate logistic regression analysis revealed that high BMI [odds ratio (OR), 25.201; p < 0.001] and ascites (OR, 25.132; p < 0.001) were significantly associated with a larger effective dose. The effective dose was significantly lesser (22.6%) in the supine position than in the standing position (p < 0.001). High BMI and ascites were independent factors associated with a larger effective dose in abdominal digital radiography. Significant dose reduction in patients with these factors may be achieved by placing the patient in the supine position during abdominal digital radiography.

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.

Sex- and dose-dependent effects of calcium ion irradiation on behavioral performance of B6D2F1 mice during contextual fear conditioning training

Science.gov (United States)

Raber, Jacob; Weber, Sydney J.; Kronenberg, Amy; Turker, Mitchell S.

2016-06-01

The space radiation environment includes energetic charged particles that may impact behavioral and cognitive performance. The relationship between the dose and the ionization density of the various types of charged particles (expressed as linear energy transfer or LET), and cognitive performance is complex. In our earlier work, whole body exposure to 28Si ions (263 MeV/n, LET = 78keV / μ m ; 1.6 Gy) affected contextual fear memory in C57BL/6J × DBA2/J F1 (B6D2F1) mice three months following irradiation but this was not the case following exposure to 48Ti ions (1 GeV/n, LET = 107keV / μ m ; 0.2 or 0.4 Gy). As an increased understanding of the impact of charged particle exposures is critical for assessment of risk to the CNS of astronauts during and following missions, in this study we used 40Ca ion beams (942 MeV/n, LET = 90keV / μm) to determine the behavioral and cognitive effects for the LET region between that of Si ions and Ti ions. 40Ca ion exposure reduced baseline activity in a novel environment in a dose-dependent manner, which suggests reduced motivation to explore and/or a diminished level of curiosity in a novel environment. In addition, exposure to 40Ca ions had sex-dependent effects on response to shock. 40Ca ion irradiation reduced the response to shock in female, but not male, mice. In contrast, 40Ca ion irradiation did not affect fear learning, memory, or extinction of fear memory for either gender at the doses employed in this study. Thus 40Ca ion irradiation affected behavioral, but not cognitive, performance. The effects of 40Ca ion irradiation on behavioral performance are relevant, as a combination of novelty and aversive environmental stimuli is pertinent to conditions experienced by astronauts during and following space missions.

Late effects of low doses and dose rates

International Nuclear Information System (INIS)

Paretzke, H.G.

1980-01-01

This paper outlines the spectrum of problems and approaches used in work on the derivation of quantitative prognoses of late effects in man of low doses and dose rates. The origins of principal problems encountered in radiation risks assessments, definitions and explanations of useful quantities, methods of deriving risk factors from biological and epidemiological data, and concepts of risk evaluation and problems of acceptance are individually discussed

Proton dose distribution measurements using a MOSFET detector with a simple dose‐weighted correction method for LET effects

Science.gov (United States)

Hotta, Kenji; Matsuura, Taeko; Matsubara, Kana; Nishioka, Shie; Nishio, Teiji; Kawashima, Mitsuhiko; Ogino, Takashi

2011-01-01

We experimentally evaluated the proton beam dose reproducibility, sensitivity, angular dependence and depth‐dose relationships for a new Metal Oxide Semiconductor Field Effect Transistor (MOSFET) detector. The detector was fabricated with a thinner oxide layer and was operated at high‐bias voltages. In order to accurately measure dose distributions, we developed a practical method for correcting the MOSFET response to proton beams. The detector was tested by examining lateral dose profiles formed by protons passing through an L‐shaped bolus. The dose reproducibility, angular dependence and depth‐dose response were evaluated using a 190 MeV proton beam. Depth‐output curves produced using the MOSFET detectors were compared with results obtained using an ionization chamber (IC). Since accurate measurements of proton dose distribution require correction for LET effects, we developed a simple dose‐weighted correction method. The correction factors were determined as a function of proton penetration depth, or residual range. The residual proton range at each measurement point was calculated using the pencil beam algorithm. Lateral measurements in a phantom were obtained for pristine and SOBP beams. The reproducibility of the MOSFET detector was within 2%, and the angular dependence was less than 9%. The detector exhibited a good response at the Bragg peak (0.74 relative to the IC detector). For dose distributions resulting from protons passing through an L‐shaped bolus, the corrected MOSFET dose agreed well with the IC results. Absolute proton dosimetry can be performed using MOSFET detectors to a precision of about 3% (1 sigma). A thinner oxide layer thickness improved the LET in proton dosimetry. By employing correction methods for LET dependence, it is possible to measure absolute proton dose using MOSFET detectors. PACS number: 87.56.‐v

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.

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.

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

Effect of low-dose ionizing radiation on luminous marine bacteria: radiation hormesis and toxicity

International Nuclear Information System (INIS)

Kudryasheva, N.S.; Rozhko, T.V.

2015-01-01

The paper summarizes studies of effects of alpha- and beta-emitting radionuclides (americium-241, uranium-235+238, and tritium) on marine microorganisms under conditions of chronic low-dose irradiation in aqueous media. Luminous marine bacteria were chosen as an example of these microorganisms; bioluminescent intensity was used as a tested physiological parameter. Non-linear dose-effect dependence was demonstrated. Three successive stages in the bioluminescent response to americium-241 and tritium were found: 1 – absence of effects (stress recognition), 2 – activation (adaptive response), and 3 – inhibition (suppression of physiological function, i.e. radiation toxicity). The effects were attributed to radiation hormesis phenomenon. Biological role of reactive oxygen species, secondary products of the radioactive decay, is discussed. The study suggests an approach to evaluation of non-toxic and toxic stages under conditions of chronic radioactive exposure. - Highlights: • Luminous bacteria demonstrate nonlinear dose-effect relation in radioactive solutions. • Response to low-dose radiation includes 3 stages: threshold, activation, inhibition. • ROS are responsible for low-dose effects of alpha-emitting radionuclides. • Luminous marine bacteria are a convenient tool to study radiation hormesis

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.

Non-linearity of dose-effect relationship at low level exposure on the example of cytogenetic effects in plant cells

International Nuclear Information System (INIS)

Oudalova, A.A.; Geras'kin, S.A.; Dikarev, V.G.; Dikareva, N.S.; Chernonog, E.V.

2007-01-01

Complete text of publication follows. There has been an increasing concern in the current scientific society and among the public about the need to protect the environment in order to maintain the ecosystem sustainability and future well-being of man. The linear non-threshold (LNT) hypothesis as the most officially acknowledged concept of biological effect of radiation fails to explain many facts on effects at low level exposures (LLE) accumulated lately. Available information on the dose-effect relationship at low doses is scarce and incomplete for non-human species despite the fact that, under conditions of increased radiation exposure, some biota species occur at a risk of higher impact than humans because of differences in ecological niches occupied. Dose-effect relationships for cytogenetic damage in the range of LLE are studied in a series os experiments with plant (Hordeum vulgare L.) meristem cells. Dose-effect dependences obtained show an obvious non-linear behavior in the LLE region. A piecewise linear model (PLM) for dose-cytogenetic effect relationship that considers an existence of dose-independent part at LLE ('plateau') is developed and specified on the data obtained. An advantage of the PLM over linear model in approximating the frequency of cytogenetic disturbances is demonstrated. From an empirical probability distribution analysis, it is shown that the increase in cytogenetic damage level is tightly connected with changes in a process of absorbed energy distribution between target volumes in terms of fraction of cells experienced a radiation hit event. An appropriateness of the LNT hypothesis to the description of cytogenetic disturbances yield in plant meristem cells in the LLE region is discussed. The results support a conclusion about indirect mechanism of mutagenesis induced by low doses. New data obtained concern a perception of fundamental mechanisms governing cell response to LLE. These findings are of general biological interest, since

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

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

COMPARING BEHAVIORAL DOSE-EFFECT CURVES FOR HUMANS AND LABORATORY ANIMALS ACUTELY EXPOSED TO TOLUENE.

Science.gov (United States)

The utility of laboratory animal data in toxicology depends upon the ability to generalize the results quantitatively to humans. To compare the acute behavioral effects of inhaled toluene in humans to those in animals, dose-effect curves were fitted by meta-analysis of published...

Clinical Effectiveness and Dose Titration in Pediatric Practice

Directory of Open Access Journals (Sweden)

Yu.V. Marushko

2016-02-01

Full Text Available The paper is devoted to the questions of usage of one of the popular antipyretic and anesthetic drug in pediatric practice — ibuprofen. In the article there are generalized literature data and own experience in ibuprofen dose titration in single dose 5 and 10 mg/kg depending on clinical situation.

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)

Temperature dependence of radiation effects in polyethylene

International Nuclear Information System (INIS)

Wu, G; Katsumura, Y.; Kudoh, H.; Morita, Y.; Seguchi, T.

2000-01-01

Temperature dependence of crosslinking and gas evolution under γ-irradiation was studied for high-density and low-density polyethylene samples in the 30-360degC range. It was found that crosslinking was the predominant process up to 300degC and the gel point decreased with increasing temperature. At above 300degC, however, the gel fraction at a given dose decreased rapidly with temperature and the action of radiation turned to enhance polyethylene degradation. Yields of H 2 and hydrocarbon gases increased with temperature and the compositions of hydrocarbons were dose dependent. (author)

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.

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.

Genotoxic effects of high dose rate X-ray and low dose rate gamma radiation in ApcMin/+ mice.

Science.gov (United States)

Graupner, Anne; Eide, Dag M; Brede, Dag A; Ellender, Michele; Lindbo Hansen, Elisabeth; Oughton, Deborah H; Bouffler, Simon D; Brunborg, Gunnar; Olsen, Ann Karin

2017-10-01

Risk estimates for radiation-induced cancer in humans are based on epidemiological data largely drawn from the Japanese atomic bomb survivor studies, which received an acute high dose rate (HDR) ionising radiation. Limited knowledge exists about the effects of chronic low dose rate (LDR) exposure, particularly with respect to the application of the dose and dose rate effectiveness factor. As part of a study to investigate the development of colon cancer following chronic LDR vs. acute HDR radiation, this study presents the results of genotoxic effects in blood of exposed mice. CBAB6 F1 Apc +/+ (wild type) and Apc Min/+ mice were chronically exposed to estimated whole body absorbed doses of 1.7 or 3.2 Gy 60 Co-γ-rays at a LDR (2.2 mGy h -1 ) or acutely exposed to 2.6 Gy HDR X-rays (1.3 Gy min -1 ). Genotoxic endpoints assessed in blood included chromosomal damage (flow cytometry based micronuclei (MN) assay), mutation analyses (Pig-a gene mutation assay), and levels of DNA lesions (Comet assay, single-strand breaks (ssb), alkali labile sites (als), oxidized DNA bases). Ionising radiation (ca. 3 Gy) induced genotoxic effects dependent on the dose rate. Chromosomal aberrations (MN assay) increased 3- and 10-fold after chronic LDR and acute HDR, respectively. Phenotypic mutation frequencies as well as DNA lesions (ssb/als) were modulated after acute HDR but not after chronic LDR. The Apc Min/+ genotype did not influence the outcome in any of the investigated endpoints. The results herein will add to the scant data available on genotoxic effects following chronic LDR of ionising radiation. Environ. Mol. Mutagen. 58:560-569, 2017. © 2017 The Authors Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society. © 2017 The Authors Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society.

Different Dose-Dependent Modes of Action of C-Type Natriuretic Peptide on Pseudomonas aeruginosa Biofilm Formation

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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.

The fitting parameters extraction of conversion model of the low dose rate effect in bipolar devices

International Nuclear Information System (INIS)

Bakerenkov, Alexander

2011-01-01

The Enhanced Low Dose Rate Sensitivity (ELDRS) in bipolar devices consists of in base current degradation of NPN and PNP transistors increase as the dose rate is decreased. As a result of almost 20-year studying, the some physical models of effect are developed, being described in detail. Accelerated test methods, based on these models use in standards. The conversion model of the effect, that allows to describe the inverse S-shaped excess base current dependence versus dose rate, was proposed. This paper presents the problem of conversion model fitting parameters extraction.

Biochemical and cellular mechanisms of low-dose effects

International Nuclear Information System (INIS)

Feinendegen, L.E.; Booz, J.; Muehlensiepen, H.

1988-01-01

The question of health effects from small radiation doses remains open. Individual cells, when being hit by single elemental doses - in low-dose irradiation - react acutely and temporarily by altering control of enzyme activity, as is demonstrated for the case of thymidine kinase. This response is not constant in that it provides a temporary protection of enzyme activity against a second irradiation, by a mechanism likely to be via improved detoxification of intracellular radicals. It must be considered that in the low-dose region radiation may also exert protection against other challenges involving radicals, causing a net beneficial effect by temporarily shielding the hit cell against radicals produced by metabolism. Since molecular alterations leading to late effects are considered a consequence of the initial cellular response, late effects from small radiation doses do not necessarily adhere to a linear dose-effect relationship. The reality of the linear relationship between the risk of late effects from high doses to small doses is an assumption, for setting dose limits, but it must not be taken for predicting health detriment from low doses. (author)

Nanosilica induced dose-dependent cytotoxicity and cell type-dependent multinucleation in HepG2 and L-02 cells