TREATMENT OF STEROID DEPENDENT ASTHMATICS WITH LOW DOSES OF CYCLOSPORINE

Directory of Open Access Journals (Sweden)

Stanislav Šuškovič

2004-01-01

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

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

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.

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

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

2015-04-01

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

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.

Dose-dependent effects of theta burst rTMS on cortical excitability and resting-state connectivity of the human motor system.

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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.

Low-dose vaporized cannabis significantly improves neuropathic pain.

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Wilsey, Barth; Marcotte, Thomas; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee

2013-02-01

We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling medium-dose (3.53%), low-dose (1.29%), or placebo cannabis with the primary outcome being visual analog scale pain intensity. Psychoactive side effects and neuropsychological performance were also evaluated. Mixed-effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the 2 active dose groups' results (P > .7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo versus low-dose, 2.9 for placebo versus medium-dose, and 25 for medium- versus low-dose. As these NNTs are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well tolerated, and neuropsychological effects were of limited duration and readily reversible within 1 to 2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. The analgesia obtained from a low dose of delta-9-tetrahydrocannabinol (1.29%) in patients, most of whom were experiencing neuropathic pain despite conventional treatments, is a clinically significant outcome. In general, the effect sizes on cognitive testing were consistent with this minimal dose. As a result, one might not anticipate a significant impact on daily functioning. Published by Elsevier Inc.

Repeated dose oral toxicity of inorganic mercury in wistar rats: biochemical and morphological alterations

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M. D. Jegoda

2013-06-01

Full Text Available Aim: The study was conducted to find out the possible toxic effect of mercuric chloride (HgCl2 at the histological, biochemical, and haematological levels in the wistar rats for 28 days. Materials and Methods: The biochemical and hematological alteration were estimated in four groups of rat (each group contain ten animals, which were treated with 0 (control, 2, 4, and 8 mg/kg body weight of HgCl2 through oral gavage. At the end of study all rats were sacrificed and subjected for histopathology. Result: A significantly (P < 0.05 higher level of serum alanine amino transferase (ALT, gamma Glutamyle Transferase, and creatinine were recorded in treatment groups, while the level of alkaline phosphtase (ALP was significantly decreased as compared to the control group. The toxic effect on hematoclogical parameter was characterized by significant decrease in hemoglobin, packed cell volume, total erythrocytes count, and total leukocyte count. Gross morphological changes include congestion, severe haemorrhage, necrosis, degenerative changes in kidneys, depletion of lymphocyte in spleen, decrease in concentration of mature spermatocyte, and edema in testis. It was notable that kidney was the most affected organ. Conclusion: Mercuric chloride (HgCl caused dose-dependent toxic effects on blood parameters and kidney. [Vet World 2013; 6(8.000: 563-567

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

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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.

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

International Nuclear Information System (INIS)

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

1979-01-01

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

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

Dose-dependent effect of fluoride on clinical and subclinical indices of fluorosis in school going children and its mitigation by supply of safe drinking water for 5 years: an Indian study.

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Khandare, Arjun L; Validandi, Vakdevi; Gourineni, Shankar Rao; Gopalan, Viswanathan; Nagalla, Balakrishna

2018-02-02

Fluorosis is a public health problem in India; to know its prevalence and severity along with its mitigation measures is very important. The present study has been undertaken with the aim to assess the F dose-dependent clinical and subclinical symptoms of fluorosis and reversal of the disease by providing safe drinking water. For this purpose, a cross-sectional study was undertaken in 1934 schoolgoing children, Nalgonda district. Study villages were categorized into control (category I, F = 0.87 mg/L), affected (category II, F = 2.53 mg/L, and category III, F = 3.77 mg/L), and intervention categories (category IV, F = water and urinary fluoride (UF) in different categories. However, there was a significant decrease in the UF levels in the intervention category IV compared to affected group (category III). Fluoride altered the clinical (dental fluorosis and stunting) and subclinical indices (urine and blood) of fluorosis in a dose-dependent manner. In conclusion, the biochemical indices were altered in a dose-dependent manner and intervention with safe drinking water for 5 years in intervention group-mitigated clinical and subclinical symptoms of fluorosis.

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

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).

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

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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

Chloroquine uptake, altered partitioning and the basis of drug resistance: evidence for chloride-dependent ionic regulation.

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Martiney, J A; Ferrer, A S; Cerami, A; Dzekunov, S; Roepe, P

1999-01-01

The biochemical mechanism of chloroquine resistance in Plasmodium falciparum remains unknown. We postulated that chloroquine-resistant strains could alter ion fluxes that then indirectly control drug accumulation within the parasite by affecting pH and/or membrane potential ('altered partitioning mechanism'). Two principal intracellular pH-regulating systems in many cell types are the amiloride-sensitive Na+/H+ exchanger (NHE), and the sodium-independent, stilbene-sensitive Cl-/HCO3- antiporter (AE). We report that under physiological conditions (balanced CO2 and HCO3-) chloroquine uptake and susceptibility are not altered by amiloride analogues. We also do not detect a significant difference in NHE activity between chloroquine-sensitive and chloroquine-resistant strains via single cell photometry methods. AE activity is dependent on the intracellular and extracellular concentrations of Cl- and HCO3- ions. Chloroquine-resistant strains differentially respond to experimental modifications in chloride-dependent homeostasis, including growth, cytoplasmic pH and pH regulation. Chloroquine susceptibility is altered by stilbene DIDS only on chloroquine-resistant strains. Our results suggest that a Cl(-)-dependent system (perhaps AE) has a significant effect on the uptake of chloroquine by the infected erythrocyte, and that alterations of this biophysical parameter may be part of the mechanism of chloroquine resistance in P. falciparum.

Application of accelerated evaluation method of alteration temperature and constant dose rate irradiation on bipolar linear regulator LM317

International Nuclear Information System (INIS)

Deng Wei; Wu Xue; Wang Xin; Zhang Jinxin; Zhang Xiaofu; Zheng Qiwen; Ma Wuying; Lu Wu; Guo Qi; He Chengfa

2014-01-01

With different irradiation methods including high dose rate irradiation, low dose rate irradiation, alteration temperature and constant dose rate irradiation, and US military standard constant high temperature and constant dose rate irradiation, the ionizing radiation responses of bipolar linear regulator LM317 from three different companies were investigated under the operating and zero biases. The results show that compared with constant high temperature and constant dose rate irradiation method, the alteration temperature and constant dose rate irradiation method can not only very rapidly and accurately evaluate the dose rate effect of three bipolar linear regulators, but also well simulate the damage of low dose rate irradiation. Experiment results make the alteration temperature and constant dose rate irradiation method successfully apply to bipolar linear regulator. (authors)

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

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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.

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)

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

Measured dose to ovaries and testes from Hodgkin's fields and determination of genetically significant dose

International Nuclear Information System (INIS)

Niroomand-Rad, A.; Cumberlin, R.

1993-01-01

The purpose of this study was to determine the genetically significant dose from therapeutic radiation exposure with Hodgkin's fields by estimating the doses to ovaries and testes. Phantom measurements were performed to verify estimated doses to ovaries and testes from Hodgkin's fields. Thermoluminescent LiF dosimeters (TLD-100) of 1 x 3 x 3 mm 3 dimensions were embedded in phantoms and exposed to standard mantle and paraaortic fields using Co-60, 4 MV, 6 MV, and 10 MV photon beams. The results show that measured doses to ovaries and testes are about two to five times higher than the corresponding graphically estimated doses for Co-60 and 4 MVX photon beams as depicted in ICRP publication 44. In addition, the measured doses to ovaries and testes are about 30% to 65% lower for 10 MV photon beams than for their corresponding Co-60 photon beams. The genetically significant dose from Hodgkin's treatment (less than 0.01 mSv) adds about 4% to the genetically significant dose contribution to medical procedures and adds less than 1% to the genetically significant dose from all sources. Therefore, the consequence to society is considered to be very small. The consequences for the individual patient are, likewise, small. 28 refs., 3 figs., 5 tabs

Conditional Selection of Genomic Alterations Dictates Cancer Evolution and Oncogenic Dependencies.

Science.gov (United States)

Mina, Marco; Raynaud, Franck; Tavernari, Daniele; Battistello, Elena; Sungalee, Stephanie; Saghafinia, Sadegh; Laessle, Titouan; Sanchez-Vega, Francisco; Schultz, Nikolaus; Oricchio, Elisa; Ciriello, Giovanni

2017-08-14

Cancer evolves through the emergence and selection of molecular alterations. Cancer genome profiling has revealed that specific events are more or less likely to be co-selected, suggesting that the selection of one event depends on the others. However, the nature of these evolutionary dependencies and their impact remain unclear. Here, we designed SELECT, an algorithmic approach to systematically identify evolutionary dependencies from alteration patterns. By analyzing 6,456 genomes from multiple tumor types, we constructed a map of oncogenic dependencies associated with cellular pathways, transcriptional readouts, and therapeutic response. Finally, modeling of cancer evolution shows that alteration dependencies emerge only under conditional selection. These results provide a framework for the design of strategies to predict cancer progression and therapeutic response. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Marijuana’s Dose-Dependent Effects in Daily Marijuana Smokers

OpenAIRE

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

2013-01-01

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

Dose dependence on stochastic radiobiological effect in radiation risk estimation

International Nuclear Information System (INIS)

Komochkov, M.M.

1999-01-01

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

Functional alterations of astrocytes in mental disorders: pharmacological significance as a drug target

Directory of Open Access Journals (Sweden)

Yutaka eKoyama

2015-07-01

Full Text Available Astrocytes play an essential role in supporting brain functions in physiological and pathological states. Modulation of their pathophysiological responses have beneficial actions on nerve tissue injured by brain insults and neurodegenerative diseases, therefore astrocytes are recognized as promising targets for neuroprotective drugs. Recent investigations have identified several astrocytic mechanisms for modulating synaptic transmission and neural plasticity. These include altered expression of transporters for neurotransmitters, release of gliotransmitters and neurotrophic factors, and intercellular communication through gap junctions. Investigation of patients with mental disorders shows morphological and functional alterations in astrocytes. According to these observations, manipulation of astrocytic function by gene mutation and pharmacological tools reproduce mental disorder-like behavior in experimental animals. Some drugs clinically used for mental disorders affect astrocyte function. As experimental evidence shows their role in the pathogenesis of mental disorders, astrocytes have gained much attention as drug targets for mental disorders. In this article, I review functional alterations of astrocytes in several mental disorders including schizophrenia, mood disorder, drug dependence, and neurodevelopmental disorders. The pharmacological significance of astrocytes in mental disorders is also discussed.

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

PA positioning significantly reduces testicular dose during sacroiliac joint radiography

Energy Technology Data Exchange (ETDEWEB)

Mekis, Nejc [Faculty of Health Sciences, University of Ljubljana (Slovenia); Mc Entee, Mark F., E-mail: mark.mcentee@ucd.i [School of Medicine and Medical Science, University College Dublin 4 (Ireland); Stegnar, Peter [Jozef Stefan International Postgraduate School, Ljubljana (Slovenia)

2010-11-15

Radiation dose to the testes in the antero-posterior (AP) and postero-anterior (PA) projection of the sacroiliac joint (SIJ) was measured with and without a scrotal shield. Entrance surface dose, the dose received by the testicles and the dose area product (DAP) was used. DAP measurements revealed the dose received by the phantom in the PA position is 12.6% lower than the AP (p {<=} 0.009) with no statistically significant reduction in image quality (p {<=} 0.483). The dose received by the testes in the PA projection in SIJ imaging is 93.1% lower than the AP projection when not using protection (p {<=} 0.020) and 94.9% lower with protection (p {<=} 0.019). The dose received by the testicles was not changed by the use of a scrotal shield in the AP position (p {<=} 0.559); but was lowered by its use in the PA (p {<=} 0.058). Use of the PA projection in SIJ imaging significantly lowers, the dose received by the testes compared to the AP projection without significant loss of image quality.

Sun-Induced Changes in Stratum Corneum Function Are Gender and Dose Dependent in a Chinese Population

Science.gov (United States)

Liu, Z.; Fluhr, J.W.; Song, S.P.; Sun, Z.; Wang, H.; Shi, Y.J.; Elias, P.M.; Man, M.-Q.

2010-01-01

Previous studies have demonstrated that UVB radiation changes the epidermal permeability barrier and stratum corneum (SC) hydration. It is well known that sun exposure causes erythema, sunburn and melanoma. However, whether daily sun exposure alters SC integrity and epidermal permeability barrier function is largely unknown, especially in Chinese subjects. In the present study, we assess the SC integrity, SC hydration and epidermal permeability barrier function following various doses of sun exposure. A total of 258 subjects (124 males and 134 females) aged 18–50 years were enrolled. A multifunctional skin physiology monitor (Courage & Khazaka MPA5) was used to measure SC hydration and transepidermal water loss (TEWL) on the forearms. In males, basal TEWL was higher with higher doses of sun exposure than with lower doses and control, whereas in females, basal TEWL was higher with lower doses of sun exposure than with higher doses and control. In the group with higher doses of sun exposure, TEWL in females was significantly lower than that in males. The barrier recovery was faster in females than in males in both control and lower-dose groups. In both males and females, barrier recovery was delayed with higher doses of sun exposure. In males, sun exposure did not alter SC hydration, while in females SC hydration was lower with lower doses of sun exposure as compared with control and higher doses of sun exposure. These results demonstrated that sun-induced changes in SC function and SC hydration vary with gender and the extent of sun exposure. PMID:20571289

DNA adducts and liver DNA replication in rats during chronic exposure to N-nitrosodimethylamine (NDMA) and their relationships to the dose-dependence of NDMA hepatocarcinogenesis.

Science.gov (United States)

Souliotis, Vassilis L; Henneman, John R; Reed, Carl D; Chhabra, Saranjit K; Diwan, Bhalchandra A; Anderson, Lucy M; Kyrtopoulos, Soterios A

2002-03-20

Exposure of rats to the hepatocarcinogen N-nitrosodimethylamine (NDMA) (0.2-2.64 ppm in the drinking water) for up to 180 days resulted in rapid accumulation of N7- and O6-methylguanine in liver and white blood cell DNA, maximum adduct levels being reached within 1-7 days, depending on the dose. The levels of both adducts remained constant up to treatment day 28, subsequently declining slowly to about 40% of maximal levels for the liver and 60% for white blood cells by day 180. In order to elucidate the role of DNA replication in NDMA hepatocarcinogenesis, changes in liver cell labeling index (LI) were also measured on treatment days 21, 120 and 180. Although the time- and dose-dependence of the observed effects were complex, a clear trend towards increased rates of hepatocyte LI, as indicated by BrdU incorporation, with increasing NDMA doses was evident, particularly above 1 ppm, a concentration above which NDMA hepatocarcinogenicity is known to increase sharply. In contrast, no increase in Kupffer cell DNA replication was found at any of the doses employed, in accordance with the low susceptibility of these cells to NDMA-induced carcinogenesis. No significant increase in the occurrence of necrotic or apoptotic cells was noted under the treatment conditions employed. These results suggest that, in addition to the accumulation of DNA damage, alterations in hepatocyte DNA replication during the chronic NDMA exposure may influence the dose-dependence of its carcinogenic efficacy.

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

PA positioning significantly reduces testicular dose during sacroiliac joint radiography

International Nuclear Information System (INIS)

Mekis, Nejc; Mc Entee, Mark F.; Stegnar, Peter

2010-01-01

Radiation dose to the testes in the antero-posterior (AP) and postero-anterior (PA) projection of the sacroiliac joint (SIJ) was measured with and without a scrotal shield. Entrance surface dose, the dose received by the testicles and the dose area product (DAP) was used. DAP measurements revealed the dose received by the phantom in the PA position is 12.6% lower than the AP (p ≤ 0.009) with no statistically significant reduction in image quality (p ≤ 0.483). The dose received by the testes in the PA projection in SIJ imaging is 93.1% lower than the AP projection when not using protection (p ≤ 0.020) and 94.9% lower with protection (p ≤ 0.019). The dose received by the testicles was not changed by the use of a scrotal shield in the AP position (p ≤ 0.559); but was lowered by its use in the PA (p ≤ 0.058). Use of the PA projection in SIJ imaging significantly lowers, the dose received by the testes compared to the AP projection without significant loss of image quality.

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....

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

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

International Nuclear Information System (INIS)

Chen, R.; Leung, P.L.

2000-01-01

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

Low Dose Vaporized Cannabis Significantly Improves Neuropathic Pain

Science.gov (United States)

Wilsey, Barth; Marcotte, Thomas D.; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee

2013-01-01

We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling either medium dose (3.53%), low dose (1.29%), or placebo cannabis with the primary outcome being VAS pain intensity. Psychoactive side-effects, and neuropsychological performance were also evaluated. Mixed effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the two active dose groups’ results (p>0.7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo vs. low dose, 2.9 for placebo vs. medium dose, and 25 for medium vs. low dose. As these NNT are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being, for all intents and purposes, as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well-tolerated, and neuropsychological effects were of limited duration and readily reversible within 1–2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. PMID:23237736

Contribution of radiodiagnosis to genetically significant dose

International Nuclear Information System (INIS)

Pele, J.M.; Ouvrard, R.

Surveys were carried out in France on 33,000 X-ray medical examinations. The genetically significant dose to the whole population from roentgenography and fluoroscopy, for typical examinations, should be about 65mrads [fr

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.

Determination of organ doses during radiological examinations and calculation of somatically significant dose

International Nuclear Information System (INIS)

Steiner, H.

1980-01-01

Examples are used to demonstrate that a shift in the point of emphasis is necessary with regard to radiation hazard in medicinal X-ray diagnosis. The parameters employed in this study to calculate somatic dose (SD) and somatically significant dose (SSD) may well be in need of modification; nevertheless the numerical estimation of SSD arrived at here appears to reflect the right order of magnitude for the estimation of somatic risk. The consideration of the threshold dose for somatic injury remains a problem. (orig./MG) [de

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

Prednisolone dose-dependently influences inflammation and coagulation during human endotoxemia

NARCIS (Netherlands)

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

2007-01-01

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

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 changes in renal 1H-/23Na MRI after adjuvant radiochemotherapy for gastric cancer

International Nuclear Information System (INIS)

Haneder, Stefan; Budjan, Johannes Michael; Schoenberg, Stefan Oswald; Konstandin, Simon; Schad, Lothar Rudi; Hofheinz, Ralf Dieter; Gramlich, Veronika; Wenz, Frederik; Lohr, Frank; Boda-Heggemann, Judit

2015-01-01

Combined radiochemotherapy (RCT) for gastric cancer with three-dimensional conformal radiotherapy (3D-CRT) results in ablative doses to the upper left kidney, while image-guided intensity-modulated radiotherapy (IG-IMRT) allows kidney sparing despite improved target coverage. Renal function in long-term gastric cancer survivors was evaluated with 3T functional magnetic resonance imaging (MRI) including diffusion-weighted imaging (DWI) and 23 Na imaging. Five healthy volunteers and 13 patients after radiotherapy were included: 11 x IG-IMRT; 1 x 3D-CRT; 1 x ''positive control'' with stereotactic body radiotherapy (SBRT) of a metastasis between the spleen/left kidney. Radiation doses were documented for the upper/middle/lower kidney subvolumes. Late toxicity was evaluated based on CTC criteria, questionnaire, and creatinine values. Morphological sequences, DWI images, and 23 Na images were acquired using a 1 H/ 23 Na-tuned body-coil before/after intravenous water load (WL). Statistics for [ 23 Na] (concentration) and apparent diffusion coefficient (ADC) values were calculated for upper/middle/lower renal subvolumes. Corticomedullary [ 23 Na] gradients and [ 23 Na] differences after WL were determined. No major morphological alteration was detected in any patient. Minor scars were observed in the cranial subvolume of the left kidney of the 3D-CRT and the whole kidney of the control SBRT patient. All participants presented a corticomedullary [ 23 Na] gradient. After WL, a significant physiological [ 23 Na] gradient decrease (p < 0.001) was observed in all HV and IG-IMRT patients. In the cranial left kidney of the 3D-CRT patient and the positive control SBRT patient, the decrease was nonsignificant (p = 0.01, p = 0.02). ADC values were altered nonsignificantly in all renal subvolumes (all participants). Renal subvolumes with doses ≥ 35 Gy showed a reduced change of the [ 23 Na] gradient after WL (p = 0.043). No participants showed clinical renal

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

affected DEGs associated with cellular signaling and immune response; 70 mGy radiation affected cell cycle regulation and DNA damage repair, cellular energy production; and 280 mGy radiation affected pathways related to cell cycle regulation and DNA repair, mitochondrial dysfunction and immune functions. Twelve genes representative of key pathways found in this study were verified by qPCR. Potential common MoAs of low-dose gamma radiation may include induction of oxidative stress, DNA damage and disturbance of oxidative phosphorylation (OXPHOS). Although common MoAs were proposed, a number of DEGs and pathways were still found to be dose-specific, potentially indicating multiple mechanisms of action (MOAs) of low-dose gamma radiation in fish. In addition, plasma glucose displayed an apparent increase with increasing radiation doses, although the results were not significantly different from the control. These findings suggested that sublethal doses of gamma radiation may cause dose-dependent transcriptional changes in the liver of Atlantic salmon after short-term exposure. The current study predicted multiple MoA for gamma radiation and may aid future impact assessment of environmental radioactivity in fish.

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

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.

Estimation of population doses from diagnostic medical examinations in Japan, 1974. III. Per caput mean marrow dose and leukemia significant dose

Energy Technology Data Exchange (ETDEWEB)

Hashizume, T; Maruyama, T; Kumamoto, Y [National Inst. of Radiological Sciences, Chiba (Japan)

1976-03-01

The mean per capita marrow dose and leukemia-significant dose from radiographic and fluoroscopic examinations in Japan have been estimated based on a 1974 nation wide survey of randomly sampled hospitals and clinics. To determine the mean marrow dose to an individual from a certain exposure of a given type of examination, the active marrow in the whole body was divided into 119 parts for an adult and 103 for a child. Dosimetric points on which the individual marrow doses were determined were set up in the center of each marrow part. The individual marrow doses at the dosimetric points in the beams of practical diagnostic x-rays were calculated on the basis of the exposure data on the patients selected in the nation wide survey, using depth dose curves experimentally determined for diagnostic x-rays. The mean individual marrow dose was averaged over the active marrow by summing, for each dosimetric point, the product of the fraction of active marrow exposed and the individual marrow dose at the dosimetric point. The leukemia significant dose was calculated by adopting a weighting factor that is, a leukemia significant factor. The factor was determined from the shape of the time-incidence curve for radiation-induced leukemia from the Hiroshima A-bomb and from the survival statistics for the average population. The resultant mean per capita marrow dose from radiographic and fluoroscopic examination was 37.0 and 70.0 mrad/person/year, respectively, with a total of 107.05 mrad/person/year. The leukemia significant dose was 32.1 mrad/person/year for radiographic examination and 61.2 mrad/person/year, with a total of 93.3. These values were compared with those of 1960 and 1969.

Radiation protection philosophy alters

International Nuclear Information System (INIS)

Firmin, G.

1977-01-01

Two significant events that have taken place this year in the field of radiation protection are reported. New SI units have been proposed (and effectively adopted), and the ICRP has revised its recommendations. Changes of emphasis in the latest recommendations (ICRP Publication 26) imply an altered radiation protection philosophy, in particular the relation of dose limits to estimates of average risk, an altered view of the critical organ approach and a new attitude to genetic dose to the population. (author)

Compliance to the prescribed dose and overall treatment time in five randomized clinical trials of altered fractionation in radiotherapy for head-and-neck carcinomas

International Nuclear Information System (INIS)

Khalil, Azza A.; Bentzen, Soeren M.; Bernier, Jacques; Saunders, Michele I.; Horiot, Jean-Claude; Bogaert, Walter van den; Cummings, Bernard J.; Dische, Stanley

2003-01-01

Purpose: To investigate compliance to the prescribed dose-fractionation schedule in five randomized controlled trials of altered fractionation in radiotherapy for head-and-neck carcinoma. Methods and Materials: Individual patient data from 2566 patients participating in the European Organization for Research and Treatment of Cancer (EORTC) 22791, EORTC 22811, EORTC 22851, Princess Margaret Hospital (PMH), and continuous hyperfractionated accelerated radiotherapy (CHART) head-and-neck trials were merged in the fractionation IMPACT (Intergroup Merger of Patient data from Altered or Conventional Treatment schedules) study database. The ideal treatment time was defined as the minimum time required to deliver a prescribed schedule. Compliance to the prescribed overall treatment time was quantified as the difference between the actual and the ideal overall time. An overall measure of compliance in an individual patient, the total dose lost (TDL), was calculated as the dose lost due to prolongation of therapy (assuming a D prolif of 0.64 Gy/day) plus the difference between the prescribed and the actual dose given. Results: The time in excess of the ideal ranged up to 97 days (average 3.9 days), and 25% of the patients had delays of 6 days or more. World Health Organization (WHO) performance status and nodal stage had a significant effect on TDL. TDL was significantly higher in the conventional than in the altered arm of the EORTC 22851 and CHART trials. In the PMH trial, TDL was significantly higher in the hyperfractionation than in the conventional arm. Centers participating in the three EORTC trials varied significantly in their compliance. There was a significant improvement in compliance in patients treated more recently. Conclusions: Even in randomized controlled trials, compliance to the prescribed radiation therapy schedule may be relatively poor, especially after conventional fractionation. This affects the interpretation of the outcome of these trials

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

Haemato-biochemical alterations induced by lead acetate toxicity in wistar rats

Directory of Open Access Journals (Sweden)

S. G. Suradkar

Full Text Available An experiment was conducted to study the haemato-biochemical alterations induced by lead acetate toxicity in 48 Wistar rats of either sex, divided uniformly into four different groups. The rats of group I received only deionised water as control while, group II, III and IV were given lead acetate @ 1 PPM, 100 PPM and 1000 PPM, in drinking deionised water respectively for 28 days. In group III and IV dose dependant significant (P<0.05 reductions in TEC, Hb, PCV and TLC were observed. No significant change was observed in neutrophil, eosinophil, basophil and monocyte count in any treatment groups, whereas the lymphocyte count decreased significantly (P<0.05 in group III and IV. A dose dependant significant (P<0.05 increase in AST, ALP, AKP, GGT, BUN and creatinine was experiential while TP and albumin levels were decreased in group III and IV. [Vet World 2009; 2(11.000: 429-431

An experimental study on the alteration of thermal enhancement ratio by combination of split dose hyperthermia irradiation

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Park, Sun Ok; Kim, Hee Seup [Ewha Womens University College of Medicine, Seoul (Korea, Republic of)

1983-06-15

The study was undertaken to evaluate the alteration of thermal enhancement ratio as a function of time intervals between two split dose hyperthermias followed by irradiation. For the experiments, 330 mice were divided into 3 groups; the first, 72 mice were used to evaluate the heat reaction by single dose hyperthermia and heat resistance by split dose hyperthermia, the second, 36 mice were used to evaluate the radiation reaction by irradiation only, and the third, 222 mice were used for TER observation by combination of single dose hyperthermia and irradiation, and TER alteration by combination of split dose hyperthermia and irradiation. For each group the skin reaction score of mouse tail was used for observation and evaluation of the result of heat and irradiation. The results obtained are summarized as follows: 1. The heating time resulting 50% necrosis (ND{sub 5}0) Was 101 minutes in 43 .deg. C and 24 minutes in 45 .deg. C hyperthermia, which indicated that three is reciprocal proportion between temperature and heating time. 2. Development of heat resistance was observed by split dose hyperthermia. 3. The degree of skin reaction by irradiation only was increased proportionally as a function of radiation dose, and calculated radiation dose corresponding to skin score 1.5 (D{sub 1}.5) was 4,137 rads. 4. Obtained thermal enhancement ratio by combination of single dose hyperthermia and irradiation was increased proportionally as a function of heating time. 5. Thermal enhancement ratio was decreased by combination of split dose hyperthermia and irradiation, which was less intense and lasted longer than development of heat resistance. In summary, these studies indicate that the alteration of thermal enhancement ratio has influence on heat resistance by split dose hyperthermia and irradiation.

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

Science.gov (United States)

Elhennawy, Mai Gamal; Lin, Hai-Shu

2018-06-15

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

β-adrenergic receptor-dependent alterations in murine cardiac transcript expression are differentially regulated by gefitinib in vivo.

Directory of Open Access Journals (Sweden)

Jennifer A Talarico

Full Text Available β-adrenergic receptor (βAR-mediated transactivation of epidermal growth factor receptor (EGFR has been shown to promote cardioprotection in a mouse model of heart failure and we recently showed that this mechanism leads to enhanced cell survival in part via regulation of apoptotic transcript expression in isolated primary rat neonatal cardiomyocytes. Thus, we hypothesized that this process could regulate cardiac transcript expression in vivo. To comprehensively assess cardiac transcript alterations in response to acute βAR-dependent EGFR transactivation, we performed whole transcriptome analysis of hearts from C57BL/6 mice given i.p. injections of the βAR agonist isoproterenol in the presence or absence of the EGFR antagonist gefitinib for 1 hour. Total cardiac RNA from each treatment group underwent transcriptome analysis, revealing a substantial number of transcripts regulated by each treatment. Gefitinib alone significantly altered the expression of 405 transcripts, while isoproterenol either alone or in conjunction with gefitinib significantly altered 493 and 698 distinct transcripts, respectively. Further statistical analysis was performed, confirming 473 transcripts whose regulation by isoproterenol were significantly altered by gefitinib (isoproterenol-induced up/downregulation antagonized/promoted by gefinitib, including several known to be involved in the regulation of numerous processes including cell death and survival. Thus, βAR-dependent regulation of cardiac transcript expression in vivo can be modulated by the EGFR antagonist gefitinib.

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

International Nuclear Information System (INIS)

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

1996-01-01

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

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

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

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.

Estimation of population doses from diagnostic medical examinations in Japan, 1974. II. Estimation of genetically significant dose

Energy Technology Data Exchange (ETDEWEB)

Hashizume, T; Maruyama, T; Kumamoto, Y [National Inst. of Radiological Sciences, Chiba (Japan)

1976-03-01

The genetically significant dose from radiographic and fluoroscopic examination in Japan has been estimated based on a 1974 nation wide survey of randomly sampled hospitals and clinics. The gonad dose during x-ray diagnosis was determined with an ionization chamber placed at the positions of ovary and testis in a Rando phantom. The instrumented phantom was irradiated with medical diagnostic x-rays on the basis of the exposure data on the patients selected in the nation wide survey. In the calculation of the genetically significant dose, the child expectancy of the patients that undergo each particular type of examination was assumed to be same as that of the general population. The resultant genetically significant dose was 11.1 and 5.43 mrad per person per year for radiography and fluoroscopy, respectively. These values were compared with those of 1960 and 1969. Though the number of examinations per year shows a yearly increase, the genetically significant dose is gradually on the decrease. This may be due to technical improvements in medical radiological practices.

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.

Ionizing radiation: down regulation of 'atm' by 2 Deoxy-D-Glucose: a dose and time dependent study

International Nuclear Information System (INIS)

Lahiri, S.S.; Saxena, N.; Hambarde, S.

2014-01-01

Exposure to Ionizing Radiation (IR) cause cell death, but it also help in radio-sensitization of cancer cells, by causing oxidative stress and DNA damage, primarily by double strand breaks. Ataxia telangiectasia mutated (atm) gene is involved in DNA double strand breaks, sensory and repair pathways. Therefore, inhibition of its expression, can lead to useful radio-sensitization of cancerous cells. Metabolic inhibitor 2-Deoxy-D-Glucose (2-DG) block glycolysis and modulates protein glycosylation (2-DG). This cause sensitization of cancer cells to radiation, which help in effective reduction in the essential dose of therapeutic ionizing radiation required for the treatment of cancer. The transcription factor Sp-1 involved, is also down-regulated by 2-DG. We have studied the effect of 2-DG at varied concentrations, applied at different pre, simultaneous as well as post irradiation time intervals with 2 Gy, 5 Gy or 10 Gy (lethal dose) of ionizing radiations. Expressions of 'atm' gene in response to the drug and/or IR of different doses were studied. Response was studied at different post irradiation time intervals, in the levels of mRNA, protein and cell survival. It was observed that exposure of human glioma cells (BMG1) to 2 Gy, 5 Gy or 10 Gy of IR alone, had differential and dose dependent effect on 'atm' expression. The 'atm' level was significantly down regulated by 2-DG, in non-irradiated as well as gamma ray irradiated cells. It was observed that BMG1 cells when treated with 2-DG and exposed to irradiation, there was no net significant alteration (normalcy was restored) in the expression level of 'atm'. It was also observed that the extent of down-regulation by pre-treatment with 2-DG, was greater than post-treatment. This work has great significance in the application of clinically relevant low dose radiotherapy for the treatment of cancer. (author)

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

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.

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

Science.gov (United States)

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

2008-09-11

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

High-dose supplementation with natural α-tocopherol does neither alter the pharmacodynamics of atorvastatin nor its phase I metabolism in guinea pigs

International Nuclear Information System (INIS)

Podszun, Maren C.; Grebenstein, Nadine; Hofmann, Ute; Frank, Jan

2013-01-01

It has been hypothesized in the literature that intake of high-dosage vitamin E supplements might alter the expression of cytochrome P 450 enzymes (CYP), particularly CYP3A4, which may lead to adverse nutrient–drug interactions. Because previously published studies reported conflicting findings, we investigated the pharmacodynamics of the lipid-lowering drug atorvastatin (ATV), a CYP3A4 substrate, in response to high-dose α-tocopherol (αT) feeding and determined protein expression and activities of relevant CYP. Groups of ten female Dunkin–Hartley guinea pigs were fed a control (5% fat) or a high-fat control diet (HFC; 21% fat, 0.15% cholesterol) or the HFC diet fortified with αT (250 mg/kg diet), ATV (300 mg/kg diet) or both ATV + αT for 6 weeks. Relative to control, HFC animals had increased serum cholesterol concentrations, which were significantly reduced by ATV. High-dose αT feeding in combination with ATV (ATV + αT), albeit not αT feeding alone (αT), significantly lowered serum cholesterol relative to HFC, but did not alter the cholesterol-lowering activity of the drug compared to the ATV treated guinea pigs. Protein expression of CYP3A4, CYP4F2, CYP20A1 and OATP C was similar in all groups. Accordingly, no differences in plasma concentrations of phase I metabolites of ATV were observed between the ATV and ATV + αT groups. In conclusion, feeding guinea pigs high-doses of αT for 6 weeks did neither alter the hepatic expression of CYP, nor the pharmacodynamics and metabolism of ATV. High-dose αT intake is thus unlikely to change the efficacy of drugs metabolized by CYP enzymes, particularly by CYP3A4. -- Highlights: ► Vitamin E-atorvastatin interactions were studied in hypercholesterolemic guinea pigs. ► High-dose α-tocopherol did not alter the lipid-lowering efficacy of atorvastatin. ► α-Tocopherol did not change the expression of CYP3A4, CYP4F2, CYP20A or OATP C. ► α-Tocopherol did not affect phase I metabolism of atorvastatin. �

High-dose supplementation with natural α-tocopherol does neither alter the pharmacodynamics of atorvastatin nor its phase I metabolism in guinea pigs

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Podszun, Maren C.; Grebenstein, Nadine [Institute of Biological Chemistry and Nutrition, University of Hohenheim, D-70599 Stuttgart (Germany); Hofmann, Ute [Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, D-70376 Stuttgart (Germany); Frank, Jan [Institute of Biological Chemistry and Nutrition, University of Hohenheim, D-70599 Stuttgart (Germany); Department of Nutrition and Food Science, University of Bonn, D-53115 Bonn (Germany)

2013-02-01

It has been hypothesized in the literature that intake of high-dosage vitamin E supplements might alter the expression of cytochrome P{sub 450} enzymes (CYP), particularly CYP3A4, which may lead to adverse nutrient–drug interactions. Because previously published studies reported conflicting findings, we investigated the pharmacodynamics of the lipid-lowering drug atorvastatin (ATV), a CYP3A4 substrate, in response to high-dose α-tocopherol (αT) feeding and determined protein expression and activities of relevant CYP. Groups of ten female Dunkin–Hartley guinea pigs were fed a control (5% fat) or a high-fat control diet (HFC; 21% fat, 0.15% cholesterol) or the HFC diet fortified with αT (250 mg/kg diet), ATV (300 mg/kg diet) or both ATV + αT for 6 weeks. Relative to control, HFC animals had increased serum cholesterol concentrations, which were significantly reduced by ATV. High-dose αT feeding in combination with ATV (ATV + αT), albeit not αT feeding alone (αT), significantly lowered serum cholesterol relative to HFC, but did not alter the cholesterol-lowering activity of the drug compared to the ATV treated guinea pigs. Protein expression of CYP3A4, CYP4F2, CYP20A1 and OATP C was similar in all groups. Accordingly, no differences in plasma concentrations of phase I metabolites of ATV were observed between the ATV and ATV + αT groups. In conclusion, feeding guinea pigs high-doses of αT for 6 weeks did neither alter the hepatic expression of CYP, nor the pharmacodynamics and metabolism of ATV. High-dose αT intake is thus unlikely to change the efficacy of drugs metabolized by CYP enzymes, particularly by CYP3A4. -- Highlights: ► Vitamin E-atorvastatin interactions were studied in hypercholesterolemic guinea pigs. ► High-dose α-tocopherol did not alter the lipid-lowering efficacy of atorvastatin. ► α-Tocopherol did not change the expression of CYP3A4, CYP4F2, CYP20A or OATP C. ► α-Tocopherol did not affect phase I metabolism of atorvastatin

Chronic administration during early adulthood does not alter the hormonally-dependent disruptive effects of delta-9-tetrahydrocannabinol (Δ9-THC) on complex behavior in female rats.

Science.gov (United States)

Winsauer, Peter J; Sutton, Jessie L

2014-02-01

This study examined whether chronic Δ(9)-THC during early adulthood would produce the same hormonally-dependent deficits in learning that are produced by chronic Δ(9)-THC during adolescence. To do this, either sham-operated (intact) or ovariectomized (OVX) female rats received daily saline or 5.6 mg/kg of Δ(9)-THC i.p. for 40 days during early adulthood. Following chronic administration, and a drug-free period to train both a learning and performance task, acute dose-effect curves for Δ(9)-THC (0.56-10 mg/kg) were established in each of the four groups (intact/saline, intact/THC, OVX/saline and OVX/THC). The dependent measures of responding under the learning and performance tasks were the overall response rate and the percentage of errors. Although the history of OVX and chronic Δ(9)-THC in early adulthood did not significantly affect non-drug or baseline behavior under the tasks, acute administration of Δ(9)-THC produced both rate-decreasing and error-increasing effects on learning and performance behavior, and these effects were dependent on their hormone condition. More specifically, both intact groups were more sensitive to the rate-decreasing and error-increasing effects of Δ(9)-THC than the OVX groups irrespective of chronic Δ(9)-THC administration, as there was no significant main effect of chronic treatment and no significant interaction between chronic treatment (saline or Δ(9)-THC) and the dose of Δ(9)-THC administered as an adult. Post mortem examination of 10 brain regions also indicated there were significant differences in agonist-stimulated GTPγS binding across brain regions, but no significant effects of chronic treatment and no significant interaction between the chronic treatment and cannabinoid signaling. Thus, acute Δ(9)-THC produced hormonally-dependent effects on learning and performance behavior, but a period of chronic administration during early adulthood did not alter these effects significantly, which is contrary to what we

Genetically significant dose assessments of occupationally exposed individuals involved in industrial and medical radiographic procedures in certain establishments in Nigeria

International Nuclear Information System (INIS)

Jibiri, N.N.; Oguntade, G. T.

2007-01-01

The main source of radiation doses received by humans from man-made sources of ionizing radiation in medicine and industry comes from X-rays. The genetic risks of ionizing radiation effects on an individual who is occupationally exposed largely depend on the magnitude of the radiation dose received, period of practice, work load and radio logical procedures involved. In this work, using the linear non-thresh old model, we have attempted to assess the level of genetic risk of occupationally exposed individuals in two medical and industrial establishments in Nigeria by estimating their genetically significant dose values. The estimation was based on continuous personnel radiation dose monitoring data for the individuals in each of the establishments over a three year period (1998-2001). The estimated genetically significant dose values in the years considered were 12 mSv for the medical, and 29 mSv for the industrial personnel. Appropriate radiation protection precautions should be taken by the personnel to adhere to standard operational practices in order to minimize the genetically significant dose resulting from radio logical practices

High-dose folic acid supplementation alters the human sperm methylome and is influenced by the MTHFR C677T polymorphism.

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Aarabi, Mahmoud; San Gabriel, Maria C; Chan, Donovan; Behan, Nathalie A; Caron, Maxime; Pastinen, Tomi; Bourque, Guillaume; MacFarlane, Amanda J; Zini, Armand; Trasler, Jacquetta

2015-11-15

Dietary folate is a major source of methyl groups required for DNA methylation, an epigenetic modification that is actively maintained and remodeled during spermatogenesis. While high-dose folic acid supplementation (up to 10 times the daily recommended dose) has been shown to improve sperm parameters in infertile men, the effects of supplementation on the sperm epigenome are unknown. To assess the impact of 6 months of high-dose folic acid supplementation on the sperm epigenome, we studied 30 men with idiopathic infertility. Blood folate concentrations increased significantly after supplementation with no significant improvements in sperm parameters. Methylation levels of the differentially methylated regions of several imprinted loci (H19, DLK1/GTL2, MEST, SNRPN, PLAGL1, KCNQ1OT1) were normal both before and after supplementation. Reduced representation bisulfite sequencing (RRBS) revealed a significant global loss of methylation across different regions of the sperm genome. The most marked loss of DNA methylation was found in sperm from patients homozygous for the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, a common polymorphism in a key enzyme required for folate metabolism. RRBS analysis also showed that most of the differentially methylated tiles were located in DNA repeats, low CpG-density and intergenic regions. Ingenuity Pathway Analysis revealed that methylation of promoter regions was altered in several genes involved in cancer and neurobehavioral disorders including CBFA2T3, PTPN6, COL18A1, ALDH2, UBE4B, ERBB2, GABRB3, CNTNAP4 and NIPA1. Our data reveal alterations of the human sperm epigenome associated with high-dose folic acid supplementation, effects that were exacerbated by a common polymorphism in MTHFR. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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.

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.

Glycation alters ligand binding, enzymatic, and pharmacological properties of human albumin.

Science.gov (United States)

Baraka-Vidot, Jennifer; Planesse, Cynthia; Meilhac, Olivier; Militello, Valeria; van den Elsen, Jean; Bourdon, Emmanuel; Rondeau, Philippe

2015-05-19

Albumin, the major circulating protein in blood plasma, can be subjected to an increased level of glycation in a diabetic context. Albumin exerts crucial pharmacological activities through its drug binding capacity, i.e., ketoprofen, and via its esterase-like activity, allowing the conversion of prodrugs into active drugs. In this study, the impact of the glucose-mediated glycation on the pharmacological and biochemical properties of human albumin was investigated. Aggregation product levels and the redox state were quantified to assess the impact of glycation-mediated changes on the structural properties of albumin. Glucose-mediated changes in ketoprofen binding properties and esterase-like activity were evaluated using fluorescence spectroscopy and p-nitrophenyl acetate hydrolysis assays, respectively. With the exception of oxidative parameters, significant dose-dependent alterations in biochemical and functional properties of in vitro glycated albumin were observed. We also found that the dose-dependent increase in levels of glycation and protein aggregation and average molecular mass changes correlated with a gradual decrease in the affinity of albumin for ketoprofen and its esterase-like property. In parallel, significant alterations in both pharmacological properties were also evidenced in albumin purified from diabetic patients. Partial least-squares regression analyses established a significant correlation between glycation-mediated changes in biochemical and pharmacological properties of albumin, highlighting the important role for glycation in the variability of the drug response in a diabetic situation.

Prenatal IV Cocaine: Alterations in Auditory Information Processing

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Charles F. Mactutus

2011-06-01

Full Text Available One clue regarding the basis of cocaine-induced deficits in attentional processing is provided by the clinical findings of changes in the infants’ startle response; observations buttressed by neurophysiological evidence of alterations in brainstem transmission time. Using the IV route of administration and doses that mimic the peak arterial levels of cocaine use in humans, the present study examined the effects of prenatal cocaine on auditory information processing via tests of the acoustic startle response (ASR, habituation, and prepulse inhibition (PPI in the offspring. Nulliparous Long-Evans female rats, implanted with an IV access port prior to breeding, were administered saline, 0.5, 1.0, or 3.0 mg/kg/injection of cocaine HCL (COC from gestation day (GD8-20 (1x/day-GD8-14, 2x/day-GD15-20. COC had no significant effects on maternal/litter parameters or growth of the offspring. At 18-20 days of age, one male and one female, randomly selected from each litter displayed an increased ASR (>30% for males at 1.0 mg/kg and >30% for females at 3.0 mg/kg. When reassessed in adulthood (D90-100, a linear dose-response increase was noted on response amplitude. At both test ages, within-session habituation was retarded by prenatal cocaine treatment. Testing the females in diestrus vs. estrus did not alter the results. Prenatal cocaine altered the PPI response function across interstimulus interval (ISI and induced significant sex-dependent changes in response latency. Idazoxan, an alpha2-adrenergic receptor antagonist, significantly enhanced the ASR, but less enhancement was noted with increasing doses of prenatal cocaine. Thus, in utero exposure to cocaine, when delivered via a protocol designed to capture prominent features of recreational usage, causes persistent, if not permanent, alterations in auditory information processing, and suggests dysfunction of the central noradrenergic circuitry modulating, if not mediating, these responses.

Molecular alterations in childhood thyroid cancer after Chernobyl accident and low-dose radiation risk

International Nuclear Information System (INIS)

Suzuki, Keiji; Mitsutake, Norisato; Yamashita, Shunichi

2012-01-01

The linear no-threshold (LNT) model of radiation carcinogenesis has been used for evaluating the risk from radiation exposure. While the epidemiological studies have supported the LNT model at doses above 100 mGy, more uncertainties are still existed in the LNT model at low doses below 100 mGy. Thus, it is urged to clarify the molecular mechanisms underlying radiation carcinogenesis. After the Chernobyl accident in 1986, significant amount of childhood thyroid cancer has emerged in the children living in the contaminated area. As the incidence of sporadic childhood thyroid cancer is very low, it is quite evident that those cancer cases have been induced by radiation exposure caused mainly by the intake of contaminated foods, such as milk. Because genetic alterations in childhood thyroid cancers have extensively been studied, it should provide a unique chance to understand the molecular mechanisms of radiation carcinogenesis. In a current review, molecular signatures obtained from the molecular studies of childhood thyroid cancer after Chernobyl accident have been overviewed, and new roles of radiation exposure in thyroid carcinogenesis will be discussed. (author)

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

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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

Hepatic lipid profiling of deer mice fed ethanol using 1H and 31P NMR spectroscopy: A dose-dependent subchronic study

International Nuclear Information System (INIS)

Fernando, Harshica; Bhopale, Kamlesh K.; Boor, Paul J.; Ansari, G.A. Shakeel; Kaphalia, Bhupendra S.

2012-01-01

Chronic alcohol abuse is a 2nd major cause of liver disease resulting in significant morbidity and mortality. Alcoholic liver disease (ALD) is characterized by a wide spectrum of pathologies starting from fat accumulation (steatosis) in early reversible stage to inflammation with or without fibrosis and cirrhosis in later irreversible stages. Previously, we reported significant steatosis in the livers of hepatic alcohol dehydrogenase (ADH)-deficient (ADH − ) vs. hepatic ADH-normal (ADH + ) deer mice fed 4% ethanol daily for 2 months [Bhopale et al., 2006, Alcohol 39, 179–188]. However, ADH − deer mice fed 4% ethanol also showed a significant mortality. Therefore, a dose-dependent study was conducted to understand the mechanism and identify lipid(s) involved in the development of ethanol-induced fatty liver. ADH − and ADH + deer mice fed 1, 2 or 3.5% ethanol daily for 2 months and fatty infiltration in the livers were evaluated by histology and by measuring dry weights of extracted lipids. Lipid metabolomic changes in extracted lipids were determined by proton ( 1 H) and 31 phosphorus ( 31 P) nuclear magnetic resonance (NMR) spectroscopy. The NMR data was analyzed by hierarchical clustering (HC) and principle component analysis (PCA) for pattern recognition. Extensive vacuolization by histology and significantly increased dry weights of total lipids found only in the livers of ADH − deer mice fed 3.5% ethanol vs. pair-fed controls suggest a dose-dependent formation of fatty liver in ADH − deer mouse model. Analysis of NMR data of ADH − deer mice fed 3.5% ethanol vs. pair-fed controls shows increases for total cholesterol, esterified cholesterol, fatty acid methyl esters (FAMEs), triacylglycerides and unsaturation, and decreases for free cholesterol, phospholipids and allylic and diallylic protons. Certain classes of neutral lipids (cholesterol esters, fatty acyl chain (-COCH 2 -) and FAMEs) were also mildly increased in ADH − deer mice fed 1 or 2

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)

[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.

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.

Frequency-Dependent Altered Functional Connections of Default Mode Network in Alzheimer’s Disease

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Youjun Li

2017-08-01

Full Text Available Alzheimer’s disease (AD is a neurodegenerative disorder associated with the progressive dysfunction of cognitive ability. Previous research has indicated that the default mode network (DMN is closely related to cognition and is impaired in Alzheimer’s disease. Because recent studies have shown that different frequency bands represent specific physiological functions, DMN functional connectivity studies of the different frequency bands based on resting state fMRI (RS-fMRI data may provide new insight into AD pathophysiology. In this study, we explored the functional connectivity based on well-defined DMN regions of interest (ROIs from the five frequency bands: slow-5 (0.01–0.027 Hz, slow-4 (0.027–0.073 Hz, slow-3 (0.073–0.198 Hz, slow-2 (0.198–0.25 Hzs and standard low-frequency oscillations (LFO (0.01–0.08 Hz. We found that the altered functional connectivity patterns are mainly in the frequency band of slow-5 and slow-4 and that the decreased connections are long distance, but some relatively short connections are increased. In addition, the altered functional connections of the DMN in AD are frequency dependent and differ between the slow-5 and slow-4 bands. Mini-Mental State Examination scores were significantly correlated with the altered functional connectivity patterns in the slow-5 and slow-4 bands. These results indicate that frequency-dependent functional connectivity changes might provide potential biomarkers for AD pathophysiology.

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

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E. L. Artanova

2011-01-01

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

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)

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

DEFF Research Database (Denmark)

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

1995-01-01

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

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)

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.

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.

Multiple toxic doses of methamphetamine alter neurotensin concentrations in various region of the rat brain

International Nuclear Information System (INIS)

Hanson, G.R.; Merchant, K.; Gibb, J.W.; Letter, A.A.

1986-01-01

The authors have previously reported that multiple high doses of methamphetamine (METH) alter neuronal monoamine metabolism and release. Recently, Hokfelt et al. showed that neurotensin, a tridecapeptide, has neurotransmitter properties which may be involved with DA neuronal activity. In the present study they investigated the possible effects of METH on the CNS neurotensin system. Five doses of METH (15 mg/kg) were administered every 6 h; control and treated rats were sacrificed 18 h after the last dose and concentrations of neurotensin-like immuno-reactivity (NTLI) were measured by radioimmunoassay. NTLI was elevated 200-300% in the nucleus accumbens, neostriatum, and substantia nigra; 30-40% increases in NTLI were measured in the hippocampus and hypothalamus. No change was observed in amygdala, A-10 or periaqueductal gray. In contrast to the above measured areas, the frontal lobe and olfactory bulb showed decreases of 25-35%. These findings demonstrate that METH treatment alters the activities of several CNS neurotensin systems, possibly due to the influence of this drug on DA pathways. The variability in the type and magnitude of these responses suggests that DA and neurotensin systems interact by more than one mechanism

Estimation of the genetically significant dose resulting from diagnostic radiology

International Nuclear Information System (INIS)

Angerstein, W.

1978-01-01

Based on the average gonad dose received per examination or per film and on the frequency of x-ray examinations (36 million per annum), the mean annual gonad dose to individuals in the GDR has been determined to be 33 mR. Considering different age groups of patients and the fact that the gonad dose to children is often significantly reduced in comparison to adults, estimates of the genetically significant dose (GSD) range from 7 to 19 mR per annum. Examinations of women have accounted for about 66 per cent of the GSD. The highest contribution to the GSD result from examinations of the following organs: kidneys, colon, bile duct (only in women), lumbar spine, pelois, hips, and proximal femur. Despite their high frequency, examinations of the stomach account for only about 3 per cent of the GSD. All thorax examinations (nearly 10,000,000 per annum) contribute less than 0.5 per cent, and the most frequent x-ray examinations of the skeletal system, skull, cervical spine, and teeth account for less than 3 per cent. The GSD values obtained are comparable with those from countries such as India, Japan, Netherlands, USSR, and USA. (author)

Assessment of genetically significant doses to the Sofia population from natural gamma background

International Nuclear Information System (INIS)

Vasilev, G.; Khristova, M.

1977-01-01

Genetically significant dose to the population of Sofia city was assessed within a program covering larger urban communities in the country. Measurements were made of gamma background exposure rates in the gonadal region. Gonad doses were estimated using a screening factor of 0.73. Based on statistical data for total number of inhabitants and number of people of reproductive age, and on the mean annual gonad doses derived, calculations were made of genetically significant dose to the Sofia population. Base-line data were thus provided for an assessment of extra radiation dose resulting from occupational radiation exposure. (author)

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

International Nuclear Information System (INIS)

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

1991-01-01

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

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

Drug- not carrier-dependent haematological and biochemical changes in a repeated dose study of cyclosporine encapsulated polyester nano- and micro-particles: Size does not matter

International Nuclear Information System (INIS)

Venkatpurwar, V.P.; Rhodes, S.; Oien, K.A.; Elliott, M.A.; Tekwe, C.D.; Jørgensen, H.G.; Kumar, M.N.V. Ravi

2015-01-01

Highlights: • The particulate delivery allows an increase in dose range without accrual of toxicities. • The altered haematological and biochemical changes are drug, but not particle dependent. • PLGA nano/microparticles are safe on subacute peroral dosing over 28 days. • Nano-toxicology, drug needs to be considered. - Abstract: Biodegradable nanoparticles are being considered more often as drug carriers to address pharmacokinetic/pharmacodynamic issues, yet nano-product safety has not been systematically proven. In this study, haematological, biochemical and histological parameters were examined on 28 day daily dosing of rats with nano- or micro-particle encapsulated cyclosporine (CsA) to confirm if any changes observed were drug or carrier dependent. CsA encapsulated poly(lactide-co-glycolide) [PLGA] nano- (nCsA) and micro-particles (mCsA) were prepared by emulsion techniques. CsA (15, 30, 45 mg/kg) were administered by oral gavage to Sprague Dawley (SD) rats over 28 days. Haematological and biochemical metrics were followed with tissue histology performed on sacrifice. Whether presented as nCsA or mCsA, 45 mg/kg dose caused significant loss of body weight and lowered food consumption compared to untreated control. Across the doses, both nCsA and mCsA produce significant decreases in lymphocyte numbers compared to controls, commensurate with the proprietary product, Neoral ® 15. Dosing with nCsA showed higher serum drug levels than mCsA presumably owing to the smaller particle size facilitating absorption. The treatment had no noticeable effects on inflammatory/oxidative stress markers or antioxidant enzyme levels, except an increase in ceruloplasmin (CP) levels for high dose nCsA/mCsA group. Further, only subtle, sub-lethal changes were observed in histology of nCsA/mCsA treated rat organs. Blank (drug-free) particles did not induce changes in the parameters studied. Therefore, it is extremely important that the encapsulated drug in the nano-products is

Age-dependent effective doses for radionuclides uniformly distributed in air

International Nuclear Information System (INIS)

Hung, Tran Van

2014-01-01

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

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

Directory of Open Access Journals (Sweden)

Soni Sachin

2008-01-01

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

Ozone dosing alters the biological potential and therapeutic outcomes of plasma rich in growth factors.

Science.gov (United States)

Anitua, E; Zalduendo, M M; Troya, M; Orive, G

2015-04-01

Until now, ozone has been used in a rather empirical way. This in-vitro study investigates, for the first time, whether different ozone treatments of plasma rich in growth factors (PRGF) alter the biological properties and outcomes of this autologous platelet-rich plasma. Human plasma rich in growth factors was treated with ozone using one of the following protocols: a continuous-flow method; or a syringe method in which constant volumes of ozone and PRGF were mixed. In both cases, ozone was added before, during and after the addition of calcium chloride. Three ozone concentrations, of the therapeutic range 20, 40 and 80 μg/mL, were tested. Fibrin clot properties, growth factor content and the proliferative effect on primary osteoblasts and gingival fibroblasts were evaluated. Ozone treatment of PRGF using the continuous flow protocol impaired formation of the fibrin scaffold, drastically reduced the levels of growth factors and significantly decreased the proliferative potential of PRGF on primary osteoblasts and gingival fibroblasts. In contrast, treatment of PRGF with ozone using the syringe method, before, during and after the coagulation process, did not alter the biological outcomes of the autologous therapy. These findings suggest that ozone dose and the way that ozone combines with PRGF may alter the biological potential and therapeutic outcomes of PRGF. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

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

2003-03-01

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

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

International Nuclear Information System (INIS)

Hung, Tran Van

2013-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2013-07-15

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

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

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.

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.

The levels of triglyceride and total cholesterol in methamphetamine dependence.

Science.gov (United States)

Zhang, Meijuan; Lv, Dezhao; Zhou, Wu; Ji, Lili; Zhou, Beibei; Chen, Han; Gu, Yingying; Zhao, Jiyun; He, Jincai

2017-04-01

The serum triglyceride (TG) and total cholesterol (TC) levels have been reported altered in the traditional drug-dependence (such as marijuana and heroin). However, studies assessing the relationships among serum TC, TG, and methamphetamine (MA)-dependence have not been described well. In this study, our aim is to explore the serum TG and TC levels in large sample of MA-dependent patients. A retrospective study was conducted in 938 MA-dependent patients who were recruited between February 2, 2008 and March 11, 2013, with social characteristics and drug-dependence history (duration of MA use, routes of drug administration, and daily dose were collected). Then, the serum levels of TC, TG, glucose (GLU), body mass index (BMI), and blood pressure were measured among the participants. Meanwhile, 985 age- and gender-matched healthy people in the physical examination center were selected as control group. Compared with the control group, significant decreases of TC, TG, GLU, and BMI were observed in MA-dependent patients (P < 0.05). Besides, we found that the daily dose of MA use was associated with TC (β = -0.079, P = 0.015) and the duration of MA use was independently related to BMI (β = -0.071, P = 0.031). This study demonstrated that the levels of TC, TG, GLU, and BMI factors altered in the MA-dependent patients. In addition, there is a negative association between MA dependence and TC and BMI.

Imprinted genes and transpositions: epigenomic targets for low dose radiation effects. Final report

International Nuclear Information System (INIS)

Jirtle, Randy L.

2012-01-01

The overall hypothesis of this grant application is that low dose ionizing radiation (LDIR) elicits adaptive responses in part by causing heritable DNA methylation changes in the epigenome. This novel postulate was tested by determining if the level of DNA methylation at the Agouti viable yellow (A vy ) metastable locus is altered, in a dose-dependent manner, by low dose radiation exposure ( vy locus in a sex-specific manner (p=0.004). Average DNA methylation was significantly increased in male offspring exposed to doses between 0.7 cGy and 7.6 cGy with maximum effects at 1.4 cGy and 3.0 cGy (p<0.01). Offspring coat color was concomitantly shifted towards pseudoagouti (p<0.01). Maternal dietary antioxidant supplementation mitigated both the DNA methylation changes and coat color shift in the irradiated offspring (p<0.05). Thus, LDIR exposure during gestation elicits epigenetic alterations that lead to positive adaptive phenotypic changes that are negated with antioxidants, indicating they are mediated in part by oxidative stress. These findings provide evidence that in the isogenic Avy mouse model epigenetic alterations resulting from LDIR play a role in radiation hormesis, bringing into question the assumption that every dose of radiation is harmful. Our findings not only have significant implications concerning the mechanism of hormesis, but they also emphasize the potential importance of this phenomenon in determining human risk at low radiation doses. Since the epigenetic regulation of genes varies markedly between species, the effect of LDIR on other epigenetically labile genes (e.g. imprinted genes) in animals and humans needs to be defined

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

MRI morphologic alterations after liver SBRT. Direct dose correlation with intermodal matching

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Boda-Heggemann, Judit; Jahnke, Anika; Jahnke, Lennart; Vogel, Lena; Simeonova-Chergou, Anna O.; Herskind, Carsten; Wenz, Frederik; Lohr, Frank [University of Heidelberg, Department of Radiation Oncology, University Medical Center Mannheim, Mannheim (Germany); Attenberger, Ulrike; Budjan, Johannes [University of Heidelberg, Department of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Mannheim (Germany)

2016-09-15

CT morphologic and histopathologic alterations have been reported after SBRT. We analyzed the correlation of MRI morphologic alterations with radiation doses to assess the potential for MRI-based dose-effect correlation in healthy liver tissue. MRI data of 24 patients with liver metastases 7±3 weeks after image-guided SBRT in deep-inspiration breath-hold were retrospectively analyzed. MRI images were intermodally matched to the planning CT and corresponding dose distribution. Absolute doses were converted to EQD{sub 2,α/β=x} with α/β values of 2, 3 for healthy liver tissue, 8 Gy for modelled predamaged liver tissue and 10 Gy for tumor tissue. A central nonenhancing area was observed within the isodose lines of nominally 48.2 ± 15.2 Gy, EQD{sub 2Gy/α/β=10} 92.5 ± 27.7 Gy. Contrast-enhancement around the central nonenhancing area was observed within the isodose lines of nominally 46.9 ± 15.3 Gy, EQD{sub 2Gy/α/β=10} 90.5 ± 28.3 Gy. Outside the high-dose volume, in the beam path, characteristic sharply defined, nonblurred MRI morphologic alterations were observed that corresponded with the following isodose lines: T1-intensity changes occurred at isodose lines of nominally 21.9 ± 6.7 Gy (EQD{sub 2,α/β=2} 42.5 ± 8.7 Gy, EQD{sub 2,α/β=3} 38.5 ± 7.6 Gy, EQD{sub 2,α/β=8} 30.2 ±6.3 Gy). T2-hyper/hypointensity was observed within isodose lines of nominally 22.4 ± 6.6 Gy (EQD{sub 2,α/β=2} 42.7 ± 8.1 Gy, EQD{sub 2,α/β=3} 38.7 ± 7 Gy; EQD{sub 2,α/β=8} 30.5 ± 5.9 Gy). Using deformable matching, direct spatial/dosimetric correlation of SBRT-induced changes in liver tissue was possible. In the PTV high-dose region, a central nonenhancing area and peripheral contrast medium accumulation was observed. Beam path doses of 38-42 Gy (EQD{sub 2,α/β=2-3}) induce characteristic MRI morphologic alterations. (orig.) [German] CT-morphologische Veraenderungen nach SBRT sind beschrieben und korrelieren mit histopathologischen Veraenderungen. Ziel war es, MRT

Gestational treatment with methylazoxymethanol (MAM) that disrupts hippocampal-dependent memory does not alter behavioural response to cocaine.

Science.gov (United States)

Featherstone, Robert E; Burton, Christie L; Coppa-Hopman, Romina; Rizos, Zoë; Sinyard, Judy; Kapur, Shitij; Fletcher, Paul J

2009-10-01

Schizophrenia is associated with increased rates of substance abuse that are thought to be the result of changes in cortical and mesolimbic dopamine activity. Previous work has shown that gestational methylazoxymethanol acetate (MAM) treatment induces increased mesolimbic dopamine activity when given around the time of embryonic day 17 (ED17), suggesting that MAM treatment may model some aspects of schizophrenia. Given that increased dopaminergic activity facilitates aspects of drug self-administration and reinstatement of drug seeking, the current experiments sought to assess cocaine self-administration in MAM treated animals. Experiment 1 examined the acquisition of cocaine self-administration in ED17 MAM and saline treated rats using a sub-threshold dose of cocaine. In experiment 2 ED17 MAM and saline treated animals were trained to self-administer cocaine and were then assessed under varying doses of cocaine (dose-response), followed by extinction and drug-induced reinstatement of responding. A subset of these animals was trained on a win-shift radial maze task, designed to detect impairments in hippocampal-dependent memory. In experiment 3, MAM and saline treated animals were assessed on a progressive ratio schedule of cocaine delivery. Finally, in experiment 4 MAM and saline treated animals were assessed on cocaine-induced locomotor activity across a range of doses of cocaine. MAM treatment disrupted performance of the win-shift task but did not alter cocaine self-administration or cocaine-induced locomotion. Implications of these results for the MAM model of schizophrenia are discussed.

He-Ne laser irradiation affects proliferation of cultured rat Schwann cells in a dose-dependent manner

International Nuclear Information System (INIS)

Breugel, H.H.F.I. van; Bar, P.R.

1993-01-01

Schwann cell proliferation is considered an essential part of Wallerian degeneration after nerve damage. Laminin, an important component of the extracellular matrix and produced by Schwann cells, provides a preferred substrate for outgrowing axons. To study whether low energy (He-Ne) laser irradiation may exert a positive effect on nerve regeneration through an effect on Schwann cells, its effect was evaluated in vitro. Schwann cells were isolated from sciatic nerves of 4-5-day old Wistar rats and cultures on 96-multiwell plates. The cells were irradiated by a He-Ne laser beam. At three consecutive days, starting either at day 5 or day 8, cells were irradiated each day for 0.5, 1, 2, 5 or 10 min. Both cell number and laminin production were determined for each irradiation condition within one experiment. Schwann cells that were irradiated from day 8 on were hardly affected by laser irradiation. However, the proliferation of cells that were irradiated starting on day 5 was significantly increased after 1, 2 and 5 min of daily irradiation, compared to non-irradiated control cultures. The lamin production per cell of these Schwann cells was not significantly altered. From these results we conclude that He-Ne laser irradiation can modulate proliferation of rat Schwann cells in vitro in a dose-dependent manner. (Author)

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

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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.

Outcome dependency alters the neural substrates of impression formation

Science.gov (United States)

Ames, Daniel L.; Fiske, Susan T.

2015-01-01

How do people maintain consistent impressions of other people when other people are often inconsistent? The present research addresses this question by combining recent neuroscientific insights with ecologically meaningful behavioral methods. Participants formed impressions of real people whom they met in a personally involving situation. fMRI and supporting behavioral data revealed that outcome dependency (i.e., depending on another person for a desired outcome) alters previously identified neural dynamics of impression formation. Consistent with past research, a functional localizer identified a region of dorsomedial PFC previously linked to social impression formation. In the main task, this ROI revealed the predicted patterns of activity across outcome dependency conditions: greater BOLD response when information confirmed (vs. violated) social expectations if participants were outcome-independent and the reverse pattern if participants were outcome-dependent. We suggest that, although social perceivers often discount expectancy-disconfirming information as noise, being dependent on another person for a desired outcome focuses impression-formation processing on the most diagnostic information, rather than on the most tractable information. PMID:23850465

Theoretical cell alteration model in the context of carcinogenesis

International Nuclear Information System (INIS)

Walsh, P.J.

1976-01-01

A model incorporating cell survival and alteration is used to discuss the general nature of cellular response to a toxic agent. Cell division and repair are discussed as regards their influence on dose-response relationships to bone-seeking radionuclides. The application of the model in its present form to specific biologic end points depends on the assumption that such end points are the result of some initial alteration

Transplantation Dose Alters the Differentiation Program of Hematopoietic Stem Cells.

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Brewer, Casey; Chu, Elizabeth; Chin, Mike; Lu, Rong

2016-05-24

Hematopoietic stem cell (HSC) transplantation is the most prevalent stem cell therapy, but it remains a risky procedure. To improve this treatment, it is important to understand how transplanted stem cells rebuild the blood and immune systems and how this process is impacted by transplantation variables such as the HSC dose. Here, we find that, in the long term following transplantation, 70%-80% of donor-HSC-derived clones do not produce all measured blood cell types. High HSC doses lead to more clones that exhibit balanced lymphocyte production, whereas low doses produce more T-cell-specialized clones. High HSC doses also produce significantly higher proportions of early-differentiating clones compared to low doses. These complex differentiation behaviors uncover the clonal-level regeneration dynamics of hematopoietic regeneration and suggest that transplantation dose can be exploited to improve stem cell therapy. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

A capacitively coupled dose-rate-dependent transient upset mechanism in a bipolar memory

International Nuclear Information System (INIS)

Turfler, R.M.; Pease, R.L.; Dinger, G.; Armstrong, B.

1992-01-01

This paper reports on a pattern sensitivity that was observed in the threshold dose rate response of a bipolar 16K PROM for radiation pulse widths of 20-100 ns. For the worst case pattern, the upset threshold was a factor of three lower than for the commonly used checkerboard pattern. The mechanism for this pattern sensitivity was found to be a capacitively coupled voltage transient on a sensitive node which caused a low-to-high transition at the output. A design fix was implemented to significantly alter the ratio of the two parasitic capacitances in a capacitive divider which reduced the amplitude of the voltage transient at the sensitive node. It was demonstrated that in the redesign, the pattern sensitivity was eliminated

Dose-dependent efficacy of the Vitex agnus castus extract Ze 440 in patients suffering from premenstrual syndrome.

Science.gov (United States)

Schellenberg, Ruediger; Zimmermann, Christian; Drewe, Jürgen; Hoexter, Godehard; Zahner, Catherine

2012-11-15

Preparations of Vitex agnus castus L. (VAC) have been shown to be effective to treat irregular menstrual cycles, cyclical mastalgia and symptoms of the premenstrual syndrome (PMS). However, the dose-effect relationship for the treatment of PMS has not yet been established. This study aimed to investigate the clinical effects of three different doses of the VAC extract Ze 440 in comparison to placebo in patients suffering from PMS. In a multicenter, double-blind, placebo-controlled, parallel-group study, 162 female patients with PMS (18-45 years) were randomized to either placebo or different doses of Ze 440 (8, 20 and 30 mg) over three menstrual cycles. PMS symptoms' severity was assessed by patients using visual analog scales (VAS) for the symptoms irritability, mood alteration, anger, headache, bloating and breast fullness. Each of the treatments was well tolerated. Improvement in the total symptom score (TSS) in the 20mg group was significantly higher than in the placebo and 8 mg treatment group. The higher dose of 30 mg, on the other hand, did not significantly decrease symptom severity compared to the 20mg treatment, providing a rational for the usage of 20mg. Corresponding results were observed with the single PMS symptom scores. This study demonstrated that the VAC extract Ze 440 was effective in relieving symptoms of PMS, when applied in a dose of 20mg. Therefore, for patients suffering from PMS, 20mg Ze 440 should be the preferred daily dose. Copyright © 2012 Elsevier GmbH. All rights reserved.

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

Human papillomavirus E6 and E7 oncoproteins alter cell cycle progression but not radiosensitivity of carcinoma cells treated with low-dose-rate radiation

International Nuclear Information System (INIS)

DeWeese, Theodore L.; Walsh, Jonathan C.; Dillehay, Larry E.; Kessis, Theodore D.; Hedrick, Lora; Cho, Kathleen R.; Nelson, William G.

1997-01-01

Purpose: Low-dose-rate radiation therapy has been widely used in the treatment of urogenital malignancies. When continuously exposed to low-dose-rate ionizing radiation, target cancer cells typically exhibit abnormalities in replicative cell-cycle progression. Cancer cells that arrest in the G2 phase of the cell cycle when irradiated may become exquisitely sensitive to killing by further low-dose-rate radiation treatment. Oncogenic human papillomaviruses (HPVs), which play a major role in the pathogenesis of uterine cervix cancers and other urogenital cancers, encode E6 and E7 transforming proteins known to abrogate a p53-dependent G1 cell-cycle checkpoint activated by conventional acute-dose radiation exposure. This study examined whether expression of HPV E6 and E7 oncoproteins by cancer cells alters the cell-cycle redistribution patterns accompanying low-dose-rate radiation treatment, and whether such alterations in cell-cycle redistribution affect cancer cell killing. Methods and Materials: RKO carcinoma cells, which contain wild-type P53 alleles, and RKO cell sublines genetically engineered to express HPV E6 and E7 oncoproteins, were treated with low-dose-rate (0.25-Gy/h) radiation and then assessed for p53 and p21WAF1/CIP1 polypeptide induction by immunoblot analysis, for cell-cycle redistribution by flow cytometry, and for cytotoxicity by clonogenic survival assay. Results: Low-dose-rate radiation of RKO carcinoma cells triggered p53 polypeptide elevations, p21WAF1/CIP1 induction, and arrest in the G1 and G2 phases of the cell cycle. In contrast, RKO cells expressing E6 and E7 transforming proteins from high-risk oncogenic HPVs (HPV 16) arrested in G2, but failed to arrest in G1, when treated with low-dose-rate ionizing radiation. Abrogation of the G1 cell-cycle checkpoint activated by low-dose-rate radiation exposure appeared to be a characteristic feature of transforming proteins from high-risk oncogenic HPVs: RKO cells expressing E6 from a low

Acute dose and low dose-rate irradiation of carcinoma cells expressing human papillomavirus E6 and E7 oncoproteins - the significance of p53, Rb and G1 arrest status

International Nuclear Information System (INIS)

DeWeese, Theodore L.; Walsh, Jonathan C.; Dillehay, Larry E.; Shao, Y.; Kessis, Theodore D.; Cho, Kathleen R.; Nelson, William G.

1995-01-01

Purpose: The development of carcinomas in a number of sites including the cervix, vulva and anus have been associated with cellular infection by human papillomaviruses (HPV), including HPV 16 and HPV 18. The mechanism by which these viruses contribute to tumor development or progression seems in part to be related to the integration of the viral genome into the host cells DNA, and the binding of p53 protein by the HPV E6 oncoprotein as well as the binding of the retinoblastoma (Rb) protein and Rb-like proteins by the HPV E7 oncoprotein. These interactions lead to loss of p53 and Rb function including loss of the G 1 cell cycle checkpoint. Although it is believed that both p53 and Rb play a role in the radiosensitivity of the cell, whether alteration in either protein enhances or diminishes cellular radiation response is not clear from the literature. Because HPV-associated tumors such as cervical cancer are often treated with acute dose and/or low dose-rate radiation, we set out to evaluate the radiation response of several carcinoma cell sublines expressing either oncogenic E6 or E7 to both types of radiation, and to determine if p53/Rb dependent G 1 arrest is an important determinant of cell fate after irradiation. Materials and Methods: We have previously developed a series of RKO colorectal carcinoma cell sublines expressing both low-risk (HPV 11) and high-risk (HPV 16) E6 and E7 genes. p53-dependent G 1 arrest is intact in RKO parental cells and cells expressing low-risk E6 proteins, while the G 1 arrest is abrogated in cells expressing high-risk E6 or E7. Clonogenic survival was assessed after exposure to acute dose (1 Gy/min) and low dose-rate (0.25 Gy/hour) radiation. The radiobiologic parameters α, β and the surviving fraction at 2 Gy (SF2) were determined. SDS-PAGE/immunoblotting was carried out to assess both p53 and p21 WAF1/CIP1 levels after exposure to radiation. Flow cytometry was performed before and after exposure to low dose-rate radiation to

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

Identification of Differential Gene Expression Patterns after Acute Exposure to High and Low Doses of Low-LET Ionizing Radiation in a Reconstituted Human Skin Tissue

Energy Technology Data Exchange (ETDEWEB)

Tilton, Susan C.; Markillie, Lye Meng; Hays, Spencer; Taylor, Ronald C.; Stenoien, David L.

2016-11-01

Our goal here was to identify dose and temporal dependent radiation responses in a complex tissue, reconstituted human skin. Direct sequencing of RNA (RNA-seq) was used to quantify altered transcripts following exposure to 0.1, 2 and 10 Gy of ionizing radiation at 3 and 8 hours. These doses include a low dose in the range of some medical diagnostic procedures (0.1 Gy), a dose typically received during radiotherapy (2.0 Gy) and a lethal dose (10 Gy). These doses could be received after an intentional or accidental radiation exposure and biomarkers are needed to rapidly and accurately triage exposed individuals. A total of 1701 genes were deemed to be significantly affected by high dose radiation exposure with the majority of genes affected at 10 Gy. A group of 29 genes including GDF15, BBC3, PPM1D, FDXR, GADD45A, MDM2, CDKN1A, TP53INP1, CYCSP27, SESN1, SESN2, PCNA, and AEN were similarly altered at both 2 and 10 Gy, but not 0.1 Gy, at multiple time points. A much larger group of up regulated genes, including those involved in inflammatory responses, was significantly altered only after a 10 Gy exposure. At high doses, down regulated genes were associated with cell cycle regulation and exhibited an apparent linear response between 2 and 10 Gy. While only a handful of genes were significantly affected by 0.1 Gy exposure using stringent statistical filters, groups of related genes regulating cell cycle progression and inflammatory responses consistently exhibited opposite trends in their regulation compared to the high dose exposures. Differential regulation of PLK1 signaling at low and high doses was confirmed using qRT-PCR. These results indicate that some alterations in gene expression are qualitatively different at low and high doses of radiation in this model system.

Undersulfation of proteoglycans and proteins alter C6 glioma cells proliferation, adhesion and extracellular matrix organization.

Science.gov (United States)

Mendes de Aguiar, Claudia B N; Garcez, Ricardo Castilho; Alvarez-Silva, Marcio; Trentin, Andréa Gonçalves

2002-11-01

Proteoglycans are considered to be important molecule in cell-microenvironment interactions. They are overexpressed in neoplastic cells modifying their growth and migration in hosts. In this work we verified that undersulfation of proteoglycans and other sulfated molecules, induced by sodium chlorate treatment, inhibited C6 glioma cells proliferation in a dose-dependent way. This effect was restored by the addition of exogenous heparin. We could not detect significant cell mortality in our culture condition. The treatment also impaired in a dose-dependent manner, C6 cell adhesion to extracellular matrix (ECM) proteins (collagen IV, laminin and fibronectin). In addition, sodium chlorate treatment altered C6 glioma cell morphology, from the fibroblast-like to a more rounded one. This effect was accompanied by increased synthesis of fibronectin and alterations in its extracellular network organization. However, we could not observe modifications on laminin organization and synthesis. The results suggest an important connection between sulfation degree with important tumor functions, such as proliferation and adhesion. We suggest that proteoglycans may modulate the glioma microenvironment network during tumor cell progression and invasion.

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

Science.gov (United States)

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

1999-01-01

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

The genetically significant dose from diagnostic radiology in Great Britain in 1977

International Nuclear Information System (INIS)

Darby, S.C.; Kendall, G.M.; Rae, S.; Wall, B.F.

1980-09-01

This report is the third in a series concerned with the annual genetically significant dose to the population of Great Britain from diagnostic radiology. It combines information from a frequency survey of diagnostic radiological examinations carried out in Great Britain in 1977 and estimates of gonadal doses for different examination types, together with population and child expectancy data. The annual genetically significant dose from diagnostic radiology carried out in Great Britain in 1977, is estimated to 118 μGy (11.8 millirad) of which 113 μGy (11.3 millirad) is contributed by diagnostic radiology carried out in National Health Service hospitals. There has been a sharp fall in the contribution from obstetric examinations since 1957 when the last national survey was carried out. The contribution from most other examination types is broadly similar and there is little evidence of a change in the overall level of genetically significant dose. This is in spite of an increase in the frequency of radiological examinations per thousand of the population of about 50 per cent. No significant differences were found as between England, Scotland and Wales. The British figure compares favourably with the levels of GSD reported from other countries with developed radiological services. (author)

Genetically significant dose from diagnostic radiology in Great Britain

Energy Technology Data Exchange (ETDEWEB)

Darby, S C; Wall, B F [National Radiological Protection Board, Harwell (UK)

1981-01-01

A brief discussion is presented of the use of population and child expectancy data to estimate the annual genetically significant dose for diagnostic radiology (GSD). The current estimate of GSD is compared with that reported in a survey 20 years previously. Comparisons are made with estimates of GSD from other countries.

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

An analysis of radiation dose reduction in paediatric interventional cardiology by altering frame rate and use of the anti-scatter grid

International Nuclear Information System (INIS)

McFadden, S L; Hughes, C M; Winder, Robert J; Mooney, R B

2013-01-01

The purpose of this work is to investigate removal of the anti-scatter grid and alteration of the frame rate in paediatric interventional cardiology (IC) and assess the impact on radiation dose and image quality. Phantom based experimental studies were performed in a dedicated cardiac catheterisation suite to investigate variations in radiation dose and image quality, with various changes in imaging parameters. Phantom based experimental studies employing these variations in technique identified that radiation dose reductions of 28%–49% can be made to the patient with minimal loss of image quality in smaller sized patients. At present, there is no standard technique for carrying out paediatric IC in the UK or Ireland, resulting in the potential for a wide variation in radiation dose. Dose reductions to patients can be achieved with slight alterations to the imaging equipment with minimal compromise to the image quality. These simple modifications can be easily implemented in clinical practice in IC centres. (paper)

Morphine Tolerance and Physical Dependence Are Altered in Conditional HIV-1 Tat Transgenic Mice.

Science.gov (United States)

Fitting, Sylvia; Stevens, David L; Khan, Fayez A; Scoggins, Krista L; Enga, Rachel M; Beardsley, Patrick M; Knapp, Pamela E; Dewey, William L; Hauser, Kurt F

2016-01-01

Despite considerable evidence that chronic opiate use selectively affects the pathophysiologic consequences of human immunodeficiency virus type 1 (HIV-1) infection in the nervous system, few studies have examined whether neuro-acquired immune deficiency syndrome (neuroAIDS) might intrinsically alter the pharmacologic responses to chronic opiate exposure. This is an important matter because HIV-1 and opiate abuse are interrelated epidemics, and HIV-1 patients are often prescribed opiates as a treatment of HIV-1-related neuropathic pain. Tolerance and physical dependence are inevitable consequences of frequent and repeated administration of morphine. In the present study, mice expressing HIV-1 Tat in a doxycycline (DOX)-inducible manner [Tat(+)], their Tat(-) controls, and control C57BL/6 mice were chronically exposed to placebo or 75-mg morphine pellets to explore the effects of Tat induction on morphine tolerance and dependence. Antinociceptive tolerance and locomotor activity tolerance were assessed using tail-flick and locomotor activity assays, respectively, and physical dependence was measured with the platform-jumping assay and recording of other withdrawal signs. We found that Tat(+) mice treated with DOX [Tat(+)/DOX] developed an increased tolerance in the tail-flick assay compared with control Tat(-)/DOX and/or C57/DOX mice. Equivalent tolerance was developed in all mice when assessed by locomotor activity. Further, Tat(+)/DOX mice expressed reduced levels of physical dependence to chronic morphine exposure after a 1-mg/kg naloxone challenge compared with control Tat(-)/DOX and/or C57/DOX mice. Assuming the results seen in Tat transgenic mice can be generalized to neuroAIDS, our findings suggest that HIV-1-infected individuals may display heightened analgesic tolerance to similar doses of opiates compared with uninfected individuals and show fewer symptoms of physical dependence. Copyright © 2015 by The American Society for Pharmacology and Experimental

Hepatic lipid profiling of deer mice fed ethanol using {sup 1}H and {sup 31}P NMR spectroscopy: A dose-dependent subchronic study

Energy Technology Data Exchange (ETDEWEB)

Fernando, Harshica; Bhopale, Kamlesh K.; Boor, Paul J.; Ansari, G.A. Shakeel; Kaphalia, Bhupendra S., E-mail: bkaphali@utmb.edu

2012-11-01

Chronic alcohol abuse is a 2nd major cause of liver disease resulting in significant morbidity and mortality. Alcoholic liver disease (ALD) is characterized by a wide spectrum of pathologies starting from fat accumulation (steatosis) in early reversible stage to inflammation with or without fibrosis and cirrhosis in later irreversible stages. Previously, we reported significant steatosis in the livers of hepatic alcohol dehydrogenase (ADH)-deficient (ADH{sup −}) vs. hepatic ADH-normal (ADH{sup +}) deer mice fed 4% ethanol daily for 2 months [Bhopale et al., 2006, Alcohol 39, 179–188]. However, ADH{sup −} deer mice fed 4% ethanol also showed a significant mortality. Therefore, a dose-dependent study was conducted to understand the mechanism and identify lipid(s) involved in the development of ethanol-induced fatty liver. ADH{sup −} and ADH{sup +} deer mice fed 1, 2 or 3.5% ethanol daily for 2 months and fatty infiltration in the livers were evaluated by histology and by measuring dry weights of extracted lipids. Lipid metabolomic changes in extracted lipids were determined by proton ({sup 1}H) and {sup 31}phosphorus ({sup 31}P) nuclear magnetic resonance (NMR) spectroscopy. The NMR data was analyzed by hierarchical clustering (HC) and principle component analysis (PCA) for pattern recognition. Extensive vacuolization by histology and significantly increased dry weights of total lipids found only in the livers of ADH{sup −} deer mice fed 3.5% ethanol vs. pair-fed controls suggest a dose-dependent formation of fatty liver in ADH{sup −} deer mouse model. Analysis of NMR data of ADH{sup −} deer mice fed 3.5% ethanol vs. pair-fed controls shows increases for total cholesterol, esterified cholesterol, fatty acid methyl esters (FAMEs), triacylglycerides and unsaturation, and decreases for free cholesterol, phospholipids and allylic and diallylic protons. Certain classes of neutral lipids (cholesterol esters, fatty acyl chain (-COCH{sub 2}-) and FAMEs) were

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)

Alterations in Brain Structure and Functional Connectivity in Alcohol Dependent Patients and Possible Association with Impulsivity.

Science.gov (United States)

Wang, Junkai; Fan, Yunli; Dong, Yue; Ma, Mengying; Ma, Yi; Dong, Yuru; Niu, Yajuan; Jiang, Yin; Wang, Hong; Wang, Zhiyan; Wu, Liuzhen; Sun, Hongqiang; Cui, Cailian

2016-01-01

Previous studies have documented that heightened impulsivity likely contributes to the development and maintenance of alcohol use disorders. However, there is still a lack of studies that comprehensively detected the brain changes associated with abnormal impulsivity in alcohol addicts. This study was designed to investigate the alterations in brain structure and functional connectivity associated with abnormal impulsivity in alcohol dependent patients. Brain structural and functional magnetic resonance imaging data as well as impulsive behavior data were collected from 20 alcohol dependent patients and 20 age- and sex-matched healthy controls respectively. Voxel-based morphometry was used to investigate the differences of grey matter volume, and tract-based spatial statistics was used to detect abnormal white matter regions between alcohol dependent patients and healthy controls. The alterations in resting-state functional connectivity in alcohol dependent patients were examined using selected brain areas with gray matter deficits as seed regions. Compared with healthy controls, alcohol dependent patients had significantly reduced gray matter volume in the mesocorticolimbic system including the dorsal posterior cingulate cortex, the dorsal anterior cingulate cortex, the medial prefrontal cortex, the orbitofrontal cortex and the putamen, decreased fractional anisotropy in the regions connecting the damaged grey matter areas driven by higher radial diffusivity value in the same areas and decreased resting-state functional connectivity within the reward network. Moreover, the gray matter volume of the left medial prefrontal cortex exhibited negative correlations with various impulse indices. These findings suggest that chronic alcohol dependence could cause a complex neural changes linked to abnormal impulsivity.

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

Science.gov (United States)

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

2018-05-01

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

Delivery of adjuvant sequential dose-dense FEC-Doc to patients with breast cancer is feasible, but dose reductions and toxicity are dependent on treatment sequence.

Science.gov (United States)

Wildiers, H; Dirix, L; Neven, P; Prové, A; Clement, P; Squifflet, P; Amant, F; Skacel, T; Paridaens, R

2009-03-01

This study prospectively investigates the impact of dose densification and altering sequence of fluorouracil, epirubicin and cyclophosphamide [FEC(100)] and docetaxel [Doc] on dose delivery and tolerability of adjuvant chemotherapy in breast cancer patients. 117 patients with high-risk primary operable breast cancer were randomized (1:1:2:2) to conventional (three cycles of 3-weekly FEC(100) then three cycles of 3-weekly Doc 100 mg/m(2) or reverse sequence) or dose-dense (dd) treatment (four 10- to 11-day cycles of FEC(75) then four 2-weekly cycles of Doc 75 mg/m(2), or the reverse). In the dd arms, pegfilgrastim was given on day 2 of each cycle, but only as secondary prophylaxis in conventional arms. The primary endpoint was the proportion of patients completing intended cycles at relative dose intensity >or=85% and this was achieved by 95% of patients in each group except for the ddDoc-->FEC group (90%). Dose intensity in the dd arms increased by 48% for FEC and 11% for docetaxel, compared with the conventional arms (both P Doc dose reductions were more frequent with dd treatment and when Doc was given after FEC. Grade 3-4 neutropenia was significantly more frequent with conventional treatment, while fatigue and hand-foot syndrome were numerically more common with dd treatment, particularly when Doc was given after FEC. Discussion Delivery of adjuvant sequential ddFEC and Doc is feasible with growth factor support, and chemotherapy sequence appeared to affect delivery of target doses and toxicity.

An Assessment of the Effects of Different Dose Levels of Gamma Rays on HPRT Gene of T-Cells from Human Peripheral Blood

International Nuclear Information System (INIS)

Bahreyni, M. T.; Rezaee, M.

2004-01-01

Ionizing radiation has been shown to produce a broad range of genetic aberrations in human and other species. Most of the genetic aberrations are deletions. To study genetic alterations, an assessment of somatic ell gene mutations induced by ionizing radiation is proper method. In this study, the intragenic and total gene deletions of 18 HPRT-mutants derived from T-lymphocytes and induced by gamma rays were analyzed. PCR amplification of individual HPRT exons and multiplex PCR. HPRT-mutants were isolated by treatment of irradiated samples with 6-thioguanine. MPCR and PCR of individual exons of HPRT demonstrated that the intragenic and total gene deletions were not significantly different. The samples including more than one deletion had non-random significantly higher frequency. Mapping of all intragenic deleltion exhibited a nonrandom distribution. Middle part of HPRT gene was more sensitive to gamma rays. The sensitivity was increased with radiation dose. This study showed that the size of deletions are dose dependent. Our results suggest that alterations in T- lymphocytes mutant genes, induced deletions, size of deletions and distribution of DNA breakpoints appeared to be dependent on low LET radiation dose. (Author) 11 refs

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.

Imprinted genes and transpositions: epigenomic targets for low dose radiation effects. Final report

Energy Technology Data Exchange (ETDEWEB)

Jirtle, Randy L.

2012-10-11

The overall hypothesis of this grant application is that low dose ionizing radiation (LDIR) elicits adaptive responses in part by causing heritable DNA methylation changes in the epigenome. This novel postulate was tested by determining if the level of DNA methylation at the Agouti viable yellow (A{sup vy}) metastable locus is altered, in a dose-dependent manner, by low dose radiation exposure (<10 cGy) during early gestation. This information is particularly important to ascertain given the increased use of CT scans in disease diagnosis, increased number of people predicted to live and work in space, and the present concern about radiological terrorism. We showed for the first time that LDIR significantly increased DNA methylation at the A{sup vy} locus in a sex-specific manner (p=0.004). Average DNA methylation was significantly increased in male offspring exposed to doses between 0.7 cGy and 7.6 cGy with maximum effects at 1.4 cGy and 3.0 cGy (p<0.01). Offspring coat color was concomitantly shifted towards pseudoagouti (p<0.01). Maternal dietary antioxidant supplementation mitigated both the DNA methylation changes and coat color shift in the irradiated offspring (p<0.05). Thus, LDIR exposure during gestation elicits epigenetic alterations that lead to positive adaptive phenotypic changes that are negated with antioxidants, indicating they are mediated in part by oxidative stress. These findings provide evidence that in the isogenic Avy mouse model epigenetic alterations resulting from LDIR play a role in radiation hormesis, bringing into question the assumption that every dose of radiation is harmful. Our findings not only have significant implications concerning the mechanism of hormesis, but they also emphasize the potential importance of this phenomenon in determining human risk at low radiation doses. Since the epigenetic regulation of genes varies markedly between species, the effect of LDIR on other epigenetically labile genes (e.g. imprinted genes) in

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

Dose- and time-dependent gene expression alterations in prostate and colon cancer cells after in vitro exposure to carbon ion and X-irradiation

Science.gov (United States)

Suetens, Annelies; Moreels, Marjan; Quintens, Roel; Soors, Els; Buset, Jasmine; Chiriotti, Sabina; Tabury, Kevin; Gregoire, Vincent; Baatout, Sarah

2015-01-01

Hadrontherapy is an advanced form of radiotherapy that uses beams of charged particles (such as protons and carbon ions). Compared with conventional radiotherapy, the main advantages of carbon ion therapy are the precise absorbed dose localization, along with an increased relative biological effectiveness (RBE). This high ballistic accuracy of particle beams deposits the maximal dose to the tumor, while damage to the surrounding healthy tissue is limited. Currently, hadrontherapy is being used for the treatment of specific types of cancer. Previous in vitro studies have shown that, under certain circumstances, exposure to charged particles may inhibit cell motility and migration. In the present study, we investigated the expression of four motility-related genes in prostate (PC3) and colon (Caco-2) cancer cell lines after exposure to different radiation types. Cells were irradiated with various absorbed doses (0, 0.5 and 2 Gy) of accelerated 13C-ions at the GANIL facility (Caen, France) or with X-rays. Clonogenic assays were performed to determine the RBE. RT-qPCR analysis showed dose- and time-dependent changes in the expression of CCDC88A, FN1, MYH9 and ROCK1 in both cell lines. However, whereas in PC3 cells the response to carbon ion irradiation was enhanced compared with X-irradiation, the effect was the opposite in Caco-2 cells, indicating cell-type–specific responses to the different radiation types. PMID:25190155

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

Science.gov (United States)

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

1995-01-01

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

Stress during Adolescence Alters Palatable Food Consumption in a Context-Dependent Manner.

Science.gov (United States)

Handy, Christine; Yanaga, Stephanie; Reiss, Avery; Zona, Nicole; Robinson, Emily; Saxton, Katherine B

2016-01-01

Food consumption and preferences may be shaped by exposure to stressful environments during sensitive periods in development, and even small changes in consumption can have important effects on long term health. Adolescence is increasingly recognized as a sensitive period, in which adverse experiences can alter development, but the specific programming effects that may occur during adolescence remain incompletely understood. The current study seeks to explore the effects of stress during late adolescence on consumption of a palatable, high-fat, high-sugar food in adulthood-under basal conditions, as well following acute stress. Male Long-Evans rats were exposed to a regimen of variable stress for seven days in late adolescence (PND 45-51). During the stress regimen, stressed animals gained significantly less weight than control animals, but weight in adulthood was unaffected by adolescent stress. Palatable food consumption differed between experimental groups, and the direction of effect depended on context; stressed rats ate significantly more palatable food than controls upon first exposure, but ate less following an acute stressor. Leptin levels and exploratory behaviors did not differ between stressed and non-stressed groups, suggesting that other factors regulate preference for a palatable food. Altered food consumption following adolescent stress suggests that rats remain sensitive to stress during late adolescence, and that adult feeding behavior may be affected by previous adverse experiences. Such programming effects highlight adolescence as a period of plasticity, with the potential to shape long term food consumption patterns and preferences.

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

Directory of Open Access Journals (Sweden)

Shu-Guang Cao

2016-03-01

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

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

Some remarks on the significance of low doses

International Nuclear Information System (INIS)

Cigna, A.A.

1989-12-01

The criteria of the present system of individual dose limitation are considered as well as the evolution of the limiting values. The assumption of the linearity of the dose-effect relationship without any threshold is probably the best approach to adopt for recommendations in radiation protection and for accounting the doses acquired by exposure to ionizing radiation. On the other hand the present evaluation of the natural background could imply a different dose-effect relationship in the low doses region and perhaps the existence of a threshold. Therefore the extrapolations which are usually made after exposures of different groups of people to low doses cannot be considered as scientifically sound. (author)

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

Science.gov (United States)

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

2006-06-07

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

SU-G-BRC-15: The Potential Clinical Significance of Dose Mapping Error for Intra- Fraction Dose Mapping for Lung Cancer Patients

Energy Technology Data Exchange (ETDEWEB)

Sayah, N [Thomas Cancer Center, Richmond, VA (United States); Weiss, E [Virginia Commonwealth University, Richmond, Virginia (United States); Watkins, W [University of Virginia, Charlottesville, VA (United States); Siebers, J [University of Virginia Health System, Charlottesville, VA (United States)

2016-06-15

Purpose: To evaluate the dose-mapping error (DME) inherent to conventional dose-mapping algorithms as a function of dose-matrix resolution. Methods: As DME has been reported to be greatest where dose-gradients overlap tissue-density gradients, non-clinical 66 Gy IMRT plans were generated for 11 lung patients with the target edge defined as the maximum 3D density gradient on the 0% (end of inhale) breathing phase. Post-optimization, Beams were copied to 9 breathing phases. Monte Carlo dose computed (with 2*2*2 mm{sup 3} resolution) on all 10 breathing phases was deformably mapped to phase 0% using the Monte Carlo energy-transfer method with congruent mass-mapping (EMCM); an externally implemented tri-linear interpolation method with voxel sub-division; Pinnacle’s internal (tri-linear) method; and a post-processing energy-mass voxel-warping method (dTransform). All methods used the same base displacement-vector-field (or it’s pseudo-inverse as appropriate) for the dose mapping. Mapping was also performed at 4*4*4 mm{sup 3} by merging adjacent dose voxels. Results: Using EMCM as the reference standard, no clinically significant (>1 Gy) DMEs were found for the mean lung dose (MLD), lung V20Gy, or esophagus dose-volume indices, although MLD and V20Gy were statistically different (2*2*2 mm{sup 3}). Pinnacle-to-EMCM target D98% DMEs of 4.4 and 1.2 Gy were observed ( 2*2*2 mm{sup 3}). However dTransform, which like EMCM conserves integral dose, had DME >1 Gy for one case. The root mean square RMS of the DME for the tri-linear-to- EMCM methods was lower for the smaller voxel volume for the tumor 4D-D98%, lung V20Gy, and cord D1%. Conclusion: When tissue gradients overlap with dose gradients, organs-at-risk DME was statistically significant but not clinically significant. Target-D98%-DME was deemed clinically significant for 2/11 patients (2*2*2 mm{sup 3}). Since tri-linear RMS-DME between EMCM and tri-linear was reduced at 2*2*2 mm{sup 3}, use of this resolution is

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-02-15

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

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

International Nuclear Information System (INIS)

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

2014-01-01

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

Overexpression of cerebral and hepatic cytochrome P450s alters behavioral activity of rat offspring following prenatal exposure to lindane

Energy Technology Data Exchange (ETDEWEB)

Johri, Ashu; Yadav, Sanjay; Dhawan, Alok [Developmental Toxicology Division, Industrial Toxicology Research Centre, P. O. Box 80, M. G. Marg, Lucknow-226 001, U. P. (India); Parmar, Devendra [Developmental Toxicology Division, Industrial Toxicology Research Centre, P. O. Box 80, M. G. Marg, Lucknow-226 001, U. P. (India)

2007-12-15

Oral administration of different doses (0.0625, 0.125 or 0.25 mg/kg corresponding to 1/1400th, 1/700th or 1/350th of LD{sub 50}) of lindane to the pregnant Wistar rats from gestation days 5 to 21 were found to produce a dose-dependent increase in the activity of cytochrome P450 (CYP)-dependent 7-ethoxyresorufin-O-deethylase (EROD), 7-pentoxyresorufin-O-dealkylase (PROD) and N-nitrosodimethylamine demethylase (NDMA-d) in brain and liver of offspring postnatally at 3 weeks. The increase in the activity of CYP monooxygenases was found to be associated with the increase in the mRNA and protein expression of xenobiotic metabolizing CYP1A, 2B and 2E1 isoenzymes in the brain and liver of offspring. Dose-dependent alterations in the parameters of spontaneous locomotor activity in the offspring postnatally at 3 weeks have suggested that increase in CYP activity may possibly lead to the formation of metabolites to the levels that may be sufficient to alter the behavioral activity of the offspring. Interestingly, the inductive effect on cerebral and hepatic CYPs was found to persist postnatally up to 6 weeks in the offspring at the relatively higher doses (0.125 and 0.25 mg/kg) of lindane and up to 9 weeks at the highest dose (0.25 mg/kg), though the magnitude of induction was less than that observed at 3 weeks. Alterations in the parameters of spontaneous locomotor activity in the offspring postnatally at 6 and 9 weeks, though significant only in the offspring at 3 and 6-week of age, have further indicated that due to the reduced activity of the CYPs during the ontogeny, lindane and its metabolites may not be effectively cleared from the brain. The data suggest that low dose prenatal exposure to the pesticide has the potential to produce overexpression of xenobiotic metabolizing CYPs in brain and liver of the offspring which may account for the behavioral changes observed in the offspring.

Overexpression of cerebral and hepatic cytochrome P450s alters behavioral activity of rat offspring following prenatal exposure to lindane

International Nuclear Information System (INIS)

Johri, Ashu; Yadav, Sanjay; Dhawan, Alok; Parmar, Devendra

2007-01-01

Oral administration of different doses (0.0625, 0.125 or 0.25 mg/kg corresponding to 1/1400th, 1/700th or 1/350th of LD 50 ) of lindane to the pregnant Wistar rats from gestation days 5 to 21 were found to produce a dose-dependent increase in the activity of cytochrome P450 (CYP)-dependent 7-ethoxyresorufin-O-deethylase (EROD), 7-pentoxyresorufin-O-dealkylase (PROD) and N-nitrosodimethylamine demethylase (NDMA-d) in brain and liver of offspring postnatally at 3 weeks. The increase in the activity of CYP monooxygenases was found to be associated with the increase in the mRNA and protein expression of xenobiotic metabolizing CYP1A, 2B and 2E1 isoenzymes in the brain and liver of offspring. Dose-dependent alterations in the parameters of spontaneous locomotor activity in the offspring postnatally at 3 weeks have suggested that increase in CYP activity may possibly lead to the formation of metabolites to the levels that may be sufficient to alter the behavioral activity of the offspring. Interestingly, the inductive effect on cerebral and hepatic CYPs was found to persist postnatally up to 6 weeks in the offspring at the relatively higher doses (0.125 and 0.25 mg/kg) of lindane and up to 9 weeks at the highest dose (0.25 mg/kg), though the magnitude of induction was less than that observed at 3 weeks. Alterations in the parameters of spontaneous locomotor activity in the offspring postnatally at 6 and 9 weeks, though significant only in the offspring at 3 and 6-week of age, have further indicated that due to the reduced activity of the CYPs during the ontogeny, lindane and its metabolites may not be effectively cleared from the brain. The data suggest that low dose prenatal exposure to the pesticide has the potential to produce overexpression of xenobiotic metabolizing CYPs in brain and liver of the offspring which may account for the behavioral changes observed in the offspring

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

Low-dose dioxins alter gene expression related to cholesterol biosynthesis, lipogenesis, and glucose metabolism through the aryl hydrocarbon receptor-mediated pathway in mouse liver

International Nuclear Information System (INIS)

Sato, Shoko; Shirakawa, Hitoshi; Tomita, Shuhei; Ohsaki, Yusuke; Haketa, Keiichi; Tooi, Osamu; Santo, Noriaki; Tohkin, Masahiro; Furukawa, Yuji; Gonzalez, Frank J.; Komai, Michio

2008-01-01

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a common environmental contaminant. TCDD binds and activates the transcription factor aryl hydrocarbon receptor (AHR), leading to adverse biological responses via the alteration of the expression of various AHR target genes. Although small amounts of TCDD are consumed via contaminated daily foodstuffs and environmental exposures, the effects of low-dose TCDD on gene expression in animal tissues have not been clarified, while a number of genes affected by high-dose TCDD were reported. In this study, we comprehensively analyzed gene expression profiles in livers of C57BL/6N mice that were orally administered relatively low doses of TCDD (5, 50, or 500 ng/kg body weight (bw) day -1 ) for 18 days. The hepatic TCDD concentrations, measured by gas chromatography-mass spectrometry, were 1.2, 17, and 1063 pg toxicity equivalent quantity (TEQ)/g, respectively. The mRNA level of the cytochrome P450 CYP1A1 was significantly increased by treatment with only TCDD 500 ng/kg bw day -1 . DNA microarray and quantitative RT-PCR analyses revealed changes in the expression of genes involved in the circadian rhythm, cholesterol biosynthesis, fatty acid synthesis, and glucose metabolism in the liver with at all doses of TCDD employed. However, repression of expression of genes involved in energy metabolism was not observed in the livers of Ahr-null mice that were administered the same dose of TCDD. These results indicate that changes in gene expression by TCDD are mediated by AHR and that exposure to low-dose TCDD could affect energy metabolism via alterations of gene expression

Di-(2 ethylhexyl phthalate and flutamide alter gene expression in the testis of immature male rats

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Yu Frank H

2009-09-01

Full Text Available Abstract We previously demonstrated that the androgenic and anti-androgenic effects of endocrine disruptors (EDs alter reproductive function and exert distinct effects on developing male reproductive organs. To further investigate these effects, we used an immature rat model to examine the effects of di-(2 ethylhexyl phthalate (DEHP and flutamide (Flu on the male reproductive system. Immature male SD rats were treated daily with DEHP and Flu on postnatal days (PNDs 21 to 35, in a dose-dependent manner. As results, the weights of the testes, prostate, and seminal vesicle and anogenital distances (AGD decreased significantly in response to high doses of DEHP or Flu. Testosterone (T levels significantly decreased in all DEHP- treated groups, whereas luteinizing hormone (LH plasma levels were not altered by any of the two treatments at PND 36. However, treatment with DEHP or Flu induced histopathological changes in the testes, wherein degeneration and disorders of Leydig cells, germ cells and dilatation of tubular lumen were observed in a dose-dependent manner. Conversely, hyperplasia and denseness of Leydig, Sertoli and germ cells were observed in rats given with high doses of Flu. The results by cDNA microarray analysis indicated that 1,272 genes were up-regulated by more than two-fold, and 1,969 genes were down-regulated in response to DEHP, Flu or both EDs. These genes were selected based on their markedly increased or decreased expression levels. These genes have been also classified on the basis of gene ontology (e.g., steroid hormone biosynthetic process, regulation of transcription, signal transduction, metabolic process, biosynthetic process.... Significant decreases in gene expression were observed in steroidogenic genes (i.e., Star, Cyp11a1 and Hsd3b. In addition, the expression of a common set of target genes, including CaBP1, Vav2, Plcd1, Lhx1 and Isoc1, was altered following exposure to EDs, suggesting that they may be marker genes to

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

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Yu, Yongbo [Capital Medical University, Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, Beijing Pediatric Research Institute, Beijing Children’s Hospital (China); Duan, Junchao; Li, Yang; Yu, Yang; Hu, Hejing; Wu, Jing; Zhang, Yannan; Li, Yanbo; CaixiaGuo; Zhou, Xianqing; Sun, Zhiwei, E-mail: zwsun@ccmu.edu.cn [Capital Medical University, School of Public Health (China)

2016-11-15

The prevalent exposure to nanosilica gained concerns about health effects of these particles on human beings. Although nanosilica-induced multinucleation has been confirmed previously, the underlying mechanism was still not clear; this study was to investigate the origination of multinucleated cells caused by nanosilica (62 nm) in both HepG2 and L-02 cells. Cell viability and cellular uptake was determined by MTT assay and transmission electron microscope (TEM), respectively. Giemsa staining was applied to detect multinucleation. To clarify the origination of multinucleated cells, fluorescent probes, PKH26 and PKH67, time-lapse observation were further conducted by confocal microscopy. Results indicated that nanosilica particles were internalized into cells and induced cytotoxicity in a dose-dependent manner. Quantification analysis showed that nanosilica significantly increased the rates of binucleated and multinucleated cells, which suggested mitotic catastrophe induction. Moreover, dynamic visualization verified that multinucleation resulted from cell fusion in HepG2 cells not in L-02 cells after nanosilica exposure, suggesting cell type-dependent multinucleation formation. Both multinucleation and cell fusion were involved in genetic instability, which emphasized the significance to explore the multinucleation induced by nanosilica via environmental, occupational and consumer product exposure.

Aspartame and the hippocampus: Revealing a bi-directional, dose/time-dependent behavioural and morphological shift in mice.

Science.gov (United States)

Onaolapo, Adejoke Y; Onaolapo, Olakunle J; Nwoha, Polycarp U

2017-03-01

Changes, in behaviour, oxidative markers of stress and hippocampal morphology were evaluated following aspartame administration. Mice, (20-22g each) were given vehicle (10ml/kg) or aspartame (20, 40, 80 and 160mg/kg) daily for 28days. They were tested in the Y-maze, radial-arm maze and elevated plus-maze (EPM) after the first and last dose of vehicle or aspartame; and then sacrificed. Hippocampal slices were analysed for aspartic acid, nitric oxide (NO) and superoxide dismutase (SOD); and processed for general histology and neuritic plaques. Glial fibrillary-acid protein (GFAP) expression and neuron-specific enolase (NSE) activities were determined. Radial-arm maze scores increased significantly after acute administration at 80 and 160mg/kg. Repeated administration at 20 and 40mg/kg (Y-maze) and at 40mg/kg (radial-arm maze) was also associated with increased scores, however, performance decreased at higher doses. EPM tests revealed anxiogenic responses following both acute and repeated administration. Significant increase in SOD and NO activities were observed at 40, 80 and 160mg/kg. Neuron counts reduced at higher doses of aspartame. At 40, 80 and 160mg/kg, fewer GFAP-reactive astrocytes were observed in the cornus ammonis, but increased GFAP-reactivity was observed in the dentate gyrus subgranular zone. NSE-positive neurons were readily identifiable within the dentate gyrus at the lower doses of aspartame; but at 160mg/kg, there was marked neuron loss and reduction in NSE-positive neurons. Oral aspartame significantly altered behaviour, anti-oxidant status and morphology of the hippocampus in mice; also, it may probably trigger hippocampal adult neurogenesis. Copyright © 2016 Elsevier Inc. All rights reserved.

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

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.)

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

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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

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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.

Onion and garlic extracts as potential antidotes for cadmium-induced biochemical alterations in prostate glands of rats.

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Ola-Mudathir, F K; Suru, S M

2015-11-01

Cadmium (Cd) has been implicated in increased prostate gland malignancy risk in both wildlife and humans. This study examines the chemoprotective roles of onion and garlic extracts on Cd-induced biochemical alterations in the prostate glands of rats. Adult male Wistar rats were randomly divided into nine groups: control group received double distilled water; Cd group received Cd alone (1.5 mg/100 g bwt per day); extract-treated groups were pre-treated with varied doses of onion and/or garlic extract (0.5 ml and 1.0 ml/100 g bwt per day) for 1 week and then co-treated with Cd (1.5 mg/100 g bwt per day) for additional 3 weeks. Oxidant/antioxidant status and acid phosphatase (ACPtotal and ACPprostatic ) activity were examined in prostate glands. Cd intoxication caused a marked (P garlic extract significantly minimised these alterations. The onion extract offered a dose-dependent protection. Our findings suggest a chemoprotective capability for onion and garlic extracts against Cd-induced biochemical alteration in the prostate glands. © 2014 Blackwell Verlag GmbH.

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

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Abhijna Chandan Chattopadhyay

2016-01-01

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

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

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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).

Characterizing dose response relationships: Chronic gamma radiation in Lemna minor induces oxidative stress and altered polyploidy level

International Nuclear Information System (INIS)

Van Hoeck, Arne; Horemans, Nele; Van Hees, May; Nauts, Robin; Knapen, Dries; Vandenhove, Hildegarde; Blust, Ronny

2015-01-01

The biological effects and interactions of different radiation types in plants are still far from understood. Among different radiation types, external gamma radiation treatments have been mostly studied to assess the biological impact of radiation toxicity in organisms. Upon exposure of plants to gamma radiation, ionisation events can cause, either directly or indirectly, severe biological damage to DNA and other biomolecules. However, the biological responses and oxidative stress related mechanisms under chronic radiation conditions are poorly understood in plant systems. In the following study, it was questioned if the Lemna minor growth inhibition test is a suitable approach to also assess the radiotoxicity of this freshwater plant. Therefore, L. minor plants were continuously exposed for seven days to 12 different dose rate levels covering almost six orders of magnitude starting from 80 μGy h"−"1 up to 1.5 Gy h"−"1. Subsequently, growth, antioxidative defence system and genomic responses of L. minor plants were evaluated. Although L. minor plants could survive the exposure treatment at environmental relevant exposure conditions, higher dose rate levels induced dose dependent growth inhibitions starting from approximately 27 mGy h"−"1. A ten-percentage growth inhibition of frond area Effective Dose Rate (EDR_1_0) was estimated at 95 ± 7 mGy h"−"1, followed by 153 ± 13 mGy h"−"1 and 169 ± 12 mGy h"−"1 on fresh weight and frond number, respectively. Up to a dose rate of approximately 5 mGy h"−"1, antioxidative enzymes and metabolites remained unaffected in plants. A significant change in catalase enzyme activity was found at 27 mGy h"−"1 which was accompanied with significant increases of other antioxidative enzyme activities and shifts in ascorbate and glutathione content at higher dose rate levels, indicating an increase in oxidative stress in plants. Recent plant research hypothesized that environmental genotoxic

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

Histological alterations in the liver of rats induced by different gold nanoparticle sizes, doses and exposure duration

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Abdelhalim Mohamed

2012-01-01

Full Text Available Abstract Background Nanoparticles (NPs can potentially cause adverse effects on organ, tissue, cellular, subcellular and protein levels due to their unusual physicochemical properties. Advances in nanotechnology have identified promising candidates for many biological and biomedical applications. Since the properties of NPs differ from that of their bulk materials, they are being increasingly exploited for medical uses and other industrial applications. The aim of the present study was to investigate the particle-size effect of gold nanoparticles (GNPs on the hepatic tissue in an attempt to cover and understand the toxicity and the potential threat of their therapeutic and diagnostic use. Methods To investigate particle-size effect of GNPs on the hepatic tissue, a total of 70 healthy male Wistar-Kyoto rats were exposed to GNPs received 50 or 100 ul of GNPs infusion of size (10, 20 and 50 nm for 3 or 7 days. Results In comparison with respective control rats, exposure to GNPs doses has produced alterations in the hepatocytes, portal triads and the sinusoids. The alterations in the hepatocytes were mainly summarized as hydropic degeneration, cloudy swelling, fatty degeneration, portal and lobular infiltrate by chronic inflammatory cells and congestive dilated central veins. Conclusions The induced histological alterations might be an indication of injured hepatocytes due to GNPs toxicity that became unable to deal with the accumulated residues resulting from metabolic and structural disturbances caused by these NPs. These alterations were size-dependent with smaller ones induced the most effects and related with time exposure of GNPs. The appearance of hepatocytes cytoplasmic degeneration and nuclear destruction may suggest that GNPs interact with proteins and enzymes of the hepatic tissue interfering with the antioxidant defense mechanism and leading to reactive oxygen species (ROS generation which in turn may induce stress in the hepatocytes to

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

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)

[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

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.

Lack of Radiation Dose or Quality Dependence of Epithelial-to-Mesenchymal Transition (EMT) Mediated by Transforming Growth Factor β

International Nuclear Information System (INIS)

Andarawewa, Kumari L.; Costes, Sylvain V.; Fernandez-Garcia, Ignacio; Chou, William S.; Ravani, Shraddha A.; Park, Howard; Barcellos-Hoff, Mary Helen

2011-01-01

Purpose: Epithelial-to-mesenchymal transition (EMT) is a phenotype that alters cell morphology, disrupts morphogenesis, and increases motility. Our prior studies have shown that the progeny of human mammary epithelial cells (HMECs) irradiated with 2 Gy undergoes transforming growth factor β (TGF-β)-mediated EMT. In this study we determined whether radiation dose or quality affected TGF-β-mediated EMT. Methods and Materials: HMECs were cultured on tissue culture plastic or in Matrigel (BD Biosciences, San Jose, CA) and exposed to low or high linear energy transfer (LET) and TGF-β (400 pg/mL). Image analysis was used to measure membrane-associated E-cadherin, a marker of functional epithelia, or fibronectin, a product of mesenchymal cells, as a function of radiation dose and quality. Results: E-cadherin was reduced in TGF-β-treated cells irradiated with low-LET radiation doses between 0.03 and 2 Gy compared with untreated, unirradiated cells or TGF-β treatment alone. The radiation quality dependence of TGF-β-mediated EMT was determined by use of 1 GeV/amu (gigaelectron volt / atomic mass unit) 56 Fe ion particles at the National Aeronautics and Space Administration's Space Radiation Laboratory. On the basis of the relative biological effectiveness of 2 for 56 Fe ion particles' clonogenic survival, TGF-β-treated HMECs were irradiated with equitoxic 1-Gy 56 Fe ion or 2-Gy 137 Cs radiation in monolayer. Furthermore, TGF-β-treated HMECs irradiated with either high- or low-LET radiation exhibited similar loss of E-cadherin and gain of fibronectin and resulted in similar large, poorly organized colonies when embedded in Matrigel. Moreover, the progeny of HMECs exposed to different fluences of 56 Fe ion underwent TGF-β-mediated EMT even when only one-third of the cells were directly traversed by the particle. Conclusions: Thus TGF-β-mediated EMT, like other non-targeted radiation effects, is neither radiation dose nor quality dependent at the doses examined.

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.

Effect of antiarrhythmic therapy with intravenous loading dose of amiodarone: evidence for an altered response in diabetic patients.

Science.gov (United States)

Iervasi, G; Clerico, A; Bonini, R; Nannipieri, M; Manfredi, C; Sabatino, L; Biagini, A; Donato, L

1998-01-01

Amiodarone, a potent class III antiarrhythmic agent with adrenergic antagonism properties, is administered increasingly to diabetic patients with cardiac arrhythmias refractory to all other available forms of therapy. Because a large percentage of diabetic patients show a perturbed autonomic regulation of the cardiovascular system, including a pertubed regulation of heart rate, we studied the antiarrhythmic response as well as the early effects (within 5 days) on heart rate of an intravenous amiodarone loading dose in diabetic patients. Seven type II (noninsulin-dependent) diabetic patients (age 64.7 +/- 9.7 years), affected by uncontrolled atrial fibrilation or atrial flutter, were enrolled for the study and a group of 12 well-matched (for age, sex and arrhythmia) nondiabetic patients served as a control group. It was found that before amiodarone administration, nondiabetic patients showed significantly wider variations in the circadian rhythm of heart rate values than diabetic patients (p = 0.0062, unpaired t-test). In all patients but one (who was nondiabetic), amiodarone treatment resulted in a cardioversion to sinus rhythm. After amiodarone administration, nondiabetic patients showed a significantly greater decrease (p = 0.0011) in heart rate values in comparison with the diabetic group (-35% vs. -20% on average, at the end of the study). Furthermore, in nondiabetic patients there was also an earlier significant fall (within the first 4 h after the start of treatment with amiodarone, p atrial fibrilation or atrial flutter may be delayed in comparison with nondiabetic patients. This altered response may be (at least in part) due to the diabetic autonomic neuropathy. Our study indicates that the presence of diabetes mellitus always must be taken into account when patients are enrolled for large, prospective, randomized trials, planned to evaluate the antiarrhythmic effects of amiodarone given intravenously.

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

Energy Technology Data Exchange (ETDEWEB)

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

2006-06-07

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

Effect of radiation on reconstitution of skin equivalent (dermal alterations); Effet de l`irradiation sur la reconstruction d`une peau equivalente (alterations dermiques)

Energy Technology Data Exchange (ETDEWEB)

Gentilhomme, E.; Bergier, J.; Richard, M.; Neveux, Y.

1994-12-31

Dermal equivalents have been treated by single doses of gamma irradiation of 10, 20, 30 and 50 Gray. Numerations at different times show a dose and time dependant diminution of cellular population. This diminution is histologically observed in dermal part of reconstituted skin, in association with cellular and functional alterations of fibroblast cells. Modifications of epidermal epithelia are also noted in some reconstituted skin. This model would be useful to apprehend the effect of a dermal irradiation lesion on the later epidermization. (author). 4 refs.

Radiation-induced hypopituitarism is dose-dependent

International Nuclear Information System (INIS)

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

1989-01-01

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

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

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.

Low-dose/dose-rate γ radiation depresses neural differentiation and alters protein expression profiles in neuroblastoma SH-SY5Y cells and C17.2 neural stem cells.

Science.gov (United States)

Bajinskis, Ainars; Lindegren, Heléne; Johansson, Lotta; Harms-Ringdahl, Mats; Forsby, Anna

2011-02-01

The effects of low doses of ionizing radiation on cellular development in the nervous system are presently unclear. The focus of the present study was to examine low-dose γ-radiation-induced effects on the differentiation of neuronal cells and on the development of neural stem cells to glial cells. Human neuroblastoma SH-SY5Y cells were exposed to (137)Cs γ rays at different stages of retinoic acid-induced neuronal differentiation, and neurite formation was determined 6 days after exposure. When SH-SY5Y cells were exposed to low-dose-rate γ rays at the onset of differentiation, the number of neurites formed per cell was significantly less after exposure to either 10, 30 or 100 mGy compared to control cells. Exposure to 10 and 30 mGy attenuated differentiation of immature C17.2 mouse-derived neural stem cells to glial cells, as verified by the diminished expression of glial fibrillary acidic protein. Proteomic analysis of the neuroblastoma cells by 2D-PAGE after 30 mGy irradiation showed that proteins involved in neuronal development were downregulated. Proteins involved in cell cycle and proliferation were altered in both cell lines after exposure to 30 mGy; however, the rate of cell proliferation was not affected in the low-dose range. The radiation-induced attenuation of differentiation and the persistent changes in protein expression is indicative of an epigenetic rather than a cytotoxic mechanism.

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

Platelet-activating factor increases platelet-dependent glycoconjugate secretion from tracheal submucosal gland

International Nuclear Information System (INIS)

Sasaki, T.; Shimura, S.; Ikeda, K.; Sasaki, H.; Takishima, T.

1989-01-01

Using isolated glands from feline trachea, we examined the effect of platelet-activating factor (PAF) on radiolabeled glycoconjugate release and glandular contraction by measuring induced tension in the absence or presence of platelets. PAF alone did not produce any significant glandular contraction nor any significant change in glycoconjugate release from isolated glands. In the presence of purified platelets containing no plasma, PAF (10(-8) to 10(-5) M) produced significant glycoconjugate secretion in a dose-dependent fashion, but it produced no significant glandular contraction. PAF-evoked glycoconjugate secretion was time dependent, reaching a peak response of 277% of control 15-30 min after the exposure of isolated glands to 10(-5) M PAF in the presence of platelets and returning to 135% of controls at 2 h. Platelets alone did not produce any significant stimulation in glycoconjugate release. CV-3988, a known PAF antagonist, inhibited the secretory response to PAF. Methysergide, a known antagonist to receptors for 5-hydroxytryptamine, did not alter PAF-evoked glycoconjugate secretion. Both indomethacin and SQ 29,548, a thromboxane receptor antagonist, abolished the PAF-evoked glycoconjugate secretion from isolated submucosal glands. Epithiomethanothromboxane A2, a stable thromboxane A2 analogue, produced a significant increase in glycoconjugate secretion in a dose-dependent fashion. These findings indicate that PAF increases glycoconjugate release in the presence of platelets and that the increase is dependent on some aspect of platelet function, namely thromboxane generation

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)

The role of radiation types and dose in induced genomic instability

International Nuclear Information System (INIS)

Kadhim Munira, A.

2007-01-01

Complete text of publication follows. Genomic Instability (GI) is defined as long-term alterations induced by low-dose exposure to a variety of genotoxic agents in mammalian cells that act to increase the 'apparent' spontaneous mutation frequency.GI is a hallmark of tumorigenic progression and is observed in the progeny of irradiated and bystander cells as the delayed and stochastic appearance of de novo chromosomal aberrations, gene mutations and delayed lethal mutations both in vitro and in vivo. It occurs at a frequency several orders of magnitude greater than would be expected for mutation in a single gene, implying that GI is a multigenic phenomenon. The expression of GI can be influenced by genotype, cell type and radiation quality; however the underlying mechanisms are not fully understood. While several studies have demonstrated GI induction by high and low LET radiation, our work on human and mouse primary cell systems has shown significant differences in the capacity to induce GI and the spectrum of alterations depending on LET. These differences might be attributed to differences in radiation track structure, radiation dose and radiation exposure regime (distribution of hit and un hit cells). In this presentation I shall review the role of radiation quality; describe the possible mechanisms underlining the observed differences between radiation type and present results of experiments demonstrating that the dose of low LET radiation might be the most significant factor in determining the role of radiation type in the induction of GI.

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)

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.

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

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 < 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.

Altered sleep composition after traumatic brain injury does not affect declarative sleep-dependent memory consolidation

Directory of Open Access Journals (Sweden)

Janna eMantua

2015-06-01

Full Text Available Individuals with a history of traumatic brain injury (TBI often report sleep disturbances, which may be caused by changes in sleep architecture or reduced sleep quality (greater time awake after sleep onset, poorer sleep efficiency, and sleep stage proportion alterations. Sleep is beneficial for memory formation, and herein we examine whether altered sleep physiology following TBI has deleterious effects on sleep-dependent declarative memory consolidation. Participants learned a list of word pairs in the morning or evening, and recall was assessed 12-hrs later, following an interval awake or with overnight sleep. Young adult participants (18-22 yrs were assigned to one of four experimental groups: TBI Sleep (n=14, TBI Wake (n=12, non-TBI Sleep (n=15, non-TBI Wake (n=15. Each TBI participant was >1 yr post-injury. Sleep physiology was measured with polysomnography. Memory consolidation was assessed by comparing change in word-pair recall over 12-hr intersession intervals. The TBI group spent a significantly greater proportion of the night in SWS than the non-TBI group at the expense of NREM1. The TBI group also had marginally lower EEG delta power during SWS in the central region. Intersession changes in recall were greater for intervals with sleep than without sleep in both groups. However, despite abnormal sleep stage proportions for individuals with a TBI history, there was no difference in the intersession change in recall following sleep for the TBI and non-TBI groups. In both Sleep groups combined, there was a positive correlation between Intersession Change and the proportion of the night in NREM2 + SWS. Overall, sleep composition is altered following TBI but such deficits do not yield insufficiencies in sleep-dependent memory consolidation.

Short-term high dose of quercetin and resveratrol alters aging markers in human kidney cells

Directory of Open Access Journals (Sweden)

Fatemeh Abharzanjani

2017-01-01

Full Text Available Background: Hyperglycemia-mediated oxidative stress implicates in etiology of kidney cell aging and diabetic nephropathy. We evaluated the effects of different doses of resveratrol and quercetin and their combination therapy on aging marker in human kidney cell culture under hyperglycemia condition. Methods: Human embryonic kidney cell (HEK-293 was cultured in Dulbecco's Modified Eagle Medium (DMEM containing 100 mM (18 mg/L for 24 h. The cells were treated with resveratrol (2.5, 5, 10 μm, quercetin (3, 6, 12 μm, and combination of these (R 2.5 μm, Q 3 μm and (R 5 μm, Q 6 μm and (R 10 μm, Q 12 μm for 48 h, and then, cells were lysed to access RNA and lysate. Results: The analysis of data showed that beta-galactosidase enzyme gene expression as an aging marker in all treatment groups has reduced in a dose-dependent manner. Gene expression of Sirtuin1 and thioredoxin (Trx in all treated groups in comparison to control group increased in a dose-dependent fashion. Trx interacting protein (TXNIP gene expression decreased in a dose-dependent manner in all treated groups, especially in resveratrol and combination therapy. Conclusions: According to the results of this research, quercetin, resveratrol, and especially combination treatments with increased expression levels of antioxidants, can reduce aging markers in HEK cell line in hyperglycemia conditions. These results lead us to use flavonoids such as resveratrol for anti-aging potential.

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.

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

International Nuclear Information System (INIS)

Sykora, Peter; Snow, Elizabeth T.

2008-01-01

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

Dose and time dependent ototoxicity of aspartame in rats.

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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.

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.

Marijuana exposure and pulmonary alterations in primates.

Science.gov (United States)

Fligiel, S E; Beals, T F; Tashkin, D P; Paule, M G; Scallet, A C; Ali, S F; Bailey, J R; Slikker, W

1991-11-01

As part of a large multidisciplinary study, we examined lungs from 24 periadolescent male rhesus monkeys that were sacrificed seven months after daily marijuana smoke inhalation of 12 months duration. Animals were divided into four exposure groups: A) high-dose (one marijuana cigarette 7 days/week), B) low-dose (one marijuana cigarette 2 days/week and sham smoke 5 days/week), C) placebo (one extracted marijuana cigarette 7 days/week), and D) sham (sham smoke 7 days/week). Lungs, removed intact, were formalin inflated, sectioned and examined. Several pathological alterations, including alveolitis, alveolar cell hyperplasia and granulomatous inflammation, were found with higher frequency in all cigarette-smoking groups. Other alterations, such as bronchiolitis, bronchiolar squamous metaplasia and interstitial fibrosis, were found most frequently in the marijuana-smoking groups. Alveolar cell hyperplasia with focal atypia was seen only in the marijuana-smoking animals. These changes represent mostly early alterations of small airways. Additional follow-up studies are needed to determine their long-term prognostic significance.

Cholecalciferol attenuates perseverative behavior associated with developmental alcohol exposure in rats in a dose-dependent manner.

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Idrus, N M; Happer, J P; Thomas, J D

2013-07-01

Alcohol is a known teratogen that is estimated to affect 2-5% of the births in the U.S. Prenatal alcohol exposure can produce physical features such as facial dysmorphology, physiological alterations such as cell loss in the central nervous system (CNS), and behavioral changes that include hyperactivity, cognitive deficits, and motor dysfunction. The range of effects associated with prenatal alcohol exposure is referred to as fetal alcohol spectrum disorders (FASD). Despite preventative measures, some women continue to drink while pregnant. Therefore, identifying interventions that reduce the severity of FASD is critical. This study investigated one such potential intervention, vitamin D3, a nutrient that exerts neuroprotective properties. The present study determined whether cholecalciferol, a common vitamin D3 nutritional supplement, could serve as a means of mitigating alcohol-related learning deficits. Using a rat model of FASD, cholecalciferol was given before, during, and after 3rd trimester equivalent alcohol exposure. Three weeks after cholecalciferol treatment, subjects were tested on a serial spatial discrimination reversal learning task. Animals exposed to ethanol committed significantly more errors compared to controls. Cholecalciferol treatment reduced perseverative behavior that is associated with developmental alcohol exposure in a dose-dependent manner. These data have important implications for the treatment of FASD and suggest that cholecalciferol may reduce some aspects of FASD. This article is part of a Special Issue entitled 'Vitamin D Workshop'. Copyright © 2012 Elsevier Ltd. All rights reserved.

Heparan sulfate proteoglycans undergo differential expression alterations in right sided colorectal cancer, depending on their metastatic character

International Nuclear Information System (INIS)

Fernández-Vega, Iván; García-Suárez, Olivia; García, Beatriz; Crespo, Ainara; Astudillo, Aurora; Quirós, Luis M.

2015-01-01

Heparan sulfate proteoglycans (HSPGs) are complex molecules involved in the growth, invasion and metastatic properties of cancerous cells. This study analyses the alterations in the expression patterns of these molecules in right sided colorectal cancer (CRC), both metastatic and non-metastatic. Twenty right sided CRCs were studied. A transcriptomic approach was used, employing qPCR to analyze both the expression of the enzymes involved in heparan sulfate (HS) chains biosynthesis, as well as the proteoglycan core proteins. Since some of these proteoglycans can also carry chondroitin sulfate (CS) chains, we include the study of the genes involved in the biosynthesis of these glycosaminoglycans. Immunohistochemical techniques were also used to analyze tissue expression of particular genes showing significant expression differences, of potential interest. Changes in proteoglycan core proteins differ depending on their location; those located intracellularly or in the extracellular matrix show very similar alteration patterns, while those located on the cell surface vary greatly depending on the nature of the tumor: glypicans 1, 3, 6 and betaglycan are affected in the non-metastatic tumors, whereas in the metastatic, only glypican-1 and syndecan-1 are modified, the latter showing opposing alterations in levels of RNA and of protein, suggesting post-transcriptional regulation in these tumors. Furthermore, in non-metastatic tumors, polymerization of glycosaminoglycan chains is modified, particularly affecting the synthesis of the tetrasaccharide linker and the initiation and elongation of CS chains, HS chains being less affected. Regarding the enzymes responsible for the modificaton of the HS chains, alterations were only found in non-metastatic tumors, affecting N-sulfation and the isoforms HS6ST1, HS3ST3B and HS3ST5. In contrast, synthesis of the CS chains suggests changes in epimerization and sulfation of the C4 and C2 in both types of tumor. Right sided CRCs show

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

International Nuclear Information System (INIS)

Silva, Cleber Feijo; Campos, Leticia Lucente

2013-01-01

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

A High-Fat Diet Causes Impairment in Hippocampal Memory and Sex-Dependent Alterations in Peripheral Metabolism

Directory of Open Access Journals (Sweden)

Erica L. Underwood

2016-01-01

Full Text Available While high-fat diets are associated with rising incidence of obesity/type-2 diabetes and can induce metabolic and cognitive deficits, sex-dependent comparisons are rarely systematically made. Effects of exclusive consumption of a high-fat diet (HFD on systemic metabolism and on behavioral measures of hippocampal-dependent memory were compared in young male and female LE rats. Littermates were fed from weaning either a HFD or a control diet (CD for 12 wk prior to testing. Sex-different effects of the HFD were observed in classic metabolic signs associated with type-2 diabetes. Males fed the HFD became obese, and had elevated fasted blood glucose levels, elevated corticosterone, and impaired glucose-tolerance, while females on the HFD exhibited only elevated corticosterone. Regardless of peripheral metabolism alteration, rats of both sexes fed the HFD were equally impaired in a spatial object recognition memory task associated with impaired hippocampal function. While the metabolic changes reported here have been characterized previously in males, the set of diet-induced effects observed here in females are novel. Impaired memory can have significant cognitive consequences, over the short-term and over the lifespan. A significant need exists for comparative research into sex-dependent differences underlying obesity and metabolic syndromes relating systemic, cognitive, and neural plasticity mechanisms.

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

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

2012-01-01

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

Hippocampal-dependent Pavlovian conditioning in adult rats exposed to binge-like doses of ethanol as neonates.

Science.gov (United States)

Lindquist, Derick H

2013-04-01

Binge-like postnatal ethanol exposure produces significant damage throughout the brain in rats, including the cerebellum and hippocampus. In the current study, cue- and context-mediated Pavlovian conditioning were assessed in adult rats exposed to moderately low (3E; 3g/kg/day) or high (5E; 5g/kg/day) doses of ethanol across postnatal days 4-9. Ethanol-exposed and control groups were presented with 8 sessions of trace eyeblink conditioning followed by another 8 sessions of delay eyeblink conditioning, with an altered context presented over the last two sessions. Both forms of conditioning rely on the brainstem and cerebellum, while the more difficult trace conditioning also requires the hippocampus. The hippocampus is also needed to gate or modulate expression of the eyeblink conditioned response (CR) based on contextual cues. Results indicate that the ethanol-exposed rats were not significantly impaired in trace EBC relative to control subjects. In terms of CR topography, peak amplitude was significantly reduced by both doses of alcohol, whereas onset latency but not peak latency was significantly lengthened in the 5E rats across the latter half of delay EBC in the original training context. Neither dosage resulted in significant impairment in the contextual gating of the behavioral response, as revealed by similar decreases in CR production across all four treatment groups following introduction of the novel context. Results suggest ethanol-induced brainstem-cerebellar damage can account for the present results, independent of the putative disruption in hippocampal development and function proposed to occur following postnatal ethanol exposure. Copyright © 2013 Elsevier B.V. All rights reserved.

Quercetin does not alter the oral bioavailability of Atorvastatin in rats.

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Koritala, Rekha; Challa, Siva Reddy; Ragam, Satheesh Kumar; Geddam, Lal Babu; Venkatesh Reddy Challa, Venkatesh Reddy; Devi, Renuka; Sattenapalli, Srinu; Babu, Narendra

2015-09-01

The study was undertaken to evaluate the effect of Quercetin on the pharmacokinetics of Atorvastatin Calcium. In-vivo Pharmacokinetic studies were performed on rats in a single dose study and multiple dose study. Rats were treated with Quercetin (10 mg/kg) and Atorvastatin Calcium (20 mg/kg) orally and blood samples were collected at (0) pretreatment and 0.5, 1, 1.5, 2, 2.5, 3, 4, 8, 12, 24 hours post treatment. Plasma concentrations of Atorvastatin were estimated by HPLC method. Quercetin treatment did not significantly alter the pharmacokinetic parameters of atorvastatin like AUC(0-24), AUC(0-α) , T(max), C(max) and T(½) in both single dose and multiple dose studies of Atorvastatin Calcium. Quercetin does not alter the oral bioavailability of Atorvastatin Calcium in rats.

Effect of low dose electron beam irradiation on the alteration layer formed during nuclear glass leaching

Energy Technology Data Exchange (ETDEWEB)

Mougnaud, S., E-mail: sarah.mougnaud@gmail.com [CEA Marcoule, DEN, DTCD, SECM, BP 17171, 30207 Bagnols-sur-Cèze cedex (France); Tribet, M. [CEA Marcoule, DEN, DTCD, SECM, BP 17171, 30207 Bagnols-sur-Cèze cedex (France); Renault, J.-P. [NIMBE, CNRS, CEA, Université Paris Saclay, CEA Saclay, 91191 Gif-sur-Yvette cedex (France); Jollivet, P. [CEA Marcoule, DEN, DTCD, SECM, BP 17171, 30207 Bagnols-sur-Cèze cedex (France); Panczer, G. [Institut Lumière Matière, UMR 5306, Université Lyon 1-CNRS, Université de Lyon, 69622 Villeurbanne cedex (France); Charpentier, T. [NIMBE, CNRS, CEA, Université Paris Saclay, CEA Saclay, 91191 Gif-sur-Yvette cedex (France); Jégou, C. [CEA Marcoule, DEN, DTCD, SECM, BP 17171, 30207 Bagnols-sur-Cèze cedex (France)

2016-12-15

This investigation concerns borosilicate glass leaching mechanisms and the evolution of alteration layer under electron beam irradiation. A simple glass doped with rare earth elements was selected in order to access mechanistic and structural information and better evaluate the effects of irradiation. It was fully leached in initially pure water at 90 °C and at high glass surface area to solution volume ratio (S/V = 20 000 m{sup −1}) in static conditions. Under these conditions, the system quickly reaches the residual alteration rate regime. A small particle size fraction (2–5 μm) was sampled in order to obtain a fairly homogeneous altered material enabling the use of bulk characterization methods. External irradiations with 10 MeV electrons up to a dose of 10 MGy were performed either before or after leaching, to investigate respectively the effect of initial glass irradiation on its alteration behavior and the irradiation stability of the alteration layer. Glass dissolution rate was analyzed by regular leachate samplings and the alteration layer structure was characterized by Raman, luminescence (continuous or time-resolved), and {sup 29}Si MAS NMR and EPR spectroscopy. It was shown that the small initial glass evolutions under irradiation did not induce any modification of the leaching kinetic nor of the structure of the alteration layer. The alteration process seemed to “smooth over” the created defects. Otherwise, the alteration layer and initial glass appeared to have different behaviors under irradiation. No Eu{sup 3+} reduction was detected in the alteration layer after irradiation and the defect creation efficiency was much lower than for initial glass. This can possibly be explained by the protective role of pore water contained in the altered material (∼20%). Moreover, a slight depolymerization of the silicon network of the altered glass under irradiation with electrons was evidenced, whereas in the initial glass it typically

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

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

Circadian transitions in radiation dose-dependent augmentation of mRNA levels for DNA damage-induced genes elicited by accurate real-time RT-PCR quantification

International Nuclear Information System (INIS)

Ishihara, Hiroshi; Tanaka, Izumi; Yakumaru, Haruko

2010-01-01

Molecular mechanisms of intracellular response after DNA-damage by exposure to ionizing radiation have been studied. In the case of cells isolated from living body of human and experimental animals, alteration of the responsiveness by physiological oscillation such as circadian rhythm must be considered. To examine the circadian variation in the response of p53-responsible genes p21, mdm2, bax, and puma, we established a method to quantitate their mRNA levels with high reproducibility and accuracy based on real-time reverse transcription polymerase chain reaction (RT-PCR) and compared the levels of responsiveness in mouse hemocytes after diurnal irradiation to that after nocturnal irradiation. Augmentations of p21 and mdm2 mRNA levels with growth-arrest and of puma mRNA before apoptosis were confirmed by time-course experiment in RAW264.7, and dose-dependent increases in the peak levels of all the RNA were shown. Similarly, the relative RNA levels of p21, mdm2, bax, and puma per glyceraldehyde-3-phosphate dehydrogenase (GAPDH) also increased dose-dependently in peripheral blood and bone marrow cells isolated from whole-body-irradiated mice. Induction levels of all messages reduced by half after nighttime irradiation as compared with daytime irradiation in blood cells. In marrow cells, nighttime irradiation enhanced the p21 and mdm2 mRNA levels than daytime irradiation. No significant difference in bax or puma mRNA levels was observed between nighttime and daytime irradiation in marrow cells. This suggests that early-stage cellular responsiveness in DNA damage-induced genes is modulated between diurnal and nocturnal irradiation. (author)

Ubiquitin-dependent system controls radiation induced apoptosis

International Nuclear Information System (INIS)

Delic, J.; Magdelenat, H.; Glaisner, S.; Magdelenat, H.; Maciorowski, Z.

1997-01-01

The selective proteolytic pathway, dependent upon 'N-end rule' protein recognition/ubiquitination and on the subsequent proteasome dependent processing of ubiquitin conjugates, operates in apoptosis induced by γ-irradiation. The proteasome inhibitor peptide aldehyde, MG132, efficiently induced apoptosis and was also able (at doses lower than those required for apoptosis induction) to potentiate apoptosis induced by DNA damage. Its specificity is suggested by the induction of the ubiquitin (UbB and UbC) and E1 (ubiquitin activating enzyme) genes and by an altered ubiquitination pattern. More selectively, a di-peptide competitor of the 'N-end rule' of ubiquitin dependent protein processing inhibited radiation induced apoptosis. This inhibition is also followed by an altered ubiquitination pattern and by activation of Poly (ADP-ribose) polymerase (PARP). These data strongly suggest that early apoptosis radiation induced events are controlled by ubiquitin-dependent proteolytic processing. (author)

Inhibitory mechanism of low-dose, whole-body irradiation with gamma-rays against tumor metastasis

International Nuclear Information System (INIS)

Yasuhiro Ohsima; Mitsutoshi Tukimoto; Shuji Kojima

2007-01-01

Complete text of publication follows. A lot of beneficial effects of low-dose irradiation are well known. Of them, an inhibitory effect of the radiation on lung metastasis is reported so far. It has been reported that low-dose whole-body irradiation with gamma rays enhanced cytotoxic immune response as one of the mechanisms. In our laboratory, it has been confirmed an enhancement of natural killer activity in mice irradiated with whole-body 0.5Gy gamma-rays. Metastasis is accomplished by multistep process, involving basement membrane destruction, local invasion, intravasation, survival in the bloodstream, extravasation into distant organs, and proliferation at the target site. Besides, a lot of growth factors and proteases are involved in these steps. As to mechanism of inhibition of tumor metastasis induced by low-dose whole-body irradiation, studies from the standpoint of tumor invasion have not been reported. Here, inhibitory effect of 0.5Gy whole-body gamma-ray irradiation on tumor metastasis and its mechanism were examined in pulmonary metastasis model mice injected with B16 melanoma cells. Consequently, 0.5Gy whole-body gamma ray irradiation significantly suppressed colony formation in the lungs. Expression of matrix metalloproteinase- 2 (MMP- 2), a proteinase related to metastasis, in lung tissues was suppressed by the radiation. Alteration of tissue inhibitor of matrix metalloproteinase (TIMP) after the gamma-ray irradiation was examined. Expression of TIMP-1 and TIMP-2 mRNA in the lungs were significantly increased. In order to clarify the inhibitory effect obtained in the in vivo metastatic lung cancer model mice, we studied effects of gamma-rays on cell proliferation, alterations of mRNA and proteins related to tumor metastasis in cultured B16 melanoma cells. Proliferation of B16 melanoma cells was decreased in a dose-dependent manner. MMP-2 mRNA expression was not altered in any doses of gamma-rays. Thought expression of the protein was slightly

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.

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.

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

Postnatal exposure to trichloroethylene alters glutathione redox homeostasis, methylation potential, and neurotrophin expression in the mouse hippocampus

Science.gov (United States)

Blossom, Sarah J.; Melnyk, Stepan; Cooney, Craig A.; Gilbert, Kathleen M.; James, S. Jill

2012-01-01

Previous studies have shown that continuous exposure throughout gestation until the juvenile period to environmentally-relevant doses of trichloroethylene (TCE) in the drinking water of MRL+/+ mice promoted adverse behavior associated with glutathione depletion in the cerebellum indicating increased sensitivity to oxidative stress. The purpose of this study was to extend our findings and further characterize the impact of TCE exposure on redox homeostasis and biomarkers of oxidative stress in the hippocampus, a brain region prone to oxidative stress. Instead of a continuous exposure, the mice were exposed to water only or two environmentally relevant doses of TCE in the drinking water postnatally from birth until 6 weeks of age. Biomarkers of plasma metabolites in the transsulfuration pathway and the transmethylation pathway of the methionine cycle were also examined. Gene expression of neurotrophins was examined to investigate a possible relationship between oxidative stress, redox imbalance and neurotrophic factor expression with TCE exposure. Our results show that hippocampi isolated from male mice exposed to TCE showed altered glutathione redox homeostasis indicating a more oxidized state. Also observed was a significant, dose dependent increase in glutathione precursors. Plasma from the TCE treated mice showed alterations in metabolites in the transsulfuration and transmethylation pathways indicating redox imbalance and altered methylation capacity. 3-Nitrotyrosine, a biomarker of protein oxidative stress, was also significantly higher in plasma and hippocampus of TCE-exposed mice compared to controls. In contrast, expression of key neurotrophic factors in the hippocampus (BDNF, NGF, and NT-3) was significantly reduced compared to controls. Our results demonstrate that low-level postnatal and early life TCE exposure modulates neurotrophin gene expression in the mouse hippocampus and may provide a mechanism for TCE-mediated neurotoxicity. PMID:22421312

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.)

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

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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.

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)

HC-Pro silencing suppressor significantly alters the gene expression profile in tobacco leaves and flowers

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Lehto Kirsi

2011-04-01

Full Text Available Abstract Background RNA silencing is used in plants as a major defence mechanism against invasive nucleic acids, such as viruses. Accordingly, plant viruses have evolved to produce counter defensive RNA-silencing suppressors (RSSs. These factors interfere in various ways with the RNA silencing machinery in cells, and thereby disturb the microRNA (miRNA mediated endogene regulation and induce developmental and morphological changes in plants. In this study we have explored these effects using previously characterized transgenic tobacco plants which constitutively express (under CaMV 35S promoter the helper component-proteinase (HC-Pro derived from a potyviral genome. The transcript levels of leaves and flowers of these plants were analysed using microarray techniques (Tobacco 4 × 44 k, Agilent. Results Over expression of HC-Pro RSS induced clear phenotypic changes both in growth rate and in leaf and flower morphology of the tobacco plants. The expression of 748 and 332 genes was significantly changed in the leaves and flowers, respectively, in the HC-Pro expressing transgenic plants. Interestingly, these transcriptome alterations in the HC-Pro expressing tobacco plants were similar as those previously detected in plants infected with ssRNA-viruses. Particularly, many defense-related and hormone-responsive genes (e.g. ethylene responsive transcription factor 1, ERF1 were differentially regulated in these plants. Also the expression of several stress-related genes, and genes related to cell wall modifications, protein processing, transcriptional regulation and photosynthesis were strongly altered. Moreover, genes regulating circadian cycle and flowering time were significantly altered, which may have induced a late flowering phenotype in HC-Pro expressing plants. The results also suggest that photosynthetic oxygen evolution, sugar metabolism and energy levels were significantly changed in these transgenic plants. Transcript levels of S

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...

Progestins alter photo-transduction cascade and circadian rhythm network in eyes of zebrafish (Danio rerio)

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Zhao, Yanbin; Fent, Karl

2016-02-01

Environmental progestins are implicated in endocrine disruption in vertebrates. Additional targets that may be affected in organisms are poorly known. Here we report that progesterone (P4) and drospirenone (DRS) interfere with the photo-transduction cascade and circadian rhythm network in the eyes of zebrafish. Breeding pairs of adult zebrafish were exposed to P4 and DRS for 21 days with different measured concentrations of 7-742 ng/L and 99-13´650 ng/L, respectively. Of totally 10 key photo-transduction cascade genes analyzed, transcriptional levels of most were significantly up-regulated, or normal down-regulation was attenuated. Similarly, for some circadian rhythm genes, dose-dependent transcriptional alterations were also observed in the totally 33 genes analyzed. Significant alterations occurred even at environmental relevant levels of 7 ng/L P4. Different patterns were observed for these transcriptional alterations, of which, the nfil3 family displayed most significant changes. Furthermore, we demonstrate the importance of sampling time for the determination and interpretation of gene expression data, and put forward recommendations for sampling strategies to avoid false interpretations. Our results suggest that photo-transduction signals and circadian rhythm are potential targets for progestins. Further studies are required to assess alterations on the protein level, on physiology and behavior, as well as on implications in mammals.

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

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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.

Key enzymes of gluconeogenesis are dose-dependently reduced in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-treated rats

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Weber, L.W.D.; Rozman, K. (Kansas Univ., Kansas City, KS (USA). Dept. of Pharmacology, Toxicology and Therapeutics Gesellschaft fuer Strahlen- und Umweltforschung mbH Muenchen (GSF), Neuherberg (Germany, F.R.). Inst. fuer Toxikologie); Lebofsky, M. (Kansas Univ., Kansas City, KS (USA). Dept. of Pharmacology, Toxicology and Therapeutics); Greim, H. (Gesellschaft fuer Strahlen- und Umweltforschung mbH Muenchen (GSF), Neuherberg (Germany, F.R.). Inst. fuer Toxikologie)

1991-02-01

Male Sprague-Dawley rats (240-245 g) were dosed ip with 5, 15, 25, or 125 {mu}g/kg -,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in corn oil. Ad libitum-fed and pair-fed controls received vehicle (4 ml/kg) alone. Two or 8 days after dosing five rats of each group were sacrificed, their livers removed and assayed for the activities of three gluconeogenic enzymes, (phosphoenol-pyruvate carboxykinase (PEPCK; EC 4.1.1.32), pyruvate carboxylase (PC; EC 6.4.1.1.), and glucose-6-phosphatase (G-6-Pase, EC 3.1.3.9)), and one glycolytic enzyme (pyruvate kinase (PK; EC 2.7.1.40)) by established procedures. The activity of PK was not affected by TCDD at either time point. The activity of G-6-Phase tended to be decreased in TCDD-treated animals, as compared to pair-fed controls, but the decrease was variable without an apparent dose-response. The activity of PEPCK was significantly decreased 2 days after dosing, but a clear dose-response was apparent only at the 8-day time point. Maximum loss of activity at the highest dose was 56% below pair-fed control levels. PC activity was slightly decreased 2 days after TCDD treatment and displayed statistically significant, dose-dependent reduction by 8 days after dosing with a 49% loss of enzyme activity after the highest dose. It is concluded that inhibition of gluconeogenesis by TCDD previously demonstrated in vivo is probably due to decreased activities of PEPCK and PC. The data also support the prevailing view that PEPCK and PC are rate-determining enzymes in gluconeogenesis. (orig.).

Transient impairment of hippocampus-dependent learning and memory in relatively low-dose of acute radiation syndrome is associated with inhibition of hippocampal neurogenesis

International Nuclear Information System (INIS)

Kim, Joong-Sun; Lee, Hae-June; Kim, Jong-Choon

2008-01-01

Neurogenesis in the adult hippocampus, which occurs constitutively, is vulnerable to ionizing radiation. In the relatively low-dose exposure of acute radiation syndrome (ARS), the change in the adult hippocampal function is poorly understood. This study analyzed the changes in apoptotic cell death and neurogenesis in the DGs of hippocampi from adult ICR mice with single whole-body gamma-irradiation using the TdT-mediated dUTP-biotin nick end-labeling (TUNEL) method and immunohistochemical markers of neurogenesis, Ki-67 and doublecortin (DCX). In addition, the hippocampus-dependent learning and memory tasks after single whole-body gamma-irradiation were examined in order to evaluate the hippocampus-related behavioral dysfunction in the relatively low-dose exposure of ARS. The number of TUNEL-positive apoptotic nuclei in the dentate gyrus (DG) was increased 6-12 h after acute gamma-irradiation (a single dose of 0.5 to 4 Gy). In contrast, the number of Ki-67- and DCX-positive cells began to decrease significantly 6 h postirradiation, reaching its lowest level 24 h after irradiation. The level of Ki-67 and DCX immunoreactivity decreased in a dose-dependent manner within the range of irradiation applied (0-4 Gy). In passive avoidance and object recognition memory test, the mice trained 1 day after acute irradiation (2 Gy) showed significant memory deficits, compared with the sham controls. In conclusion, the pattern of the hippocampus-dependent memory dysfunction is consistent with the change in neurogenesis after acute irradiation. It is suggested that a relatively low dose of ARS in adult ICR mice is sufficiently detrimental to interrupt the functioning of the hippocampus, including learning and memory, possibly through the inhibition of neurogenesis. (author)

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

Heparin induced alterations in clearance and distribution of blood-borne microparticles following operative trauma.

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Saba, T M; Antikatzides, T G

1979-04-01

The influence of systemic heparin administration on the vascular clearance and tissue distribution of blood-borne microparticles was evaluated in normal rats and rats after operation (laparotomy plus intestinal manipulation) utilizing an (131)I- colloid which is phagocytized by the reticuloendothelial system (RES). Intravenous heparin administration (100 USP/100g body weight) into normal animals three minutes prior to colloid injection (50 mg/lOOg) induced a significant increase in pulmonary localization of the microparticles as compared to nonheparinized control rats, while hepatic and splenic uptake were decreased. Surgical trauma decreased hepatic RE uptake and increased pulmonary localization of the microparticles when injected systemically at 60 minutes postsurgery. Heparin administration 60 minutes after surgery and three minutes prior to colloid injection, magnified the increased pulmonary localization response with an associated further depression of the RES. The ability of heparin to alter both RE clearance function and lung localization of microparticles was dose dependent and a function of the interval between heparin administration and systemic particulate infusion. Thus, low dose heparin administration was capable of stimulating RE activity while heparin in doses of excess of 50 USP units/lOOg body weight decreased RE function. These findings suggest that the functional state of the hepatic RE system can be greatly affected in a dose-dependent manner by systemic heparin administration which may influence distribution of blood-borne microparticles.

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)

The effect of infectious dose on humoral and cellular immune responses in Chlamydophila caviae primary ocular infection.

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Ana Filipovic

Full Text Available Following infection, the balance between protective immunity and immunopathology often depends on the initial infectious load. Several studies have investigated the effect of infectious dose; however, the mechanism by which infectious dose affects disease outcomes and the development of a protective immune response is not known. The aim of this study was to investigate how the infectious dose modulates the local and systemic humoral and the cellular immune responses during primary ocular chlamydial infection in the guinea pig animal model. Guinea pigs were infected by ocular instillation of a Chlamydophila caviae-containing eye solution in the conjunctival sac in three different doses: 1×102, 1×104, and 1×106 inclusion forming units (IFUs. Ocular pathology, chlamydial clearance, local and systemic C. caviae-specific humoral and cellular immune responses were assessed. All inocula of C. caviae significantly enhanced the local production of C. caviae-specific IgA in tears, but only guinea pigs infected with the higher doses showed significant changes in C. caviae-specific IgA levels in vaginal washes and serum. On complete resolution of infection, the low dose of C. caviae did not alter the ratio of CD4+ and CD8+ cells within guinea pigs' submandibular lymph node (SMLN lymphocytes while the higher doses increased the percentages of CD4+ and CD8+ cells within the SMLN lymphocytes. A significant negative correlation between pathology intensity and the percentage of CD4+ and CD8+ cells within SMLN lymphocyte pool at selected time points post-infection was recorded for both 1×104, and 1×106 IFU infected guinea pigs. The relevance of the observed dose-dependent differences on the immune response should be further investigated in repeated ocular chlamydial infections.

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

International Nuclear Information System (INIS)

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

2017-01-01

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

Phenobarbital at Low Dose in the presence of Curcumin Decreases Progress of Cancer in Rats

International Nuclear Information System (INIS)

Mazen, G.M.A.

2011-01-01

This current investigation was conducted on male albino rats to elucidate the effects of curcumin alone or in the presence of phenobarbital at low dose to decrease the progress of hepato-gastrointestinal carcinogenesis induced by N-diethylnitrosoamine (DEN) in rats. As a result of cancer induction, the levels of serum tumour markers [carcino-embryonic antigen (CEA), alpha-fetoprotein (AFP) and cancer antigen (CA19.9)] were significantly elevated. On the other hand, glutathione (GSH) and glutathione peroxidase (GPx) were decreased significantly in blood, liver, stomach and intestine whereas the levels of malondialdehyde (MAD) in liver, stomach and intestine were significantly elevated in the cancer group of rats in comparison to their corresponding control group. The administration of curcumin alone or together with phenobarbital ameliorated all these alterations depending on the time of administration. The data of this study suggested that low dose of phenobarbital in the presence of curcumin may inhibit the development of hepato-gastrointestinal carcinogenesis initiated with DEN.

Effects of 14-day oral low dose selenium nanoparticles and selenite in rat—as determined by metabolite pattern determination

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Niels Hadrup

2016-10-01

Full Text Available Selenium (Se is an essential element with a small difference between physiological and toxic doses. To provide more effective and safe Se dosing regimens, as compared to dosing with ionic selenium, nanoparticle formulations have been developed. However, due to the nano-formulation, unexpected toxic effects may occur. We used metabolite pattern determination in urine to investigate biological and/or toxic effects in rats administered nanoparticles and for comparison included ionic selenium at an equimolar dose in the form of sodium selenite. Low doses of 10 and 100 fold the recommended human high level were employed to study the effects at borderline toxicity. Evaluations of all significantly changed putative metabolites, showed that Se nanoparticles and sodium selenite induced similar dose dependent changes of the metabolite pattern. Putative identified metabolites included increased decenedioic acid and hydroxydecanedioic acid for both Se formulations whereas dipeptides were only increased for selenite. These effects could reflect altered fatty acid and protein metabolism, respectively.

Sodium bicarbonate causes dose-dependent increases in cerebral blood flow in infants and children with single ventricle physiology

Science.gov (United States)

Buckley, Erin M.; Naim, Maryam Y.; Lynch, Jennifer M.; Goff, Donna A.; Schwab, Peter J.; Diaz, Laura K.; Nicolson, Susan C.; Montenegro, Lisa M.; Lavin, Natasha A.; Durduran, Turgut; Spray, Thomas L.; Gaynor, J. William; Putt, Mary E.; Yodh, A.G.; Fogel, Mark A.; Licht, Daniel J.

2013-01-01

Background Sodium bicarbonate (NaHCO3) is a common treatment for metabolic acidemia, however little definitive information exists regarding its treatment efficacy and cerebral hemodynamic effects. This pilot observational study quantifies relative changes in cerebral blood flow (rCBF) and oxy and deoxy-hemoglobin concentrations (ΔHbO2 and ΔHb) due to bolus administration of NaHCO3 in patients with mild base deficits. Methods Infants and children with hypoplastic left heart syndrome (HLHS) were recruited prior to cardiac surgery. NaHCO3 was given as needed for treatment of base deficit. Diffuse optical spectroscopies were employed for 15 minutes post-injection to non-invasively monitor ΔHb, ΔHbO2 and rCBF relative to baseline prior to NaHCO3 administration. Results Twenty-two anesthetized and mechanically ventilated HLHS patients (1 day to 4 years old) received a median (interquartile range) dose of 1.1 (0.8, 1.8) mEq/kg NaHCO3 administered intravenously over 10–20 seconds to treat a base deficit of −4 (−6, −3) mEq/l. NaHCO3 caused significant dose-dependent increases in rCBF, however population averaged ΔHb or Δ4HbO2 compared to controls were not significant. Conclusions Dose-dependent increases in cerebral blood flow (CBF) caused by bolus NaHCO3 are an important consideration in vulnerable populations wherein risk of rapid CBF fluctuations does not outweigh the benefit of treating a base deficit. PMID:23403802

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)

Detection of radioiodine-induced cytogenetic alterations in circulating lymphocytes of thyroid patients

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Kasuba, V [Inst. for Medical Recearch and Occupational Health, Zagreb (Croatia). Laboratory for Mutagenesis; Konrady, A; Koeteles, G J [Frederic Joliot-Curie National Research Institute for Radiobiology and Radiohygiene, Budapest (Hungary); Kusic, Z [Clinical Hospital Sestre Milosrdnice, Zagreb (Croatia). Dept. of Oncology and Nuclear Medicine

1994-10-01

Radioiodines are often used for experimental purposes and for diagnosis and therapy in clinical practice. Human population might also be exposed to radioiodines in nuclear accidents. The ionizing energy of radioiodine affects not only the thyroid where it concentrates but also other tissues, especially the lymphocytes during their circulation through and around the gland containing the radioisotopes. Therefore, it seemed to be of interest to carry out investigations concerning the cytogenetic alterations in blood lymphocytes of patients treated with iodine-131. The method of choice was the relatively easily performable micronucleus assay in cytokinesis-blocked cultures of human peripheral lymphocytes. The test was performed on blood samples of 30 patients before the radioisotope treatment and one, two and four days after, one as well as 6 and - in a few cases - 12 weeks later. The amounts of iodine-131 injected were dependent on the clinical practices to reach the therapeutic radiation doses for hyperthyroidism and adenomas and were in the range of 220 and 5180 MBq. it was observed that the micronucleus frequency increased in the treated hyperthyroid patients while in patients with toxic adenomas the radioiodine did not result in an increase or even as compared to the pretreatment values in a few cases decreased values were seen. The results suggest individual differences in radiosensitivity as well as that the frequency of cytogenetic alterations depend on the physiological or pathological conditions of the thyroid. The significance of this observation will be discussed for dose assessments by cytogenetic techniques due to internal radioiodine. (author).

Alterations in carbohydrates and the protein metabolism of the harmful freshwater vector snail Lymnaea acuminata induced by the Euphorbia tirucalli latex extract.

Science.gov (United States)

Tiwari, Sudhanshu; Singh, A

2005-11-01

To know the short- as well as long-term effect of aqueous latex extracts of Euphorbia tirucalli on carbohydrate and protein metabolism, the snail Lymnaea acuminata was exposed to sublethal doses of 0.37 and 0.55 mg/L for a 24-h and 0.20 and 0.31 mg/L for a 96-h exposure period. Significant (P<0.05) alterations in the glycogen, pyruvate, lactate, total protein, and free amino acid level, as well as in the activity of enzyme lactic dehydrogenase, succinic dehydrogenase, cytochrome oxidase, protease, aspartate aminotransaminase, and alanine aminotransaminase were observed in the nervous, hepatopancreatic, and ovotestis tissues of the freshwater vector snail L. acuminata exposed to sublethal doses of E. tirucalli latex extract. The alterations in all biochemical parameters were significantly (P<0.05) time and dose dependent. After the 7th day of the withdrawal of treatment, there was significant (P<0.05) recovery in glycogen, pyruvate, lactate, total protein, and the free amino acid level and in the activity of the lactic dehydrogenase, succinic dehydrogenase, cytochrome oxidase, protease, aspartate aminotransaminase and alanine aminotransaminase enzymes in all three of the studied tissues of the snail, which supports the view that the plant product is safe for use as a molluscicide for the control of harmful freshwater vector snails in the aquatic environment.

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.

Characterizing dose response relationships: Chronic gamma radiation in Lemna minor induces oxidative stress and altered polyploidy level.

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Van Hoeck, Arne; Horemans, Nele; Van Hees, May; Nauts, Robin; Knapen, Dries; Vandenhove, Hildegarde; Blust, Ronny

2015-12-01

The biological effects and interactions of different radiation types in plants are still far from understood. Among different radiation types, external gamma radiation treatments have been mostly studied to assess the biological impact of radiation toxicity in organisms. Upon exposure of plants to gamma radiation, ionisation events can cause, either directly or indirectly, severe biological damage to DNA and other biomolecules. However, the biological responses and oxidative stress related mechanisms under chronic radiation conditions are poorly understood in plant systems. In the following study, it was questioned if the Lemna minor growth inhibition test is a suitable approach to also assess the radiotoxicity of this freshwater plant. Therefore, L. minor plants were continuously exposed for seven days to 12 different dose rate levels covering almost six orders of magnitude starting from 80 μGy h(-1) up to 1.5 Gy h(-1). Subsequently, growth, antioxidative defence system and genomic responses of L. minor plants were evaluated. Although L. minor plants could survive the exposure treatment at environmental relevant exposure conditions, higher dose rate levels induced dose dependent growth inhibitions starting from approximately 27 mGy h(-1). A ten-percentage growth inhibition of frond area Effective Dose Rate (EDR10) was estimated at 95 ± 7 mGy h(-1), followed by 153 ± 13 mGy h(-1) and 169 ± 12 mGy h(-1) on fresh weight and frond number, respectively. Up to a dose rate of approximately 5 mGy h(-1), antioxidative enzymes and metabolites remained unaffected in plants. A significant change in catalase enzyme activity was found at 27 mGy h(-1) which was accompanied with significant increases of other antioxidative enzyme activities and shifts in ascorbate and glutathione content at higher dose rate levels, indicating an increase in oxidative stress in plants. Recent plant research hypothesized that environmental genotoxic stress conditions

Altered Long- and Short-Range Functional Connectivity in Patients with Betel Quid Dependence: A Resting-State Functional MRI Study

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Tao Liu

2016-12-01

Full Text Available Objective: Addiction is a chronic relapsing brain disease. Brain structural abnormalities may constitute an abnormal neural network that underlies the risk of drug dependence. We hypothesized that individuals with Betel Quid Dependence (BQD have functional connectivity alterations that can be described by long- and short-range functional connectivity density(FCD maps. Methods: We tested this hypothesis using functional magnetic resonance imaging (fMRI data from subjects of the Han ethnic group in Hainan, China. Here, we examined BQD individuals (n = 33 and age-, sex-, and education-matched healthy controls (HCs (n = 32 in a rs-fMRI study to observe FCD alterations associated with the severity of BQD. Results: Compared with HCs, long-range FCD was decreased in the right anterior cingulate cortex (ACC and increased in the left cerebellum posterior lobe (CPL and bilateral inferior parietal lobule (IPL in the BQD group. Short-range FCD was reduced in the right ACC and left dorsolateral prefrontal cortex (dlPFC, and increased in the left CPL. The short-range FCD alteration in the right ACC displayed a negative correlation with the Betel Quid Dependence Scale (BQDS (r=-0.432, P=0.012, and the long-range FCD alteration of left IPL showed a positive correlation with the duration of BQD(r=0.519, P=0.002 in BQD individuals. Conclusions: fMRI revealed differences in long- and short- range FCD in BQD individuals, and these alterations might be due to BQ chewing, BQ dependency, or risk factors for developing BQD.

Time and dose dependent expression in the proteome of human peripheral blood mononuclear cells with γ-irradiation

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Nishad, S.; Ghosh, Anu

2014-01-01

The aim of present study is to investigate time and dose dependent differential protein expression pattern of human peripheral blood mononuclear cells (PBMCs) after acute gamma irradiation. For this purpose, PBMCs extracted from eight healthy individuals were irradiated using 60 Co gamma rays (0.3 Gy and 1 Gy) and compared with sham irradiated controls. Total proteins were extracted 1 and 4 hour post irradiation and analyzed using 2-D gel electrophoresis. A fold change of 1.5 in spot intensity was considered as 'biological significant'. Protein identification was performed by MALDI-TOF mass spectrometry. The MS/MS spectra were interrogated using Mascot 2.1 for searching against SWISS-PROT database. One-hour post irradiation, 18 proteins showed a significant difference between the sham (0 Gy) and 0.3 Gy irradiated group (6 proteins up-regulated and 12 proteins down-regulated) and 17 proteins between the sham (0 Gy) and 1 Gy irradiated group (9 proteins up-regulated and 8 down-regulated). Four hours after irradiation, 16 proteins were differentially expressed between the sham irradiated and 0.3 Gy treated group (5 proteins up-regulated and 11 proteins downregulated). Relatively high dose of 1 Gy showed modulation of 13 proteins (5 proteins upregulated and 8 proteins down regulated) after 4 hours. There were 15 proteins that were observed both at the early time point of 1-hour and the late time point of 4-hour. Important among these were, proteins involved in cytoskeletal organization like Actin, Plastin-2, Vinculin, PDZ and LIM domain protein, WD repeat containing protein and the chaperone proteins like HSP 90-alpha and Protein disulfide-isomerase A3. Proteins like thiol specific antioxidant peroxiredoxin-6 (indicating increased levels of ROS and oxidative stress) showed dose specific expression while proteins like Ras-related Rap-1b-like protein (involved in cell survival) were observed with both 0.3 Gy and 1 Gy. During the study, human peripheral blood

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

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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

X-ray induced alterations in the differentiation and mineralization potential of murine preosteoblastic cells

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Hu, Yueyuan; Lau, Patrick; Baumstark-Khan, Christa; Hellweg, Christine E.; Reitz, Günther

2012-05-01

To evaluate the effects of ionizing radiation (IR) on murine preosteoblastic cell differentiation, we directed OCT-1 cells to the osteoblastic lineage by treatment with a combination of β-glycerophosphate (β-GP), ascorbic acid (AA), and dexamethasone (Dex). In vitro mineralization was evaluated based on histochemical staining and quantification of the hydroxyapatite content of the extracellular bone matrix. Expression of mRNA encoding Runx2, transforming growth factor β1 (TGF-β1), osteocalcin (OCN), and p21CDKN1A was analyzed. Exposure to IR reduced the growth rate and diminished cell survival of OCT-1 cells under standard conditions. Notably, calcium content analysis revealed that deposition of mineralized matrix increased significantly under osteogenic conditions after X-ray exposure in a time-dependent manner. In this study, higher radiation doses exert significant overall effects on TGF-β1, OCN, and p21CDKN1A gene expression, suggesting that gene expression following X-ray treatment is affected in a dose-dependent manner. Additionally, we verified that Runx2 was suppressed within 24 h after irradiation at 2 and 4 Gy. Although further studies are required to verify the molecular mechanism, our observations strongly suggest that treatment with IR markedly alters the differentiation and mineralization process of preosteoblastic cells.

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

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

2014-01-01

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

Dose-rate dependence of thermoluminescence response

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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.)

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

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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.

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.

Baccaurea angulata fruit juice ameliorates altered hematological and biochemical biomarkers in diet-induced hypercholesterolemic rabbits.

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Ahmed, Idris Adewale; Mikail, Maryam Abimbola; Ibrahim, Muhammad

2017-06-01

Hypercholesterolemia is an important risk factor linked to the alteration of blood hematology and clinical chemistry associated with the development and progression of atherosclerosis. Previous studies have demonstrated the safety and potential health benefits of Baccaurea angulata (BA) fruit. We hypothesized that the oral administration of BA fruit juice could ameliorate the alteration in the hematological and biochemical biomarkers of diet-induced hypercholesterolemic rabbits. The aim of this study was to investigate the effects of different doses of BA juice on the hematological and biochemical biomarkers in normo- and hypercholesterolemic rabbits. Thirty-five healthy adult New Zealand White rabbits were assigned to seven different groups for 90days of diet intervention. Four atherogenic groups were fed a 1% cholesterol diet and 0, 0.5, 1.0, and 1.5mL of BA juice per kg of rabbit daily. The other three normal groups were fed a commercial rabbit pellet diet and 0, 0.5, and 1.0mL of BA juice per kg of rabbit daily. Baseline and final blood samples after 90days of repeated administration BA juice were analyzed for hematological parameters while serum, aortic and hepatic lysates were analyzed for lipid profiles and other biochemical biomarkers. The alteration of the hemopoietic system, physiological changes in serum and tissues lipid profiles and other biochemicals resulting from the consumption of a high-cholesterol diet were significantly (Pjuice. Improvements of the biomarkers in rabbits were dose-dependent, markedly enhanced at the highest dose of juice (1.5mL/kg/day). The results suggest potential health benefits of the antioxidant-rich BA fruit juice against hypercholesterolemia-associated hematological and biochemical alterations in the rabbit. Copyright © 2017 Elsevier Inc. All rights reserved.

Age and Chronicity of Administration Dramatically Influenced the Impact of Low Dose Paraquat Exposure on Behavior and Hypothalamic-Pituitary-Adrenal Activity

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Chris A. Rudyk

2017-07-01

Full Text Available Little is known of the age-dependent and long-term consequences of low exposure levels of the herbicide and dopaminergic toxicant, paraquat. Thus, we assessed the dose-dependent effects of paraquat using a typical short-term (3 week exposure procedure, followed by an assessment of the effects of chronic (16 weeks exposure to a very low dose (1/10th of what previously induced dopaminergic neuronal damage. Short term paraquat treatment dose-dependently induced deficits in locomotion, sucrose preference and Y-maze performance. Chronic low dose paraquat treatment had a very different pattern of effects that were also dependent upon the age of the animal: in direct contrast to the short-term effects, chronic low dose paraquat increased sucrose consumption and reduced forced swim test (FST immobility. Yet these effects were age-dependent, only emerging in mice older than 13 months. Likewise, Y-maze spontaneous alternations and home cage activity were dramatically altered as a function of age and paraquat chronicity. In both the short and long-term exposure studies, increased corticosterone and altered hippocampal glucocorticoid receptor (GR levels were induced by paraquat, but surprisingly these effects were blunted in the older mice. Thus, paraquat clearly acts as a systemic stressor in terms of corticoid signaling and behavioral outcomes, but that paradoxical effects may occur with: (a repeated exposure at; (b very low doses; and (c older age. Collectively, these data raise the possibility that repeated “hits” with low doses of paraquat in combination with aging processes might have promoted compensatory outcomes.

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

Intracavitary brachytherapy significantly enhances local control of early T-stage nasopharyngeal carcinoma: the existence of a dose-tumor-control relationship above conventional tumoricidal dose

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Teo, Peter Man Lung; Leung, Sing Fai; Lee, Wai Yee; Zee, Benny

2000-01-01

Purpose: To study the efficacy of intracavitary brachytherapy (ICT) in early T-stage nasopharyngeal carcinoma (NPC). Methods and Materials: All T1 and T2 (nasal infiltration) NPC treated with a curative intent from 1984 to 1996 were analyzed (n = 509). One hundred sixty-three patients were given ICT after radical external radiotherapy (ERT) (Group A). They were compared with 346 patients treated by ERT alone (Group B). The ERT delivered the tumoricidal dose (uncorrected BED-10 ≥75 Gy) to the primary tumor and did not differ between the two groups in technique or dosage. The ICT delivered a dose of 18-24 Gy in 3 fractions over 15 days to a point 1 cm perpendicular to the midpoint of the plane of the sources. ICT was used to treat local persistence diagnosed at 4-6 weeks after ERT (n = 101) or as an adjuvant for the complete responders to ERT (n = 62). Results: The two groups did not differ in patients' age or sex, rate of distant metastasis, rate of regional failure, overall survival, or the follow-up duration. However, Group A had significantly more T2 lesions and Group B had significantly more advanced N-stages. Local failure was significantly less (crude rates 6.75% vs. 13.0%; 5-year actuarial rates 5.40% vs. 10.3%) and the disease-specific mortality was significantly lower (crude rates 14.1 % vs. 21.7%; 5-year actuarial rates 11.9% vs. 16.4%) in Group A compared to Group B. Multivariate analysis showed that the ICT was the only significant prognostic factor predictive for fewer local failures (Cox regression p = 0.0328, risk ratio = 0.49, 95% confidence interval (95% CI) = 0.256-0.957). However, when ICT was excluded from the Cox regression model, the total physical dose or the total BED-10 uncorrected for tumor repopulation during the period of radiotherapy became significant in predicting ultimate local failure rate. The two groups were comparable in the incidence rates of each individual chronic radiation complication and the actuarial cumulative rate of

Genomic alterations during p53-dependent apoptosis induced by γ-irradiation of Molt-4 leukemia cells.

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Rouba Hage-Sleiman

Full Text Available Molt-4 leukemia cells undergo p53-dependent apoptosis accompanied by accumulation of de novo ceramide after 14 hours of γ-irradiation. In order to identify the potential mediators involved in ceramide accumulation and the cell death response, differentially expressed genes were identified by Affymetrix Microarray Analysis. Molt-4-LXSN cells, expressing wild type p53, and p53-deficient Molt-4-E6 cells were irradiated and harvested at 3 and 8 hours post-irradiation. Human genome U133 plus 2.0 array containing >47,000 transcripts was used for gene expression profiling. From over 10,000 probes, 281 and 12 probes were differentially expressed in Molt-4-LXSN and Molt-4-E6 cells, respectively. Data analysis revealed 63 (upregulated and 20 (downregulated genes (>2 fold in Molt-4-LXSN at 3 hours and 140 (upregulated and 21 (downregulated at 8 hours post-irradiation. In Molt-4-E6 cells, 5 (upregulated genes each were found at 3 hours and 8 hours, respectively. In Molt-4-LXSN cells, a significant fraction of the genes with altered expression at 3 hours were found to be involved in apoptosis signaling pathway (BCL2L11, p53 pathway (PMAIP1, CDKN1A and FAS and oxidative stress response (FDXR, CROT and JUN. Similarly, at 8 hours the genes with altered expression were involved in the apoptosis signaling pathway (BAX, BIK and JUN, p53 pathway (BAX, CDKN1A and FAS, oxidative stress response (FDXR and CROT and p53 pathway feedback loops 2 (MDM2 and CDKN1A. A global molecular and biological interaction map analysis showed an association of these altered genes with apoptosis, senescence, DNA damage, oxidative stress, cell cycle arrest and caspase activation. In a targeted study, activation of apoptosis correlated with changes in gene expression of some of the above genes and revealed sequential activation of both intrinsic and extrinsic apoptotic pathways that precede ceramide accumulation and subsequent execution of apoptosis. One or more of these altered genes

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

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

2015-04-01

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

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.)

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)

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

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

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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.

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.

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.

Dose specification for 192Ir high dose rate brachytherapy in terms of dose-to-water-in-medium and dose-to-medium-in-medium

International Nuclear Information System (INIS)

Fonseca, Gabriel Paiva; Yoriyaz, Hélio; Tedgren, Åsa Carlsson; Nilsson, Josef; Persson, Maria; Reniers, Brigitte; Verhaegen, Frank

2015-01-01

Dose calculation in high dose rate brachytherapy with 192 Ir is usually based on the TG-43U1 protocol where all media are considered to be water. Several dose calculation algorithms have been developed that are capable of handling heterogeneities with two possibilities to report dose: dose-to-medium-in-medium (D m,m ) and dose-to-water-in-medium (D w,m ). The relation between D m,m and D w,m for 192 Ir is the main goal of this study, in particular the dependence of D w,m on the dose calculation approach using either large cavity theory (LCT) or small cavity theory (SCT). A head and neck case was selected due to the presence of media with a large range of atomic numbers relevant to tissues and mass densities such as air, soft tissues and bone interfaces. This case was simulated using a Monte Carlo (MC) code to score: D m,m, D w,m (LCT), mean photon energy and photon fluence. D w,m (SCT) was derived from MC simulations using the ratio between the unrestricted collisional stopping power of the actual medium and water. Differences between D m,m and D w,m (SCT or LCT) can be negligible (<1%) for some tissues e.g. muscle and significant for other tissues with differences of up to 14% for bone. Using SCT or LCT approaches leads to differences between D w,m (SCT) and D w,m (LCT) up to 29% for bone and 36% for teeth. The mean photon energy distribution ranges from 222 keV up to 356 keV. However, results obtained using mean photon energies are not equivalent to the ones obtained using the full, local photon spectrum. This work concludes that it is essential that brachytherapy studies clearly report the dose quantity. It further shows that while differences between D m,m and D w,m (SCT) mainly depend on tissue type, differences between D m,m and D w,m (LCT) are, in addition, significantly dependent on the local photon energy fluence spectrum which varies with distance to implanted sources. (paper)

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)

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

International Nuclear Information System (INIS)

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

1995-01-01

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

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

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

2013-01-01

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

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

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

2012-06-01

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

Microstructure and Ultrastructure Alterations in the Pallium of Immature Mice Exposed to Cadmium.

Science.gov (United States)

Yang, X F; Han, Q G; Liu, D Y; Zhang, H T; Fan, G Y; Ma, J Y; Wang, Z L

2016-11-01

The aim of this study was to investigate microstructure and ultrastructure alterations in the pallium of immature mice exposed to cadmium. Forty immature mice were randomly divided into control, 1/100 LD 50 (1.87 mg/kg, low), 1/50 LD 50 (3.74 mg/kg, medium), and 1/25 LD 50 (7.48 mg/kg, high) dose groups. After oral cadmium exposure for 40 days, the pallium of mice was obtained for microstructure and ultrastructure studies. The results showed that both microstructure and ultrastructure alterations of the pallium were observed in all treated mice and the most obvious alterations were in the high dose group. Microstructural analysis showed seriously congested capillary in the pia mater of the pallium in the high cadmium group. Meanwhile, vacuolar degenerate or karyopyknosis presented in some neurocytes, capillary quantity, and the number of apoptotic cells increased, some neurocytes became hypertrophy, the pia mater separated from the cortex, and local hemorrhage and accompanied inflammatory cell infiltration were also observed. Ultrastructural analysis showed that rough endoplasmic reticulum was expanded, heterochromatin marginalized, perinuclear space distinctly broadened, swelling and vacuolization mitochondria appeared, synapse was swelling, presynaptic and postsynaptic membranes presented fusion, and most of mitochondrial cristae were ambiguous. The results indicated that cadmium exposure for 40 days induced dose-dependent microstructure and ultrastructure alterations in pallium of immature mice.

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

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M.F.R. Silva

1998-03-01

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

Chlordecone, a mixed pregnane X receptor (PXR) and estrogen receptor alpha (ERα) agonist, alters cholesterol homeostasis and lipoprotein metabolism in C57BL/6 mice

International Nuclear Information System (INIS)

Lee, Junga; Scheri, Richard C.; Zhang Yuan; Curtis, Lawrence R.

2008-01-01

Chlordecone (CD) is one of many banned organochlorine (OC) insecticides that are widespread persistent organic pollutants. OC insecticides alter lipid homeostasis in rodents at doses that are not neurotoxic or carcinogenic. Pretreatment of mice or rats with CD altered tissue distribution of a subsequent dose of [ 14 C]CD or [ 14 C]cholesterol (CH). Nuclear receptors regulate expression of genes important in the homeostasis of CH and other lipids. In this study, we report that CD suppresses in vitro reporter systems for human liver X receptors (LXRs) and activates those for human farnesoid X receptor (FXR), pregnane X receptor (PXR) and estrogen receptor α (ERα) in a concentration-dependent manner (0-50 μM). Consistent with human PXR activation in vitro, three days after a single dose of CD (15 mg/kg) hepatic microsomal CYP3A11 protein increases in C57BL/6 mice. CD decreases hepatic CH ester content without altering total CH concentration. Apolipoprotein A-I (apoA-I) contents of hepatic lipoprotein-rich and microsomal fractions of CD-treated mice are higher than controls. There is a significant reduction in non-high density lipoprotein CH but not apolipoprotein B-48/100 (apoB-48/100) in plasma from CD-treated mice after a 4 h fast. At 14 days after 15 mg CD/kg apoA-I and apoB-100 proteins but not CYP3A11 protein in hepatic microsomes are similar to controls. This work indicates that altered CH homeostasis is a mode of OC insecticide action of relevance after a single dose. This at least partially explains altered CH tissue distribution in CD-pretreated mice

The Dose-Dependent Effects of Vascular Risk Factors on Dynamic Compensatory Neural Processes in Mild Cognitive Impairment

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Haifeng Chen

2018-05-01

Full Text Available Background/Objectives: Mild cognitive impairment (MCI has been associated with risk for Alzheimer's Disease (AD. Previous investigations have suggested that vascular risk factors (VRFs were associated with cognitive decline and AD pathogenesis, and the intervention of VRFs may be a possible way to prevent dementia. However, in MCI, little is known about the potential impacts of VRFs on neural networks and their neural substrates, which may be a neuroimaging biomarker of the disease progression.Methods: 128 elderly Han Chinese participants (67 MCI subjects and 61 matched normal elderly with or without VRFs (hypertension, diabetes mellitus, hypercholesterolemia, smoking and alcohol drinking underwent the resting-state functional magnetic resonance imaging (fMRI and neuropsychological tests. We obtained the default mode network (DMN to identify alterations in MCI with the varying number of the VRF and analyzed the significant correlation with behavioral performance.Results: The effects of VRF on the DMN were primarily in bilateral dorsolateral prefrontal cortex (DLPFC (i.e., middle frontal gyrus. Normal elderly showed the gradually increased functional activity of DLPFC, while a fluctuant activation of DLPFC was displayed in MCI with the growing number of the VRF. Interestingly, the left DLPFC further displayed significantly dynamic correlation with executive function as the variation of VRF loading. Initial level of compensation was observed in normal aging and none-vascular risk factor (NVRF MCI, while these compensatory neural processes were suppressed in One-VRF MCI and were subsequently re-aroused in Over-One-VRF MCI.Conclusions: These findings suggested that the dose-dependent effects of VRF on DLPFC were highlighted in MCI, and the dynamic compensatory neural processes that fluctuated along with variations of VRF loading could be key role in the progression of MCI.

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.

Left ventricular wall stress and sarcoplasmic reticulum Ca(2+)-ATPase gene expression in renal hypertensive rats: dose-dependent effects of ACE inhibition and AT1-receptor blockade.

Science.gov (United States)

Zierhut, W; Studer, R; Laurent, D; Kästner, S; Allegrini, P; Whitebread, S; Cumin, F; Baum, H P; de Gasparo, M; Drexler, H

1996-05-01

Cardiac hypertrophy is associated with altered Ca2+ handling and may predispose to the development of LV dysfunction and cardiac failure. At the cellular level, the re-expression of ANF represents a well-established marker of myocyte hypertrophy while the decreased expression of the sarcoplasmatic reticulum (SR) Ca(2+)-ATPase is thought o play a crucial role in the alterations of Ca2+ handling and LV function. We assessed the dose-dependent effect of chronic ACE inhibition or AT1 receptor blockade on cardiac function in relation to the cardiac expression of the SR Ca(2+)-ATPase and ANF. Renal hypertensive rats (2K-1C) were treated for 12 weeks with three different doses of the ACE inhibitor benazepril, the AT1-receptor antagonist valsartan (each drug 0.3, 3, and 10 mg/kg per day i.p.) or placebo. LV dimensions, hypertrophy and wall stress were determined in vivo by magnetic resonance imaging and the gene expressions of ANF and SR Ca(2+)-ATPase were quantified by Northern blot. Low doses of both drugs did not affect blood pressure, hypertrophy, systolic wall stress and the ANF and SR Ca(2+)-ATPase gene expression. High doses of each drug reduced systolic blood pressure, wall stress, and LV hypertrophy to a similar extent and to values comparable to normotensive, age-matched rats. In addition, high dose treatment reduced LV end-systolic and end-diastolic volume as compared to untreated 2K-1C animals and normalized the mRNA levels of both ANF and SR Ca(2+)-ATPase (as compared to normotensive animals). We conclude that in this model, high doses of ACE inhibition and AT1-receptor blockade are necessary to normalize systolic blood pressure, LV hypertrophy and systolic LV wall stress which, in turn, is associated with restoration of a normal cardiac phenotype with respect to SR Ca(2+)-ATPase and ANF and normalization of cardiac function.

Transforming growth factor-β2 induces morphological alteration of human corneal endothelial cells in vitro

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Jing Wang

2014-10-01

Full Text Available AIM:To investigate the morphological altering effect of transforming growth factor-β2 (TGF-β2 on untransfected human corneal endothelial cells (HCECs in vitro.METHODS: After untransfected HCECs were treated with TGF-β2 at different concentrations, the morphology, cytoskeleton distribution, and type IV collagen expression of the cells were examined with inverted contrast light microscopy, fluorescence microscopy, immunofluorescence or Western Blot.RESULTS:TGF-β2 at the concentration of 3-15 μg/L had obviously alterative effects on HCECs morphology in dose and time-dependent manner, and 9 μg/L was the peak concentration. TGF-β2 (9 μg/L altered HCE cell morphology after treatment for 36h, increased the mean optical density (P<0.01 and the length of F-actin, reduced the mean optical density (P<0.01 of the collagen type IV in extracellular matrix (ECM and induced the rearrangement of F-actin, microtubule in cytoplasm and collagen type IV in ECM after treatment for 72h. CONCLUTION:TGF-β2 has obviously alterative effect on the morphology of HCECs from polygonal phenotype to enlarged spindle-shaped phenotype, in dose and time-dependence manner by inducing more, elongation and alignment of F-actin, rearrangement of microtubule and larger spread area of collagen type IV.

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

NARCIS (Netherlands)

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

2015-01-01

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

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.

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.

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.

Effect of different doses of oxytocin on cardiac electrophysiology and arrhythmias induced by ischemia.

Science.gov (United States)

Houshmand, Fariba; Faghihi, Mahdieh; Imani, Alireza; Kheiri, Soleiman

2017-01-01

The onset of acute myocardial ischemia (MI) is accompanied by a rapid increase in electrical instability and often fatal ventricular arrhythmias. This study investigated that whether oxytocin (OT) can modulate ischemia-induced arrhythmias and considered relationships between the severity of arrhythmia and the electrocardiogram parameters during ischemia. OT (0.0001-1 μg) was administrated intraperitoneally 30 min before ischemia. To examine receptor involved, a selective OT-receptor antagonist, atosiban (ATO), was infused 10 min before OT. OT caused a significant and biphasic dose-dependent reduction in ectopic heart activity and arrhythmia score. OT doses that reduced ventricular arrhythmia elicited significant increase in QT interval. OT attenuated the electrophysiological changes associated with MI and there was significant direct relationship between QRS duration and arrhythmia score. ATO treatment reduced beneficial effects of OT on arrhythmogenesis. Nevertheless, ATO failed to alter OT effects on premature ventricular contractions. We assume that the ability of OT to modulate the electrical activity of the heart may play an important role in the antiarrhythmic actions of OT.

Effect of different doses of oxytocin on cardiac electrophysiology and arrhythmias induced by ischemia

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Fariba Houshmand

2017-01-01

Full Text Available The onset of acute myocardial ischemia (MI is accompanied by a rapid increase in electrical instability and often fatal ventricular arrhythmias. This study investigated that whether oxytocin (OT can modulate ischemia-induced arrhythmias and considered relationships between the severity of arrhythmia and the electrocardiogram parameters during ischemia. OT (0.0001–1 μg was administrated intraperitoneally 30 min before ischemia. To examine receptor involved, a selective OT-receptor antagonist, atosiban (ATO, was infused 10 min before OT. OT caused a significant and biphasic dose-dependent reduction in ectopic heart activity and arrhythmia score. OT doses that reduced ventricular arrhythmia elicited significant increase in QT interval. OT attenuated the electrophysiological changes associated with MI and there was significant direct relationship between QRS duration and arrhythmia score. ATO treatment reduced beneficial effects of OT on arrhythmogenesis. Nevertheless, ATO failed to alter OT effects on premature ventricular contractions. We assume that the ability of OT to modulate the electrical activity of the heart may play an important role in the antiarrhythmic actions of OT.

Dose-dependent high-resolution electron ptychography

International Nuclear Information System (INIS)

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

2016-01-01

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

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

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

2015-08-26

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

State-dependent alterations of lipid profiles in patients with bipolar disorder.

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Huang, Yu-Jui; Tsai, Shang-Ying; Chung, Kuo-Hsuan; Chen, Pao-Huan; Huang, Shou-Hung; Kuo, Chian-Jue

2018-07-01

Objective Serum lipid levels may be associated with the affective severity of bipolar disorder, but data on lipid profiles in Asian patients with bipolar disorder and the lipid alterations in different states of opposite polarities are scant. We investigated the lipid profiles of patients in the acute affective, partial, and full remission state in bipolar mania and depression. Methods The physically healthy patients aged between 18 and 45 years with bipolar I disorder, as well as age-matched healthy normal controls were enrolled. We compared the fasting blood levels of glucose, cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein of manic or depressed patients in the acute phase and subsequent partial and full remission with those of their normal controls. Results A total of 32 bipolar manic patients (12 women and 20 men), 32 bipolar depressed participants (18 women and 14 men), and 64 healthy control participants took part in this study. The mean cholesterol level in acute mania was significantly lower than that in acute depression (p bipolar mania. Conclusion Circulating lipid profiles may be easily affected by affective states. The acute manic state may be accompanied by state-dependent lower cholesterol and triglyceride levels relative to that in other mood states.

Dexmedetomidine Dose Dependently Enhances the Local Anesthetic Action of Lidocaine in Inferior Alveolar Nerve Block: A Randomized Double-Blind Study.

Science.gov (United States)

Ouchi, Kentaro; Sugiyama, Kazuna

2016-01-01

Dexmedetomidine (DEX) dose dependently enhances the local anesthetic action of lidocaine in rats. We hypothesized that the effect might also be dose dependent in humans. We evaluated the effect of various concentrations of DEX with a local anesthetic in humans. Eighteen healthy volunteers were randomly assigned by a computer to receive 1.8 mL of 1 of 4 drug combinations: (1) 1% lidocaine with 2.5 ppm (parts per million) (4.5 μg) DEX, (2) lidocaine with 5.0 ppm (9.0 μg) DEX, (3) lidocaine with 7.5 ppm (13.5μg) DEX, or (4) lidocaine with 1:80,000 (22.5 μg) adrenaline (AD), to produce inferior alveolar nerve block. Pulp latency and lower lip numbness (for assessing onset and duration of anesthesia) were tested, and sedation level, blood pressure, and heart rate were recorded every 5 minutes for 20 minutes, and every 10 minutes from 20 to 60 minutes. Pulp latency of each tooth increased compared with baseline, from 5 to 15 minutes until 60 minutes. There were no significant intergroup differences at any time point. Anesthesia onset was not different between groups. Anesthesia duration was different between groups (that with DEX 7.5 ppm was significantly longer than that with DEX 2.5 ppm and AD; there was no difference between DEX 2.5 ppm and AD). Blood pressure decreased from baseline in the 5.0 and 7.5 ppm DEX groups at 30 to 60 minutes, although there was no hypotension; moreover, heart rate did not change in any group. Sedation score did not indicate deep sedation in any of the groups. Dexmedetomidine dose dependently enhances the local anesthetic action of lidocaine in humans. Dexmedetomidine at 2.5 ppm produces similar enhancement of local anesthesia effect as addition of 1:80,000 AD.

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

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

2015-10-15

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

Basic investigations on the performance of a normoxic polymer gel with tetrakis-hydroxy-methyl-phosphonium chloride as an oxygen scavenger: Reproducibility, accuracy, stability, and dose rate dependence

International Nuclear Information System (INIS)

Bayreder, Christian; Georg, Dietmar; Moser, Ewald; Berg, Andreas

2006-01-01

Magnetic resonance (MR)-based polymer gel dosimetry using normoxic polymer gels, represents a new dosimetric method specially suited for high-resolution three-dimensional dosimetric problems. The aim of this study was to investigate the dose response with regard to stability, accuracy, reproducibility, and the dose rate dependence. Tetrakis-hydroxy-methyl-phosphonium chloride (THPC) is used as an oxygen scavenger, and methacrylic acid as a monomer. Accuracy, reproducibility, and dose resolution were determined for MR protocols at low spatial resolution (typical for clinical scanners), medium, and microimaging-resolution protocols at three different dose levels. The dose-response stability and preirradiation-induced variations in R2, related to the time interval between preparation and irradiation of the polymer gel, were investigated. Also postirradiation stability of the polymer gel was considered. These experiments were performed using a 60 Co beam (E=1.2 MV) in a water phantom. Moreover, we investigated the dose rate dependence in the low, medium, and saturation dose region of the normoxic polymer gel using a linear accelerator at photon energy of 25 MV. MR scanning was performed on a 3 T whole body scanner (MEDSPEC 30/80, BRUKER BIOSPIN, Ettlingen, Germany) using several coils and different gradient systems adapted to the acquired spatial resolution investigated. For T2-parameter selective imaging and determination of the relaxation rate R2=1/T2, a multiple spin echo sequence with 20 equidistant echoes was used. With regard to preirradiation induced variations R2 increases significantly with the increasing time interval between the polymer gel preparation and irradiation. Only a slight increase in R2 can be observed for varying the postirradiation-time solely. The dose reproducibility at voxel volumes of about 1.4x1.4x2 mm 3 is better than 2%. The accuracy strongly depends on the calibration curve. THPC represents a very effective oxygen scavenger in

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

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Eric J Griez

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

Long-term dietary supplementation with low-dose nobiletin ameliorates hepatic steatosis, insulin resistance, and inflammation without altering fat mass in diet-induced obesity.

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Kim, Young-Je; Choi, Myung-Sook; Woo, Je Tae; Jeong, Mi Ji; Kim, Sang Ryong; Jung, Un Ju

2017-08-01

We evaluated the long-term effect of low-dose nobiletin (NOB), a polymethoxylated flavone, on diet-induced obesity and related metabolic disturbances. C57BL/6J mice were fed a high-fat diet (HFD, 45 kcal% fat) with or without NOB (0.02%, w/w) for 16 weeks. NOB did not alter food intake or body weight. Despite increases in fatty acid oxidation-related genes expression and enzymes activity in adipose tissue, NOB did not affect adipose tissue weight due to simultaneous increases in lipogenic genes expression and fatty acid synthase activity. However, NOB significantly decreased not only pro-inflammatory genes expression in adipose tissue but also proinflammatory cytokine levels in plasma. NOB-supplemented mice also showed improved glucose tolerance and insulin resistance, along with decreased levels of plasma insulin, free fatty acids, total cholesterol, non-HDL-cholesterol, and apolipoprotein B. In addition, NOB caused significant decreases in hepatic lipid droplet accumulation and triglyceride content by activating hepatic fatty acid oxidation-related enzymes. Hepatic proinflammatory TNF-α mRNA expression, collagen accumulation, and plasma levels of aminotransferases, liver damage indicators, were also significantly lower in NOB-supplemented mice. These findings suggest that long-term supplementation with low-dose NOB can protect against HFD-induced inflammation, insulin resistance, dyslipidemia, and nonalcoholic fatty liver disease, without ameliorating adiposity. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Local and hematological alterations induced by Philodryas olfersii snake venom in mice.

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Oliveira, Juliana S; Sant'Anna, Luciana B; Oliveira Junior, Manoel C; Souza, Pamella R M; Andrade Souza, Adilson S; Ribeiro, Wellington; Vieira, Rodolfo P; Hyslop, Stephen; Cogo, José C

2017-06-15

Envenomation by the South American opisthoglyphous snake Philodryas olfersii causes local pain, edema, erythema and ecchymosis; systemic envenomation is rare. In this work, we examined the inflammatory activity of P. olfersii venom (10, 30 and 60 μg) in mouse gastrocnemius muscle 6 h after venom injection. Intramuscular injection of venom did not affect hematological parameters such as red cell count, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration. The venom caused thrombocytopenia (at all three doses), leukopenia and lymphopenia (both at the two highest doses), as well as neutrophilia (30 μg), monocytosis (30 μg) and basophilia (10 μg). Of the cytokines that were screened [IL-1β, IL-6, IL-10, IL-13, IL-17, TNF-α, IFN-γ, MIP-2 and KC] and IGF-1, only IGF-1 showed a significant increase in its circulating concentration, seen with 60 μg of venom; there were no significant changes in the cytokines compared to control mice. Histological analysis revealed the presence of edema, an inflammatory infiltrate and progressive myonecrosis. Edema and myonecrosis were greatest with 60 μg of venom, while the inflammatory infiltrate was greatest with 10 μg of venom. All venom doses caused the migration of polymorphonuclear and mononuclear leukocytes into muscle, but with no significant dose-dependence in the response. These findings show that, at the doses tested, P. olfersii venom does not cause hematological alterations and has limited effect on circulating cytokine concentrations. These data also confirm that the principal effects of the venom in mice are local edema, inflammatory cell infiltration and myonecrosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

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,

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.

Low-dose BPA exposure alters the mesenchymal and epithelial transcriptomes of the mouse fetal mammary gland.

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Perinaaz R Wadia

Full Text Available Exposure of rodent fetuses to low doses of the endocrine disruptor bisphenol A (BPA causes subtle morphological changes in the prenatal mammary gland and results in pre-cancerous and cancerous lesions during adulthood. To examine whether the BPA-induced morphological alterations of the fetal mouse mammary glands are a associated with changes in mRNA expression reflecting estrogenic actions and/or b dependent on the estrogen receptor α (ERα, we compared the transcriptomal effects of BPA and the steroidal estrogen ethinylestradiol (EE2 on fetal mammary tissues of wild type and ERα knock-out mice. Mammary glands from fetuses of dams exposed to vehicle, 250 ng BPA/kg BW/d or 10 ng EE2/kg BW/d from embryonic day (E 8 were harvested at E19. Transcriptomal analyses on the ductal epithelium and periductal stroma revealed altered expression of genes involved in the focal adhesion and adipogenesis pathways in the BPA-exposed stroma while genes regulating the apoptosis pathway changed their expression in the BPA-exposed epithelium. These changes in gene expression correlated with previously reported histological changes in matrix organization, adipogenesis, and lumen formation resulting in enhanced maturation of the fat-pad and delayed lumen formation in the epithelium of BPA-exposed fetal mammary glands. Overall similarities in the transcriptomal effects of BPA and EE2 were more pronounced in the epithelium, than in the stroma. In addition, the effects of BPA and EE2 on the expression of various genes involved in mammary stromal-epithelial interactions were suppressed in the absence of ERα. These observations support a model whereby BPA and EE2 act directly on the stroma, which expresses ERα, ERβ and GPR30 in fetal mammary glands, and that the stroma, in turn, affects gene expression in the epithelium, where ERα and ERβ are below the level of detection at this stage of development.

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

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

2005-01-01

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

Radiation dose reduction without compromise to image quality by alterations of filtration and focal spot size in cerebral angiography

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Kim, Dong Joon; Park, Min Keun; Jung, Da Eun; Kang, Jung Han; Kim, Byung Moon [Dept. of Radiology, Yonsei University College of Medicine, Seoul (Korea, Republic of)

2017-08-01

Different angiographic protocols may influence the radiation dose and image quality. In this study, we aimed to investigate the effects of filtration and focal spot size on radiation dose and image quality for diagnostic cerebral angiography using an in-vitro model and in-vivo patient groups. Radiation dose and image quality were analyzed by varying the filtration and focal spot size on digital subtraction angiography exposure protocols (1, inherent filtration + large focus; 2, inherent + small; 3, copper + large; 4, copper + small). For the in-vitro analysis, a phantom was used for comparison of radiation dose. For the in-vivo analysis, bilateral paired injections, and patient cohort groups were compared for radiation dose and image quality. Image quality analysis was performed in terms of contrast, sharpness, noise, and overall quality. In the in-vitro analysis, the mean air kerma (AK) and dose area product (DAP)/frame were significantly lower with added copper filtration (protocols 3 and 4). In the in-vivo bilateral paired injections, AK and DAP/frame were significantly lower with filtration, without significant difference in image quality. The patient cohort groups with added filtration (protocols 3 and 4) showed significant reduction of total AK and DAP/patient without compromise to the image quality. Variations in focal spot size showed no significant differences in radiation dose and image quality. Addition of filtration for angiographic exposure studies can result in significant total radiation dose reduction without loss of image quality. Focal spot size does not influence radiation dose and image quality. The routine angiographic protocol should be judiciously investigated and implemented.

Physical requirements for measurement of radiation dose and their relationship to personnel dose meter design and use

International Nuclear Information System (INIS)

Chabot, G.E. Jr.; Jimenez, M.A.; Skrable, K.W.

1978-01-01

This paper stems from the concerns of the authors with both the design of current personnel dose meters and the interpretation of dose information from them in light of the actual physical requirements to measure dose. These concerns have been reinforced and extended following a comparative study of the responses of particular TLD and film systems and as the result of a recent national survey on personnel dosimetry conducted by the authors. Among the major points discussed are the systems available for penetrating and shallow dose assessment, dose meter calibration, the measurement and interpretation of skin dose, and the deficiencies of neutron albedo dose meters for routine personnel use. Calibration considerations address the questions of whether or not a phantom should be used and the difference in interpretation of responses with and without a phantom; the relationship between calculated and measured doses; and electronic equilibrium considerations in the measurement of photon doses. Matters of importance in relation to skin dose measurement include techniques in use to interpret skin dose from dose meter response; the appropriateness of evaluation of the surface dose to the live skin layer versus the average dose to the live skin layer and the limitations and requirements on dose meter design with respect to the dose being evaluated; and the significance of dose meter response in relationship to currently used beta calibration standards. Regarding the use of TLD albedo type neutron dose meters currently available, considerations are extended to the strong energy spectral dependence of the dose meter response and the possibility of making significant over or underestimations of neutron dose equivalent, depending on the calibration techniques used and the spectral quality encountered. (author)

Renal tissue alterations were size-dependent with smaller ones induced more effects and related with time exposure of gold nanoparticles

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Jarrar Bashir M

2011-09-01

Full Text Available Abstract Background Gold nanoparticles (GNPs have important application for cell labeling and imaging, drug delivery, diagnostic and therapeutic purposes mainly in cancer. Nanoparticles (NPs are being increasingly exploited for medical applications. The aim of the present study was to investigate the particle-size and period effects of administration of GNPs on the renal tissue in an attempt to address their potential toxicity. Methods A total of 70 healthy male Wistar-Kyoto rats were exposed to GNPs received 50 or 100 μl of GNPs infusion of size (10, 20 and 50 nm for 3 or 7 days to investigate particle-size effect of GNPs on the renal tissue. Animals were randomly divided into groups, 6 GNPs-treated rats groups and one control group. Groups 1, 2 and 3 received infusion of 50 μl GNPs of size 10 nm (3 or 7 days, size 20 nm (3 or 7 days and 50 nm (3 or 7 days, respectively; while groups 4, 5 and 6 received infusion of 100 μl GNPs of size 10 nm, size 20 nm and 50 nm, respectively. Stained sections of control and treated rats kidneys were examined for renal tissue alterations induced by GNPs. Results In comparison with respective control rats, exposure to GNPs doses has produced the following renal tubular alterations: cloudy swelling, vacuolar degeneration, hyaline droplets and casts, anisokaryosis, karopyknosis, karyorrhexis and karyolysis. The glomeruli showed moderate congestion with no hypercelluraity, mesangial proliferation or basement membrane thickening. The histological alterations were mainly seen in the cortex and the proximal renal convoluted tubules were more affected than the distal ones. Conclusions The induced histological alterations might be an indication of injured renal tubules due to GNPs toxicity that became unable to deal with the accumulated residues resulting from metabolic and structural disturbances caused by these NPs. The findings may suggest that GNPs interact with proteins and enzymes of the renal tissue

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-06-15

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

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

International Nuclear Information System (INIS)

Zhou, Y; Scott, A; Allahverdian, J

2014-01-01

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

High-dose alcohol intoxication differentially modulates cognitive subprocesses involved in response inhibition.

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Stock, Ann-Kathrin; Schulz, Tom; Lenhardt, Martin; Blaszkewicz, Meinolf; Beste, Christian

2016-01-01

Aside from well-known physiological effects, high-dose alcohol intoxication (a.k.a. binge drinking) can lead to aversive social and legal consequences because response inhibition is usually compromised under the influence of alcohol. Although the behavioral aspects of this phenomenon were reported on extensively, the underlying neurophysiological mechanisms mediating this disinhibition are unclear. To close this gap, we used both behavioral and neurophysiological measures (event-related potentials, ERPs) to investigate which subprocesses of response inhibition are altered under the influence of high-dose alcohol intoxication. Using a within-subject design, we asked young healthy participants (n = 27) to complete a GO/NOGO task once sober and once intoxicated (approximately 1.2‰). During intoxication, high-dose alcohol effects were highest in a condition where the participants could not rely on automated stimulus-response mapping processes during response inhibition. In this context, the NOGO-P3 (ERP), that likely depends on dopaminergic signaling within mesocorticolimbic pathways and is thought to reflect motor inhibition and/or the evaluation of inhibitory processes, was altered in the intoxicated state. In contrast to this, the N2 component, which largely depends on nigrostriatal dopamine pathways and is thought to reflect inhibition on a pre-motor level, was not altered. Based on these results, we demonstrate that alcohol-induced changes of dopaminergic neurotransmission do not exert a global effect on response inhibition. Instead, changes are highly subprocess-specific and seem to mainly target mesocorticolimbic pathways that contribute to motor inhibition and the evaluation of such. © 2014 Society for the Study of Addiction.

Influência da dependência energética de dosímetros termoluminescentes na medida da dose na entrada da pele em procedimentos radiográficos Influence of thermoluminescent dosimeters energy dependence on the measurement of entrance skin dose in radiographic procedures

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Mércia Liane de Oliveira

2010-04-01

greatest variation on thermoluminescent responses as a function of the effective radiation beam. CONCLUSION: The tested materials showed an appropriate performance for detecting X radiation on standard and clinical X-ray beams. Although CaSO4:Dy and LiF:Mg,Ti samples present a significant energy dependence in the considered energy range, these materials can be utilized for measuring entrance skin doses, provided appropriate correction factors are applied.

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.

Ultraviolet B radiation increases hairless mouse mast cells in a dose-dependent manner and alters distribution of UV-induced mast cell growth factor

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Kligman, L.H.; Murphy, G.F. [Pennsylvania Univ., Philadelphia, PA (United States). School of Medicine

1996-01-01

In studies of the effects of chronic UVB irradiation on dermal connective tissue in the hairless mouse, we observed that the number and size of mast cells was increased. Because mast cells are known to be associated with connective tissue remodeling, we examined and quantified the effect of increasing UVB (290-320 nm)doses on this cell. Groups of mice were exposed to filtered FS-40 Westinghouse lamps (290-400 nm: peak irradiance 313 nm) for 1-5 minimal erythema doses (MED) thrice weekly for 10 weeks. Appropriate controls were included. Biopsies, processed for light microscopy, were stained with toluidine blue. Mast cells were counted in 15 high-magnification fields per specimen with upper and lower dermis scored separately. Significant increases in large densely granular mast cells occurred at 2 MED in the lower dermic in association with the UVB-exacerbated granulomatous reaction. In the upper dermis, mast cells were significantly increased with 3 MED. These findings suggest that mast cells may play a dual role in UV-irradiated skin with those in the lower dermis related to inflammation processes and those in the upper dermis involved in connective tissue modeling. To gain understanding of the mechanism of mast cell recruitment and maturation, we examined the effect of UVB on mast cell growth factor expression. This was enhanced in the epidermis by UVB, with a shift from cytoplasmic staining to membrane-associated or intercellular staining at 2 MED and higher. Dermal dendritic and mononuclear cells also showed increased reactivity. (Author).

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

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

2016-01-01

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

Impact of therapeutic and high doses of florfenicol on kidney and liver functional indicators in goat

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Jan Muhammad Shah

2016-10-01

Full Text Available Aim: The aim of this study was to evaluate the impact of therapeutic and high doses of florfenicol on kidney and liver functional indicators in goat species. Materials and Methods: Six mature, healthy goats (combine breed and sex with average weight 25 kg were selected for this study. The therapeutic (20 mg/kg b.w. and high doses (40 and 60 mg of florfenicol were administered for 3 days with 24 h interval. Blood samples were collected at 0, 24, 48, 72, 96, and 120 h following the each administered dose. Results: The results showed that the therapeutic dose of florfenicol produced nonsignificant effect on serum urea, creatinine, total protein (TP, alkaline phosphatase (ALP, gamma-glutamyl transferase (GGT and bilirubin on all timings, and increased (p<0.05 the serum glutamic oxaloacetic transaminase (SGOT and serum glutamate-pyruvate transaminase (SGPT levels for 48 h. Whereas the high doses of florfenicol (40 and 60 mg significantly altered the kidney and liver functional indicators in the blood. In contrast with control, the serum urea level was (p<0.01 increased at all timing points. Creatinine values were altered (p<0.01, <0.05 in increasing manner from 24 to 96 h. The high dose of 40 mg decreased the TP (p<0.05 for 72 h and 60 mg persisted same effect (p<0.01 up to 120 h. The indices of ALP, GGT, SGOT, and SGPT were raised (p<0.01, <0.05 at all timings. The bilirubin indexes also (p<0.05 elevated from 48 to 72. Conclusion: It was concluded that the high doses of florfenicol produced reversible dose-dependent effects on functional indicators of kidney and liver such as urea, creatinine, TP, ALP, SGOT, SGPT, GGT, and bilirubin.

Noise exposure of immature rats can induce different age-dependent extra-auditory alterations that can be partially restored by rearing animals in an enriched environment.

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Molina, S J; Capani, F; Guelman, L R

2016-04-01

It has been previously shown that different extra-auditory alterations can be induced in animals exposed to noise at 15 days. However, data regarding exposure of younger animals, that do not have a functional auditory system, have not been obtained yet. Besides, the possibility to find a helpful strategy to restore these changes has not been explored so far. Therefore, the aims of the present work were to test age-related differences in diverse hippocampal-dependent behavioral measurements that might be affected in noise-exposed rats, as well as to evaluate the effectiveness of a potential neuroprotective strategy, the enriched environment (EE), on noise-induced behavioral alterations. Male Wistar rats of 7 and 15 days were exposed to moderate levels of noise for two hours. At weaning, animals were separated and reared either in standard or in EE cages for one week. At 28 days of age, different hippocampal-dependent behavioral assessments were performed. Results show that rats exposed to noise at 7 and 15 days were differentially affected. Moreover, EE was effective in restoring all altered variables when animals were exposed at 7 days, while a few were restored in rats exposed at 15 days. The present findings suggest that noise exposure was capable to trigger significant hippocampal-related behavioral alterations that were differentially affected, depending on the age of exposure. In addition, it could be proposed that hearing structures did not seem to be necessarily involved in the generation of noise-induced hippocampal-related behaviors, as they were observed even in animals with an immature auditory pathway. Finally, it could be hypothesized that the differential restoration achieved by EE rearing might also depend on the degree of maturation at the time of exposure and the variable evaluated, being younger animals more susceptible to environmental manipulations. Copyright © 2016 Elsevier B.V. All rights reserved.

2,3-Butanedione monoxime facilitates successful resuscitation in a dose-dependent fashion in a pig model of cardiac arrest.

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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.

Gonadal dose in routine diagnostic examinations

International Nuclear Information System (INIS)

Weber, J.; Koen, J.A.; Akkermans, J.A.

1974-01-01

Gonadal doses caused by stray radiation produced during radiodiagnostic investigations were measured with thermoluminescent dosemeters in various hospitals in the Netherlands. Significantly different gonadal doses were measured depending upon the hospital where the investigations were carried out. The mean dose of an examination type in one country can only be determined with any accuracy if measurements in a large number of hospitals are performed

Effect of sublethal doses of gamma radiation on DNA super helicity and survival of human fibroblasts

International Nuclear Information System (INIS)

Koceva-Chyla, A.

1992-01-01

Effect of sublethal doses of gamma radiation on cell survival and DNA super helicity in human fibroblasts was studied. Cell survival was estimated on the basis the basis of clonal growth of irradiated fibroblasts in monolayer culture in vitro. The nucleoid sedimentation technique was used to study ionizing radiation-induced DNA damage in vivo as well as to examine DNA super helicity. Increased concentrations of ethidium bromine (EB) were used to titrate the DNA super coiling response in non-irradiated cells. This response consisted of a relaxation phase (1-5 μg/ml EB) and rewinding phase (5-20 μg/ml EB). Observed biphasic dependence of sedimentation distance of nucleoid on the concentration of EB suggests the dye altered the amount of DNA super coiling in situ. The degree of DNA super coiling and thus the sedimentation rate of nucleoid in absence of EB was very sensitive to strand break induced in DNA by the doses of gamma radiation employed in the cell survival assay. Doses of 2-8 Gy of gamma radiation induced a dose -dependent reduction in the sedimentation of nucleoid. Loss of negative DNA super coiling was initially rapid (about 30% after the dose of 2 Gy) and then proceeded at a slower rate (about 35% and 48% after the doses of 4 Gy and 8 Gy respectively), indicating a significant relaxation of nucleoid structure at the doses of gamma radiation greater than 4 Gy, at which also significant decrease in fibroblasts survival occurred. Significant loss of negative DNA super coiling within the range of doses of gamma radiation resulting in significant decrease of cell survival suggests that destabilizing effect of radiation on DNA tertiary- and quaternary structures (extensive DNA breaks and relaxation of nucleonic super helicity) disturb normal functions and replications of genomic DNA, in consequence leading to a reproductive death of cells. Considering the sensitivity and simplicity of the method, the nucleoid sedimentation technique might be also a useful tool

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)

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

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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.

A review of radiology staff doses and dose monitoring requirements

International Nuclear Information System (INIS)

Martin, C. J.

2009-01-01

Studies of radiation doses received during X-ray procedures by radiology, cardiology and other clinical staff have been reviewed. Data for effective dose (E), and doses to the eyes, thyroid, hands and legs have been analysed. These data have been supplemented with local measurements to determine the most exposed part of the hand for monitoring purposes. There are ranges of 60-100 in doses to individual tissues reported in the literature for similar procedures at different centres. While ranges in the doses per unit dose-area product (DAP) are between 10 and 25, large variations in dose result from differences in the sensitivity of the X-ray equipment, the type of procedure and the operator technique, but protection factors are important in maintaining dose levels as low as possible. The influence of shielding devices is significant for determining the dose to the eyes and thyroid, and the position of the operator, which depends on the procedure, is the most significant factor determining doses to the hands. A second body dosemeter worn at the level of the collar is recommended for operators with high workloads for use in assessment of effective dose and the dose to the eye. It is proposed that the third quartile values from the distributions of dose per unit DAP identified in the review might be employed in predicting the orders of magnitude of doses to the eye, thyroid and hands, based on interventional operator workloads. Such dose estimates could be employed in risk assessments when reviewing protection and monitoring requirements. A dosemeter worn on the little finger of the hand nearest to the X-ray tube is recommended for monitoring the hand. (authors)

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

International Nuclear Information System (INIS)

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

2009-01-01

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

Pharyngeal and cervical cancer incidences significantly correlate with personal UV doses among whites in the United States.

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Godar, Dianne E; Tang, Rong; Merrill, Stephen J

2014-09-01

Because we found UV-exposed oral tissue cells have reduced DNA repair and apoptotic cell death compared with skin tissue cells, we asked if a correlation existed between personal UV dose and the incidences of oral and pharyngeal cancer in the United States. We analyzed the International Agency for Research on Cancer's incidence data for oral and pharyngeal cancers by race (white and black) and sex using each state's average annual personal UV dose. We refer to our data as 'white' rather than 'Caucasian,' which is a specific subgroup of whites, and 'black' rather than African-American because blacks from other countries around the world reside in the U.S. Most oropharyngeal carcinomas harboured human papilloma virus (HPV), so we included cervical cancer as a control for direct UV activation. We found significant correlations between increasing UV dose and pharyngeal cancer in white males (p=0.000808) and females (p=0.0031) but not in blacks. Shockingly, we also found cervical cancer in whites to significantly correlate with increasing UV dose (p=0.0154). Thus, because pharyngeal and cervical cancer correlate significantly with increasing personal UV dose in only the white population, both direct (DNA damage) and indirect (soluble factors) effects may increase the risk of HPV-associated cancer. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Dose-rate evidence for two kinds of radiation damage in stationary-phase mammalian cells

International Nuclear Information System (INIS)

Metting, N.F.; Braby, L.A.; Roesch, W.C.; Nelson, J.M.

1985-01-01

Survival based on colony formation was measured for starved plateau-phase Chinese hamster ovary (CHO) cells exposed to 250 kVp X rays at dose rates of 0.0031, 0.025, 0.18, 0.31, and 1.00 Gy/min. A large dose-rate effect was demonstrated. Delayed plating experiments and dose response experiments following a conditioning dose, both using a dose rate of 1.00 Gy/min and plating delays of up to 48 hr, were also used to investigate the alternative repair hypotheses. There is clearly a greater change in survival in dose-rate experiments than in the other experiments. Thus the authors believe that a process which depends on the square of the concentration of initial damage, and which alters the effect of initial damage on cell survival is being observed. They have applied the damage accumulation model to separate the single-event damage from this concentration-dependent form and estimate the repair rate for the latter type to be 70 min for their CHO cells

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

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

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

2008-02-21

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

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

International Nuclear Information System (INIS)

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

2008-01-01

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

Transcription factors and stress response gene alterations in human keratinocytes following Solar Simulated Ultra Violet Radiation.

Science.gov (United States)

Marais, Thomas L Des; Kluz, Thomas; Xu, Dazhong; Zhang, Xiaoru; Gesumaria, Lisa; Matsui, Mary S; Costa, Max; Sun, Hong

2017-10-19

Ultraviolet radiation (UVR) from sunlight is the major effector for skin aging and carcinogenesis. However, genes and pathways altered by solar-simulated UVR (ssUVR), a mixture of UVA and UVB, are not well characterized. Here we report global changes in gene expression as well as associated pathways and upstream transcription factors in human keratinocytes exposed to ssUVR. Human HaCaT keratinocytes were exposed to either a single dose or 5 repetitive doses of ssUVR. Comprehensive analyses of gene expression profiles as well as functional annotation were performed at 24 hours post irradiation. Our results revealed that ssUVR modulated genes with diverse cellular functions changed in a dose-dependent manner. Gene expression in cells exposed to a single dose of ssUVR differed significantly from those that underwent repetitive exposures. While single ssUVR caused a significant inhibition in genes involved in cell cycle progression, especially G2/M checkpoint and mitotic regulation, repetitive ssUVR led to extensive changes in genes related to cell signaling and metabolism. We have also identified a panel of ssUVR target genes that exhibited persistent changes in gene expression even at 1 week after irradiation. These results revealed a complex network of transcriptional regulators and pathways that orchestrate the cellular response to ssUVR.

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

International Nuclear Information System (INIS)

Nishizaki, Chihiro; Endo, Akira; Takahashi, Fumiaki

2006-06-01

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

Methamidophos alters sperm function and DNA at different stages of spermatogenesis in mice

International Nuclear Information System (INIS)

Urióstegui-Acosta, Mayrut; Hernández-Ochoa, Isabel; Sánchez-Gutiérrez, Manuel; Piña-Guzmán, Belem; Rafael-Vázquez, Leticia; Solís-Heredia, M.J.; Martínez-Aguilar, Gerardo; Quintanilla-Vega, Betzabet

2014-01-01

Methamidophos (MET) is a highly toxic organophosphate (OP) pesticide that is widely used in developing countries. MET has male reproductive effects, including decreased fertility. We evaluated MET effects on sperm quality, fertilization and DNA integrity, exploring the sensitivity of different stages of spermatogenesis. Adult male mice received MET (3.75 or 5 mg/kg-bw/ip/day/4 days) and were euthanized 1, 28 or 45 days post-treatment (dpt) to evaluate MET's effects on epididymal maturation, meiosis or mitosis, respectively. Spermatozoa were obtained from the cauda epididymis–vas deferens and were evaluated for sperm quality, acrosome reaction (AR; Coomassie staining), mitochondrial membrane potential (by JC-1), DNA damage (comet assay), oxidative damage (malondialdehyde (MDA) production), in vitro fertilization and protein phosphorylation (immunodetection), and erythrocyte acetylcholinesterase (AChE) activity. At 1-dpt, MET inhibited AChE (43–57%) and increased abnormal cells (6%). While at 28- and 45-dpt, sperm motility and viability were significantly reduced with an increasing MET dose, and abnormal morphology increased at 5 mg/kg/day/4 days. MDA and mitochondrial activity were not affected at any dose or time. DNA damage (OTM and %DNA) was observed at 5 mg/kg/day/4 days in a time-dependent manner, whereas both parameters were altered in cells from mice exposed to 3.75 mg/kg/day/4 days only at 28-dpt. Depending on the time of collection, initial-, spontaneous- and induced-AR were altered at 5 mg/kg/day/4 days, and the fertilization capacity also decreased. Sperm phosphorylation (at serine and tyrosine residues) was observed at all time points. Data suggest that meiosis and mitosis are the more sensitive stages of spermatogenesis for MET reproductive toxicity compared to epididymal maturation. - Highlights: • Methamidophos alters sperm cell function at different stages of spermatogenesis. • Testicular stages of spermatogenesis are more sensitive to

Methamidophos alters sperm function and DNA at different stages of spermatogenesis in mice

Energy Technology Data Exchange (ETDEWEB)

Urióstegui-Acosta, Mayrut; Hernández-Ochoa, Isabel [Departamento de Toxicología, CINVESTAV-IPN, D.F. (Mexico); Sánchez-Gutiérrez, Manuel [Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Hidalgo (Mexico); Piña-Guzmán, Belem [Instituto Politécnico Nacional-UPIBI, D.F. (Mexico); Rafael-Vázquez, Leticia; Solís-Heredia, M.J.; Martínez-Aguilar, Gerardo [Departamento de Toxicología, CINVESTAV-IPN, D.F. (Mexico); Quintanilla-Vega, Betzabet, E-mail: mquintan@cinvestav.mx [Departamento de Toxicología, CINVESTAV-IPN, D.F. (Mexico)

2014-09-15

Methamidophos (MET) is a highly toxic organophosphate (OP) pesticide that is widely used in developing countries. MET has male reproductive effects, including decreased fertility. We evaluated MET effects on sperm quality, fertilization and DNA integrity, exploring the sensitivity of different stages of spermatogenesis. Adult male mice received MET (3.75 or 5 mg/kg-bw/ip/day/4 days) and were euthanized 1, 28 or 45 days post-treatment (dpt) to evaluate MET's effects on epididymal maturation, meiosis or mitosis, respectively. Spermatozoa were obtained from the cauda epididymis–vas deferens and were evaluated for sperm quality, acrosome reaction (AR; Coomassie staining), mitochondrial membrane potential (by JC-1), DNA damage (comet assay), oxidative damage (malondialdehyde (MDA) production), in vitro fertilization and protein phosphorylation (immunodetection), and erythrocyte acetylcholinesterase (AChE) activity. At 1-dpt, MET inhibited AChE (43–57%) and increased abnormal cells (6%). While at 28- and 45-dpt, sperm motility and viability were significantly reduced with an increasing MET dose, and abnormal morphology increased at 5 mg/kg/day/4 days. MDA and mitochondrial activity were not affected at any dose or time. DNA damage (OTM and %DNA) was observed at 5 mg/kg/day/4 days in a time-dependent manner, whereas both parameters were altered in cells from mice exposed to 3.75 mg/kg/day/4 days only at 28-dpt. Depending on the time of collection, initial-, spontaneous- and induced-AR were altered at 5 mg/kg/day/4 days, and the fertilization capacity also decreased. Sperm phosphorylation (at serine and tyrosine residues) was observed at all time points. Data suggest that meiosis and mitosis are the more sensitive stages of spermatogenesis for MET reproductive toxicity compared to epididymal maturation. - Highlights: • Methamidophos alters sperm cell function at different stages of spermatogenesis. • Testicular stages of spermatogenesis are more sensitive to

Angular dependence on the records of dose in radiochromic films strips

Energy Technology Data Exchange (ETDEWEB)

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

2016-10-15

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

D-Methionine attenuated cisplatin-induced vestibulotoxicity through altering ATPase activities and oxidative stress in guinea pigs

International Nuclear Information System (INIS)

Cheng, P.-W.; Liu, S.-H.; Young, Y.-H.; Lin-Shiau, Shoei-Yn

2006-01-01

Cisplatin has been used as a chemotherapeutic agent to treat many kinds of malignancies. Its damage to the vestibulo-ocular reflex (VOR) system has been reported. However, the underlying biochemical change in the inner ear or central vestibular nervous system is not fully understood. In this study, we attempted to examine whether cisplatin-induced vestibulotoxicity and D-methionine protection were correlated with the changes of ATPase activities and oxidative stress of ampullary tissue of vestibules as well as cerebellar cortex (the inhibitory center of VOR system) of guinea pigs. By means of a caloric test coupled with electronystagmographic recordings, we found that cisplatin exposure caused a dose-dependent (1, 3, or 5 mg/kg) vestibular dysfunction as revealed by a decrease of slow phase velocity (SPV). In addition, cisplatin significantly inhibited the Na + , K + -ATPase and Ca 2+ -ATPase activities in the ampullary tissue with a good dose-response relationship but not those of cerebellar cortex. Regression analysis indicated that a decrease of SPV was well correlated with the reduction of Na + , K + -ATPase and Ca 2+ -ATPase activities of the ampullary tissue. D-Methionine (300 mg/kg) reduced both abnormalities of SPV and ATPase activities in a correlated manner. Moreover, cisplatin exposure led to a significant dose-dependent increase of lipid peroxidation and nitric oxide concentrations of the vestibules, which could be significantly suppressed by D-methionine. However, cisplatin did not alter the levels of lipid peroxidation and nitric oxide of the cerebellum. In conclusion, cisplatin inhibited ATPase activities and increased oxidative stress in guinea pig vestibular labyrinths. D-Methionine attenuated cisplatin-induced vestibulotoxicity associated with ionic disturbance through its antioxidative property

Dose energy dependence in proton imaging with thin detector

Energy Technology Data Exchange (ETDEWEB)

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

2012-07-15

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

Induction of Cell Death through Alteration of Oxidants and Antioxidants in Epithelial Cells Exposed to High Energy Protons

Science.gov (United States)

Ramesh, Govindarajan; Wu, Honglu

2012-01-01

Radiation affects several cellular and molecular processes including double strand breakage, modifications of sugar moieties and bases. In outer space, protons are the primary radiation source which poses a range of potential health risks to astronauts. On the other hand, the use of proton radiation for tumor radiation therapy is increasing as it largely spares healthy tissues while killing tumor tissues. Although radiation related research has been conducted extensively, the molecular toxicology and cellular mechanisms affected by proton radiation remain poorly understood. Therefore, in the present study, we irradiated rat epithelial cells (LE) with different doses of protons and investigated their effects on cell proliferation and cell death. Our data showed an inhibition of cell proliferation in proton irradiated cells with a significant dose dependent activation and repression of reactive oxygen species (ROS) and antioxidants, glutathione and superoxide dismutase respectively as compared to control cells. In addition, apoptotic related genes such as caspase-3 and -8 activities were induced in a dose dependent manner with corresponding increased levels of DNA fragmentation in proton irradiated cells than control cells. Together, our results show that proton radiation alters oxidant and antioxidant levels in the cells to activate apoptotic pathway for cell death.

Dose-dependent stimulation of hepatic retinoic acid hydroxylation/oxidation and glucuronidation in brook trout, Salvelinus fontinalis, after exposure to 3,3{prime}, 4,4{prime}-tetrachlorobiphenyl

Energy Technology Data Exchange (ETDEWEB)

Boyer, P.M.; Ndayibagira, A.; Spear, P.A.

2000-03-01

Extremely low stores of vitamin A have been reported in fish and birds inhabiting regions contaminated by coplanar polychlorinated biphenyls (PCBs) and other organochlorines, suggesting many possible effects on retinoid biochemical pathways. Metabolic imbalances associated with biologically active retinoids (e.g., retinoic acid) could be associated with tetratogenesis, edema, growth inhibition, reproductive impairment, immunosuppression, and susceptibility to cancer. Sexually mature brook trout were injected imtraperitoneally with the coplanar PCB 3,3{prime}, 4,4{prime}-tetrachlorobiphenyl (TCBP) and again 4 weeks later. At 8 weeks, retinoic acid metabolism was measured in liver microsomes. To the authors' knowledge, retinoic acid conjugation by UDP-glucuronyltransferase is described here for the first time in fish. A substantial rate of glucuronidation was detected in the microsomes from control brook trout, which tended to increase over the dose range of TCBP. Glucuronidation was significantly greater in fish receiving the 10 {micro}g/g body weight dose level. Metabolism through the cytochrome P450 system was also dose-dependent, resulting in significantly greater production of 4-hydroxyretinoic acid at the 10 {micro}g/g dose level. In contrast, subsequent oxidation to 4-oxo-retinoic acid was greatest at the 1 {micro}g/g dose level and did not increase further at higher doses. Liver stores of dehydroretinyl palmitate/oleate were significantly decreased at the 5 and 10 {micro}g/g dose levels.

Ciprofloxacin provokes SOS-dependent changes in respiration and membrane potential and causes alterations in the redox status of Escherichia coli.

Science.gov (United States)

Smirnova, Galina V; Tyulenev, Aleksey V; Muzyka, Nadezda G; Peters, Mikhail A; Oktyabrsky, Oleg N

2017-01-01

An in-depth understanding of the physiological response of bacteria to antibiotic-induced stress is needed for development of new approaches to combatting microbial infections. Fluoroquinolone ciprofloxacin causes phase alterations in Escherichia coli respiration and membrane potential that strongly depend on its concentration. Concentrations lower than the optimal bactericidal concentration (OBC) do not inhibit respiration during the first phase. A dose higher than the OBC provokes immediate SOS-independent inhibition of respiration and growth that can contribute to a decreased SOS response and lowered susceptibility to high concentrations of ciprofloxacin. Cells retain their metabolic activity, membrane potential and accelerated K + uptake and produce low levels of superoxide and H 2 O 2 during the first phase. The time before initiation of the second phase is inversely correlated with the ciprofloxacin concentration. The second phase is SOS-dependent and characterized by respiratory inhibition, membrane depolarization, K + and glutathione leakage and cessation of glucose consumption and may be considered as cell death. atpA, gshA and kefBkefC knockouts, which perturb fluxes of protons and K + , can modify the degree and duration of respiratory inhibition and potassium retention. Loss of K + efflux channels KefB and KefC enhances the susceptibility of E. coli to ciprofloxacin. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Dose and temporal effects on gene expression profiles of urothelial cells from rats exposed to diuron

International Nuclear Information System (INIS)

Ihlaseh-Catalano, Shadia M.; Bailey, Kathryn A.; Cardoso, Ana Paula F.; Ren, Hongzu; Fry, Rebecca C.; Camargo, João Lauro V.de; Wolf, Douglas C.

2014-01-01

Diuron (3-(3,4-dichlorophenyl)-1,1-dimethylurea) is a substituted urea herbicide that at high dietary levels (2500 ppm) induces rat urinary bladder hyperplasia after 20 weeks of exposure and neoplasia after 2 years. The effects on the urothelium after short-term exposure have not been described. The present 7-day study evaluated the dose-dependency of urothelial alterations in the urinary bladder using light microscopy, scanning electron microscopy, and genome-wide transcriptional profiling. Male Wistar rats were fed 0, 125, 500, 2500 ppm diuron for 7 days. The urinary bladder and isolated urothelial cells of these animals were processed for microscopic examination and gene expression profiling, respectively. No significant treatment-related morphologic effects were observed. The number of differentially expressed genes (DEGs) in the exposed groups increased with diuron levels. Diuron-altered genes involved in cell-to-cell interactions and tissue organization were identified in all treatment groups. After 7 days of diuron exposure, transcriptional responses were observed in the urothelium in the absence of clear morphologic changes. These morphological findings are different from those observed in a previous study in which 20 weeks of diuron exposure was associated with simple hyperplasia secondary to the persistent cytotoxicity and necrosis associated with continuous cellular regeneration. Comparison of the gene expression profiles of rats exposed to the 2500 ppm carcinogenic diuron dose for 7 days versus 20 weeks revealed few similarities between these two time points at the gene or pathway level. Taken together, these data provide insight into the dose- and temporal-dependent morphological and transcriptional changes associated with diuron exposure that may lead to the development of tumors in the rat urinary bladder

Angular dependence of dose equivalent response of an albedo neutron dosimeter

International Nuclear Information System (INIS)

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

1994-01-01

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

Dynamic Metabolic Disruption in Rats Perinatally Exposed to Low Doses of Bisphenol-A.

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Marie Tremblay-Franco

Full Text Available Along with the well-established effects on fertility and fecundity, perinatal exposure to endocrine disrupting chemicals, and notably to xeno-estrogens, is strongly suspected of modulating general metabolism. The metabolism of a perinatally exposed individual may be durably altered leading to a higher susceptibility of developing metabolic disorders such as obesity and diabetes; however, experimental designs involving the long term study of these dynamic changes in the metabolome raise novel challenges. 1H-NMR-based metabolomics was applied to study the effects of bisphenol-A (BPA, 0; 0.25; 2.5, 25 and 250 μg/kg BW/day in rats exposed perinatally. Serum and liver samples of exposed animals were analyzed on days 21, 50, 90, 140 and 200 in order to explore whether maternal exposure to BPA alters metabolism. Partial Least Squares-Discriminant Analysis (PLS-DA was independently applied to each time point, demonstrating a significant pair-wise discrimination for liver as well as serum samples at all time-points, and highlighting unequivocal metabolic shifts in rats perinatally exposed to BPA, including those exposed to lower doses. In BPA exposed animals, metabolism of glucose, lactate and fatty acids was modified over time. To further explore dynamic variation, ANOVA-Simultaneous Component Analysis (A-SCA was used to separate data into blocks corresponding to the different sources of variation (Time, Dose and Time*Dose interaction. A-SCA enabled the demonstration of a dynamic, time/age dependent shift of serum metabolome throughout the rats' lifetimes. Variables responsible for the discrimination between groups clearly indicate that BPA modulates energy metabolism, and suggest alterations of neurotransmitter signaling, the latter finding being compatible with the neurodevelopmental effect of this xenoestrogen. In conclusion, long lasting metabolic effects of BPA could be characterized over 200 days, despite physiological (and thus metabolic changes

Cocaine and Pavlovian fear conditioning: dose-effect analysis.

Science.gov (United States)

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.

Dose-response curve for blood exposed to gamma-neutron mixed field by conventional cytogenetic method

International Nuclear Information System (INIS)

Brandao, Jose Odinilson de C.; Souza, Priscilla L.G.; Santos, Joelan A.L.; Vilela, Eudice C.; Lima, Fabiana F.; Calixto, Merilane S.; Santos, Neide

2009-01-01

There is increasing concern about airline crew members (about one million worldwide) are exposed to measurable neutrons doses. Historically, cytogenetic biodosimetry assays have been based on quantifying asymmetrical chromosome alterations (dicentrics, centric rings and acentric fragments) in mytogen-stimulated T-lymphocytes in their first mitosis after radiation exposure. Increased levels of chromosome damage in peripheral blood lymphocytes are a sensitive indicator of radiation exposure and they are routinely exploited for assessing radiation absorbed dose after accidental or occupational exposure. Since radiological accidents are not common, not all nations feel that it is economically justified to maintain biodosimetry competence. However, dependable access to biological dosimetry capabilities is completely critical in event of an accident. In this paper the dose-response curve was measured for the induction of chromosomal alterations in peripheral blood lymphocytes after chronic exposure in vitro to neutron-gamma mixes field. Blood was obtained from one healthy donor and exposed to two neutron-gamma mixed field from sources 241 AmBe (20 Ci) at the Neutron Calibration Laboratory (NCL-CRCN/NE-PE-Brazil). The evaluated absorbed doses were 0.2 Gy; 1.0 Gy and 2.5 Gy. The dicentric chromosomes were observed at metaphase, following colcemid accumulation and 1000 well-spread metaphase figures were analyzed for the presence of dicentrics by two experienced scorers after painted by giemsa 5%. Our preliminary results showed a linear dependence between radiations absorbed dose and dicentric chromosomes frequencies. Dose-response curve described in this paper will contribute to the construction of calibration curve that will be used in our laboratory for biological dosimetry. (author)

Dose-response curve for blood exposed to gamma-neutron mixed field by conventional cytogenetic method

Energy Technology Data Exchange (ETDEWEB)

Brandao, Jose Odinilson de C.; Souza, Priscilla L.G.; Santos, Joelan A.L.; Vilela, Eudice C.; Lima, Fabiana F., E-mail: jodinilson@cnen.gov.b, E-mail: fflima@cnen.gov.b, E-mail: jasantos@cnen.gov.b [Centro Regional de Ciencias Nucleares do Nordeste (CRCN-NE/CNEN-PE), Recife, PE (Brazil); Calixto, Merilane S.; Santos, Neide, E-mail: santos_neide@yahoo.com.b [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Dept. de Genetica

2009-07-01

There is increasing concern about airline crew members (about one million worldwide) are exposed to measurable neutrons doses. Historically, cytogenetic biodosimetry assays have been based on quantifying asymmetrical chromosome alterations (dicentrics, centric rings and acentric fragments) in mytogen-stimulated T-lymphocytes in their first mitosis after radiation exposure. Increased levels of chromosome damage in peripheral blood lymphocytes are a sensitive indicator of radiation exposure and they are routinely exploited for assessing radiation absorbed dose after accidental or occupational exposure. Since radiological accidents are not common, not all nations feel that it is economically justified to maintain biodosimetry competence. However, dependable access to biological dosimetry capabilities is completely critical in event of an accident. In this paper the dose-response curve was measured for the induction of chromosomal alterations in peripheral blood lymphocytes after chronic exposure in vitro to neutron-gamma mixes field. Blood was obtained from one healthy donor and exposed to two neutron-gamma mixed field from sources {sup 241}AmBe (20 Ci) at the Neutron Calibration Laboratory (NCL-CRCN/NE-PE-Brazil). The evaluated absorbed doses were 0.2 Gy; 1.0 Gy and 2.5 Gy. The dicentric chromosomes were observed at metaphase, following colcemid accumulation and 1000 well-spread metaphase figures were analyzed for the presence of dicentrics by two experienced scorers after painted by giemsa 5%. Our preliminary results showed a linear dependence between radiations absorbed dose and dicentric chromosomes frequencies. Dose-response curve described in this paper will contribute to the construction of calibration curve that will be used in our laboratory for biological dosimetry. (author)

Brassinolide Increases Potato Root Growth In Vitro in a Dose-Dependent Way and Alleviates Salinity Stress

Directory of Open Access Journals (Sweden)

Yueqing Hu

2016-01-01

Full Text Available Brassinosteroids (BRs are steroidal phytohormones that regulate various physiological processes, such as root development and stress tolerance. In the present study, we showed that brassinolide (BL affects potato root in vitro growth in a dose-dependent manner. Low BL concentrations (0.1 and 0.01 μg/L promoted root elongation and lateral root development, whereas high BL concentrations (1–100 μg/L inhibited root elongation. There was a significant (P<0.05 positive correlation between root activity and BL concentrations within a range from 0.01 to 100 μg/L, with the peak activity of 8.238 mg TTC·g−1 FW·h−1 at a BL concentration of 100 μg/L. Furthermore, plants treated with 50 μg/L BL showed enhanced salt stress tolerance through in vitro growth. Under this scenario, BL treatment enhanced the proline content and antioxidant enzymes’ (superoxide dismutase, peroxidase, and catalase activity and reduced malondialdehyde content in potato shoots. Application of BL maintain K+ and Na+ homeostasis by improving tissue K+/Na+ ratio. Therefore, we suggested that the effects of BL on root development from stem fragments explants as well as on primary root development are dose-dependent and that BL application alleviates salt stress on potato by improving root activity, root/shoot ratio, and antioxidative capacity in shoots and maintaining K+/Na+ homeostasis in potato shoots and roots.

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

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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.

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

International Nuclear Information System (INIS)

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

2014-01-01

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

Dose-dependent effects of 17-ß-estradiol on pituitary thyrotropin content and secretion in vitro

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Moreira R.M.

1997-01-01

Full Text Available We studied the basal and thyrotropin-releasing hormone (TRH (50 nM induced thyrotropin (TSH release in isolated hemipituitaries of ovariectomized rats treated with near-physiological or high doses of 17-ß-estradiol benzoate (EB; sc, daily for 10 days or with vehicle (untreated control rats, OVX. One group was sham-operated (normal control. The anterior pituitary glands were incubated in Krebs-Ringer bicarbonate medium, pH 7.4, at 37oC in an atmosphere of 95% O2/5% CO2. Medium and pituitary TSH was measured by specific RIA (NIDDK-RP-3. Ovariectomy induced a decrease (P<0.05 in basal TSH release (normal control = 44.1 ± 7.2; OVX = 14.7 ± 3.0 ng/ml and tended to reduce TRH-stimulated TSH release (normal control = 33.0 ± 8.1; OVX = 16.6 ± 2.4 ng/ml. The lowest dose of EB (0.7 µg/100 g body weight did not reverse this alteration, but markedly increased the pituitary TSH content (0.6 ± 0.06 µg/hemipituitary; P<0.05 above that of OVX (0.4 ± 0.03 µg/hemipituitary and normal rats (0.46 ± 0.03 µg/hemipituitary. The intermediate EB dose (1.4 µg/100 g body weight induced a nonsignificant tendency to a higher TSH response to TRH compared to OVX and a lower response compared to normal rats. Conversely, in the rats treated with the highest dose (14 µg/100 g body weight, serum 17-ß-estradiol was 17 times higher than normal, and the basal and TRH-stimulated TSH release, as well as the pituitary TSH content, was significantly (P<0.05 reduced compared to normal rats and tended to be even lower than the values observed for the vehicle-treated OVX group, suggesting an inhibitory effect of hyperestrogenism. In conclusion, while reinforcing the concept of a positive physiological regulatory role of estradiol on the TSH response to TRH and on the pituitary stores of the hormone, the present results suggest an inhibitory effect of high levels of estrogen on these responses

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

Sex-dependent alteration of cardiac cytochrome P450 gene expression by doxorubicin in C57Bl/6 mice.

Science.gov (United States)

Grant, Marianne K O; Seelig, Davis M; Sharkey, Leslie C; Zordoky, Beshay N

2017-01-01

There is inconclusive evidence about the role of sex as a risk factor for doxorubicin (DOX)-induced cardiotoxicity. Recent experimental studies have shown that adult female rats are protected against DOX-induced cardiotoxicity. However, the mechanisms of this sexual dimorphism are not fully elucidated. We have previously demonstrated that DOX alters the expression of several cytochrome P450 (CYP) enzymes in the hearts of male rats. Nevertheless, the sex-dependent effect of DOX on the expression of CYP enzymes is still not known. Therefore, in the present study, we determined the effect of acute DOX exposure on the expression of CYP genes in the hearts of both male and female C57Bl/6 mice. Acute DOX cardiotoxicity was induced by a single intraperitoneal injection of 20 mg/kg DOX in male and female adult C57Bl/6 mice. Cardiac function was assessed 5 days after DOX exposure by trans-thoracic echocardiography. Mice were euthanized 1 day or 6 days after DOX or saline injection. Thereafter, the hearts were harvested and weighed. Heart sections were evaluated for pathological lesions. Total RNA was extracted and expression of natriuretic peptides, inflammatory and apoptotic markers, and CYP genes was measured by real-time PCR. Adult female C57Bl/6 mice were protected from acute DOX-induced cardiotoxicity as they show milder pathological lesions, less inflammation, and faster recovery from DOX-induced apoptosis and DOX-mediated inhibition of beta-type natriuretic peptide. Acute DOX exposure altered the gene expression of multiple CYP genes in a sex-dependent manner. In 24 h, DOX exposure caused male-specific induction of Cyp1b1 and female-specific induction of Cyp2c29 and Cyp2e1. Acute DOX exposure causes sex-dependent alteration of cardiac CYP gene expression. Since cardiac CYP enzymes metabolize several endogenous compounds to biologically active metabolites, sex-dependent alteration of CYP genes may play a role in the sexual dimorphism of acute DOX

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

Science.gov (United States)

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

2012-06-01

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

Avoidance behaviour and anxiety in rats irradiated with a sublethal dose of gamma-rays.

Science.gov (United States)

Tomášová, Lenka; Smajda, B; Bona, M

2011-12-01

The aim of this study was to assess, whether a sublethal dose of gamma-rays will influence the avoidance behaviour and anxiety in rats and whether the response to radiation depends on time of day of its application. Adult male Wistar rats were tested in elevated plus-maze, in hot plate test and in the light/dark box in 4 regular intervals during a day. After two weeks the animals were irradiated with a whole-body dose 6 Gy of gamma-rays. One day after irradiation the animals were repeatedly tested in the same way, as before irradiation. In the plus-maze test an increased level of anxiety was established. The irradiation significantly decreased the locomotor activity of rats, but the extent of exploratory and comfortable behaviour were not altered. After irradiation, an elevated aversion to the thermal stimulus was observed in the hot plate test. The effects of radiation were more pronounced in the light period of the day, than in the dark one. No significant differences in aversion to light were detected after irradiation. The obtained results indicate, that sublethal doses of ionizing radiation can markedly influence the reactivity of animals to adverse stimuli, their motoric activity and emotional status, as well.

Relationship between noise, dose, and pitch in cardiac multi-detector row CT.

Science.gov (United States)

Primak, Andrew N; McCollough, Cynthia H; Bruesewitz, Michael R; Zhang, Jie; Fletcher, Joel G

2006-01-01

In spiral computed tomography (CT), dose is always inversely proportional to pitch. However, the relationship between noise and pitch (and hence noise and dose) depends on the scanner type (single vs multi-detector row) and reconstruction mode (cardiac vs noncardiac). In single detector row spiral CT, noise is independent of pitch. Conversely, in noncardiac multi-detector row CT, noise depends on pitch because the spiral interpolation algorithm makes use of redundant data from different detector rows to decrease noise for pitch values less than 1 (and increase noise for pitch values > 1). However, in cardiac spiral CT, redundant data cannot be used because such data averaging would degrade the temporal resolution. Therefore, the behavior of noise versus pitch returns to the single detector row paradigm, with noise being independent of pitch. Consequently, since faster rotation times require lower pitch values in cardiac multi-detector row CT, dose is increased without a commensurate decrease in noise. Thus, the use of faster rotation times will improve temporal resolution, not alter noise, and increase dose. For a particular application, the higher dose resulting from faster rotation speeds should be justified by the clinical benefits of the improved temporal resolution. RSNA, 2006

Recommendations on dose buildup factors used in models for calculating gamma doses for a plume

International Nuclear Information System (INIS)

Hedemann Jensen, P.; Thykier-Nielsen, S.

1980-09-01

Calculations of external γ-doses from radioactivity released to the atmosphere have been made using different dose buildup factor formulas. Some of the dose buildup factor formulas are used by the Nordic countries in their respective γ-dose models. A comparison of calculated γ-doses using these dose buildup factors shows that the γ-doses can be significantly dependent on the buildup factor formula used in the calculation. Increasing differences occur for increasing plume height, crosswind distance, and atmospheric stability and also for decreasing downwind distance. It is concluded that the most accurate γ-dose can be calculated by use of Capo's polynomial buildup factor formula. Capo-coefficients have been calculated and shown in this report for γ-energies below the original lower limit given by Capo. (author)

Oral Supplementation of Melatonin Protects against Fibromyalgia-Related Skeletal Muscle Alterations in Reserpine-Induced Myalgia Rats.

Science.gov (United States)

Favero, Gaia; Trapletti, Valentina; Bonomini, Francesca; Stacchiotti, Alessandra; Lavazza, Antonio; Rodella, Luigi Fabrizio; Rezzani, Rita

2017-06-29

Fibromyalgia is a chronic syndrome characterized by widespread musculoskeletal pain and an extensive array of other symptoms including disordered sleep, fatigue, depression and anxiety. Important factors involved in the pathogenic process of fibromyalgia are inflammation and oxidative stress, suggesting that ant-inflammatory and/or antioxidant supplementation might be effective in the management and modulation of this syndrome. Recent evidence suggests that melatonin may be suitable for this purpose due to its well known ant-inflammatory, antioxidant and analgesic effects. Thus, in the current study, the effects of the oral supplementation of melatonin against fibromyalgia-related skeletal muscle alterations were evaluated. In detail, 90 Sprague Dawley rats were randomly treated with reserpine, to reproduce the pathogenic process of fibromyalgia and thereafter they received melatonin. The animals treated with reserpine showed moderate alterations at hind limb skeletal muscles level and had difficulty in moving, together with significant morphological and ultrastructural alterations and expression of inflammatory and oxidative stress markers in the gastrocnemius muscle. Interestingly, melatonin, dose and/or time dependently, reduced the difficulties in spontaneous motor activity and the musculoskeletal morphostructural, inflammatory, and oxidative stress alterations. This study suggests that melatonin in vivo may be an effective tool in the management of fibromyalgia-related musculoskeletal morphofunctional damage.

GABAB-receptor activation alters the firing pattern of dopamine neurons in the rat substantia nigra.

Science.gov (United States)

Engberg, G; Kling-Petersen, T; Nissbrandt, H

1993-11-01

Previous electrophysiological experiments have emphasized the importance of the firing pattern for the functioning of midbrain dopamine (DA) neurons. In this regard, excitatory amino acid receptors appear to constitute an important modulatory control mechanism. In the present study, extracellular recording techniques were used to investigate the significance of GABAB-receptor activation for the firing properties of DA neurons in the substantia nigra (SN) in the rat. Intravenous administration of the GABAB-receptor agonist baclofen (1-16 mg/kg) was associated with a dose-dependent regularization of the firing pattern, concomitant with a reduction in burst firing. At higher doses (16-32 mg/kg), the firing rate of the DA neurons was dose-dependently decreased. Also, microiontophoretic application of baclofen regularized the firing pattern of nigral DA neurons, including a reduction of burst firing. Both the regularization of the firing pattern and inhibition of firing rate produced by systemic baclofen administration was antagonized by the GABAB-receptor antagonist CGP 35348 (200 mg/kg, i.v.). The GABAA-receptor agonist muscimol produced effects on the firing properties of DA neurons that were opposite to those observed following baclofen, i.e., an increase in firing rate accompanied by a decreased regularity. The NMDA receptor antagonist MK 801 (0.4-3.2 mg/kg, i.v.) produced a moderate, dose-dependent increase in the firing rate of the nigral DA neurons as well as a slightly regularized firing pattern. Pretreatment with MK 801 (3.2 mg/kg, i.v., 3-10 min) did neither promote nor prevent the regularization of the firing pattern or inhibition of firing rate on the nigral DA neurons produced by baclofen. The present results clearly show that GABAB-receptors can alter the firing pattern of nigral DA neurons, hereby counterbalancing the previously described ability of glutamate to induce burst firing activity on these neurons.

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

International Nuclear Information System (INIS)

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

1985-01-01

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

Whole body exposure of mice to secondhand smoke induces dose-dependent and persistent promutagenic DNA adducts in the lung

International Nuclear Information System (INIS)

Kim, Sang-In; Arlt, Volker M.; Yoon, Jae-In; Cole, Kathleen J.; Pfeifer, Gerd P.; Phillips, David H.; Besaratinia, Ahmad

2011-01-01

Secondhand smoke (SHS) exposure is a known risk factor for lung cancer in lifelong nonsmokers. However, the underlying mechanism of action of SHS in lung carcinogenesis remains elusive. We have investigated, using the 32 P-postlabeling assay, the genotoxic potential of SHS in vivo by determining the formation and kinetics of repair of DNA adducts in the lungs of mice exposed whole body to SHS for 2 or 4 months (5 h/day, 5 days/week), and an ensuing one-month recovery period. We demonstrate that exposure of mice to SHS elicits a significant genotoxic response as reflected by the elevation of DNA adduct levels in the lungs of SHS-exposed animals. The increases in DNA adduct levels in the lungs of SHS-exposed mice are dose-dependent as they are related to the intensity and duration of SHS exposure. After one month of recovery in clean air, the levels of lung DNA adducts in the mice exposed for 4 months remain significantly higher than those in the mice exposed for 2 months (P < 0.0005), levels in both groups being significantly elevated relative to controls (P < 0.00001). Our experimental findings accord with the epidemiological data showing that exposure to smoke-derived carcinogens is a risk factor for lung cancer; not only does the magnitude of risk depend upon carcinogen dose, but it also becomes more irreversible with prolonged exposure. The confirmation of epidemiologic data by our experimental findings is of significance because it strengthens the case for the etiologic involvement of SHS in nonsmokers' lung cancer. Identifying the etiologic factors involved in the pathogenesis of lung cancer can help define future strategies for prevention, early detection, and treatment of this highly lethal malignancy.

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

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Júlio Alves Cardoso Filho

2008-07-01

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

Low-dose caffeine physical dependence in humans.

Science.gov (United States)

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

1990-12-01

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

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.

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.

Genetically significant dose and sex ratio of the offsprings of patient treated with 131I for hyperthyroidism

International Nuclear Information System (INIS)

Takeshita, Akihisa

1975-01-01

The gonadal doses following the 131 I treatment of 6 male and 14 female patients with hyperthyroidism were calculated by the method of MIRD, measuring daily radioactivity in the thyroid gland and circulating blood. The testicular dose was 0.52 +- 0.256 rads and the ovarian dose was 0.632 +- 0.488 rads per mCi. In 1965, the genetically significant dose from 131 I treatment of 925 patients with hyperthyroidism was estimated to be 0.0136 mrads/person/year. The genetically significant dose would amount to 0.0613 mrads/person/year, assuming that the total amount of 131 I supplied for treatment in 1965 was administered to treat the hyperthyroid patients with an age-and sex distribution similar to that of the above mentioned group of patients. Sex ratios of the offspring of male and female patients treated with 131 I from 1953 to 1966 were compared with those of offspring born to male and female patients before the treatment. The proportion of males was higher among the offspring of male patients after 131 I treatment than among the offspring of the controls, but the difference was not statistically significant. The sex ratio of the offspring of female patients was not different from that of controls. The mean age of the parents at the times of their children's birth after 131 I treatment was 2.6 - 6.0 year older in male patients and 2.8 - 2.9 year older in female patients than that of controls. (J.P.N.)

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

International Nuclear Information System (INIS)

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

1994-01-01

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

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

Science.gov (United States)

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

2015-05-27

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

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

International Nuclear Information System (INIS)

Dufey, F; Walsh, L; Sogl, M; Tschense, A; Schnelzer, M; Kreuzer, M

2013-01-01

An increased risk of mortality from primary liver cancers among uranium miners has been observed in various studies. An analysis of the data from a German uranium miner cohort (the ‘Wismut cohort’) was used to assess the relationship with ionising radiation. To that end the absorbed organ dose due to high and low linear energy transfer radiation was calculated for 58 987 miners with complete information on radiation exposure from a detailed job–exposure matrix. 159 deaths from liver cancer were observed in the follow-up period from 1946 to 2003. Relative risk models with either linear or categorical dependence on high and low linear energy transfer radiation liver doses were fitted by Poisson regression, stratified on age and calendar year. The linear trend of excess relative risk in a model with both low and high linear transfer radiation is −0.8 (95% confidence interval (CI): −3.7, 2.1) Gy −1 and 48.3 (95% CI: −32.0, 128.6) Gy −1 for low and high linear energy transfer radiation, respectively, and thus not statistically significant for either dose. The increase of excess relative risk with equivalent liver dose is 0.57 (95% CI: −0.69, 1.82) Sv −1 . Adjustment for arsenic only had a negligible effect on the radiation risk. In conclusion, there is only weak evidence for an increase of liver cancer mortality with increasing radiation dose in the German uranium miners cohort considered. However, both a lack of statistical power and potential misclassification of primary liver cancer are issues. (paper)

Alteration of sodium, potassium-adenosine triphosphatase activity in rabbit ciliary processes by cyclic adenosine monophosphate-dependent protein kinase

International Nuclear Information System (INIS)

Delamere, N.A.; Socci, R.R.; King, K.L.

1990-01-01

The response of sodium, potassium-adenosine triphosphatase (Na,K-ATPase) to cyclic adenosine monophosphate (cAMP)-dependent protein kinase was examined in membranes obtained from rabbit iris-ciliary body. In the presence of the protein kinase together with 10(-5) M cAMP, Na,K-ATPase activity was reduced. No change in Na,K-ATPase activity was detected in response to the protein kinase without added cAMP. Likewise cAMP alone did not alter Na,K-ATPase activity. Reduction of Na,K-ATPase activity was also observed in the presence of the cAMP-dependent protein kinase catalytic subunit. The response of the enzyme to the kinase catalytic subunit was also examined in membranes obtained from rabbit ciliary processes. In the presence of 8 micrograms/ml of the catalytic subunit, ciliary process Na,K-ATPase activity was reduced by more than 50%. To examine whether other ATPases were suppressed by the protein kinase, calcium-stimulated ATPase activity was examined; its activity was stimulated by the catalytic subunit. To test whether the response of the ciliary process Na,K-ATPase is unique, experiments were also performed using membrane preparations from rabbit lens epithelium or rabbit kidney; the catalytic subunit significantly reduced the activity of Na,K-ATPase from the kidney but not the lens. These Na,K-ATPase studies suggest that in the iris-ciliary body, cAMP may alter sodium pump activity. In parallel 86Rb uptake studies, we observed that ouabain-inhibitable potassium uptake by intact pieces of iris-ciliary body was reduced by exogenous dibutryl cAMP or by forskolin

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

International Nuclear Information System (INIS)

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

2008-01-01

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

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

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

International Nuclear Information System (INIS)

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

2009-01-01

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

TH-C-19A-03: Characterization of the Dose Per Pulse Dependence of Various Detectors Used in Quality Assurance of FFF Treatment Plans

Energy Technology Data Exchange (ETDEWEB)

Karan, T [Stronach Regional Cancer Center, Newmarket, ON (Canada); Viel, F; Atwal, P; Gete, E; Camborde, M; Horwood, R; Strgar, V; Duzenli, C [British Columbia Cancer Agency, Vancouver, BC (Canada)

2014-06-15

Purpose: To present the dose per pulse dependence of various QA devices under Flattening Filter Free (FFF) conditions. Methods: Air and liquid filled ion chamber arrays, diode arrays, radiochromic film and optically stimulated luminescence detectors were investigated. All detectors were irradiated under similar conditions of varying dose per pulse on a TrueBeam linac. Dose per pulse was controlled by varying SSD from 70 to 160 cm providing a range from ~0.5 to ~3 mGy per pulse. MU rates of up to 2400 MU/min for 10X FFF and 1400 MU/min for the 6X FFF beam were used. Beam pulses were counted using the Profiler™ diode array and pulse timing was confirmed by examining linac node files. Delivered doses were calculated with the Eclipse™ treatment planning system. Results: The detectors show a range of behaviors depending on the detector type, as expected. Diode arrays show up to 4% change in sensitivity (sensitivity increases with increasing dose per pulse) over the range tested. Air and liquid ion chambers arrays show a change in sensitivity of up to 3% (air) and 6% (liquid) (sensitivity decreases with increasing dose per pulse) while film and OSLD do not demonstrate a dependence on dose per pulse. Conclusion: Dependence of detector response on dose per pulse varies considerably depending on detector design. Interplay between dose per pulse and MU rate also exists for some detectors. Due diligence is required to characterize detector response prior to implementation of a QA protocol for FFF treatment delivery. During VMAT delivery, the MU rate may also vary dramatically within a treatment fraction. We intend to further investigate the implications of this for VMAT FFF patient specific quality assurance. T Karan and F Viel have received partial funding through the Varian Research program.

TH-C-19A-03: Characterization of the Dose Per Pulse Dependence of Various Detectors Used in Quality Assurance of FFF Treatment Plans

International Nuclear Information System (INIS)

Karan, T; Viel, F; Atwal, P; Gete, E; Camborde, M; Horwood, R; Strgar, V; Duzenli, C

2014-01-01

Purpose: To present the dose per pulse dependence of various QA devices under Flattening Filter Free (FFF) conditions. Methods: Air and liquid filled ion chamber arrays, diode arrays, radiochromic film and optically stimulated luminescence detectors were investigated. All detectors were irradiated under similar conditions of varying dose per pulse on a TrueBeam linac. Dose per pulse was controlled by varying SSD from 70 to 160 cm providing a range from ~0.5 to ~3 mGy per pulse. MU rates of up to 2400 MU/min for 10X FFF and 1400 MU/min for the 6X FFF beam were used. Beam pulses were counted using the Profiler™ diode array and pulse timing was confirmed by examining linac node files. Delivered doses were calculated with the Eclipse™ treatment planning system. Results: The detectors show a range of behaviors depending on the detector type, as expected. Diode arrays show up to 4% change in sensitivity (sensitivity increases with increasing dose per pulse) over the range tested. Air and liquid ion chambers arrays show a change in sensitivity of up to 3% (air) and 6% (liquid) (sensitivity decreases with increasing dose per pulse) while film and OSLD do not demonstrate a dependence on dose per pulse. Conclusion: Dependence of detector response on dose per pulse varies considerably depending on detector design. Interplay between dose per pulse and MU rate also exists for some detectors. Due diligence is required to characterize detector response prior to implementation of a QA protocol for FFF treatment delivery. During VMAT delivery, the MU rate may also vary dramatically within a treatment fraction. We intend to further investigate the implications of this for VMAT FFF patient specific quality assurance. T Karan and F Viel have received partial funding through the Varian Research program

Age and sex dependence in tumorigenesis in mice by continuous low-dose-rate gamma-ray whole-body irradiation

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