TH-C-18A-09: Exam and Patient Parameters Affecting the DNA Damage Response Following CT Studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Elgart, S; Adibi, A; Bostani, M

Purpose: To identify exam and patient parameters affecting the biological response to CT studies using in vivo and ex vivo blood samples. Methods: Blood samples were collected under IRB approval from 16 patients undergoing clinically-indicated CT exams. Blood was procured prior to, immediately after and 30minutes following irradiation. A sample of preexam blood was placed on the patient within the exam region for ex vivo analysis. Whole blood samples were fixed immediately following collection and stained for γH2AX to assess DNA damage response (DDR). Median fluorescence of treated samples was compared to non-irradiated control samples for each patient. Patients weremore » characterized by observed biological kinetic response: (a) fast — phosphorylation increased by 2minutes and fell by 30minutes, (b) slow — phosphorylation continued to increase to 30minutes and (c) none — little change was observed or irradiated samples fell below controls. Total dose values were normalized to exam time for an averaged dose-rate in dose/sec for each exam. Relationships between patient biological responses and patient and exam parameters were investigated. Results: A clearer dose response at 30minutes is observed for young patients (<61yoa; R2>0.5) compared to old patients (>61yoa; R{sup 2}<0.11). Fast responding patients were significantly younger than slow responding patients (p<0.05). Unlike in vivo samples, age did not significantly affect the patient response ex vivo. Additionally, fast responding patients received exams with significantly smaller dose-rate than slow responding patients (p<0.05). Conclusion: Age is a significant factor in the biological response suggesting that DDR may be more rapid in a younger population and slower as the population ages. Lack of an agerelated response ex vivo suggests a systemic response to radiation not present when irradiated outside the body. Dose-rate affects the biological response suggesting that patient response may be related to scan timing and dose delivery within an exam protocol. All authors receive(d) funding from a Master Research Agreement from Siemens Healthcare with UCLA Radiological Sciences.« less

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

PubMed

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

2016-11-01

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

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

PubMed Central

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

2016-01-01

Beam damage caused by energetic electrons in the transmission electron microscope is a fundamental constraint limiting the collection of artifact-free information. Through understanding the influence of the electron beam, experimental routines may be adjusted to improve the data collection process. Investigations of CeO2 indicate that there is not a critical dose required for the accumulation of electron beam damage. Instead, measurements using annular dark field scanning transmission electron microscopy and electron energy loss spectroscopy demonstrate that the onset of measurable damage occurs when a critical dose rate is exceeded. The mechanism behind this phenomenon is that oxygen vacancies created by exposure to a 300 keV electron beam are actively annihilated as the sample re-oxidizes in the microscope environment. As a result, only when the rate of vacancy creation exceeds the recovery rate will beam damage begin to accumulate. This observation suggests that dose-intensive experiments can be accomplished without disrupting the native structure of the sample when executed using dose rates below the appropriate threshold. Furthermore, the presence of an encapsulating carbonaceous layer inhibits processes that cause beam damage, markedly increasing the dose rate threshold for the accumulation of damage. PMID:27469265

OSL studies of local bricks for retrospective dosimetric application

NASA Astrophysics Data System (ADS)

Singh, A. K.; Menon, S. N.; Kadam, S. Y.; Koul, D. K.; Datta, D.

2016-09-01

Luminescence properties of quartz extracted from bricks has been reported worldwide for its use in dose estimation in case of nuclear or radiological accident. Accordingly, in this study the feasibility of utilizing the optically stimulated luminescence (OSL) emission of quartz extracted from red bricks collected from three different locations in and around Mumbai, India for retrospective dosimetry was explored. Thermoluminescence and OSL characterization of the samples were carried out. The growth curve, thermal stability and equivalent dose plateau of the OSL signal suggested the signals to be well behaving. Subsequently, the dose recovery tests carried for different administered doses, using single aliquot regenerative protocol, demonstrated the feasibility of the OSL emissions of these samples for dose evaluation in retrospective dosimetry.

Examining Radiation-Induced In Vivo and In Vitro Gene Expression Changes of the Peripheral Blood in Different Laboratories for Biodosimetry Purposes: First RENEB Gene Expression Study.

PubMed

Abend, M; Badie, C; Quintens, R; Kriehuber, R; Manning, G; Macaeva, E; Njima, M; Oskamp, D; Strunz, S; Moertl, S; Doucha-Senf, S; Dahlke, S; Menzel, J; Port, M

2016-02-01

The risk of a large-scale event leading to acute radiation exposure necessitates the development of high-throughput methods for providing rapid individual dose estimates. Our work addresses three goals, which align with the directive of the European Union's Realizing the European Network of Biodosimetry project (EU-RENB): 1. To examine the suitability of different gene expression platforms for biodosimetry purposes; 2. To perform this examination using blood samples collected from prostate cancer patients (in vivo) and from healthy donors (in vitro); and 3. To compare radiation-induced gene expression changes of the in vivo with in vitro blood samples. For the in vitro part of this study, EDTA-treated whole blood was irradiated immediately after venipuncture using single X-ray doses (1 Gy/min(-1) dose rate, 100 keV). Blood samples used to generate calibration curves as well as 10 coded (blinded) samples (0-4 Gy dose range) were incubated for 24 h in vitro, lysed and shipped on wet ice. For the in vivo part of the study PAXgene tubes were used and peripheral blood (2.5 ml) was collected from prostate cancer patients before and 24 h after the first fractionated 2 Gy dose of localized radiotherapy to the pelvis [linear accelerator (LINAC), 580 MU/min, exposure 1-1.5 min]. Assays were run in each laboratory according to locally established protocols using either microarray platforms (2 laboratories) or qRT-PCR (2 laboratories). Report times on dose estimates were documented. The mean absolute difference of estimated doses relative to the true doses (Gy) were calculated. Doses were also merged into binary categories reflecting aspects of clinical/diagnostic relevance. For the in vitro part of the study, the earliest report time on dose estimates was 7 h for qRT-PCR and 35 h for microarrays. Methodological variance of gene expression measurements (CV ≤10% for technical replicates) and interindividual variance (≤twofold for all genes) were low. Dose estimates based on one gene, ferredoxin reductase (FDXR), using qRT-PCR were as precise as dose estimates based on multiple genes using microarrays, but the precision decreased at doses ≥2 Gy. Binary dose categories comprising, for example, unexposed compared with exposed samples, could be completely discriminated with most of our methods. Exposed prostate cancer blood samples (n = 4) could be completely discriminated from unexposed blood samples (n = 4, P < 0.03, two-sided Fisher's exact test) without individual controls. This could be performed by introducing an in vitro-to-in vivo correction factor of FDXR, which varied among the laboratories. After that the in vitro-constructed calibration curves could be used for dose estimation of the in vivo exposed prostate cancer blood samples within an accuracy window of ±0.5 Gy in both contributing qRT-PCR laboratories. In conclusion, early and precise dose estimates can be performed, in particular at doses ≤2 Gy in vitro. Blood samples of prostate cancer patients exposed to 0.09-0.017 Gy could be completely discriminated from pre-exposure blood samples with the doses successfully estimated using adjusted in vitro-constructed calibration curves.

Reference levels of background radioactivity for beach sands and soils in İnebolu/Kastamonu-Turkey

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kurnaz, Aslı, E-mail: akurnaz@kastamonu.edu.tr; Türkdoğan, Savaş, E-mail: savas-turk-dogan@hotmail.com; Hançerlioğulları, Aybaba, E-mail: aybaba@kastamonu.edu.tr

This paper presents the measurement results of environmental radioactivity levels for İnebolu district (tourist area), Kastamonu-Turkey. The radioactivity concentrations of {sup 238}U, {sup 232}Th, {sup 40}K and the fission product {sup 137}Cs in soil samples collected from 13 region surroundings of study area and in 12 beach sand samples collected from along the coast of İnebolu were determined. To evaluate the radiological hazard of the natural radioactivity, based on the measured concentrations of these radionuclides, the mean absorbed gamma dose and the annual effective dose were evaluated separately, and found to be 112.90 nGy h-1 and 138.46 µSv y-1 for soilmore » samples and 75.19 nGy h-1 and 92.22 µSv y-1 for beach sand samples, respectively. The results show that İnebolu does not have high background.« less

Reference levels of background radioactivity for beach sands and soils in İnebolu/Kastamonu-Turkey

NASA Astrophysics Data System (ADS)

Kurnaz, Aslı; Türkdoǧan, Savaş; Hançerlioǧulları, Aybaba; ćetiner, M. Atıf

2016-03-01

This paper presents the measurement results of environmental radioactivity levels for İnebolu district (tourist area), Kastamonu-Turkey. The radioactivity concentrations of 238U, 232Th, 40K and the fission product 137Cs in soil samples collected from 13 region surroundings of study area and in 12 beach sand samples collected from along the coast of İnebolu were determined. To evaluate the radiological hazard of the natural radioactivity, based on the measured concentrations of these radionuclides, the mean absorbed gamma dose and the annual effective dose were evaluated separately, and found to be 112.90 nGy h-1 and 138.46 µSv y-1 for soil samples and 75.19 nGy h-1 and 92.22 µSv y-1 for beach sand samples, respectively. The results show that İnebolu does not have high background.

Use of probability analysis to establish routine bioassay screening levels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carbaugh, E.H.; Sula, M.J.; McFadden, K.M.

1990-09-01

Probability analysis was used by the Hanford Internal Dosimetry Program to establish bioassay screening levels for tritium and uranium in urine. Background environmental levels of these two radionuclides are generally detectable by the highly sensitive urine analysis procedures routinely used at Hanford. Establishing screening levels requires balancing the impact of false detection with the consequence of potentially undetectable occupation dose. To establish the screening levels, tritium and uranium analyses were performed on urine samples collected from workers exposed only to environmental sources. All samples were collected at home using a simulated 12-hour protocol for tritium and a simulated 24-hour collectionmore » protocol for uranium. Results of the analyses of these samples were ranked according to tritium concentration or total sample uranium. The cumulative percentile was calculated and plotted using log-probability coordinates. Geometric means and screening levels corresponding to various percentiles were estimated by graphical interpolation and standard calculations. The potentially annual internal dose associated with a screening level was calculated. Screening levels were selected corresponding to the 99.9 percentile, implying that, on the average, 1 out of 1000 samples collected from an unexposed worker population would be expected to exceed the screening level. 4 refs., 2 figs.« less

Uranium analysis in some food samples collected from Bathinda area of Punjab, India

NASA Astrophysics Data System (ADS)

Kumar, Mukesh; Prasher, Sangeeta; Singh, Surinder

2009-07-01

To strengthen the radiation protection infrastructure in Bathinda, the uranium concentration in daily diet of the residents has been measured and its associated radiation risks were estimated for the adult population. Food samples were collected from major cancer prone areas of the district, from which daily diets were prepared. These diet samples were analyzed using fission track technique. The measured values of the uranium content were found to vary from 0.38 mBq/g in mustard seeds to 4.60 mBq/g in wheat. In case of milk the uranium content is found to vary from 28.57-213.36 mBq/ℓ with mean concentration of 61.35 mBq/ℓ. This leads to a daily dietary intake of 0.90 Bq/day. The measured value of 0.90 Bq d-1, contributes to 1.12 mSv to the cumulative effective dose to the population. This dose is much large than the International Commission for Radiological Protection (ICRP) annual effective dose limit of 1 mSv for the general public [1]. Therefore, it would pose significant health hazard.

Direct Measurement of Perchlorate Exposure Biomarkers in a Highly Exposed Population: A Pilot Study

PubMed Central

Wong, Michelle; Copan, Lori; Olmedo, Luis; Patton, Sharyle; Haas, Robert; Atencio, Ryan; Xu, Juhua; Valentin-Blasini, Liza

2011-01-01

Exposure to perchlorate is ubiquitous in the United States and has been found to be widespread in food and drinking water. People living in the lower Colorado River region may have perchlorate exposure because of perchlorate in ground water and locally-grown produce. Relatively high doses of perchlorate can inhibit iodine uptake and impair thyroid function, and thus could impair neurological development in utero. We examined human exposures to perchlorate in the Imperial Valley among individuals consuming locally grown produce and compared perchlorate exposure doses to state and federal reference doses. We collected 24-hour urine specimen from a convenience sample of 31 individuals and measured urinary excretion rates of perchlorate, thiocyanate, nitrate, and iodide. In addition, drinking water and local produce were also sampled for perchlorate. All but two of the water samples tested negative for perchlorate. Perchlorate levels in 79 produce samples ranged from non-detect to 1816 ppb. Estimated perchlorate doses ranged from 0.02 to 0.51 µg/kg of body weight/day. Perchlorate dose increased with the number of servings of dairy products consumed and with estimated perchlorate levels in produce consumed. The geometric mean perchlorate dose was 70% higher than for the NHANES reference population. Our sample of 31 Imperial Valley residents had higher perchlorate dose levels compared with national reference ranges. Although none of our exposure estimates exceeded the U. S. EPA reference dose, three participants exceeded the acceptable daily dose as defined by bench mark dose methods used by the California Office of Environmental Health Hazard Assessment. PMID:21394205

Radiometric assessment of natural radioactivity levels of agricultural soil samples collected in Dakahlia, Egypt.

PubMed

Issa, Shams A M

2013-01-01

Determination of the natural radioactivity has been carried out, by using a gamma-ray spectrometry [NaI (Tl) 3″ × 3″] system, in surface soil samples collected from various locations in Dakahlia governorate, Egypt. These locations form the agriculturally important regions of Egypt. The study area has many industries such as chemical, paper, organic fertilisers and construction materials, and the soils of the study region are used as a construction material. Therefore, it becomes necessary to study the natural radioactivity levels in soil to assess the dose for the population in order to know the health risks. The activity concentrations of (226)Ra, (232)Th and (40)K in the soil ranged from 5.7 ± 0.3 to 140 ± 7, from 9.0 ± 0.4 to 139 ± 7 and from 22 ± 1 to 319 ± 16 Bq kg(-1), respectively. The absorbed dose rate, annual effective dose rate, radium equivalent (Req), excess lifetime cancer risk, hazard indices (Hex and Hin) and annual gonadal dose equivalent, which resulted from the natural radionuclides in the soil were calculated.

The relationship between blood and muscle samples to monitor for residues of the antibiotic enrofloxacin in chickens.

PubMed

Reyes-Herrera, I; Schneider, M J; Blore, P J; Donoghue, D J

2011-02-01

In 2005, the US Food and Drug Administration withdrew approval for use of enrofloxacin in poultry, thus effectively imposing zero tolerance for residues of this antibiotic in poultry. Conventional residue monitoring for most antibiotics, including enrofloxacin, involves removing poultry carcasses from the processing line and collecting muscle tissues for analysis. Because of the loss of valuable edible products and the difficulties and expense of sampling all the carcasses, only a small portion of carcasses are tested for violative residues. Unlike muscle tissue, blood is readily available from all birds at the beginning of processing and may be used to screen for illegal residues in all poultry carcasses. It is unknown, however, if enrofloxacin concentrations in blood are predictive of muscle concentrations. In an effort to evaluate this relationship, 156 broiler chickens, 5 wk of age, were dosed with either 25 or 50 µg/mL of enrofloxacin for 3 or 7 d, respectively, in the drinking water. Blood and muscle samples were collected at 0, 1, 3, 6, 12, and 24 h (n = 6 birds/group) during the first dosing day, every 48 h during the dosing period, and every 12 h during the withdrawal period for up to 60 h after withdrawal. Enrofloxacin residues were determined in all blood and tissue samples during the dosing periods and in most of the withdrawal period for both doses. These results support the potential to use blood to screen for illegal enrofloxacin residues in edible poultry tissues in an effort to protect the human food supply.

Contributions of Various Radiological Sources to Background in a Suburban Environment

DOE PAGES

Milvenan, Richard D.; Hayes, Robert B.

2016-11-01

This work is a brief overview and comparison of dose rates stemming from both indoor and outdoor natural background radiation and household objects within a suburban environment in North Carolina. Combined gamma and beta dose rates were taken from indoor objects that ranged from the potassium in fruit to the americium in smoke detectors. For outdoor measurements, various height and time data samples were collected to show fluctuations in dose rate due to temperature inversion and geometric attenuation. Although each sample tested proved to have a statistically significant increase over background using Students t-test, no sample proved to be moremore » than a minor increase in natural radiation dose. Furthermore, the relative contributions from natural radioactivity such as potassium in foods and common household items are shown to be easily distinguished from background using standard handheld instrumentation when applied in a systematic, methodological manner.« less

Studies on radiation dose due to radioactive elements present in ground water and soil samples around Mysore city, India.

PubMed

Chandrashekara, M S; Veda, S M; Paramesh, L

2012-04-01

A systematic study of the ground water and soil samples collected from different locations around Mysore city (12(°)N and 76(°)E) has been carried out. (226)Ra activity concentration in water samples varies from 0.28 to 189 mBq l(-1) with a geometric mean (GM) of 4.75 mBq l(-1) and (222)Rn concentration in ground water varies from 4.25 to 435 Bq l(-1) with a GM of 25.9 Bq l(-1). The GM of inhalation and ingestion doses due to (222)Rn in water is 65.2 and 5.43, µSv y(-1), respectively. The measured GM gamma dose rate in air is 85.4 nGy h(-1) and absorbed dose rate estimated from the measured activity of radionuclides is 92.6 nGy h(-1).

Contributions of Various Radiological Sources to Background in a Suburban Environment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Milvenan, Richard D.; Hayes, Robert B.

This work is a brief overview and comparison of dose rates stemming from both indoor and outdoor natural background radiation and household objects within a suburban environment in North Carolina. Combined gamma and beta dose rates were taken from indoor objects that ranged from the potassium in fruit to the americium in smoke detectors. For outdoor measurements, various height and time data samples were collected to show fluctuations in dose rate due to temperature inversion and geometric attenuation. Although each sample tested proved to have a statistically significant increase over background using Students t-test, no sample proved to be moremore » than a minor increase in natural radiation dose. Furthermore, the relative contributions from natural radioactivity such as potassium in foods and common household items are shown to be easily distinguished from background using standard handheld instrumentation when applied in a systematic, methodological manner.« less

Radiation dose in the high background radiation area in Kerala, India.

PubMed

Christa, E P; Jojo, P J; Vaidyan, V K; Anilkumar, S; Eappen, K P

2012-03-01

A systematic radiological survey has been carried out in the region of high-background radiation area in Kollam district of Kerala to define the natural gamma-radiation levels. One hundred and forty seven soil samples from high-background radiation areas and five samples from normal background region were collected as per standard sampling procedures and were analysed for (238)U, (232)Th and (40)K by gamma-ray spectroscopy. External gamma dose rates at all sampling locations were also measured using a survey meter. The activities of (238)U, (232)Th and (40)K was found to vary from 17 to 3081 Bq kg(-1), 54 to 11976 Bq kg(-1) and BDL (67.4 Bq kg(-1)) to 216 Bq kg(-1), respectively, in the study area. Such heterogeneous distribution of radionuclides in the region may be attributed to the deposition phenomenon of beach sand soil in the region. Radium equivalent activities were found high in several locations. External gamma dose rates estimated from the levels of radionuclides in soil had a range from 49 to 9244 nGy h(-1). The result of gamma dose rate measured at the sampling sites using survey meter showed an excellent correlation with dose rates computed from the natural radionuclides estimated from the soil samples.

Exposure of school children to polycyclic aromatic hydrocarbons, heavy metals and radionuclides in the urban soil of Kragujevac city, Central Serbia.

PubMed

Stajic, J M; Milenkovic, B; Pucarevic, M; Stojic, N; Vasiljevic, I; Nikezic, D

2016-03-01

The concentrations of radionuclides, polycyclic aromatic hydrocarbons (PAHs) and heavy metals were measured in soil samples collected from school backyards and playgrounds in Kragujevac, one of the largest cities of Central Serbia. The activity concentrations of (226)Ra, (232)Th, (40)K and (137)Cs were determined using the HPGe semiconductor detector. The average values were 34.6, 44.7, 428.9 and 45.1 Bq kg(-1), respectively. The correlation between the activity concentrations of (226)Ra in the soil samples and the results of the previous measurement of (222)Rn concentrations in the indoor air was examined. The absorbed dose rates, the annual effective doses and excess lifetime cancer risk were also estimated. The activity concentrations of (226)Ra and (232)Th have shown normal distribution. The collected soil samples were analysed for PAHs by HPLC. All analysed soil samples contained PAHs, and their total amounts (for 15 measured compounds) were found to be between 0.038 and 3.136 mg kg(-1) of absolutely dry soil (a.d.s). In addition the concentrations of As, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb and Zn were measured in the fourteen soil samples collected from the playgrounds of kindergartens. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evaluation of radiological impacts of tenorm in the Tunisian petroleum industry.

PubMed

Hrichi, Hajer; Baccouche, Souad; Belgaied, Jamel-Eddine

2013-01-01

The health impacts associated with uncontrolled release of TENORM in products and wastes released in the petroleum industry are of great concern. In this study, evaluation of TENORM in the Tunisian petroleum products and wastes is presented. Fourteen products samples, twelve waste samples and three samples from the surrounding environment were collected from the Tunisian Refinery STIR site and from two onshore production oilfields. The activity concentrations of (232)Th, (226)Ra and (40)K for all samples were determined using gamma-ray spectrometry with High Purity Germanium (HPGe) detector. The activity concentrations of (224)Ra were calculated only for scale samples. The radium equivalent activity, external and internal hazard indices, absorbed doses rates in air and annual effective dose were also estimated. It was noticed that maximum value of Ra(eq) activity was found to be 398 Bq/kg in scale (w8) collected from an onshore production oilfield which exceeds the maximum Ra(eq) value of 370 Bq/kg recommended for safe use. All hazard indices indicated that scale samples (w6, w7, w8 and w11) could be a significant waste problem especially sample (w8). In this study, the radium isotopic data were used to provide an estimate of scale samples ages by the use of the (224)Ra/(228)Ra activity ratio dating method. Ages of collected scales were found to be in the range 0.91-2.4 years. In this work, radioactivity (NORM contamination) in samples collected from the refinery STIR are showed to be insignificant if compared to those from onshore oilfield production sites. Copyright © 2012 Elsevier Ltd. All rights reserved.

Evaluation of external and internal irradiation on uranium mining enterprise staff by tooth enamel EPR spectroscopy

NASA Astrophysics Data System (ADS)

Zhumadilov, Kassym; Ivannikov, Alexander; Khailov, Artem; Orlenko, Sergei; Skvortsov, Valeriy; Stepanenko, Valeriy; Kuterbekov, Kairat; Toyoda, Shin; Kazymbet, Polat; Hoshi, Masaharu

2017-11-01

In order to estimate radiation effects on uranium enterprise staff and population teeth samples were collected for EPR tooth enamel dosimetry from population of Stepnogorsk city and staff of uranium mining enterprise in Shantobe settlment (Akmola region, North of Kazakhstan). By measurements of tooth enamel EPR spectra, the total absorbed dose in the enamel samples and added doses after subtraction of the contribution of natural background radiation are determined. For the population of Stepnogorsk city average added dose value of 4 +/- 11 mGy with variation of 51 mGy was obtained. For the staff of uranium mining enterprise in Shantobe settlment average value of added dose 95 +/- 20 mGy, with 85 mGy variation was obtained. Higher doses and the average value and a large variation for the staff, probably is due to the contribution of occupational exposure.

Population pharmacokinetic analysis of clopidogrel in healthy Jordanian subjects with emphasis optimal sampling strategy.

PubMed

Yousef, A M; Melhem, M; Xue, B; Arafat, T; Reynolds, D K; Van Wart, S A

2013-05-01

Clopidogrel is metabolized primarily into an inactive carboxyl metabolite (clopidogrel-IM) or to a lesser extent an active thiol metabolite. A population pharmacokinetic (PK) model was developed using NONMEM(®) to describe the time course of clopidogrel-IM in plasma and to design a sparse-sampling strategy to predict clopidogrel-IM exposures for use in characterizing anti-platelet activity. Serial blood samples from 76 healthy Jordanian subjects administered a single 75 mg oral dose of clopidogrel were collected and assayed for clopidogrel-IM using reverse phase high performance liquid chromatography. A two-compartment (2-CMT) PK model with first-order absorption and elimination plus an absorption lag-time was evaluated, as well as a variation of this model designed to mimic enterohepatic recycling (EHC). Optimal PK sampling strategies (OSS) were determined using WinPOPT based upon collection of 3-12 post-dose samples. A two-compartment model with EHC provided the best fit and reduced bias in C(max) (median prediction error (PE%) of 9.58% versus 12.2%) relative to the basic two-compartment model, AUC(0-24) was similar for both models (median PE% = 1.39%). The OSS for fitting the two-compartment model with EHC required the collection of seven samples (0.25, 1, 2, 4, 5, 6 and 12 h). Reasonably unbiased and precise exposures were obtained when re-fitting this model to a reduced dataset considering only these sampling times. A two-compartment model considering EHC best characterized the time course of clopidogrel-IM in plasma. Use of the suggested OSS will allow for the collection of fewer PK samples when assessing clopidogrel-IM exposures. Copyright © 2013 John Wiley & Sons, Ltd.

Defined daily doses (DDD) do not accurately reflect opioid doses used in contemporary chronic pain treatment.

PubMed

Nielsen, Suzanne; Gisev, Natasa; Bruno, Raimondo; Hall, Wayne; Cohen, Milton; Larance, Briony; Campbell, Gabrielle; Shanahan, Marian; Blyth, Fiona; Lintzeris, Nicholas; Pearson, Sallie; Mattick, Richard; Degenhardt, Louisa

2017-05-01

To assess how well the defined daily dose (DDD) metric reflects opioid utilisation among chronic non-cancer pain patients. Descriptive, cross-sectional study, utilising a 7-day medication diary. Community-based treatment settings, Australia. A sample of 1101 people prescribed opioids for chronic non-cancer pain. Opioid dose data was collected via a self-completed 7-day medication diary capturing names, strengths and doses of each medication taken in the past week. Median daily dose was calculated for each opioid. Comparisons were made to the World Health Organization's (WHO) DDD metric. WHO DDDs ranged from 0.6 to 7.1 times the median opioid doses used by the sample. For transdermal fentanyl and oral hydromorphone, the median dose was comparable with the DDD. The DDD for methadone was 0.6 times lower than the median doses used by this sample of chronic pain patients. In contrast, the DDD for oxycodone and transdermal buprenorphine, the most commonly used strong opioids for chronic pain in Australia, was two to seven times higher than actual doses used. For many opioids, there are key differences between the actual doses used in clinical practice and the WHO's DDDs. The interpretation of opioid utilisation studies using population-level DDDs may be limited, and a recalibration of the DDD for many opioids or the reporting of opioid utilisation in oral morphine equivalent doses is recommended. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Changes in antimicrobial susceptibility in a population of Escherichia coli isolated from feedlot cattle administered ceftiofur crystalline-free acid.

PubMed

Lowrance, T Courtney; Loneragan, Guy H; Kunze, David J; Platt, Tammy M; Ives, Samuel E; Scott, H Morgan; Norby, Bo; Echeverry, Alejandro; Brashears, Mindy M

2007-05-01

To determine effects of administration of ceftiofur crystalline-free acid (CCFA) on antimicrobial susceptibility of Escherichia coli in feedlot cattle. 61 feedlot steers. A cohort study was conducted. Steers were housed in pens (5 pens with 10 steers and 1 pen with 11 steers). Five steers in each pen were administered CCFA, and 5 served as control steers (1 pen had 6 control steers). The CCFA administration included a single-dose regimen (6.6 mg/kg, SC, on day 0), two-thirds-dose regimen (4.4 mg/kg, SC, on day 0), and 3-dose regimen (6.6 mg/kg, SC, on days 0, 6, and 13). Fecal samples were collected on days 0, 2, 6, 9, 13, 16, 20, and 28. Fecal samples were collected immediately before CCFA administration. Minimum inhibitory concentrations of 15 antimicrobials were determined for 3 E coli isolates/fecal sample. Escherichia coli were enumerated by use of direct-plating techniques. Resistance to 1 or more antimicrobials was detected in 986 of 1,441 (68.4%) isolates recovered. Administration of CCFA was associated with a transient increase in the population of ceftiofur-resistant isolates. Susceptibility returned to day 0 values (ie, samples collected immediately before CCFA administration) approximately 2 weeks after completion of CCFA administration. Agreement between ceftiofur resistance and co-resistance to ampicillin, chloramphenicol, streptomycin, sulfisoxazole, and tetracycline was almost perfect (kappa 0.97). We did not detect variation in susceptibility of E coli recovered from commingled control steers. Administration of CCFA provided selection pressure that favored transient expansion of multiple-resistant variants.

Pharmacokinetic evaluation of three different intramuscular doses of nandrolone decanoate: analysis of serum and urine samples in healthy men.

PubMed

Bagchus, Wilma M; Smeets, Jean M W; Verheul, Herman A M; De Jager-Van Der Veen, Suzanne M; Port, Andreas; Geurts, T B Paul

2005-05-01

The pharmacokinetics of nandrolone in serum and urine were investigated in healthy young men after a single im injection of 50 mg (n = 20), 100 mg (n = 17), or 150 mg (n = 17) nandrolone decanoate. Blood samples were collected before treatment and for up to 32 d after dosing. In addition, in the 50- and 150-mg groups, 24-h urine samples were collected before treatment and on d 1, 7, and 33 after treatment; in the 150-mg group, additional samples were collected after 3 and 6 months. Serum concentrations and the area under the curve of nandrolone increased proportionally with the dose administered. The peak serum concentration ranged from 2.14 ng/ml in the 50-mg group to 4.26 ng/ml in the 100-mg group and 5.16 ng/ml in the 150-mg group. The peak serum concentration was reached after 30 h (50 and 100 mg) and 72 h (150 mg), whereas the terminal half-life was 7-12 d. In urine, pretreatment concentrations of 19-norandrosterone (19-NA) and/or 19-noretiocholanolone (19-NE) were detected in five of 37 subjects (14%). In the 50-mg group, 19-NA and/or 19-NE could be detected at least until 33 d after injection in 16 of 17 subjects (94%). In the 150-mg group, who were presumed to have not previously used nandrolone, nandrolone metabolites could be detected for up to 6 months in eight of 12 subjects (67%) for 19-NE and in 10 of 12 subjects (83%) for 19-NA.

Large-Scale Variability of Inpatient Tacrolimus Therapeutic Drug Monitoring at an Academic Transplant Center: a Retrospective Study.

PubMed

Strohbehn, Garth W; Pan, Warren W; Petrilli, Christopher M; Heidemann, Lauren; Larson, Sophia; Aaronson, Keith D; Johnson, Matt; Ellies, Tammy; Heung, Michael

2018-04-30

Inpatient tacrolimus therapeutic drug monitoring (TDM) lacks standardized guidelines. In this study, the authors analyzed variability in the pre-analytical phase of the inpatient tacrolimus TDM process at their institution. Patients receiving tacrolimus (twice-daily formulation) and tacrolimus laboratory analysis were included in the study. Times of tacrolimus administration and laboratory study collection were extracted and time distribution plots for each step in the inpatient TDM process were generated. Trough levels were drawn appropriately in 25.9% of the cases. Timing between doses was consistent, with 91.9% of the following dose administrations occurring 12 +/- 2 hours after the previous dose. Only 38.1% of the drug administrations occurred within one hour of laboratory study collection. Tacrolimus-related patient safety events were reported at a rate of 1.9 events per month while incorrect timing of TDM sample collection occurred approximately 200 times per month. Root cause analysis identified a TDM process marked by a lack of communication and coordination of drug administration and TDM sample collection. Extrapolating findings nationwide, we estimate $22 million in laboratory costs wasted annually. Based on this large single-center study, the authors concluded that the inpatient TDM process is prone to timing errors, thus is financially wasteful, and at its worst harmful to patients due to clinical decisions being made on the basis of unreliable data. Further work is needed on systems solutions to better align the laboratory study collection and drug administration processes.

Rapamycin Pharmacokinetic and Pharmacodynamic Relationships in Osteosarcoma: A Comparative Oncology Study in Dogs

PubMed Central

Paoloni, Melissa C.; Mazcko, Christina; Fox, Elizabeth; Fan, Timothy; Lana, Susan; Kisseberth, William; Vail, David M.; Nuckolls, Kaylee; Osborne, Tanasa; Yalkowsy, Samuel; Gustafson, Daniel; Yu, Yunkai; Cao, Liang; Khanna, Chand

2010-01-01

Background Signaling through the mTOR pathway contributes to growth, progression and chemoresistance of several cancers. Accordingly, inhibitors have been developed as potentially valuable therapeutics. Their optimal development requires consideration of dose, regimen, biomarkers and a rationale for their use in combination with other agents. Using the infrastructure of the Comparative Oncology Trials Consortium many of these complex questions were asked within a relevant population of dogs with osteosarcoma to inform the development of mTOR inhibitors for future use in pediatric osteosarcoma patients. Methodology/Principal Findings This prospective dose escalation study of a parenteral formulation of rapamycin sought to define a safe, pharmacokinetically relevant, and pharmacodynamically active dose of rapamycin in dogs with appendicular osteosarcoma. Dogs entered into dose cohorts consisting of 3 dogs/cohort. Dogs underwent a pre-treatment tumor biopsy and collection of baseline PBMC. Dogs received a single intramuscular dose of rapamycin and underwent 48-hour whole blood pharmacokinetic sampling. Additionally, daily intramuscular doses of rapamycin were administered for 7 days with blood rapamycin trough levels collected on Day 8, 9 and 15. At Day 8 post-treatment collection of tumor and PBMC were obtained. No maximally tolerated dose of rapamycin was attained through escalation to the maximal planned dose of 0.08 mg/kg (2.5 mg/30kg dog). Pharmacokinetic analysis revealed a dose-dependent exposure. In all cohorts modulation of the mTOR pathway in tumor and PBMC (pS6RP/S6RP) was demonstrated. No change in pAKT/AKT was seen in tumor samples following rapamycin therapy. Conclusions/Significance Rapamycin may be safely administered to dogs and can yield therapeutic exposures. Modulation pS6RP/S6RP in tumor tissue and PBMCs was not dependent on dose. Results from this study confirm that the dog may be included in the translational development of rapamycin and potentially other mTOR inhibitors. Ongoing studies of rapamycin in dogs will define optimal schedules for their use in cancer and evaluate the role of rapamycin use in the setting of minimal residual disease. PMID:20543980

Treatability of organic matter derived from surface and subsurface waters of drinking water catchments.

PubMed

Awad, John; van Leeuwen, John; Liffner, Joel; Chow, Christopher; Drikas, Mary

2016-02-01

The treatability of NOM present in runoff and subsurface waters from discrete zero-order catchments (ZOCs) with three land management practices (Australian native vegetation, pine plantation, grasslands) on varying soil textures of a closed drinking water reservoir-catchment was investigated. Subsurface water samples were collected by lysimeters and shallow piezometers and surface waters by installation of barriers that diverted waters to collection devices. For small sample volumes collected, a 'micro' jar testing procedure was developed to assess the treatability of organics by enhanced coagulation using alum, under standardised conditions. DOM present in water samples was quantified by measurement of DOC and UV absorbance (at 254 nm) and characterized using these and F-EEM. The mean alum dose rate (mg alum per mg DOC removed or Al/DOC) was found to be lower for DOM from sandy soil ZOCs (21.1 ± 11.0 Al/DOC) than from clayey soil ZOCs (38.6 ± 27.7 Al/DOC). ZOCs with Pinus radiata had prominent litter layers (6.3 ± 2.6 cm), and despite differences in soil textures showed similarity in DOM character in subsurface waters, and in alum dose rates (22.2 ± 5.5 Al/DOC). For sandy soil ZOCs, the lowest alum dose rates (16.5 ± 10.6 Al/DOC) were for waters from native vegetation catchment while, for clayey soil ZOCs, waters from pine vegetation had the lowest alum dose rates (23.0 ± 5.0 Al/DOC). Where ZOCs have a prominent O horizon, soil minerals had no apparent influence on the treatability of DOM. Copyright © 2015 Elsevier Ltd. All rights reserved.

Assessment of natural radioactivity levels in soil samples from some areas in Assiut, Egypt.

PubMed

El-Gamal, Hany; Farid, M El-Azab; Abdel Mageed, A I; Hasabelnaby, M; Hassanien, Hassanien M

2013-12-01

The natural radioactivity of soil samples from Assiut city, Egypt, was studied. The activity concentrations of 28 samples were measured with a NaI(Tl) detector. The radioactivity concentrations of (226)Ra, (232)Th, and (40)K showed large variations, so the results were classified into two groups (A and B) to facilitate the interpretation of the results. Group A represents samples collected from different locations in Assiut and characterized by low activity concentrations with average values of 46.15 ± 9.69, 30.57 ± 4.90, and 553.14 ± 23.19 for (226)Ra, (232)Th, and (40)K, respectively. Group B represents samples mainly collected from the area around Assiut Thermal Power Plant and characterized by very high activity concentrations with average values of 3,803 ± 145, 1,782 ± 98, and 1,377 ± 78 for (226)Ra, (232)Th, and (40)K, respectively. In order to evaluate the radiological hazard of the natural radioactivity, the radium equivalent activity (Raeq), the absorbed dose rate (D), the annual effective dose rate (E), the external hazard index (H ex), and the annual gonadal dose equivalent (AGDE) have been calculated and compared with the internationally approved values. For group A, the calculated averages of these parameters are in good agreement with the international recommended values except for the absorbed dose rate and the AGDE values which are slightly higher than the international recommended values. However, for group B, all obtained averages of these parameters are much higher by several orders of magnitude than the international recommended values. The present work provides a background of radioactivity concentrations in the soil of Assiut.

Prediction of Normal Organ Absorbed Doses for [177Lu]Lu-PSMA-617 Using [44Sc]Sc-PSMA-617 Pharmacokinetics in Patients With Metastatic Castration Resistant Prostate Carcinoma.

PubMed

Khawar, Ambreen; Eppard, Elisabeth; Sinnes, Jean Phlippe; Roesch, Frank; Ahmadzadehfar, Hojjat; Kürpig, Stefan; Meisenheimer, Michael; Gaertner, Florian C; Essler, Markus; Bundschuh, Ralph A

2018-04-23

In vivo pharmacokinetic analysis of [Sc]Sc-PSMA-617 was used to determine the normal organ-absorbed doses that may result from therapeutic activity of [Lu]Lu-PSMA-617 and to predict the maximum permissible activity of [Lu]Lu-PSMA-617 for patients with metastatic castration-resistant prostate carcinoma. Pharmacokinetics of [Sc]Sc-PSMA-617 was evaluated in 5 patients with metastatic castration-resistant prostate carcinoma using dynamic PET/CT, followed by 3 static PET/CT acquisitions and blood sample collection over 19.5 hours, as well as urine sample collection at 2 time points. Total activity measured in source organs by PET imaging, as well as counts per milliliter measured in blood and urine samples, was decay corrected back to the time of injection using the half-life of Sc. Afterward, forward decay correction using the half-life of Lu was performed, extrapolating the pharmacokinetics of [Sc]Sc-PSMA-617 to that of [Lu]Lu-PSMA-617. Source organs residence times and organ-absorbed doses for [Lu]Lu-PSMA-617 were calculated using OLINDA/EXM software. Bone marrow self-dose was determined with indirect blood-based method, and urinary bladder contents residence time was estimated by trapezoidal approximation. The maximum permissible activity of [Lu]Lu-PSMA-617 was calculated for each patient considering external beam radiotherapy toxicity limits for radiation absorbed doses to kidneys, bone marrow, salivary glands, and whole body. The predicted mean organ-absorbed doses were highest in the kidneys (0.44 mSv/MBq), followed by the salivary glands (0.23 mSv/MBq). The maximum permissible activity was highly variable among patients; limited by whole body-absorbed dose (1 patient), marrow-absorbed dose (1 patient), and kidney-absorbed dose (3 patients). [Sc]Sc-PSMA-617 PET/CT imaging is feasible and allows theoretical extrapolation of the pharmacokinetics of [Sc]Sc-PSMA-617 to that of [Lu]Lu-PSMA-617, with the intent of predicting normal organ-absorbed doses and maximum permissible activity in patients scheduled for therapy with [Lu]Lu-PSMA-617.

Age, Weight, and CYP2D6 Genotype Are Major Determinants of Primaquine Pharmacokinetics in African Children

PubMed Central

Gonçalves, Bronner P.; Pett, Helmi; Tiono, Alfred B.; Murry, Daryl; Sirima, Sodiomon B.; Niemi, Mikko; Bousema, Teun; Drakeley, Chris

2017-01-01

ABSTRACT Low-dose primaquine is recommended to prevent Plasmodium falciparum malaria transmission in areas threatened by artemisinin resistance and areas aiming for malaria elimination. Community treatment campaigns with artemisinin-based combination therapy in combination with the gametocytocidal primaquine dose target all age groups, but no studies thus far have assessed the pharmacokinetics of this gametocytocidal drug in African children. We recruited 40 children participating in a primaquine efficacy trial in Burkina Faso to study primaquine pharmacokinetics. These children received artemether-lumefantrine and either a 0.25- or a 0.40-mg/kg primaquine dose. Seven blood samples were collected from each participant for primaquine and carboxy-primaquine plasma levels determinations: one sample was collected before primaquine administration and six after primaquine administration according to partially overlapping sampling schedules. Physiological population pharmacokinetic modeling was used to assess the impact of weight, age, and CYP2D6 genotype on primaquine and carboxy-primaquine pharmacokinetics. Despite linear weight normalized dosing, the areas under the plasma concentration-time curves and the peak concentrations for both primaquine and carboxy-primaquine increased with age and body weight. Children who were CYP2D6 poor metabolizers had higher levels of the parent compound, indicating a lower primaquine CYP2D6-mediated metabolism. Our data indicate that primaquine and carboxy-primaquine pharmacokinetics are influenced by age, weight, and CYP2D6 genotype and suggest that dosing strategies may have to be reconsidered to maximize the transmission-blocking properties of primaquine. (This study has been registered at ClinicalTrials.gov under registration no. NCT01935882.) PMID:28289025

Natural radioactivity of riverbank sediments of the Maritza and Tundja Rivers in Turkey.

PubMed

Aytas, Sule; Yusan, Sabriye; Aslani, Mahmoud A A; Karali, Turgay; Turkozu, D Alkim; Gok, Cem; Erenturk, Sema; Gokce, Melis; Oguz, K Firat

2012-01-01

This article represents the first results of the natural radionuclides in the Maritza and Tundja river sediments, in the vicinity of Edirne city, Turkey. The aim of the article is to describe the natural radioactivity concentrations as a baseline for further studies and to obtain the distribution patterns of radioactivity in trans-boundary river sediments of the Maritza and Tundja, which are shared by Turkey, Bulgaria and Greece. Sediment samples were collected during the period of August 2007-April 2010. The riverbank sediment samples were analyzed firstly for their pH, organic matter content and soil texture. The gross alpha/beta and (238)U, (232)Th and (40)K activity concentrations were then investigated in the collected sediment samples. The mean and standard error of mean values of gross alpha and gross beta activity concentrations were found as 91 ± 11, 410 ± 69 Bq/kg and 86 ± 11, 583 ± 109 Bq/kg for the Maritza and Tundja river sediments, respectively. Moreover, the mean and standard error of mean values of (238)U, (232)Th and (40)K activity concentrations were determined as 219 ± 68, 128 ± 55, 298 ± 13 and as 186 ± 98, 121 ± 68, 222 ± 30 Bq/kg for the Maritza and Tundja River, respectively. Absorbed dose rates (D) and annual effective dose equivalent s have been calculated for each sampling point. The average value of adsorbed dose rate and effective dose equivalent were found as 191 and 169 nGy/h; 2 and 2 mSv/y for the Maritza and the Tundja river sediments, respectively.

Dose rate estimation of the Tohoku hynobiid salamander, Hynobius lichenatus, in Fukushima.

PubMed

Fuma, Shoichi; Ihara, Sadao; Kawaguchi, Isao; Ishikawa, Takahiro; Watanabe, Yoshito; Kubota, Yoshihisa; Sato, Youji; Takahashi, Hiroyuki; Aono, Tatsuo; Ishii, Nobuyoshi; Soeda, Haruhi; Matsui, Kumi; Une, Yumi; Minamiya, Yukio; Yoshida, Satoshi

2015-05-01

The radiological risks to the Tohoku hynobiid salamanders (class Amphibia), Hynobius lichenatus due to the Fukushima Dai-ichi Nuclear Power Plant accident were assessed in Fukushima Prefecture, including evacuation areas. Aquatic egg clutches (n = 1 for each sampling date and site; n = 4 in total), overwintering larvae (n = 1-5 for each sampling date and site; n = 17 in total), and terrestrial juveniles or adults (n = 1 or 3 for each sampling date and site; n = 12 in total) of H. lichenatus were collected from the end of April 2011 to April 2013. Environmental media such as litter (n = 1-5 for each sampling date and site; n = 30 in total), soil (n = 1-8 for each sampling date and site; n = 31 in total), water (n = 1 for each sampling date and site; n = 17 in total), and sediment (n = 1 for each sampling date and site; n = 17 in total) were also collected. Activity concentrations of (134)Cs + (137)Cs were 1.9-2800, 0.13-320, and 0.51-220 kBq (dry kg) (-1) in the litter, soil, and sediment samples, respectively, and were 0.31-220 and <0.29-40 kBq (wet kg)(-1) in the adult and larval salamanders, respectively. External and internal absorbed dose rates to H. lichenatus were calculated from these activity concentration data, using the ERICA Assessment Tool methodology. External dose rates were also measured in situ with glass dosimeters. There was agreement within a factor of 2 between the calculated and measured external dose rates. In the most severely contaminated habitat of this salamander, a northern part of Abukuma Mountains, the highest total dose rates were estimated to be 50 and 15 μGy h(-1) for the adults and overwintering larvae, respectively. Growth and survival of H. lichenatus was not affected at a dose rate of up to 490 μGy h(-1) in the previous laboratory chronic gamma-irradiation experiment, and thus growth and survival of this salamander would not be affected, even in the most severely contaminated habitat in Fukushima Prefecture. However, further studies of the adult salamanders may be required in order to examine whether the most severe radioactive contamination has any effects on sensitive endpoints, since the estimated highest dose rate to the adults exceeded some of the guidance dose rates proposed by various organisations and programmes for the protection of amphibians, which range from 4 to 400 μGy h(-1). Conversely, at one site in Nakadori, a moderately contaminated region in Fukushima Prefecture, the dose rate to the adult salamanders in spring of 2012 was estimated to be 0.2 μGy h(-1). Estimated dose rates to the overwintering larvae in spring of 2012 were 1 and 0.2 μGy h(-1) at one site in Nakadori, and in Aizu, a less contaminated region in Fukushima Prefecture, respectively. These results suggest that there is a low risk that H. lichenatus will be affected by radioactive contamination in these districts, though further studies on dose rate estimation are required for definitive risk characterisation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Acetaminophen-cysteine adducts during therapeutic dosing and following overdose

PubMed Central

2011-01-01

Background Acetaminophen-cysteine adducts (APAP-CYS) are a specific biomarker of acetaminophen exposure. APAP-CYS concentrations have been described in the setting of acute overdose, and a concentration >1.1 nmol/ml has been suggested as a marker of hepatic injury from acetaminophen overdose in patients with an ALT >1000 IU/L. However, the concentrations of APAP-CYS during therapeutic dosing, in cases of acetaminophen toxicity from repeated dosing and in cases of hepatic injury from non-acetaminophen hepatotoxins have not been well characterized. The objective of this study is to describe APAP-CYS concentrations in these clinical settings as well as to further characterize the concentrations observed following acetaminophen overdose. Methods Samples were collected during three clinical trials in which subjects received 4 g/day of acetaminophen and during an observational study of acetaminophen overdose patients. Trial 1 consisted of non-drinkers who received APAP for 10 days, Trial 2 consisted of moderate drinkers dosed for 10 days and Trial 3 included subjects who chronically abuse alcohol dosed for 5 days. Patients in the observational study were categorized by type of acetaminophen exposure (single or repeated). Serum APAP-CYS was measured using high pressure liquid chromatography with electrochemical detection. Results Trial 1 included 144 samples from 24 subjects; Trial 2 included 182 samples from 91 subjects and Trial 3 included 200 samples from 40 subjects. In addition, we collected samples from 19 subjects with acute acetaminophen ingestion, 7 subjects with repeated acetaminophen exposure and 4 subjects who ingested another hepatotoxin. The mean (SD) peak APAP-CYS concentrations for the Trials were: Trial 1- 0.4 (0.20) nmol/ml, Trial 2- 0.1 (0.09) nmol/ml and Trial 3- 0.3 (0.12) nmol/ml. APAP-CYS concentrations varied substantially among the patients with acetaminophen toxicity (0.10 to 27.3 nmol/ml). No subject had detectable APAP-CYS following exposure to a non-acetaminophen hepatotoxin. Conclusions Lower concentrations of APAP-CYS are detectable after exposure to therapeutic doses of acetaminophen and higher concentrations are detected after acute acetaminophen overdose and in patients with acetaminophen toxicity following repeated exposure. PMID:21401949

Treatment of carprofen overdose with therapeutic plasma exchange in a dog.

PubMed

Kjaergaard, Astrid B; Davis, Jennifer L; Acierno, Mark J

2018-06-13

To report the use of therapeutic plasma exchange (TPE) in a dog with carprofen toxicosis. A 6-year-old female neutered Bichon Frise weighing 6.9 kg was examined after it had ingested 72 mg/kg carprofen. Mild dehydration without azotemia and with a urine specific gravity of 1.050 was noted at presentation. Treatment consisted of induction of emesis, symptomatic medical therapy, and TPE. The TPE achieved 1.5 plasma volume exchanges over 3 hours. Blood samples and effluent samples were collected every 30 minutes during TPE and additional blood samples were collected 11 and 35 hours after treatment. Carprofen concentrations in these samples were determined by high-pressure liquid chromatography. A 51% reduction in serum carprofen concentration was achieved following TPE. This report describes the successful reduction of plasma carprofen concentration in a dog using TPE. Although recent studies suggest that this particular dog may not have received a toxic dose, a 51% reduction of plasma carprofen concentration was achieved over 180 minutes, and TPE may be beneficial for treatment of dogs that have ingested higher doses. © Veterinary Emergency and Critical Care Society 2018.

Maternal Methadone Dose, Placental Methadone Concentrations, and Neonatal Outcomes

PubMed Central

de Castro, Ana; Jones, Hendreé E.; Johnson, Rolley E.; Gray, Teresa R.; Shakleya, Diaa M.; Huestis, Marilyn A.

2015-01-01

BACKGROUND Few investigations have used placenta as an alternative matrix to detect in utero drug exposure, despite its availability at the time of birth and the large amount of sample. Methadone-maintained opioid-dependent pregnant women provide a unique opportunity to examine the placental disposition of methadone and metabolite [2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP)], to explore their correlations with maternal methadone dose and neonatal outcomes, and to test the ability to detect in utero exposure to illicit drugs. METHODS We calculated the correlations of placental methadone and EDDP concentrations and their correlations with maternal methadone doses and neonatal outcomes. Cocaine- and opiate-positive placenta results were compared with the results for meconium samples and for urine samples collected throughout gestation. RESULTS Positive correlations were found between placental methadone and EDDP concentrations (r = 0.685), and between methadone concentration and methadone dose at delivery (r = 0.542), mean daily dose (r = 0.554), mean third-trimester dose (r = 0.591), and cumulative daily dose (r = 0.639). The EDDP/methadone concentration ratio was negatively correlated with cumulative daily dose (r = 0.541) and positively correlated with peak neonatal abstinence syndrome (NAS) score (r = 0.513). Placental EDDP concentration was negatively correlated with newborn head circumference (r = 0.579). Cocaine and opiate use was detected in far fewer placenta samples than in thrice-weekly urine and meconium samples, a result suggesting a short detection window for placenta. CONCLUSIONS Quantitative methadone and EDDP measurement may predict NAS severity. The placenta reflects in utero drug exposure for a shorter time than meconium but may be useful when meconium is unavailable or if documentation of recent exposure is needed. PMID:21245372

Immunogenicity, reactogenicity and safety of human rotavirus vaccine (RIX4414) in Indian infants.

PubMed

Narang, Anil; Bose, Anuradha; Pandit, Anand Nilkanth; Dutta, Phalguni; Kang, Gagandeep; Bhattacharya, Sujit Kumar; Datta, Sanjoy Kumar; Suryakiran, P V; Delem, Andrée; Han, Htay Htay; Bock, Hans Ludwig

2009-06-01

This study was undertaken to assess the immunogenicity, reactogenicity and safety of two doses of an oral live-attenuated human rotavirus vaccine, strain RIX4414 (Rotarix()) in an Indian setting. The seroconversion rate observed one month post-dose 2 in the RIX4414 group 58.3% [95% CI: 48.7; 67.4] was significantly higher when compared to the placebo group 6.3%; [95% CI: 2.5; 12.5]. The reactogenicity and safety profile was similar for both groups. Healthy infants (N = 363), approximately eight weeks of age were enrolled to receive two doses of RIX4414 vaccine (n = 182) or placebo (n = 181) separated by one month. To assess the immune response, blood samples were taken before vaccination and one month post-dose 2 of RIX4414/placebo. Solicited symptoms were collected for eight-days post each dose and safety data was collected throughout the study. Two doses of RIX4414 (Rotarix()) were immunogenic, had a good safety profile and were well-tolerated when administered to healthy Indian infants. ClinicalTrials.gov; NCT00289172; eTrack 103792.

Dose Responses of Ibuprofen In Vitro on Platelet Aggregation and Coagulation in Human and Pig Blood Samples.

PubMed

Martini, Wenjun Z; Rodriguez, Cassandra M; Deguzman, Rodolfo; Guerra, Jessica B; Martin, Angela K; Pusateri, Anthony E; Cap, Andrew P; Dubick, Michael A

2016-05-01

Ibuprofen is commonly used by warfighters in the deployed environment. This study investigated its dose effects on in vitro coagulation in human and pig blood. Blood samples were collected from 6 normal volunteers and 6 healthy pigs and processed to make platelet-adjusted samples (100 × 10(3)/μL, common transfusion trigger in trauma). Ibuprofen was added to the samples at concentrations of 0 μg/mL (control), the concentration from the highest recommended oral dose (163 μg/mL, 1×), and 2×, 4×, 8×, 10×, 12×, 16×, and 20×. Platelet aggregation by Chrono-Log aggregometer and coagulation by rotational thrombelastogram (Rotem) were assessed at 15 minutes after the addition of ibuprofen. A robust inhibition of ibuprofen on arachidonic acid-induced platelet aggregation was observed at all doses tested in human or pig blood. Collagen-stimulated platelet aggregation was inhibited starting at 1× in human blood and 4× in pig blood. Rotem measurements were similarly compromised in pig and human blood starting at 16×, except clot formation time was prolonged at 1× in human blood (all p < 0.05). Ibuprofen inhibited platelet aggregation at recommended doses, and compromised coagulation at higher doses. Human blood was more sensitive to ibuprofen inhibition. Further effort is needed to investigate ibuprofen dose responses on coagulation in vivo. Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.

Statistical analysis of radiation dose derived from ingestion of foods

NASA Astrophysics Data System (ADS)

Dougherty, Ward L.

2001-09-01

This analysis undertook the task of designing and implementing a methodology to determine an individual's probabilistic radiation dose from ingestion of foods utilizing Crystal Ball. A dietary intake model was determined by comparing previous existing models. Two principal radionuclides were considered-Lead210 (Pb-210) and Radium 226 (Ra-226). Samples from three different local grocery stores-Publix, Winn Dixie, and Albertsons-were counted on a gamma spectroscopy system with a GeLi detector. The same food samples were considered as those in the original FIPR database. A statistical analysis, utilizing the Crystal Ball program, was performed on the data to assess the most accurate distribution to use for these data. This allowed a determination of a radiation dose to an individual based on the above-information collected. Based on the analyses performed, radiation dose for grocery store samples was lower for Radium-226 than FIPR debris analyses, 2.7 vs. 5.91 mrem/yr. Lead-210 had a higher dose in the grocery store sample than the FIPR debris analyses, 21.4 vs. 518 mrem/yr. The output radiation dose was higher for all evaluations when an accurate estimation of distributions for each value was considered. Radium-226 radiation dose for FIPR and grocery rose to 9.56 and 4.38 mrem/yr. Radiation dose from ingestion of Pb-210 rose to 34.7 and 854 mrem/yr for FIPR and grocery data, respectively. Lead-210 was higher than initial doses for many reasons: Different peak examined, lower edge of detection limit, and minimum detectable concentration was considered. FIPR did not utilize grocery samples as a control because they calculated radiation dose that appeared unreasonably high. Consideration of distributions with the initial values allowed reevaluation of radiation does and showed a significant difference to original deterministic values. This work shows the value and importance of considering distributions to ensure that a person's radiation dose is accurately calculated. Probabilistic dose methodology was proved to be a more accurate and realistic method of radiation dose determination. This type of methodology provides a visual presentation of dose distribution that can be a vital aid in risk methodology.

Effectiveness of the training material in drug-dose calculation skills.

PubMed

Basak, Tulay; Aslan, Ozlem; Unver, Vesile; Yildiz, Dilek

2016-07-01

The aim of study was to evaluate the effectiveness of the training material based on low-level environmental fidelity simulation in drug-dose calculation skills in senior nursing students. A quasi-experimental design with one group. The sample included senior nursing students attending a nursing school in Turkey in the period December 2012-January 2013. Eighty-two senior nursing students were included in the sample. Data were obtained using a data collection form which was developed by the researchers. A paired-sample t-test was used to compare the pretest and post-test scores. The difference between the mean pretest score and the mean post-test score was statistically significant (P < 0.05). This study revealed that the training material based on low-level environmental fidelity simulation positively impacted accurate drug-dose calculation skills in senior nursing students. © 2016 Japan Academy of Nursing Science.

Comparison of direct sampling and brochoalveolar lavage for determining active drug concentrations in the pulmonary epithelial lining fluid of calves injected with enrofloxacin or tilmicosin.

PubMed

Foster, D M; Sylvester, H J; Papich, M G

2017-12-01

Antibiotic distribution to interstitial fluid (ISF) and pulmonary epithelial fluid (PELF) was measured and compared to plasma drug concentrations in eight healthy calves. Enrofloxacin (Baytril ® 100) was administered at a dose of 12.5 mg/kg subcutaneously (SC), and tilmicosin (Micotil ® 300) was administered at a dose of 20 mg/kg SC. PELF, sampled by two different methods-bronchoalveolar lavage (BAL) and direct sampling (DS)-plasma, and ISF were collected from each calf and measured for tilmicosin, enrofloxacin and its metabolite ciprofloxacin by HPLC. Pharmacokinetic analysis was performed on the concentrations in each fluid, for each drug. The enrofloxacin/ciprofloxacin concentration as measured by AUC in DS samples was 137 ± 72% higher than in plasma, but in BAL samples, this value was 535 ± 403% (p < .05). The concentrations of tilmicosin in DS and BAL samples exceeded plasma drug concentrations by 567 ± 189% and 776 ± 1138%, respectively. The enrofloxacin/ciprofloxacin concentrations collected by DS were significantly different than those collected by BAL, but the tilmicosin concentrations were not significantly different between the two methods. Concentrations of enrofloxacin/ciprofloxacin exceeded the MIC values for bovine respiratory disease pathogens but tilmicosin did not reach MIC levels for these pathogens in any fluids. © 2017 John Wiley & Sons Ltd.

Biota dose assessment of small mammals sampled near uranium mines in northern Arizona

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jannik, T.; Minter, K.; Kuhne, W.

In 2015, the U. S. Geological Survey (USGS) collected approximately 50 small mammal carcasses from Northern Arizona uranium mines and other background locations. Based on the highest gross alpha results, 11 small mammal samples were selected for radioisotopic analyses. None of the background samples had significant gross alpha results. The 11 small mammals were identified relative to the three ‘indicator’ mines located south of Fredonia, AZ on the Kanab Plateau (Kanab North Mine, Pinenut Mine, and Arizona 1 Mine) (Figure 1-1) and are operated by Energy Fuels Resources Inc. (EFRI). EFRI annually reports soil analysis for uranium and radium-226 usingmore » Arizona Department of Environmental Quality (ADEQ)-approved Standard Operating Procedures for Soil Sampling (EFRI 2016a, 2016b, 2017). In combination with the USGS small mammal radioiosotopic tissue analyses, a biota dose assessment was completed by Savannah River National Laboratory (SRNL) using the RESidual RADioactivity-BIOTA (RESRAD-BIOTA, V. 1.8) dose assessment tool provided by the Argonne National Laboratory (ANL 2017).« less

SU-E-I-33: Establishment of CT Diagnostic Reference Levels in Province Nova Scotia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tonkopi, E; Abdolell, M; Duffy, S

2015-06-15

Purpose: To evaluate patient radiation dose from the most frequently performed CT examinations and to establish provincial diagnostic reference levels (DRLs) as a tool for protocol optimization. Methods: The study investigated the following CT examinations: head, chest, abdomen/pelvis, and chest/abdomen/pelvis (CAP). Dose data, volume CT dose index (CTDIvol) and dose-length product (DLP), were collected from 15 CT scanners installed during 2004–2014 in 11 hospital sites of Nova Scotia. All scanners had dose modulation options and multislice capability (16–128 detector rows). The sample for each protocol included 15 average size patients (70±20 kg). Provincial DRLs were calculated as the 75th percentilemore » of patient dose distributions. The differences in dose between hospitals were evaluated with a single factor ANOVA statistical test. Generalized linear modeling was used to determine the factors associated with higher radiation dose. A sample of 36 abdominal studies performed on three different scanners was blinded and randomized for an assessment by an experienced radiologist who graded the imaging quality of anatomic structures. Results: Data for 900 patients were collected. The DRLs were proposed using CTDIvol (mGy) and DLP (mGy*cm) values for CT head (67 and 1049, respectively), chest (12 and 393), abdomen/pelvis (16 and 717), and CAP (14 and 1034). These DRLs were lower than the published national data except for the head CTDIvol. The differences between the means of the dose distributions from each scanner were statistically significant (p<0.05) for all examinations. A very weak correlation was found between the dose and the scanner age or the number of slices with Pearson’s correlation coefficients of 0.011–0.315. The blinded analysis of image quality demonstrated no clinically significant difference except for the noise category. Conclusion: Provincial DRLs were established for typical CT examinations. The variations in dose between the hospitals suggested a large potential for optimization of examinations. Radiology Research Foundation grant.« less

Studying levels of Fukushima-derived radioactivity in sockeye salmon collected on the west coast of Vancouver Island

NASA Astrophysics Data System (ADS)

Domingo, T.; Starosta, K.; Chester, A.; Williams, J.; Ross, P. S.

2017-11-01

To investigate potential radioisotope contamination from the Fukushima nuclear accident, measurements of 10 sockeye salmon (Oncorhynchus nerka) collected on June 21 and June 31, 2014 in the Alberni Inlet on the west coast of Vancouver Island, British Columbia, Canada were performed using low-background gamma-ray spectroscopy. Activity concentrations of the anthropogenic radioisotopes 134Cs and 137Cs as well as the naturally occurring radioisotope 40K were measured. Detection of 137Cs occurred in half of the sockeye with activity concentrations ranging from 0.23 to 1.43 Bq/kg dry weight. The 134Cs isotope was detected in a single sockeye salmon with activity concentrations (±σ) measured in the two subsamples of 0.31(8) and 0.37(10) Bq/kg dry weight. The dose contribution from each of the measured radionuclides was calculated. In the sockeye salmon with the greatest radiocesium concentrations, the dose contribution from anthropogenic radiocesium (134Cs+137Cs) was found to be 450 times less than the dose from naturally occurring radionuclides in the same sample. In conclusion, the total radiocesium activity concentration in every sample is at least 500 times lower than Health Canada's action levels for radioactively contaminated food following a nuclear emergency. Assuming all seafood has as much radiocesium as the most contaminated sample measured, the added annual dose from radiocesium to an adult individual with an average Canadian level of seafood consumption would be 0.046 μSv per year.

Multiple-dose pharmacokinetics and safety of bevirimat, a novel inhibitor of HIV maturation, in healthy volunteers.

PubMed

Martin, David E; Blum, Robert; Doto, Judy; Galbraith, Hal; Ballow, Charles

2007-01-01

Bevirimat [3-O-(3',3'-dimethylsuccinyl)-betulinic acid] is a novel inhibitor of HIV-1 maturation. This study was performed to investigate the pharmacokinetics and safety of bevirimat during repeated dosing in healthy volunteers. The study was a 10-day, randomised, double-blind, placebo-controlled, dose escalation study. A total of 48 healthy male volunteers, aged 19-54 years, took part in the study. Treatment was administered for 10 days in six escalating dose cohorts (n = 8 in each cohort; 6 bevirimat, 2 placebo). The doses of bevirimat given in each successive cohort were 25 mg, 50 mg, 75 mg (with 150 mg loading dose), 100 mg, 150 mg and 200mg. Safety follow-up was performed 28 days after the first dose. PHARMACOKINETIC AND STATISTICAL ANALYSIS: Plasma bevirimat levels were measured from blood samples collected pre-dose on days 1-10 and then at approximately 48-hour intervals until 21 days after dosing started. On days 1 and 10, further blood samples were obtained at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours after dosing. Urine samples were collected in the morning on days 1, 5 and 11 and at the end of the study for the measurement of cortisol and 6beta-hydroxycortisol. The pharmacokinetic parameters of bevirimat were estimated using non-compartmental methods. Dose proportionality of exposure to bevirimat, assessed by the maximum plasma concentration and the area under the plasma concentration-time curve. The mean terminal elimination half-life of bevirimat ranged from 56.3 to 69.5 hours, and the mean clearance ranged from 173.9 to 185.8 mL/hour. Bevirimat showed approximately 4-fold greater accumulation on day 10 compared with day 1, and the degree of accumulation was similar with all doses. Maximum plasma concentrations ranged from 8 to 58 microg/mL at day 10. Testing for dose-proportionality showed that exposure to bevirimat was proportional to the dose, both after a single dose and after repeat dosing for 10 days. Measurement of the urinary 6beta-hydroxycortisol/cortisol ratio indicated that bevirimat did not affect cytochrome P450 3A activity. Repeated dosing with bevirimat for 10 days was well tolerated. There was no increase in adverse events observed for bevirimat compared with placebo, and no serious adverse events occurred. No clinically relevant changes in vital signs, physical examination or clinical laboratory evaluations were observed. Bevirimat shows dose-proportional pharmacokinetics during repeated dosing for 10 days. Its accumulation is approximately 4-fold greater on day 10 compared with day 1. Repeated dosing with bevirimat is well tolerated. These properties make bevirimat potentially suitable for inclusion in highly active antiretroviral therapy regimens.

Kidney Injury Associated with Telavancin Dosing Regimen in an Animal Model

PubMed Central

Ledesma, Kimberly R.; Bowers, Dana R.; Zhou, Jian; Truong, Luan D.

2015-01-01

The elevation of serum creatinine levels is a concern with telavancin therapy. We examined the onset of kidney injury associated with telavancin in an animal model. Urine samples were collected at baseline and daily to determine the concentrations of kidney injury molecule 1 (KIM-1), a marker for early kidney injury. When a clinically relevant exposure of telavancin was given daily to rats, some differences in kidney injury were attributed to the dosing regimen. Further investigations of alternative telavancin dosing regimens are warranted. PMID:25712358

Ocular topotecan pharmacokinetics following topical administration to rabbits for diffused anterior retinoblastoma.

PubMed

Taich, Paula; Del Sole, Maria; Buontempo, Fabian; Williams, Gustavo; Winter, Ursula; Sgroi, Mariana; Chantada, Guillermo; Schaiquevich, Paula

2017-05-01

We characterized and compared the in-vivo absorption of topotecan into the aqueous humor after instillation of aqueous and ointment formulations. A lanolin/petrolatum ointment was used. New Zealand rabbits were instilled with topotecan solution (6 μg, group A), a single 10 μg dose of topotecan ointment (group B) or with five 10 μg doses of topotecan ointment (group C). Aqueous humor samples were collected at different times. Corneal samples were collected only for group A. Topotecan was quantified using HPLC, and pharmacokinetic parameters were calculated. Acute corneal epithelial toxicity was assessed after multiple instillations of topotecan ointment. Total topotecan maximum aqueous humor concentration (C max ) was 16.1, 69.9 and 287 ng/ml in group A, B and C, respectively. A single dose of topotecan ointment increased threefold and sevenfold the aqueous humor C max , and exposure compared to the aqueous formulation. Aqueous humor concentrations from group C eyes were substantially above the cytotoxic concentration for retinoblastoma cells. No corneal toxicity was evident after ointment instillation. Topotecan penetrated into the aqueous humor of the rabbit eye after multiple doses of an ointment in concentrations pharmacologically active against retinoblastoma cells without eliciting acute toxicity. Topotecan ointment may translate to the clinical treatment of anterior segment disseminated retinoblastoma. © 2016 Royal Pharmaceutical Society.

Clinical Validation of a miRNA Blood Test to Identify High-Risk Individuals Eligible for Low-Dose Computed Tomography Screening for Lung Cancer Early Detection

DTIC Science & Technology

2015-10-01

screening. The project requires the use of serum samples obtained from at-risk subjects (heavy smokers with defined characteristics) undergoing...screening. The project requires the use of serum samples obtained from at-risk subjects (heavy smokers with defined characteristics) that were collected

Aripiprazole effects on self-administration and pharmacodynamics of intravenous cocaine and cigarette smoking in humans.

PubMed

Lofwall, Michelle R; Nuzzo, Paul A; Campbell, Charles; Walsh, Sharon L

2014-06-01

Aripiprazole is a partial agonist at dopamine (D2) and serotonin (5-HT1a) receptors and 5-HT2 antagonist. Because cocaine affects dopamine and serotonin, this study assessed whether aripiprazole could diminish the reinforcing efficacy of cocaine. Secondary aims evaluated aripiprazole on ad lib cigarette smoking and with a novel 40-hr smoking abstinence procedure. Adults with regular cocaine and cigarette use completed this inpatient double blind, randomized, placebo-controlled mixed-design study. A placebo lead-in was followed by randomization to aripiprazole (0, 2 or 10 mg/day/p.o.; n = 7 completed/group). Three sets of test sessions, each consisting of 3 cocaine sample-choice (i.e., self-administration) sessions and 1 dose-response session, were conducted (once during the lead-in and twice after randomization). Sample sessions tested each cocaine dose (0, 20 and 40 mg/70 kg, i.v.) in random order; subjective, observer-rated and physiologic outcomes were collected. Later that day, participants chose between the morning's sample dose or descending amounts of money over 7 trials. In dose response sessions, all doses were given 1 hr apart in ascending order for pharmacodynamic and pharmacokinetic assessment. Two sets of smoking topography sessions were conducted during the lead-in and after randomization; 1 with and 1 without 40 hr of smoking abstinence. Number of ad lib cigarettes smoked during non-session days was collected. Cocaine produced prototypic effects, but aripiprazole did not significantly alter these effects or smoking outcomes. The smoking abstinence procedure reliably produced nicotine withdrawal and craving and increased smoking modestly. These data do not support further investigation of aripiprazole for cocaine or tobacco use disorder treatment. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Reactogenicity and safety of a liquid human rotavirus vaccine (RIX4414) in healthy adults, children and infants in China

PubMed Central

Li, Rong-Cheng; Li, Yan-Ping; Mo, Zhao-Jun; Luo, Dong; Huang, Teng; Kong, Ji-Lian; Wang, Lao-Hong; Song, Ning-Sheng; Liu, Aixue; Zhang, Helen; Liao, Xueyan; Karkada, Naveen; Han, Htay Htay

2013-01-01

We report the findings of three randomized, double-blind, placebo-controlled Phase I studies undertaken to support licensure of the liquid formulation of the human G1P[8] rotavirus (RV) vaccine (RIX4414; GlaxoSmithKline Biologicals SA) in China. Healthy adults aged 18–45 y (n = 48) and children aged 2–6 y (n = 50) received a single dose of the human RV vaccine or placebo. Healthy infants (n = 50) aged 6–16 weeks at the time of first vaccination received two oral doses of the human RV vaccine or placebo according to a 0, 1 mo schedule. In infants, blood samples were collected prior to vaccination and one month post-dose 2 to assess anti-RV IgA antibody concentrations using ELISA. Stool samples were collected from all infants on the day of each vaccination, at 7 and 15 d after each vaccination and one month post-dose 2. Stool samples were analyzed by ELISA for detection of RV antigen to assess RV antigen excretion. The reactogenicity profile of the human RV vaccine was found to be comparable to that of placebo in all age groups studied. The anti-RV IgA antibody seroconversion rate in infants after two vaccine doses was 86.7% (95% CI: 59.5–98.3). Vaccine take in infants who received the liquid human RV vaccine was 86.7% (95% CI: 59.5–98.3). A Phase III efficacy study of the human RV vaccine in the infant population in China has now been completed (ROTA-075/NCT01171963). PMID:23807360

Characterization of Libby, MT amphibole (LA) elongated particles for toxicology studies: Field Collection, sample preparation, dose characterization, and particle counting methods using SEM/EDS

EPA Science Inventory

Since 1999, the US EPA and USGS have been studying the chemistry, mineralogy, and morphology of the amphiboles from the Rainy Creek Complex of Libby, MT (LA), following an increased incidence of lung and pleural diseases. LA material collected in 2000 (LA2000) was described in M...

Estimation of background radiation doses for the Peninsular Malaysia's population by ESR dosimetry of tooth enamel.

PubMed

Rodzi, Mohd; Zhumadilov, Kassym; Ohtaki, Megu; Ivannikov, Alexander; Bhattacharjee, Deborshi; Fukumura, Akifumi; Hoshi, Masaharu

2011-08-01

Background radiation dose is used in dosimetry for estimating occupational doses of radiation workers or determining radiation dose of an individual following accidental exposure. In the present study, the absorbed dose and the background radiation level are determined using the electron spin resonance (ESR) method on tooth samples. The effect of using different tooth surfaces and teeth exposed with single medical X-rays on the absorbed dose are also evaluated. A total of 48 molars of position 6-8 were collected from 13 district hospitals in Peninsular Malaysia. Thirty-six teeth had not been exposed to any excessive radiation, and 12 teeth had been directly exposed to a single X-ray dose during medical treatment prior to extraction. There was no significant effect of tooth surfaces and exposure with single X-rays on the measured absorbed dose of an individual. The mean measured absorbed dose of the population is 34 ± 6.2 mGy, with an average tooth enamel age of 39 years. From the slope of a regression line, the estimated annual background dose for Peninsular Malaysia is 0.6 ± 0.3 mGy y(-1). This value is slightly lower than the yearly background dose for Malaysia, and the radiation background dose is established by ESR tooth measurements on samples from India and Russia.

Estimating systemic exposure to ethinyl estradiol from an oral contraceptive.

PubMed

Westhoff, Carolyn L; Pike, Malcolm C; Tang, Rosalind; DiNapoli, Marianne N; Sull, Monica; Cremers, Serge

2015-05-01

This study was conducted to compare single-dose pharmacokinetics of ethinyl estradiol in an oral contraceptive with steady-state values and to assess whether any simpler measures could provide an adequate proxy of the "gold standard" 24-hour steady-state area under the curve (AUC) value. Identification of a simple, less expensive measure of systemic ethinyl estradiol exposure would be useful for larger studies that are designed to assess the relationship between an individual's ethinyl estradiol exposure and side-effects. We collected 13 samples over 24 hours for pharmacokinetic analysis on days 1 and 21 of the first cycle of a monophasic oral contraceptive that contained 30 μg ethinyl estradiol and 150 μg levonorgestrel in 17 nonobese healthy white women. We also conducted an abbreviated single-dose 9-sample pharmacokinetic analysis after a month washout. Ethinyl estradiol was measured by liquid chromatography-tandem mass spectrometry. We compared results of a full 13-sample steady-state pharmacokinetic analysis with results that had been calculated with the use of fewer samples (9 or 5) and after the single doses. We calculated Pearson correlation coefficients to evaluate the relationships between these estimates of systemic ethinyl estradiol exposure. The AUC, maximum, and 24-hour values were similar after the 2 single oral contraceptive doses (AUC; r=0.92). The steady-state 13-sample 24-hour AUC value was correlated highly with the average 9-sample AUC value after the 2 single doses (r=0.81; P=.0002). This correlation remained the same if the number of single-dose samples was reduced to 4, taken at time 1, 2.5, 4, and 24 hours. The 24-hour value at steady-state was correlated highly with the 24-hour steady-state AUC value (r=0.92; P<.0001). The average of the 24-hour values after the 2 single doses was also correlated quite highly with the steady-state AUC value (r=0.72; P=.0026). Limited blood sampling, including results from 2 single doses, gave highly correlated estimates of an oral contraceptive user's steady-state ethinyl estradiol exposure. Copyright © 2015 Elsevier Inc. All rights reserved.

Population Pharmacokinetics and Optimal Sampling Strategy for Model-Based Precision Dosing of Melphalan in Patients Undergoing Hematopoietic Stem Cell Transplantation.

PubMed

Mizuno, Kana; Dong, Min; Fukuda, Tsuyoshi; Chandra, Sharat; Mehta, Parinda A; McConnell, Scott; Anaissie, Elias J; Vinks, Alexander A

2018-05-01

High-dose melphalan is an important component of conditioning regimens for patients undergoing hematopoietic stem cell transplantation. The current dosing strategy based on body surface area results in a high incidence of oral mucositis and gastrointestinal and liver toxicity. Pharmacokinetically guided dosing will individualize exposure and help minimize overexposure-related toxicity. The purpose of this study was to develop a population pharmacokinetic model and optimal sampling strategy. A population pharmacokinetic model was developed with NONMEM using 98 observations collected from 15 adult patients given the standard dose of 140 or 200 mg/m 2 by intravenous infusion. The determinant-optimal sampling strategy was explored with PopED software. Individual area under the curve estimates were generated by Bayesian estimation using full and the proposed sparse sampling data. The predictive performance of the optimal sampling strategy was evaluated based on bias and precision estimates. The feasibility of the optimal sampling strategy was tested using pharmacokinetic data from five pediatric patients. A two-compartment model best described the data. The final model included body weight and creatinine clearance as predictors of clearance. The determinant-optimal sampling strategies (and windows) were identified at 0.08 (0.08-0.19), 0.61 (0.33-0.90), 2.0 (1.3-2.7), and 4.0 (3.6-4.0) h post-infusion. An excellent correlation was observed between area under the curve estimates obtained with the full and the proposed four-sample strategy (R 2  = 0.98; p < 0.01) with a mean bias of -2.2% and precision of 9.4%. A similar relationship was observed in children (R 2  = 0.99; p < 0.01). The developed pharmacokinetic model-based sparse sampling strategy promises to achieve the target area under the curve as part of precision dosing.

Detection Times of Diazepam, Clonazepam, and Alprazolam in Oral Fluid Collected From Patients Admitted to Detoxification, After High and Repeated Drug Intake.

PubMed

Nordal, Kristin; Øiestad, Elisabeth L; Enger, Asle; Christophersen, Asbjorg S; Vindenes, Vigdis

2015-08-01

Clonazepam, diazepam, and alprazolam are benzodiazepines with sedative, anticonvulsant, and anxiolytic effects, but their prevalence in drug abuse and drug overdoses has long been recognized. When detection times for psychoactive drugs in oral fluid are reported, they are most often based on therapeutic doses administered in clinical studies. Repeated ingestions of high doses, as seen after drug abuse, are however likely to cause positive samples for extended time periods. Findings of drugs of abuse in oral fluid collected from imprisoned persons might lead to negative sanctions, and the knowledge of detection times of these drugs is thus important to ensure correct interpretation. The aim of this study was to investigate the time window of detection for diazepam, clonazepam, and alprazolam in oral fluid from drug addicts admitted to detoxification. Twenty-five patients with a history of heavy drug abuse admitted to a detoxification ward were included. Oral fluid was collected daily in the morning and the evening and urine samples every morning for 10 days, using the Intercept device. Whole blood samples were collected if the patient accepted. The cutoff levels in oral fluid were 1.3 ng/mL for diazepam, N-desmethyldiazepam, and 7-aminoclonazepam and 1 ng/mL for clonazepam and alprazolam. In urine, the cutoff levels for quantifications were 30 ng/mL for alprazolam, alpha-OH-alprazolam, and 7-aminoclonazepam, 135 ng/mL for N-desmethyldizepam, and 150 ng/mL for 3-OH-diazepam and for all the compounds, the cutoff for the screening analyses were 200 ng/mL. The maximum detection times for diazepam and N-desmethyldiazepam in oral fluid were 7 and 9 days, respectively. For clonazepam and 7-aminoclonazepam, the maximum detection times in oral fluid were 5 and 6 days, respectively. The maximum detection time for alprazolam in oral fluid was 2.5 days. New ingestions were not suspected in any of the cases, because the corresponding concentrations in urine were decreasing. Results from blood samples revealed that high doses of benzodiazepines had been ingested before admission, and explains the longer detection times in oral fluids than reported previously after intake of therapeutic doses of these drugs. This study has shown that oral fluid might be a viable alternative medium to urine when the abuse of benzodiazepines is suspected.

Aripiprazole effects on self-administration and pharmacodynamics of intravenous cocaine and cigarette smoking in humans

PubMed Central

Lofwall, M.R.; Nuzzo, P.A.; Campbell, C.; Walsh, S.L.

2014-01-01

Aripiprazole is a partial agonist at dopamine D2 and serotonin 5-HT1a receptors and antagonist at 5-HT2 receptors. Because both dopamine and serotonin systems are involved in the action of cocaine, this study aimed to determine if aripiprazole could diminish the reinforcing efficacy of cocaine. Secondary aims evaluated aripiprazole effects on ad lib cigarette smoking and a novel 40-hour cigarette smoking abstinence procedure. Healthy adults with regular cocaine and cigarette use completed this ~30-day inpatient double blind, randomized, placebo-controlled mixed-design study. An oral placebo lead-in period was followed by randomization to oral aripiprazole (0, 2 or 10 mg daily; n=7 completed/group). Three sets of test sessions, each consisting of three cocaine sample-choice (i.e., self-administration) sessions and one dose-response session, were conducted (during the lead-in period and after randomization before and after achieving aripiprazole steady state). Sample-choice sessions tested three cocaine doses (0, 20, and 40 mg/70 kg, i.v.) with one dose (random order) administered in each sample session; subjective, observer-rated and physiologic outcomes were collected repeatedly before and after cocaine administration. Later that day, participants chose between receiving the sample dose from that morning or descending amounts of money for seven trials ($19, 16, 13, 10, 7, 4, 1). Dose response sessions administered the three cocaine doses in ascending order for pharmacodynamic and potential pharmacokinetic assessment. A set of two cigarette smoking topography sessions were conducted during placebo lead-in and after randomization; one with and one without 40-hours of cigarette smoking abstinence. Number of ad lib cigarettes smoked during non-session days was also collected. Cocaine produced prototypic pharmacodynamic effects and self-administration; neither were significantly altered by aripiprazole. The 40-hour smoking abstinence procedure reliably produced nicotine withdrawal and craving and increased smoking modestly. Aripiprazole did not significantly alter smoking outcomes. These data do not support the further investigation of aripiprazole for the treatment of cocaine or tobacco use disorders. PMID:24467369

Mixed species radioiodine air sampling readout and dose assessment system

DOEpatents

Distenfeld, Carl H.; Klemish, Jr., Joseph R.

1978-01-01

This invention provides a simple, reliable, inexpensive and portable means and method for determining the thyroid dose rate of mixed airborne species of solid and gaseous radioiodine without requiring highly skilled personnel, such as health physicists or electronics technicians. To this end, this invention provides a means and method for sampling a gas from a source of a mixed species of solid and gaseous radioiodine for collection of the mixed species and readout and assessment of the emissions therefrom by cylindrically, concentrically and annularly molding the respective species around a cylindrical passage for receiving a conventional probe-type Geiger-Mueller radiation detector.

Radioactivity concentrations and dose assessment in surface soil samples from east and south of Marmara region, Turkey.

PubMed

Kiliç, Onder; Belivermis, Murat; Topçuoğlu, Sayhan; Cotuk, Yavuz; Coşkun, Mahmut; Cayir, Akin; Küçer, Rahmi

2008-01-01

The activity concentrations of 137Cs, 40K, 232Th, 238U and 226Ra were measured in surface soil samples from East and South of Marmara region, Turkey. The physico-chemical parameters (organic matter, CaCO3 contents and pH-value) of the soil samples were determined in the samples collected from 100 sampling stations. The average activity concentrations of 137Cs, 40K, 232Th, 238U and 226Ra were found to be 27.46+/-21.84, 442.51+/-189.85, 26.63+/-15.90, 21.77+/-12.08 and 22.45+/-13.31 Bq kg(-1), respectively. The mean value of total annual external gamma radiation dose equivalent for the natural radionuclides was calculated to be 54.86 microSv. The current data were compared with those found in the other locations of Turkey and different countries.

Disposition of acetaminophen in milk, saliva, and plasma of lactating women.

PubMed

Berlin, C M; Yaffe, S J; Ragni, M

1980-01-01

Acetaminophen (APAP) is a widely used analgesic and antipyretic, but its disposition in human milk has not yet been reported. Twelve nursing mothers (nursing two to 22 months) were given a single 650-mg peroral dose of APAP. Simultaneous saliva and milk samples were collected at zero, 1/4, 1/2, 3/4, 1, 2, 3, 5, 8, 12, and 24 hours after maternal dosing. In two mothers, plasma samples were also obtained at several points during the first six hours. Single voided urine samples were collected from the infants three to five hours after maternal dosing (two hours after nursing at peak maternal milk levels). All samples were assayed for APAP by high pressure liquid chromatography (HPCL) using a mobile phase of 0.05 M Na acetate pH 4.0-acetonitrile (93:10) with n-butyryl-p-aminophenol as the internal standard. APAP appeared in saliva and milk in the 1/4-hour samples; peak level (10-15 micrograms/ml) were achieved by one to two hours. Saliva/milk ratios during the elimination phase ranged from 0.7 to 1.1, with most values between 0.8 and 0.9. In two patients studied, saliva/plasma ratios were 0.9 to 1.0. Elimination phase t 1/2 (calculated from beta) ranged from 1.35 to 3.50 (x = 2.28 +/- SD 0.69) hours for milk, and from 1.72 to 3.30 (x = 2.48 +/- 0.56) hours for saliva. There was close agreement between saliva t 1/2 and milk t 1/2 for each patient. Assuming each infant ingested 90 ml milk at 3, 6, and 9 hours after maternal ingestion of APAP, the amount of APAP available for ingestion ranged from 0.28 to 1.51 mg (x = 0.88 +/- 0.31) or from 0.04% to 0.23% (x = 0.14 +/- 0.04) of maternal dose. Neither APAP nor metabolite was detected in nursing infants' urine. Maternal APAP ingestion in usual analgesic doses does not appear to present a risk to the nursing infant.

Influence of Gestational Age and Body Weight on the Pharmacokinetics of Labetalol in Pregnancy

PubMed Central

Fischer, James H.; Sarto, Gloria E.; Hardman, Jennifer; Endres, Loraine; Jenkins, Thomas M.; Kilpatrick, Sarah J.; Jeong, Hyunyoung; Geller, Stacie; Deyo, Kelly; Fischer, Patricia A.; Rodvold, Keith A.

2015-01-01

Background and Objectives Labetalol is frequently prescribed for treatment of hypertension during pregnancy. However, the influence of pregnancy on labetalol pharmacokinetics is uncertain, with inconsistent findings reported by previous studies. This study examined the population pharmacokinetics of oral labetalol during and after pregnancy in women receiving labetalol for hypertension. Methods Data were collected from 57 women receiving the drug for hypertension from the 12th week of pregnancy through 12 weeks postpartum using a prospective, longitudinal design. A sparse sampling strategy guided collection of plasma samples. Samples were assayed for labetalol by high performance liquid chromatography. Estimation of population pharmacokinetic parameters and covariate effects was performed by nonlinear mixed effects modeling using NONMEM. Final population model was validated by bootstrap analysis and visual predictive check. Simulations were performed with the final model to evaluate the appropriate body weight to guide labetalol dosing. Results Lean body weight (LBW) and gestational age, i.e., weeks of pregnancy, were identified as significantly influencing oral clearance (CL/F) of labetalol, with CL/F ranging from 1.4-fold greater than postpartum values at 12 weeks gestational age to 1.6-fold greater at 40 weeks. Doses adjusted for LBW provide more consistent drug exposure than doses adjusted for total body weight. The apparent volumes of distribution for the central compartment and at steady-state were 1.9-fold higher during pregnancy. Conclusions Gestational age and LBW impact the pharmacokinetics of labetalol during pregnancy and have clinical implications for adjusting labetalol doses in these women. PMID:24297680

USE OF AN INTEGRATED APPROACH TO EVALUATE YOUNG CHILDREN'S ACTIVITIES

EPA Science Inventory

Linking a young child's activity pattern data with the environmental, biological, and personal samples that are collected during an exposure assessment is important in evaluating potential exposures and dose associated with environmental contaminants. A number of different appro...

Creatinine as a normalization factor to estimate the representativeness of urine sample - Intra-subject and inter-subject variability studies.

PubMed

Sawant, Pramilla D; Kumar, Suja Arun; Wankhede, Sonal; Rao, D D

2018-06-01

In-vitro bioassay monitoring generally involves analysis of overnight urine samples (~12 h) collected from radiation workers to estimate the excretion rate of radionuclides from the body. The unknown duration of sample collection (10-16 h) adds to the overall uncertainty in computation of internal dose. In order to minimize this, IAEA recommends measurement of specific gravity or creatinine excretion rate in urine. Creatinine is excreted at a steady rate with normally functioning kidneys therefore, can be used as a normalization factor to infer the duration of collection and/or dilution of the sample, if any. The present study reports the chemical procedure standardized and its application for the estimation of creatinine as well as creatinine co-efficient in normal healthy individuals. Observations indicate higher inter-subject variability and lower constancy in daily excretion of creatinine for the same subject. Thus creatinine excretion rate may not be a useful indicator for extrapolating to 24 h sample collection. Copyright © 2018 Elsevier Ltd. All rights reserved.

Study of thermoluminescence response of purple to violet amethyst quartz from Balikesir, Turkey

NASA Astrophysics Data System (ADS)

Nur, N.; Yeğingil, Z.; Topaksu, M.; Kurt, K.; Doğan, T.; Sarıgül, N.; Yüksel, M.; Altunal, V.; Özdemir, A.; Güçkan, V.; Günay, I.

2015-09-01

In thermoluminescence (TL) dosimetry, the phosphor amethyst quartz as a thermoluminescent, appears to be one of the materials arousing the highest interest. In this study the dosimetric characteristics of natural amethyst quartz crystals collected from Balikesir-Dursunbey (Turkey) were investigated for the purpose of determination of the general properties that phosphors should have in order to be useful for thermoluminescence dosimetry. The natural thermoluminescence was drained by annealing the powder samples at 450 °C for 1.5 h. The effects of high temperature annealing, dose response curves, glow curves after a postirradiation annealing, reusability of the samples and storage of trapped electrons in dark at room temperature were clarified through irradiating the samples with the desired exposures by 90Sr/90Y beta particles. Isothermal annealing before and after irradiation was found to have a definite effect upon the TL glow curve of amethyst crystal powder. The same sample varied in sensitivity depending upon its previous thermal and radiation history. The peak heights of the glow peaks were examined with respect to dose response at dose levels between 1 Gy and 5 kGy. The intermediate temperature (IT) and high temperature (HT) peaks of 230 °C and 300 °C, respectively, exhibit dose-response curves as superlinear when dose is on the logarithmic scale except the dose response of 300 °C peak for the dose values of 1 < D < 20 Gy in which linear dose response was acquired. At the end of the storage time between exposure and readout which was about one month at room temperature, the emitted light reduction was 14% comparing to the initial state. Repeating the measurements of the same sample, exposed with 0.1, 0.5, 0.8 and 1 kGy beta exposures, resulted in between 4% and 11% increase in the TL sensitivity of the material.

Effect of injected rotenone on the production and composition of urine from the rainbow trout (Salmo gairdneri)

USGS Publications Warehouse

Erickson, D.A.; Gingerich, W.H.

1986-01-01

Renal function was evaluated in adult rainbow trout (Salmo gairdneri) dosed i.a. with rotenone at 225 and 275 μg/kg. The chemical composition of urine samples and urine flow rates collected over a 5-h pretreatment period were compared with hourly urine samples collected over a 5-h posttreatment period. Significant increases in osmolality and in concentrations of sodium, potassium, chloride, glucose, and total protein were observed in the urine of treated fish. Urine solute concentrations reached maximum values within 1 to 3 h after treatment and decreased thereafter, indicating that the effects were reversible. Concentrations of sodium and chloride were highly correlated in 2-h posttreatment urine samples at the low (r = 0.922) and high (r = 0.981) rotenone treatments. Urine flow rates were reduced in trout at each dose of rotenone but the decrease in volume of urine voided was not dose-dependent. In a separate study, [14C]polyethylene glycol was used as a filtration marker to determine the effect of rotenone treatment (225 &mu:g/kg) on urine flow rate, glomerular filtration rate, and renal water reabsorption. We showed that posttreatment urine flow rates were reduced partly by reduced glomerular filtration and partly by increased water reabsorption. Transient increases in plasma osmolality and hematocrit also were observed 0.5 h after rotenone treatment.

Radionuclides (210Po and 210Pb) and Some Heavy Metals in Fish and Sediments in Lake Bafa, Turkey, and the Contribution of 210Po to the Radiation Dose.

PubMed

Manav, Ramazan; Uğur Görgün, Aysun; Filizok, Işık

2016-11-09

The pollution level of Lake Bafa was investigated by collecting fish samples { Dicentrarchus labrax (sea bass), Liza ramada (mullet) and Anguilla anguilla (eel)}, surface sediment, and core samples. In all these samples, 210 Po and 210 Pb concentrations were estimated, and total annual dose rates were obtained for each species. Some heavy metal (Cr, Ni, Pb, Cd, Mn, Fe, and Zn) concentration levels were obtained for the fish and a core sample. The sediment mass accumulation rate was found to be 3.27 g·m -2 ·day -1 (0.119 g·cm -2 ·y -1 ) from a core sample. The heavy metal concentrations in the vertical profile of samples from the core were also observed. The measured concentration of Zn, Pb, Cd, and Cr were between the ERL (effects range low) and ERM (effects range median) limits, while Ni concentrations were higher than the ERM limit. The observed concentrations of Cd, Pb, and Zn in fish samples did not exceed the limits in accordance with Turkish Food Regulations. Further, the maximum effective dose equivalent of 210 Po in the area was found to be 1.169 µSv·y -1 .

(32)P measurment of urine samples and internal dose assessment for radiation workers in life science laboratories.

PubMed

Yoon, S; Pak, M-J; Park, S; Yoo, J; Ha, W-H; Jang, H-K; Kim, J K

2014-12-01

(32)P measurements of urine samples and internal dose assessments were conducted for workers in life science laboratories. A procedure for sample pre-treatment was established and validation was performed to exclude interference and to detect (32)P levels accurately. The detection conditions for Cherenkov radiation were evaluated and the accuracy of Cherenkov radiation measurements validated. The analytical and measurement procedures were applied to urine samples collected from 11 workers from life sciences laboratories. The results of the measurements generally indicated very low background radiation levels, but daily urine samples from two workers were above the minimum detectable activity. The (32)P concentrations for two of the workers were 29.3  ±  10.4 Bq•d(-1) and 24.1  ±  11.8 Bq•d(-1), respectively, at intake levels of 4.12 kBq and 2.61 kBq. The effective doses for these two workers were 4.6 μSv and 2.9 μSv. Overall, the results indicate very low levels of radioactivity, except for cases related to specific working conditions.

Measurement of natural radioactivity in Jordanian building materials and their contribution to the public indoor gamma dose rate.

PubMed

Sharaf, J M; Hamideen, M S

2013-10-01

This study is undertaken to determine the activity concentration of (226)Ra, (232)Th and (40)K in samples of commonly used building materials in Jordan. Samples of seven different materials were collected from construction sites and local agencies supplying raw construction materials and analyzed using a HPGe gamma-ray spectrometer, taking into account self-attenuation in bulk samples. The average specific activity concentrations of (226)Ra, (232)Th, and (40)K ranged from 2.84 to 41.52, 0.78 to 58.42. and 3.74 to 897 Bq/kg, respectively. All the samples had radium equivalent activities well below the limit of 370 Bq/kg set by the Organization for Economic Cooperation and Development (OECD, 1979). External and internal hazard indices, absorbed dose and annual effective dose rate associated with the radionuclides of interest were calculated and compared with the international legislation and guidance. In general, most of the activities did not exceed the recommended international limits, except for granite and ceramic samples which are usually used as secondary building materials in Jordan. Copyright © 2013 Elsevier Ltd. All rights reserved.

Strong relationship between oral dose and tenofovir hair levels in a randomized trial: hair as a potential adherence measure for pre-exposure prophylaxis (PrEP).

PubMed

Liu, Albert Y; Yang, Qiyun; Huang, Yong; Bacchetti, Peter; Anderson, Peter L; Jin, Chengshi; Goggin, Kathy; Stojanovski, Kristefer; Grant, Robert; Buchbinder, Susan P; Greenblatt, Ruth M; Gandhi, Monica

2014-01-01

Pre-exposure prophylaxis (PrEP) trials using tenofovir-based regimens have demonstrated that high levels of adherence are required to evaluate efficacy; the incorporation of objective biomarkers of adherence in trial design has been essential to interpretation, given the inaccuracy of self-report. Antiretroviral measurements in scalp hair have been useful as a marker of long-term exposure in the HIV treatment setting, and hair samples are relatively easy and inexpensive to collect, transport, and store for analysis. To evaluate the relationship between dose and tenofovir concentrations in hair, we examined the dose proportionality of tenofovir in hair in healthy, HIV-uninfected adults. A phase I, crossover pharmacokinetic study was performed in 24 HIV-negative adults receiving directly-observed oral tenofovir tablets administered 2, 4, and 7 doses/week for 6 weeks, with a ≥3-week break between periods. Small samples of hair were collected after each six-week period and analyzed for tenofovir concentrations. Geometric-mean-ratios compared levels between each pair of dosing conditions. Intensive plasma pharmacokinetic studies were performed during the daily-dosing period to calculate areas-under-the-time-concentration curves (AUCs). Over 90% of doses were observed per protocol. Median tenofovir concentrations in hair increased monotonically with dose. A log-linear relationship was seen between dose and hair levels, with an estimated 76% (95% CI 60-93%) increase in hair level per 2-fold dose increase. Tenofovir plasma AUCs modestly predicted drug concentrations in hair. This study found a strong linear relationship between frequency of dosing and tenofovir levels in scalp hair. The analysis of quantitative drug levels in hair has the potential to improve adherence measurement in the PrEP field and may be helpful in determining exposure thresholds for protection and explaining failures in PrEP trials. Hair measures for adherence monitoring may also facilitate adherence measurement in real-world settings and merit further investigation in upcoming PrEP implementation studies and programs. ClinicalTrials.gov NCT00903084.

Strong Relationship between Oral Dose and Tenofovir Hair Levels in a Randomized Trial: Hair as a Potential Adherence Measure for Pre-Exposure Prophylaxis (PrEP)

PubMed Central

Liu, Albert Y.; Yang, Qiyun; Huang, Yong; Bacchetti, Peter; Anderson, Peter L.; Jin, Chengshi; Goggin, Kathy; Stojanovski, Kristefer; Grant, Robert; Buchbinder, Susan P.; Greenblatt, Ruth M.; Gandhi, Monica

2014-01-01

Background Pre-exposure prophylaxis (PrEP) trials using tenofovir-based regimens have demonstrated that high levels of adherence are required to evaluate efficacy; the incorporation of objective biomarkers of adherence in trial design has been essential to interpretation, given the inaccuracy of self-report. Antiretroviral measurements in scalp hair have been useful as a marker of long-term exposure in the HIV treatment setting, and hair samples are relatively easy and inexpensive to collect, transport, and store for analysis. To evaluate the relationship between dose and tenofovir concentrations in hair, we examined the dose proportionality of tenofovir in hair in healthy, HIV-uninfected adults. Methods A phase I, crossover pharmacokinetic study was performed in 24 HIV-negative adults receiving directly-observed oral tenofovir tablets administered 2, 4, and 7 doses/week for 6 weeks, with a ≥3-week break between periods. Small samples of hair were collected after each six-week period and analyzed for tenofovir concentrations. Geometric-mean-ratios compared levels between each pair of dosing conditions. Intensive plasma pharmacokinetic studies were performed during the daily-dosing period to calculate areas-under-the-time-concentration curves (AUCs). Results Over 90% of doses were observed per protocol. Median tenofovir concentrations in hair increased monotonically with dose. A log-linear relationship was seen between dose and hair levels, with an estimated 76% (95% CI 60–93%) increase in hair level per 2-fold dose increase. Tenofovir plasma AUCs modestly predicted drug concentrations in hair. Conclusions This study found a strong linear relationship between frequency of dosing and tenofovir levels in scalp hair. The analysis of quantitative drug levels in hair has the potential to improve adherence measurement in the PrEP field and may be helpful in determining exposure thresholds for protection and explaining failures in PrEP trials. Hair measures for adherence monitoring may also facilitate adherence measurement in real-world settings and merit further investigation in upcoming PrEP implementation studies and programs. Trial Registration ClinicalTrials.gov +NCT00903084. PMID:24421901

One should avoid retro-orbital pharmacokinetic sample collections for intranasal dosing in rats: Illustration of spurious pharmacokinetics generated for anti-migraine drugs zolmitriptan and eletriptan.

PubMed

Patel, Harilal; Patel, Prakash; Modi, Nirav; Shah, Shaival; Ghoghari, Ashok; Variya, Bhavesh; Laddha, Ritu; Baradia, Dipesh; Dobaria, Nitin; Mehta, Pavak; Srinivas, Nuggehally R

2017-08-30

Because of the avoidance of first pass metabolic effects due to direct and rapid absorption with improved permeability, intranasal route represents a good alternative for extravascular drug administration. The aim of the study was to investigate the intranasal pharmacokinetics of two anti-migraine drugs (zolmitriptan and eletriptan), using retro-orbital sinus and jugular vein sites sampling. In a parallel study design, healthy male Sprague-Dawley (SD) rats aged between 8 and 12weeks were divided into groups (n=4 or 5/group). The animals of individual groups were dosed intranasal (~1.0mg/kg) and oral doses of 2.1mg/kg of either zolmitriptan or eletriptan. Serial blood sampling was performed from jugular vein or retro-orbital site and plasma samples were analyzed for drug concentrations using LC-MS/MS assay. Standard pharmacokinetics parameters such as T max , C max , AUC last , AUC 0-inf and T 1/2 were calculated and statistics of derived parameters was performed using unpaired t-test. After intranasal dosing, the mean pharmacokinetic parameters C max and AUC inf of zolmitriptan/eletriptan showed about 17-fold and 3-5-fold higher values for retro-orbital sampling as compared to the jugular vein sampling site. Whereas after oral administration such parameters derived for both drugs were largely comparable between the two sampling sites and statistically non-significant. In conclusion, the assessment of plasma levels after intranasal administration with retro-orbital sampling would result in spurious and misleading pharmacokinetics. Copyright © 2017 Elsevier B.V. All rights reserved.

Radon survey and soil gamma doses in primary schools of Batman, Turkey.

PubMed

Damla, Nevzat; Aldemir, Kamuran

2014-06-01

A survey was conducted to evaluate levels of indoor radon and gamma doses in 42 primary schools located in Batman, southeastern Anatolia, Turkey. Indoor radon measurements were carried out using CR-39 solid-state nuclear track detector-based radon dosimeters. The overall mean annual (222)Rn activity in the surveyed area was found to be 49 Bq m(-3) (equivalent to an annual effective dose of 0.25 mSv). However, in one of the districts (Besiri) the maximum radon value turned out to be 307 Bq m(-3). The estimated annual effective doses are less than the recommended action level (3-10 mSv). It is found that the radon concentration decreases with increasing floor number. The concentrations of natural and artificial radioisotopes were determined using gamma-ray spectroscopy for soil samples collected in close vicinity of the studied schools. The mean gamma activity concentrations in the soil samples were 31, 25, 329 and 12 Bq kg(-1) for (226)Ra, (232)Th, (40)K and (137)Cs, respectively. The radiological parameters such as the absorbed dose rate in air and the annual effective dose equivalent were calculated. These radiological parameters were evaluated and compared with the internationally recommended values.

Transfer of Low Dose Aspirin Into Human Milk.

PubMed

Datta, Palika; Rewers-Felkins, Kathleen; Kallem, Raja Reddy; Baker, Teresa; Hale, Thomas W

2017-05-01

Aspirin has antipyretic and anti-inflammatory properties and is frequently used by pregnant and lactating women. However, its transfer in human milk when administered at low dose has not been reported. Research aim: This study aimed to evaluate the transfer of acetylsalicylic acid and its metabolite, salicylic acid, into human milk following the use of low dose aspirin. In this study, milk samples were collected at 0, 1, 2, 4, 8, 12, and 24 hours from seven breastfeeding women after a steady-state daily dose of 81 mg of aspirin. Milk levels of acetylsalicylic acid and salicylic acid were determined by liquid chromatography-tandem mass spectrometry. Acetylsalicylic acid levels were below the limit of quantification (0.61 ng/ml) in all the milk samples, whereas salicylic acid was detected at very low concentrations. The average concentration of salicylic acid observed was 24 ng/ml and the estimated relative infant dose was 0.4%. Acetylsalicylic acid transfer into milk is so low that it is undetectable even by highly sophisticated methodology. Salicylic acid does appear in the human milk in comparatively low amounts, which are probably subclinical in infants. Thus, the daily use of an 81-mg dose of aspirin should be considered safe during lactation.

Tear film concentrations of doxycycline following oral administration in ophthalmologically normal dogs.

PubMed

Collins, Sean P; Labelle, Amber L; Dirikolu, Levent; Li, Zhong; Mitchell, Mark A; Hamor, Ralph E

2016-09-01

OBJECTIVE To determine tear film concentrations of doxycycline in ophthalmologically normal dogs following oral doxycycline administration. DESIGN Crossover study. ANIMALS 10 privately owned dolichocephalic or mesaticephalic dogs free of ophthalmic disease. PROCEDURES Dogs were randomly assigned to receive doxycycline hyclate first at 5 mg/kg (2.3 mg/lb) or 10 mg/kg (4.5 mg/lb), PO, every 12 hours for 5 days, beginning on day 1. Doxycycline was administered 1 hour prior to feeding. Tear samples were collected from days 1 through 10 approximately 3 hours after the morning dose was administered. Following a 3-week washout period, dogs received the alternative dose in the same conditions. Doxycycline concentration in tear samples from 1 eye (same eye used for both sessions) was measured via liquid chromatography-mass spectrometry and compared between the 2 doxycycline doses. RESULTS Doxycycline was detected in tear samples of all dogs from days 1 through 10 for both doxycycline doses. Median peak doxycycline concentrations for the 5 mg/kg and 10 mg/kg doses were 2.19 ng/mL on day 3 and 4.32 ng/mL on day 4, respectively. Concentrations differed significantly with time, but this difference was not influenced by dose, dose order, or eye. A significant positive correlation was identified between doxycycline concentration and body weight (r = 0.22). CONCLUSIONS AND CLINICAL RELEVANCE Detectable doxycycline concentrations were achieved in the tear film of ophthalmologically normal dogs following oral administration of doxycycline at 5 or 10 mg/kg, every 12 hours. Dose had no significant effect on tear film concentration of the drug.

Abuse Liability and Reinforcing Efficacy of Oral Tramadol in Humans

PubMed Central

Babalonis, Shanna; Lofwall, Michelle R.; Nuzzo, Paul A.; Siegel, Anthony J.; Walsh, Sharon L.

2012-01-01

BACKGROUND Tramadol, a monoaminergic reuptake inhibitor, is hepatically metabolized to an opioid agonist (M1). This atypical analgesic is generally considered to have limited abuse liability. Recent reports of its abuse have increased in the U.S., leading to more stringent regulation in some states, but not nationally. The purpose of this study was to examine the relative abuse liability and reinforcing efficacy of tramadol in comparison to a high (oxycodone) and low efficacy (codeine) opioid agonist. METHODS Nine healthy, non-dependent prescription opioid abusers (6 male, 3 female) participated in this within-subject, randomized, double blind, placebo-controlled study. Participants completed 14 paired sessions (7 sample, 7 self-administration). During each sample session, an oral dose of tramadol (200, 400 mg), oxycodone (20, 40 mg), codeine (100, 200 mg) or placebo was administered, and a full array of abuse liability measures was collected. During self-administration sessions, volunteers were given the opportunity to work (via progressive ratio) for the sample dose or money. RESULTS All active doses were self-administered; placebo engendered no responding. The high doses of tramadol and oxycodone were readily self-administered (70%, 59% of available drug, respectively); lower doses and both codeine doses maintained intermediate levels of drug taking. All three drugs dose-dependently increased measures indicative of abuse liability, relative to placebo; however, the magnitude and time course of these and other pharmacodynamic effects varied qualitatively across drugs. CONCLUSIONS This study demonstrates that, like other mu opioids, higher doses of tramadol function as reinforcers in opioid abusers, providing new empirical data for regulatory evaluation. PMID:23098678

SaMpling Antibiotics in Renal Replacement Therapy (SMARRT): an observational pharmacokinetic study in critically ill patients.

PubMed

Roberts, Jason A; Choi, Gordon Y S; Joynt, Gavin M; Paul, Sanjoy K; Deans, Renae; Peake, Sandra; Cole, Louise; Stephens, Dianne; Bellomo, Rinaldo; Turnidge, John; Wallis, Steven C; Roberts, Michael S; Roberts, Darren M; Lassig-Smith, Melissa; Starr, Therese; Lipman, Jeffrey

2016-03-01

Optimal antibiotic dosing is key to maximising patient survival, and minimising the emergence of bacterial resistance. Evidence-based antibiotic dosing guidelines for critically ill patients receiving RRT are currently not available, as RRT techniques and settings vary greatly between ICUs and even individual patients. We aim to develop a robust, evidence-based antibiotic dosing guideline for critically ill patients receiving various forms of RRT. We further aim to observe whether therapeutic antibiotic concentrations are associated with reduced 28-day mortality. We designed a multi-national, observational pharmacokinetic study in critically ill patients requiring RRT. The study antibiotics will be vancomycin, linezolid, piperacillin/tazobactam and meropenem. Pharmacokinetic sampling of each patient's blood, RRT effluent and urine will take place during two separate dosing intervals. In addition, a comprehensive data set, which includes the patients' demographic and clinical parameters, as well as modality, technique and settings of RRT, will be collected. Pharmacokinetic data will be analysed using a population pharmacokinetic approach to identify covariates associated with changes in pharmacokinetic parameters in critically ill patients with AKI who are undergoing RRT for the five commonly prescribed antibiotics. Using the comprehensive data set collected, the pharmacokinetic profile of the five antibiotics will be constructed, including identification of RRT and other factors indicative of the need for altered antibiotic dosing requirements. This will enable us to develop a dosing guideline for each individual antibiotic that is likely to be relevant to any critically ill patient with acute kidney injury receiving any of the included forms of RRT. Australian New Zealand Clinical Trial Registry ( ACTRN12613000241730 ) registered 28 February 2013.

Pharmacokinetics of a single intramuscular injection of ceftiofur crystalline-free acid in red-tailed hawks (Buteo jamaicensis).

PubMed

Sadar, Miranda J; Hawkins, Michelle G; Byrne, Barbara A; Cartoceti, Andrew N; Keel, Kevin; Drazenovich, Tracy L; Tell, Lisa A

2015-12-01

To determine the pharmacokinetics and adverse effects at the injection site of ceftiofur crystalline-free acid (CCFA) following IM administration of 1 dose to red-tailed hawks (Buteo jamaicensis). 7 adult nonreleasable healthy red-tailed hawks. In a randomized crossover study, CCFA (10 or 20 mg/kg) was administered IM to each hawk and blood samples were obtained. After a 2-month washout period, administration was repeated with the opposite dose. Muscle biopsy specimens were collected from the injection site 10 days after each sample collection period. Pharmacokinetic data were calculated. Minimum inhibitory concentrations of ceftiofur for various bacterial isolates were assessed. Mean peak plasma concentrations of ceftiofur-free acid equivalent were 6.8 and 15.1 μg/mL for the 10 and 20 mg/kg doses, respectively. Mean times to maximum plasma concentration were 6.4 and 6.7 hours, and mean terminal half-lives were 29 and 50 hours, respectively. Little to no muscle inflammation was identified. On the basis of a target MIC of 1 μg/mL and target plasma ceftiofur concentration of 4 μg/mL, dose administration frequencies for infections with gram-negative and gram-positive organisms were estimated as every 36 and 45 hours for the 10 mg/kg dose and every 96 and 120 hours for the 20 mg/kg dose, respectively. Study results suggested that CCFA could be administered IM to red-tailed hawks at 10 or 20 mg/kg to treat infections with ceftiofur-susceptible bacteria. Administration resulted in little to no inflammation at the injection site. Additional studies are needed to evaluate effects of repeated CCFA administration.

Randomized clinical trial: pharmacokinetics and safety of multimatrix mesalamine for treatment of pediatric ulcerative colitis.

PubMed

Cuffari, Carmen; Pierce, David; Korczowski, Bartosz; Fyderek, Krzysztof; Van Heusen, Heather; Hossack, Stuart; Wan, Hong; Edwards, Alena Y Z; Martin, Patrick

2016-01-01

Limited data are available on mesalamine (5-aminosalicylic acid; 5-ASA) use in pediatric ulcerative colitis (UC). To evaluate pharmacokinetic and safety profiles of 5-ASA and metabolite acetyl-5-ASA (Ac-5-ASA) after once-daily, oral administration of multimatrix mesalamine to children and adolescents with UC. Participants (5-17 years of age; 18-82 kg, stratified by weight) with UC received multi-matrix mesalamine 30, 60, or 100 mg/kg/day once daily (to 4,800 mg/day) for 7 days. Blood samples were collected pre-dose on days 5 and 6. On days 7 and 8, blood and urine samples were collected and safety was evaluated. 5-ASA and Ac-5-ASA plasma and urine concentrations were analyzed by non-compartmental methods and used to develop a population pharmacokinetic model. Fifty-two subjects (21 [30 mg/kg]; 22 [60 mg/kg]; 9 [100 mg/kg]) were randomized. On day 7, systemic exposures of 5-ASA and Ac-5-ASA exhibited a dose-proportional increase between 30 and 60 mg/kg/day cohorts. For 30, 60, and 100 mg/kg/day doses, mean percentages of 5-ASA absorbed were 29.4%, 27.0%, and 22.1%, respectively. Simulated steady-state exposures and variabilities for 5-ASA and Ac-5-ASA (coefficient of variation approximately 50% and 40%-45%, respectively) were similar to those observed previously in adults at comparable doses. Treatment-emergent adverse events were reported by ten subjects. Events were similar among different doses and age groups with no new safety signals identified. Children and adolescents with UC receiving multimatrix mesalamine demonstrated 5-ASA and Ac-5-ASA pharmacokinetic profiles similar to historical adult data. Multimatrix mesalamine was well tolerated across all dose and age groups. ClinicalTrials.gov Identifier: NCT01130844.

Phase I Pharmacokinetic and Pharmacodynamic Study of the Oral, Small-Molecule Mitogen-Activated Protein Kinase Kinase 1/2 Inhibitor AZD6244 (ARRY-142886) in Patients With Advanced Cancers

PubMed Central

Adjei, Alex A.; Cohen, Roger B.; Franklin, Wilbur; Morris, Clive; Wilson, David; Molina, Julian R.; Hanson, Lorelei J.; Gore, Lia; Chow, Laura; Leong, Stephen; Maloney, Lara; Gordon, Gilad; Simmons, Heidi; Marlow, Allison; Litwiler, Kevin; Brown, Suzy; Poch, Gregory; Kane, Katie; Haney, Jerry; Eckhardt, S. Gail

2009-01-01

Purpose To assess the tolerability, pharmacokinetics (PKs), and pharmacodynamics (PDs) of the mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor AZD6244 (ARRY-142886) in patients with advanced cancer. Patients and Methods In part A, patients received escalating doses to determine the maximum-tolerated dose (MTD). In both parts, blood samples were collected to assess PK and PD parameters. In part B, patients were stratified by cancer type (melanoma v other) and randomly assigned to receive the MTD or 50% MTD. Biopsies were collected to determine inhibition of ERK phosphorylation, Ki-67 expression, and BRAF, KRAS, and NRAS mutations. Results Fifty-seven patients were enrolled. MTD in part A was 200 mg bid, but this dose was discontinued in part B because of toxicity. The 50% MTD (100 mg bid) was well tolerated. Rash was the most frequent and dose-limiting toxicity. Most other adverse events were grade 1 or 2. The PKs were less than dose proportional, with a median half-life of approximately 8 hours and inhibition of ERK phosphorylation in peripheral-blood mononuclear cells at all dose levels. Paired tumor biopsies demonstrated reduced ERK phosphorylation (geometric mean, 79%). Five of 20 patients demonstrated ≥ 50% inhibition of Ki-67 expression, and RAF or RAS mutations were detected in 10 of 26 assessable tumor samples. Nine patients had stable disease (SD) for ≥ 5 months, including two patients with SD for 19 (thyroid cancer) and 22 (uveal melanoma plus renal cancer) 28-day cycles. Conclusion AZD6244 was well tolerated with target inhibition demonstrated at the recommended phase II dose. PK analyses supported twice-daily dosing. Prolonged SD was seen in a variety of advanced cancers. Phase II studies are ongoing. PMID:18390968

Clinical research on erythrocyte deformability with different doses of He-Ne exposure in patient with ischemia disease

NASA Astrophysics Data System (ADS)

Zhao, Yanping; Liu, Song-hao; Sun, Jinbo; Luo, Gangyue; Hua, Rong; Liu, Qianqin

2005-01-01

The aim of this study was to test human erythrocyte deformability with the exposure of erythrocyte from apoplexy patient and other ischemia diseases, contracted with normal donors' blood sample, and the doses-effect of Low-power He_Ne laser in vitro were discussed. Fresh blood sample from adult health donors and patients with different diseases such as apoplexy, diabetes, heart block etc in emergency department were collected and divided into different groups in which there were no less than 6 persons. Fresh human blood samples were irradiated with a He-Ne laser (Lamba=632.8nm), power output around 4.5MW, 9MW, 15mW, and 18mW, et al., exposure time from 7.5min, 15min, and 30min, operating in continuous wave. Measurements of human erythrocyte deformability were taken. Erythrocyte deformability appearance shown some different in the health contracted group and the other ischemia disease group. Some notice difference also shown among some disease group with nonirradiation and the same disease group with laser irradiation. The dose-effects of He-Ne laser therapy was discussed on the further research on the erythrocyte deformability of blood sample from patients with apoplexy disease treated with He-Ne laser at different doses, and a certain optimal doses which could take a beneficial effect in clinic were speculated on. This study revealed that the He-Ne laser have some different effects on erythrocyte deformability in vitro, which were related with the disease condition, red cell state, and outpower-doses, et al closely.

Sequim Marine Research Laboratory routine environmental measurements during CY-1978. [Monitoring for laboratory-related radioactivity and pollutants in environment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Houston, J.R.; Blumer, P.J.

1979-03-01

Environmental data collected during 1978 in the vicinity of the Marine Research Laboratory show continued compliance with all applicable state and federal regulations and furthermore show no detectable change from conditions that existed in previous years. Samples collected for radiological analysis included soil, drinking water, bay water, clams, and seaweed. Radiation dose rates at 1 meter aboveground were also measured.

Extended Detection of Amphetamine and Methamphetamine in Oral Fluid.

PubMed

Andås, Hilde T; Enger, Asle; Øiestad, Åse Marit L; Vindenes, Vigdis; Christophersen, Asbjørg S; Huestis, Marilyn A; Øiestad, Elisabeth L

2016-02-01

Amphetamine and methamphetamine are popular drugs of abuse worldwide and are important components of drug monitoring programs. Windows of detection for amphetamine and methamphetamine in oral fluid after high doses have not been investigated. Repeated high-dose ingestions are likely to cause positive samples for extended periods. Common routes of administration of amphetamine/methamphetamine in Norway are oral intake or injection. The aim of this study was to investigate windows of detection for amphetamine and methamphetamine in oral fluid from drug addicts under sustained abstinence during detoxification. Twenty-five patients admitted to a closed detoxification unit were included in this study. Oral fluid samples were collected daily in the morning and evening, and urine every morning for 10 days. A blood sample was drawn during the first 5 days after admission if the patient consented. Oral fluid results were compared with urine results to determine whether a new ingestion occurred. Oral fluid was collected with the Intercept oral fluid collection device. In-house cutoff concentrations for amphetamine and methamphetamine were 6.8 and 7.5 mcg/L, respectively, in oral fluid, and 135 and 149 mcg/L, respectively, in urine. Amphetamines were detected in 11 oral fluid, 5 urine, and 2 blood specimens from 25 patients. Patients self-reported amphetamines intake of up to 0.5-2 g daily. Windows of detection for amphetamine and methamphetamine in oral fluid were up to 8 days, longer than in urine at the applied cutoff values. These data confirm that oral fluid is a viable alternative to urine for monitoring amphetamine abuse, and that these substances might be detected in oral fluid for at least 1 week after ingestion of high doses. Such long detection times were, as far as we are aware, never reported previously for oral fluid amphetamines.

Low-dose x-ray tomography through a deep convolutional neural network

DOE PAGES

Yang, Xiaogang; De Andrade, Vincent; Scullin, William; ...

2018-02-07

Synchrotron-based X-ray tomography offers the potential of rapid large-scale reconstructions of the interiors of materials and biological tissue at fine resolution. However, for radiation sensitive samples, there remain fundamental trade-offs between damaging samples during longer acquisition times and reducing signals with shorter acquisition times. We present a deep convolutional neural network (CNN) method that increases the acquired X-ray tomographic signal by at least a factor of 10 during low-dose fast acquisition by improving the quality of recorded projections. Short exposure time projections enhanced with CNN show similar signal to noise ratios as compared with long exposure time projections and muchmore » lower noise and more structural information than low-dose fats acquisition without CNN. We optimized this approach using simulated samples and further validated on experimental nano-computed tomography data of radiation sensitive mouse brains acquired with a transmission X-ray microscopy. We demonstrate that automated algorithms can reliably trace brain structures in datasets collected with low dose-CNN. As a result, this method can be applied to other tomographic or scanning based X-ray imaging techniques and has great potential for studying faster dynamics in specimens.« less

Low-dose x-ray tomography through a deep convolutional neural network

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Xiaogang; De Andrade, Vincent; Scullin, William

Synchrotron-based X-ray tomography offers the potential of rapid large-scale reconstructions of the interiors of materials and biological tissue at fine resolution. However, for radiation sensitive samples, there remain fundamental trade-offs between damaging samples during longer acquisition times and reducing signals with shorter acquisition times. We present a deep convolutional neural network (CNN) method that increases the acquired X-ray tomographic signal by at least a factor of 10 during low-dose fast acquisition by improving the quality of recorded projections. Short exposure time projections enhanced with CNN show similar signal to noise ratios as compared with long exposure time projections and muchmore » lower noise and more structural information than low-dose fats acquisition without CNN. We optimized this approach using simulated samples and further validated on experimental nano-computed tomography data of radiation sensitive mouse brains acquired with a transmission X-ray microscopy. We demonstrate that automated algorithms can reliably trace brain structures in datasets collected with low dose-CNN. As a result, this method can be applied to other tomographic or scanning based X-ray imaging techniques and has great potential for studying faster dynamics in specimens.« less

Assessment of Annual Effective Dose for Natural Radioactivity of Gamma Emitters in Biscuit Samples in Iraq.

PubMed

Abojassim, Ali Abid; Al-Alasadi, Lubna A; Shitake, Ahmed R; Al-Tememie, Faeq A; Husain, Afnan A

2015-09-01

Biscuits are an important type of food, widely consumed by babies in Iraq and other countries. This work uses gamma spectroscopy to measure the natural radioactivity due to long-lived gamma emitters in children's biscuits; it also estimates radiation hazard indices, that is, the radium equivalent activity, the representative of gamma level index, the internal hazard index, and the annual effective dose in children. Ten samples were collected from the Iraqi market from different countries of origin. The average specific activities for (226)Ra, (232)Th, and (40)K were 9.390, 3.1213, and 214.969 Bq/kg, respectively, but the average of the radium equivalent activity and the internal hazard index were 33.101 Bq/kg and 0.107, respectively. The total average annual effective dose from consumption by adults, children, and infants is estimated to be 0.655, 1.009, and 0.875 mSv, respectively. The values found for specific activity, radiation hazard indices, and annual effective dose in all samples in this study were lower than worldwide median values for all groups; therefore, these values are found to be safe.

Thyroid hormones and thyroid disease in relation to perchlorate dose and residence near a superfund site.

PubMed

Gold, Ellen B; Blount, Benjamin C; O'Neill Rasor, Marianne; Lee, Jennifer S; Alwis, Udeni; Srivastav, Anup; Kim, Kyoungmi

2013-07-01

Perchlorate is a widely occurring contaminant, which can competitively inhibit iodide uptake and thus thyroid hormone production. The health effects of chronic low dose perchlorate exposure are largely unknown. In a community-based study, we compared thyroid function and disease in women with differing likelihoods of prior and current perchlorate exposure. Residential blocks were randomly selected from areas: (1) with potential perchlorate exposure via drinking water; (2) with potential exposure to environmental contaminants; and (3) neighboring but without such exposures. Eligibility included having lived in the area for ≥6 months and aged 20-50 years during 1988-1996 (during documented drinking water well contamination). We interviewed 814 women and collected blood samples (assayed for thyroid stimulating hormone and free thyroxine) from 431 interviewed women. Daily urine samples were assayed for perchlorate and iodide for 178 premenopausal women with blood samples. We performed multivariable regression analyses comparing thyroid function and disease by residential area and by urinary perchlorate dose adjusted for urinary iodide levels. Residential location and current perchlorate dose were not associated with thyroid function or disease. No persistent effect of perchlorate on thyroid function or disease was found several years after contaminated wells were capped.

Extending the Collection Duration of Breath Samples for Enteric Methane Emission Estimation Using the SF6 Tracer Technique

PubMed Central

Pinares-Patiño, César; Gere, José; Williams, Karen; Gratton, Roberto; Juliarena, Paula; Molano, German; MacLean, Sarah; Sandoval, Edgar; Taylor, Grant; Koolaard, John

2012-01-01

Simple Summary Extended sample collection for the SF6 tracer technique is desirable for extensive grazing systems. Breath samples from eight cows were collected while lucerne silage was fed to achieve fixed intakes among the cows. Samples were collected over a 10-day period, using either apparatuses used in New Zealand (NZL) or Argentina (ARG), and either daily, over two consecutive 5-day periods or over a 10-day period (in duplicate). The NZL system had a greater sampling success and more consistent CH4 emission estimates than the ARG system, with no differences in mean emissions among sample collection periods. This study showed that extended sample collection is feasible, but definitive evaluation under grazing situation is required before a decision on recommendation can be made. Abstract The daily sample collection protocol of the sulphur hexafluoride (SF6) tracer technique for the estimation of methane (CH4) emissions from ruminants may not be practical under extensive grazing systems. Here, under controlled conditions, we evaluated extended periods of sampling as an alternative to daily sample collections. Eight rumen-fistulated cows were housed and fed lucerne silage to achieve common daily feed intakes of 6.4 kg dry matter per cow. Following SF6 permeation tube dosing, eight sampling lines were fitted to the breath collection harness, so that a common gas mix was available to each line. Half of the lines collected samples into PVC yokes using a modified capillary system as commonly used in New Zealand (NZL), and half collected samples into stainless steel cylinders using a ball-bearing flow restrictor as used in Argentina (ARG), all within a 10-day time frame, either daily, across two consecutive 5-day periods or across one 10-day period (in duplicate). The NZL system had greater sampling success (97.3 vs. 79.5%) and yielded more consistent CH4 emission estimates than the ARG system. Emission estimates from NZL daily, NZL 5-day and NZL 10-day samplings were 114, 110 and 111 g d−1, respectively. Extended sample collection protocol may be feasible, but definitive evaluation of this alternative as well as sample collection systems is required under grazing situations before a decision on recommendation can be made. PMID:26486921

Seasonal variation in the nature of DOM in a river and drinking water reservoir of a closed catchment.

PubMed

Awad, John; van Leeuwen, John; Chow, Christopher W K; Smernik, Ronald J; Anderson, Sharolyn J; Cox, Jim W

2017-01-01

Dissolved organic matter (DOM) in surface waters used for drinking purposes can vary markedly in character depending on its source within catchments and the timing and intensity of rainfall events. Here we report the findings of a study on the character and concentration of DOM in waters collected during different seasons from Myponga River and Reservoir, South Australia. The character of DOM was assessed in terms of its treatability by enhanced coagulation and potential for disinfection by-product i.e. trihalomethane (THM) formation. During the wet seasons (winter and spring), water samples from the river had higher DOC concentrations (X¯: 21 mg/L) and DOM of higher average molecular weight (AMW: 1526 Da) than waters collected during the dry seasons (summer and autumn: DOC: 13 mg/L; AMW: 1385 Da). Even though these features led to an increase in the percentage removal of organics by coagulation with alum (64% for wet compared with 53% for dry season samples) and a lower alum dose rate (10 versus 15 mg alum/mg DOC removal), there was a higher THM formation potential (THMFP) from wet season waters (treated waters: 217 μg/L vs 172 μg/L). For reservoir waters, samples collected during the wet seasons had an average DOC concentration (X¯: 15 mg/L), percentage removal of organics by alum (54%), alum dose rates (13 mg/mg DOC) and THMFP (treated waters: 207 μg/L) that were similar to samples collected during the dry seasons (mean DOC: 15 mg/L; removal of organics: 52%; alum dose rate: 13 mg/mg DOC; THMFP: 212 μg/L for treated waters). These results show that DOM present in river waters and treatability by alum are highly impacted by seasonal environmental variations. However these in reservoir waters exhibit less seasonal variability. Storage of large volumes of water in the reservoir enables mixing of influent waters and stabilization of water quality. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

A Phase I clinical trial of lodenafil carbonate, a new phosphodiesterase Type 5 (PDE5) inhibitor, in healthy male volunteers.

PubMed

Mendes, Gustavo D; dos Santos Filho, Hilton Oliveira; dos Santos Pereira, Alberto; Mendes, Fabiana D; Ilha, Jaime O; Alkharfy, Khalid M; De Nucci, Gilberto

2012-12-01

Lodenafil carbonate is a new phosphodiesterase Type 5 (PDE5) inhibitor used in treatment of erectile dysfunction. The present study was conducted to evaluate the safety, tolerability, and pharmacokinetics of lodenafil carbonate after administering ascending (1 - 100 mg) single oral doses to healthy male volunteers (n = 33). The study was an open label, dose-escalation, Phase I clinical trial involving the administration of single oral doses of lodenafil carbonate. Lodenafil carbonate was administered sequentially, escalating in single doses of 1 mg - 100 mg with a washout period of at least 1 week between each dose. The progression to the next dose was allowed after clinical and laboratory exams, Ambulatory Monitoring of Arterial Pressure (AMAP) without relevant clinical modifications and adverse events without clinical relevancy. Blood samples were collected at pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 14, 16, 20 and 24 h post-dosing. Plasma samples for measurement of lodenafil carbonate and lodenafil were analyzed by liquid chromatography coupled to tandem mass spectrometry. No serious adverse events were observed, and none of the subjects discontinued the study due to intolerance. The AMAP measurements, clinical and laboratory exams and ECG revealed no significant changes even at higher doses. Lodenafil carbonate was not detected in any samples, indicating that it acts as a prodrug. The mean lodenafil pharmacokinetic parameters for tmax and t1/2 were 1.6 ( ± 0.4) h and 3.3 ( ± 1.1) h, respectively. This study demonstrated that lodenafil carbonate was well tolerated and showed a good safety profile in healthy male volunteers.

Public health risk assessment associated with heavy metal and arsenic exposure near an abandoned mine (Kirki, Greece).

PubMed

Nikolaidis, Christos; Orfanidis, Moysis; Hauri, Dimitri; Mylonas, Stratos; Constantinidis, Theodore

2013-12-01

The 'Agios Philippos' lead-zinc mine in the Kirki region (NE Greece) is now closed, but its legacy of heavy metal contamination remains at the site. At present, management of the contaminated land is of major concern. The area is in a reclamation process and requires immediate remediation action, whereas human risks need to be carefully evaluated. In order to assess these risks, samples from around the mine were collected and analyzed and a scenario involving the oral, dermal, and inhaled doses of arsenic and heavy metals was formulated. A Monte Carlo approach was undertaken, in order to model the average daily dose and quantify the corresponding hazard index and cancer risk. A toxicological risk was associated with samples collected in the vicinity of the mine (floatation, mine tailings) and a pronounced carcinogenic risk for arsenic was evident at the broader occupational/environmental setting. These findings urge for immediate rehabilitation actions that will mitigate population exposures and promote long-term environmental safety in the area.

Strategies to assess systemic exposure of chemicals in subchronic/chronic diet and drinking water studies.

PubMed

Saghir, Shakil A; Mendrala, Alan L; Bartels, Michael J; Day, Sue J; Hansen, Steve C; Sushynski, Jacob M; Bus, James S

2006-03-15

Strategies were developed for the estimation of systemically available daily doses of chemicals, diurnal variations in blood levels, and rough elimination rates in subchronic feeding/drinking water studies, utilizing a minimal number of blood samples. Systemic bioavailability of chemicals was determined by calculating area under the plasma concentration curve over 24 h (AUC-24 h) using complete sets of data (> or =5 data points) and also three, two, and one selected time points. The best predictions of AUC-24 h were made when three time points were used, corresponding to Cmax, a mid-morning sample, and C(min). These values were found to be 103 +/- 10% of the original AUC-24 h, with 13 out of 17 values ranging between 96 and 105% of the original. Calculation of AUC-24 h from two samples (Cmax and Cmin) or one mid-morning sample afforded slightly larger variations in the calculated AUC-24 h (69-136% of the actual). Following drinking water exposure, prediction of AUC-24 h using 3 time points (Cmax, mid-morning, and Cmin) was very close to actual values (80-100%) among mice, while values for rats were only 63% of the original due to less frequent drinking behavior of rats during the light cycle. Collection and analysis of 1-3 blood samples per dose may provide insight into dose-proportional or non-dose-proportional differences in systemic bioavailability, pointing towards saturation of absorption or elimination or some other phenomenon warranting further investigation. In addition, collection of the terminal blood samples from rats, which is usually conducted after 18 h of fasting, will be helpful in rough estimation of blood/plasma half-life of the compound. The amount of chemical(s) and/or metabolite(s) in excreta and their possible use as biomarkers in predicting the daily systemic exposure levels are also discussed. Determining these parameters in the early stages of testing will provide critical information to improve the appropriate design of other longer-term toxicity studies.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saghir, Shakil A.; Mendrala, Alan L.; Bartels, Michael J.

Strategies were developed for the estimation of systemically available daily doses of chemicals, diurnal variations in blood levels, and rough elimination rates in subchronic feeding/drinking water studies, utilizing a minimal number of blood samples. Systemic bioavailability of chemicals was determined by calculating area under the plasma concentration curve over 24 h (AUC-24 h) using complete sets of data ({>=}5 data points) and also three, two, and one selected time points. The best predictions of AUC-24 h were made when three time points were used, corresponding to C {sub max}, a mid-morning sample, and C {sub min}. These values were foundmore » to be 103 {+-} 10% of the original AUC-24 h, with 13 out of 17 values ranging between 96 and 105% of the original. Calculation of AUC-24 h from two samples (C {sub max} and C {sub min}) or one mid-morning sample afforded slightly larger variations in the calculated AUC-24 h (69-136% of the actual). Following drinking water exposure, prediction of AUC-24 h using 3 time points (C {sub max}, mid-morning, and C {sub min}) was very close to actual values (80-100%) among mice, while values for rats were only 63% of the original due to less frequent drinking behavior of rats during the light cycle. Collection and analysis of 1-3 blood samples per dose may provide insight into dose-proportional or non-dose-proportional differences in systemic bioavailability, pointing towards saturation of absorption or elimination or some other phenomenon warranting further investigation. In addition, collection of the terminal blood samples from rats, which is usually conducted after 18 h of fasting, will be helpful in rough estimation of blood/plasma half-life of the compound. The amount of chemical(s) and/or metabolite(s) in excreta and their possible use as biomarkers in predicting the daily systemic exposure levels are also discussed. Determining these parameters in the early stages of testing will provide critical information to improve the appropriate design of other longer-term toxicity studies.« less

A novel approach for estimating ingested dose associated with paracetamol overdose

PubMed Central

Zurlinden, Todd J.; Heard, Kennon

2015-01-01

Aim In cases of paracetamol (acetaminophen, APAP) overdose, an accurate estimate of tissue‐specific paracetamol pharmacokinetics (PK) and ingested dose can offer health care providers important information for the individualized treatment and follow‐up of affected patients. Here a novel methodology is presented to make such estimates using a standard serum paracetamol measurement and a computational framework. Methods The core component of the computational framework was a physiologically‐based pharmacokinetic (PBPK) model developed and evaluated using an extensive set of human PK data. Bayesian inference was used for parameter and dose estimation, allowing the incorporation of inter‐study variability, and facilitating the calculation of uncertainty in model outputs. Results Simulations of paracetamol time course concentrations in the blood were in close agreement with experimental data under a wide range of dosing conditions. Also, predictions of administered dose showed good agreement with a large collection of clinical and emergency setting PK data over a broad dose range. In addition to dose estimation, the platform was applied for the determination of optimal blood sampling times for dose reconstruction and quantitation of the potential role of paracetamol conjugate measurement on dose estimation. Conclusions Current therapies for paracetamol overdose rely on a generic methodology involving the use of a clinical nomogram. By using the computational framework developed in this study, serum sample data, and the individual patient's anthropometric and physiological information, personalized serum and liver pharmacokinetic profiles and dose estimate could be generated to help inform an individualized overdose treatment and follow‐up plan. PMID:26441245

A novel approach for estimating ingested dose associated with paracetamol overdose.

PubMed

Zurlinden, Todd J; Heard, Kennon; Reisfeld, Brad

2016-04-01

In cases of paracetamol (acetaminophen, APAP) overdose, an accurate estimate of tissue-specific paracetamol pharmacokinetics (PK) and ingested dose can offer health care providers important information for the individualized treatment and follow-up of affected patients. Here a novel methodology is presented to make such estimates using a standard serum paracetamol measurement and a computational framework. The core component of the computational framework was a physiologically-based pharmacokinetic (PBPK) model developed and evaluated using an extensive set of human PK data. Bayesian inference was used for parameter and dose estimation, allowing the incorporation of inter-study variability, and facilitating the calculation of uncertainty in model outputs. Simulations of paracetamol time course concentrations in the blood were in close agreement with experimental data under a wide range of dosing conditions. Also, predictions of administered dose showed good agreement with a large collection of clinical and emergency setting PK data over a broad dose range. In addition to dose estimation, the platform was applied for the determination of optimal blood sampling times for dose reconstruction and quantitation of the potential role of paracetamol conjugate measurement on dose estimation. Current therapies for paracetamol overdose rely on a generic methodology involving the use of a clinical nomogram. By using the computational framework developed in this study, serum sample data, and the individual patient's anthropometric and physiological information, personalized serum and liver pharmacokinetic profiles and dose estimate could be generated to help inform an individualized overdose treatment and follow-up plan. © 2015 The British Pharmacological Society.

Dynamic X-ray diffraction sampling for protein crystal positioning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scarborough, Nicole M.; Godaliyadda, G. M. Dilshan P.; Ye, Dong Hye

A sparse supervised learning approach for dynamic sampling (SLADS) is described for dose reduction in diffraction-based protein crystal positioning. Crystal centering is typically a prerequisite for macromolecular diffraction at synchrotron facilities, with X-ray diffraction mapping growing in popularity as a mechanism for localization. In X-ray raster scanning, diffraction is used to identify the crystal positions based on the detection of Bragg-like peaks in the scattering patterns; however, this additional X-ray exposure may result in detectable damage to the crystal prior to data collection. Dynamic sampling, in which preceding measurements inform the next most information-rich location to probe for image reconstruction,more » significantly reduced the X-ray dose experienced by protein crystals during positioning by diffraction raster scanning. The SLADS algorithm implemented herein is designed for single-pixel measurements and can select a new location to measure. In each step of SLADS, the algorithm selects the pixel, which, when measured, maximizes the expected reduction in distortion given previous measurements. Ground-truth diffraction data were obtained for a 5 µm-diameter beam and SLADS reconstructed the image sampling 31% of the total volume and only 9% of the interior of the crystal greatly reducing the X-ray dosage on the crystal. Furthermore, by usingin situtwo-photon-excited fluorescence microscopy measurements as a surrogate for diffraction imaging with a 1 µm-diameter beam, the SLADS algorithm enabled image reconstruction from a 7% sampling of the total volume and 12% sampling of the interior of the crystal. When implemented into the beamline at Argonne National Laboratory, without ground-truth images, an acceptable reconstruction was obtained with 3% of the image sampled and approximately 5% of the crystal. The incorporation of SLADS into X-ray diffraction acquisitions has the potential to significantly minimize the impact of X-ray exposure on the crystal by limiting the dose and area exposed for image reconstruction and crystal positioning using data collection hardware present in most macromolecular crystallography end-stations.« less

Dynamic X-ray diffraction sampling for protein crystal positioning

DOE PAGES

Scarborough, Nicole M.; Godaliyadda, G. M. Dilshan P.; Ye, Dong Hye; ...

2017-01-01

A sparse supervised learning approach for dynamic sampling (SLADS) is described for dose reduction in diffraction-based protein crystal positioning. Crystal centering is typically a prerequisite for macromolecular diffraction at synchrotron facilities, with X-ray diffraction mapping growing in popularity as a mechanism for localization. In X-ray raster scanning, diffraction is used to identify the crystal positions based on the detection of Bragg-like peaks in the scattering patterns; however, this additional X-ray exposure may result in detectable damage to the crystal prior to data collection. Dynamic sampling, in which preceding measurements inform the next most information-rich location to probe for image reconstruction,more » significantly reduced the X-ray dose experienced by protein crystals during positioning by diffraction raster scanning. The SLADS algorithm implemented herein is designed for single-pixel measurements and can select a new location to measure. In each step of SLADS, the algorithm selects the pixel, which, when measured, maximizes the expected reduction in distortion given previous measurements. Ground-truth diffraction data were obtained for a 5 µm-diameter beam and SLADS reconstructed the image sampling 31% of the total volume and only 9% of the interior of the crystal greatly reducing the X-ray dosage on the crystal. Furthermore, by usingin situtwo-photon-excited fluorescence microscopy measurements as a surrogate for diffraction imaging with a 1 µm-diameter beam, the SLADS algorithm enabled image reconstruction from a 7% sampling of the total volume and 12% sampling of the interior of the crystal. When implemented into the beamline at Argonne National Laboratory, without ground-truth images, an acceptable reconstruction was obtained with 3% of the image sampled and approximately 5% of the crystal. The incorporation of SLADS into X-ray diffraction acquisitions has the potential to significantly minimize the impact of X-ray exposure on the crystal by limiting the dose and area exposed for image reconstruction and crystal positioning using data collection hardware present in most macromolecular crystallography end-stations.« less

Dynamic X-ray diffraction sampling for protein crystal positioning

PubMed Central

Scarborough, Nicole M.; Godaliyadda, G. M. Dilshan P.; Ye, Dong Hye; Kissick, David J.; Zhang, Shijie; Newman, Justin A.; Sheedlo, Michael J.; Chowdhury, Azhad U.; Fischetti, Robert F.; Das, Chittaranjan; Buzzard, Gregery T.; Bouman, Charles A.; Simpson, Garth J.

2017-01-01

A sparse supervised learning approach for dynamic sampling (SLADS) is described for dose reduction in diffraction-based protein crystal positioning. Crystal centering is typically a prerequisite for macromolecular diffraction at synchrotron facilities, with X-ray diffraction mapping growing in popularity as a mechanism for localization. In X-ray raster scanning, diffraction is used to identify the crystal positions based on the detection of Bragg-like peaks in the scattering patterns; however, this additional X-ray exposure may result in detectable damage to the crystal prior to data collection. Dynamic sampling, in which preceding measurements inform the next most information-rich location to probe for image reconstruction, significantly reduced the X-ray dose experienced by protein crystals during positioning by diffraction raster scanning. The SLADS algorithm implemented herein is designed for single-pixel measurements and can select a new location to measure. In each step of SLADS, the algorithm selects the pixel, which, when measured, maximizes the expected reduction in distortion given previous measurements. Ground-truth diffraction data were obtained for a 5 µm-diameter beam and SLADS reconstructed the image sampling 31% of the total volume and only 9% of the interior of the crystal greatly reducing the X-ray dosage on the crystal. Using in situ two-photon-excited fluorescence microscopy measurements as a surrogate for diffraction imaging with a 1 µm-diameter beam, the SLADS algorithm enabled image reconstruction from a 7% sampling of the total volume and 12% sampling of the interior of the crystal. When implemented into the beamline at Argonne National Laboratory, without ground-truth images, an acceptable reconstruction was obtained with 3% of the image sampled and approximately 5% of the crystal. The incorporation of SLADS into X-ray diffraction acquisitions has the potential to significantly minimize the impact of X-ray exposure on the crystal by limiting the dose and area exposed for image reconstruction and crystal positioning using data collection hardware present in most macromolecular crystallography end-stations. PMID:28009558

Dynamic X-ray diffraction sampling for protein crystal positioning.

PubMed

Scarborough, Nicole M; Godaliyadda, G M Dilshan P; Ye, Dong Hye; Kissick, David J; Zhang, Shijie; Newman, Justin A; Sheedlo, Michael J; Chowdhury, Azhad U; Fischetti, Robert F; Das, Chittaranjan; Buzzard, Gregery T; Bouman, Charles A; Simpson, Garth J

2017-01-01

A sparse supervised learning approach for dynamic sampling (SLADS) is described for dose reduction in diffraction-based protein crystal positioning. Crystal centering is typically a prerequisite for macromolecular diffraction at synchrotron facilities, with X-ray diffraction mapping growing in popularity as a mechanism for localization. In X-ray raster scanning, diffraction is used to identify the crystal positions based on the detection of Bragg-like peaks in the scattering patterns; however, this additional X-ray exposure may result in detectable damage to the crystal prior to data collection. Dynamic sampling, in which preceding measurements inform the next most information-rich location to probe for image reconstruction, significantly reduced the X-ray dose experienced by protein crystals during positioning by diffraction raster scanning. The SLADS algorithm implemented herein is designed for single-pixel measurements and can select a new location to measure. In each step of SLADS, the algorithm selects the pixel, which, when measured, maximizes the expected reduction in distortion given previous measurements. Ground-truth diffraction data were obtained for a 5 µm-diameter beam and SLADS reconstructed the image sampling 31% of the total volume and only 9% of the interior of the crystal greatly reducing the X-ray dosage on the crystal. Using in situ two-photon-excited fluorescence microscopy measurements as a surrogate for diffraction imaging with a 1 µm-diameter beam, the SLADS algorithm enabled image reconstruction from a 7% sampling of the total volume and 12% sampling of the interior of the crystal. When implemented into the beamline at Argonne National Laboratory, without ground-truth images, an acceptable reconstruction was obtained with 3% of the image sampled and approximately 5% of the crystal. The incorporation of SLADS into X-ray diffraction acquisitions has the potential to significantly minimize the impact of X-ray exposure on the crystal by limiting the dose and area exposed for image reconstruction and crystal positioning using data collection hardware present in most macromolecular crystallography end-stations.

Radioactivity of peat mud used in therapy.

PubMed

Karpińska, Maria; Mnich, Krystian; Kapała, Jacek; Bielawska, Agnieszka; Kulesza, Grzegorz; Mnich, Stanisław

2016-02-01

The aim of the study was to determine the contents of natural and artificial isotopes in peat mud and to estimate the radiation dose absorbed via skin in patients during standard peat mud treatment. The analysis included 37 samples collected from 8 spas in Poland. The measurements of isotope concentration activity were conducted with the use of gamma spectrometry methods. The skin dose in a standard peat mud bath therapy is approximately 300 nSv. The effective dose of such therapy is considered to be 22 nSv. The doses absorbed during peat mud therapy are 5 orders of magnitude lower than effective annual dose absorbed from the natural radiation background by a statistical Pole (3.5 mSv). Neither therapeutic nor harmful effect is probable in case of such a small dose of ionising radiation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Low-Level Analytical Methodology Updates to Support Decontaminant Performance Evaluations

DTIC Science & Technology

2011-06-01

from EPDM and tire rubber coupon materials that were spiked with a known amount of the chemical agent VX, treated with bleach decontaminant, and...to evaluate the performance of bleach decontaminant on EPDM and tire rubber coupons. Dose-confirmation or Tool samples were collected by delivering...components • An aging or damaged analytical column • Dirty detector • Other factors related to general instrument and/or sample analysis performance

Use of a sparse sampling study design to assess transfer of tramadol and its O-desmethyl metabolite into transitional breast milk.

PubMed

Ilett, Kenneth F; Paech, Michael J; Page-Sharp, Madhu; Sy, Sherwin K; Kristensen, Judith H; Goy, Raymond; Chua, Sebastian; Christmas, Tracey; Scott, Karen L

2008-05-01

There are presently no published data on tramadol transfer into breast milk or on its effects in the breastfed infant. We have provided quantitative data on the absolute and relative infant doses of rac-tramadol and it rac-O-desmethyl metabolite for the breastfed infant. We have also demonstrated a novel sparse sampling data collection method for investigating infant exposure via milk. To investigate the transfer of rac-tramadol and its rac-O-desmethyl metabolite into transitional milk, and assess unwanted effects in the breastfed infant. Tramadol HCl (100 mg six hourly) was administered to 75 breastfeeding mothers for postoperative analgesia on days 2-4 after Caesarian section. Milk and plasma samples were collected after administration of four or more doses. Rac-tramadol and rac-O-desmethyltramadol were measured by high performance liquid chromatography. Milk : plasma ratio (M : P) and infant doses were calculated by standard methods. The behavioural characteristics of the exposed breastfed infants and a matched control group of infants not exposed to tramadol were also studied. RESULTS At steady-state, mean (95% CI) M : P was 2.2 (2.0, 2.4) for rac-tramadol and 2.8 (2.5, 3.1) for rac-O-desmethyltramadol. The estimated absolute and relative infant doses were 112 (102, 122) microg kg(-1) day(-1) and 30 (28, 32) microg kg(-1) day(-1), and 2.24% (2.04, 2.44)% and 0.64% (0.59, 0.69)% for rac-tramadol and rac-O-desmethyltramadol, respectively. The exposed infants and control breastfed infants had similar characteristics, including Apgar scores at birth and Neurologic and Adaptive Capacity Scores. The combined relative infant dose of 2.88% at steady-state was low. The similarity of NACS in exposed infants and controls suggests that there were no significant behavioural adverse effects. We conclude that short-term maternal use of tramadol during establishment of lactation is compatible with breastfeeding.

Annual radiological environmental operating report: Browns Ferry Nuclear Plant, 1992. Operations Services/Technical Programs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1993-04-01

This report describes the environmental radiological monitoring program conducted by TVA in the vicinity of Browns Ferry Nuclear Plant (BFN) in 1992. The program includes the collection of samples from the environment and the determination of the concentrations of radioactive materials in the samples. Samples are taken from stations in the general area of the plant and from areas not influenced by plant operations. Station locations are selected after careful consideration of the weather patterns and projected radiation doses to the various areas around the plant. Material sampled includes air, water, milk, foods, vegetation, soil, fish, sediment, and direct radiationmore » levels. Results from stations near the plant are compared with concentrations from control stations and with preoperational measurements to determine potential impacts of plant operations. Small amounts of Co-60 and Cs-134 were found in sediment samples downstream from the plant. This activity in stream sediment would result in no measurable increase over background in the dose to the general public.« less

Pharmacokinetic Modeling of Intranasal Scopolamine in Plasma Saliva and Urine

NASA Technical Reports Server (NTRS)

Wu, L.; Tam, V. H.; Chow, D. S. L.; Putcha, L.

2015-01-01

An intranasal gel dosage formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness (SMS). The bioavailability and pharmacokinetics (PK) were evaluated under IND (Investigational New Drug) guidelines. The aim of the project was to develop a PK model that can predict the relationships among plasma, saliva and urinary scopolamine concentrations using data collected from the IND clinical trial protocol with INSCOP. Twelve healthy human subjects were administered at three dose levels (0.1, 0.2 and 0.4 mg) of INSCOP. Serial blood, saliva and urine samples were collected between 5 min to 24 h after dosing and scopolamine concentrations were measured by using a validated LC-MS-MS assay. PK compartmental models, using actual dosing and sampling time, were established using Phoenix (version 1.2). Model selection was based on a likelihood ratio test on the difference of criteria (-2LL (i.e. log-likelihood ratio test)) and comparison of the quality of fit plots. The results: Predictable correlations among scopolamine concentrations in compartments of plasma, saliva and urine were established, and for the first time the model satisfactorily predicted the population and individual PK of INSCOP in plasma, saliva and urine. The model can be utilized to predict the INSCOP plasma concentration by saliva and urine data, and it will be useful for monitoring the PK of scopolamine in space and other remote environments using non-invasive sampling of saliva and/or urine.

SPL7013 Gel (VivaGel®) Retains Potent HIV-1 and HSV-2 Inhibitory Activity following Vaginal Administration in Humans

PubMed Central

Price, Clare F.; Tyssen, David; Sonza, Secondo; Davie, Ashley; Evans, Sonya; Lewis, Gareth R.; Xia, Shirley; Spelman, Tim; Hodsman, Peter; Moench, Thomas R.; Humberstone, Andrew; Paull, Jeremy R.A.; Tachedjian, Gilda

2011-01-01

SPL7013 Gel (VivaGel®) is a microbicide in development for prevention of HIV and HSV. This clinical study assessed retention and duration of antiviral activity following vaginal administration of 3% SPL7013 Gel in healthy women. Participants received 5 single doses of product with ≥5 days between doses. A cervicovaginal fluid (CVF) sample was collected using a SoftCup™ pre-dose, and immediately, or 1, 3, 12 or 24 h post-dose. HIV-1 and HSV-2 antiviral activities of CVF samples were determined in cell culture assays. Antiviral activity in the presence of seminal plasma was also tested. Mass and concentration of SPL7013 in CVF samples was determined. Safety was assessed by reporting of adverse events. Statistical analysis was performed using the Wilcoxon signed-rank test with Bonferroni adjustment; p≤0.003 was significant. Eleven participants completed the study. Inhibition of HIV-1 and HSV-2 by pre-dose CVF samples was negligible. CVF samples obtained immediately after dosing almost completely inhibited (median, interquartile range) HIV-1 [96% (95,97)] and HSV-2 [86% (85,94)], and activity was maintained in all women at 3 h (HIV-1 [96% (95,98), p = 0.9]; HSV-2 [94% (91,97), p = 0.005]). At 24 h, >90% of initial HIV-1 and HSV-2 inhibition was maintained in 6/11 women. SPL7013 was recovered in CVF samples obtained at baseline (46% of 105 mg dose). At 3 and 24 h, 22 mg and 4 mg SPL7013, respectively, were recovered. More than 70% inhibition of HIV-1 and HSV-2 was observed if there was >0.5 mg SPL7013 in CVF samples. High levels of antiviral activity were retained in the presence of seminal plasma. VivaGel was well tolerated with no signs or symptoms of vaginal, vulvar or cervical irritation reported. Potent antiviral activity was observed against HIV-1 and HSV-2 immediately following vaginal administration of VivaGel, with activity maintained for at least 3 h post-dose. The data provide evidence of antiviral activity in a clinical setting, and suggest VivaGel could be administered up to 3 h before coitus. Trial Registration The study is registered at ClinicalTrials.gov under identifier: NCT00740584 PMID:21935377

Tamoxifen dose and serum concentrations of tamoxifen and six of its metabolites in routine clinical outpatient care.

PubMed

Jager, N G L; Rosing, H; Schellens, J H M; Linn, S C; Beijnen, J H

2014-02-01

A sensitive and selective HPLC-MS/MS assay was used to analyze steady-state serum concentrations of tamoxifen, N-desmethyltamoxifen (E)-endoxifen, (Z)-endoxifen, N-desmethyl-4'-hydroxytamoxifen, 4-hydroxytamoxifen, and 4'-hydroxytamoxifen to support therapeutic drug monitoring (TDM) in patients treated with tamoxifen according to standard of care. When the (Z)-endoxifen serum concentration was below the predefined therapeutic threshold concentration of 5.9 ng/mL, the clinician was advised to increase the tamoxifen dose and to collect another serum sample. Paired serum samples from patients at one dose level at different time points during the tamoxifen treatment were used to assess the intra-patient variability. A total of 251 serum samples were analyzed, obtained from 205 patients. Of these patients, 197 used 20 mg tamoxifen per day and 8 patients used 10 mg/day. There was wide variability in tamoxifen and metabolite concentrations within the dosing groups. The threshold concentration for (Z)-endoxifen was reached in one patient (12 %) in the 10 mg group, in 153 patients (78 %) in the 20 mg group, and in 26 (96 %) of the patients who received a dose increase to 30 or 40 mg/day. Dose increase from 20 to 30 or 40 mg per day resulted in a significant increase in the mean serum concentrations of all analytes (p < 0.001). The mean intra-patient variability was between 10 and 20 % for all analytes. These results support the suitability of TDM for optimizing the tamoxifen treatment. It is shown that tamoxifen dose is related to (Z)-endoxifen exposure and increasing this dose leads to a higher serum concentration of tamoxifen and its metabolites. The low intra-patient variability suggests that only one serum sample is needed for TDM, making this a relatively noninvasive way to optimize the patient's treatment.

Effect of milk thistle on the pharmacokinetics of indinavir in healthy volunteers.

PubMed

Piscitelli, Stephen C; Formentini, Elizabeth; Burstein, Aaron H; Alfaro, Raul; Jagannatha, Shyla; Falloon, Judith

2002-05-01

To characterize the pharmacokinetics of indinavir in the presence and absence of milk thistle and to determine the offset of any effect of milk thistle on indinavir disposition. Prospective open-label drug interaction study. Outpatient clinic. Ten healthy volunteers. Intervention. Blood samples were collected over 8 hours after the volunteers took four doses of indinavir 800 mg every 8 hours on an empty stomach for baseline pharmacokinetics. This dosing and sampling were repeated after the subjects took milk thistle 175 mg (confirmed to contain silymarin 153 mg, the active ingredient) 3 times/day for 3 weeks. After an 11-day washout, indinavir dosing and blood sampling were repeated to evaluate the offset of any potential interaction. Indinavir concentrations were measured by using a validated high-performance liquid chromatography method. The following pharmacokinetic parameters were determined: highest concentration (Cmax), hour-0 concentration, hour-8 concentration (C8), time to reach Cmax, and area under the plasma concentration-time curve over the 8-hour dosing interval (AUC8). Milk thistle did not alter significantly the overall exposure of indinavir, as evidenced by a 9% reduction in the indinavir AUC8 after 3 weeks of dosing with milk thistle, although the least squares mean trough level (C8) was significantly decreased by 25%. Milk thistle in commonly administered dosages should not interfere with indinavir therapy in patients infected with the human immunodeficiency virus.

Evaluation of Environmental Contamination and Estimated Radiation Doses for the Return to Residents’ Homes in Kawauchi Village, Fukushima Prefecture

PubMed Central

Taira, Yasuyuki; Hayashida, Naomi; Yamaguchi, Hitoshi; Yamashita, Shunichi; Endo, Yuukou; Takamura, Noboru

2012-01-01

To evaluate the environmental contamination and radiation exposure dose rates due to artificial radionuclides in Kawauchi Village, Fukushima Prefecture, the restricted area within a 30-km radius from the Fukushima Dai-ichi Nuclear Power Plant (FNPP), the concentrations of artificial radionuclides in soil samples, tree needles, and mushrooms were analyzed by gamma spectrometry. Nine months have passed since samples were collected on December 19 and 20, 2011, 9 months after the FNPP accident, and the prevalent dose-forming artificial radionuclides from all samples were 134Cs and 137Cs. The estimated external effective doses from soil samples were 0.42–7.2 µSv/h (3.7–63.0 mSv/y) within the 20-km radius from FNPP and 0.0011–0.38 µSv/h (0.010–3.3 mSv/y) within the 20–30 km radius from FNPP. The present study revealed that current levels are sufficiently decreasing in Kawauchi Village, especially in areas within the 20- to 30-km radius from FNPP. Thus, residents may return their homes with long-term follow-up of the environmental monitoring and countermeasures such as decontamination and restrictions of the intake of foods for reducing unnecessary exposure. The case of Kawauchi Village will be the first model for the return to residents’ homes after the FNPP accident. PMID:23049869

Efficacy of the nematode-trapping fungus Duddingtonia flagrans against three species of gastro-intestinal nematodes in laboratory faecal cultures from sheep and goats.

PubMed

Waghorn, T S; Leathwick, D M; Chen, L-Y; Skipp, R A

2003-12-30

The ability of the nematode-killing fungus Duddingtonia flagrans to reduce number of infective larvae of three species of gastro-intestinal parasitic nematodes developing in dung was investigated in both goats and sheep. Groups of lambs and kids (12-20 weeks old) were given mono-specific infections of Haemonchus contortus, Ostertagia (Teladorsagia) circumcincta or Trichostrongylus colubriformis. Following patency of the infections (t1) faecal samples were collected for determination of faecal nematode egg count (FEC) and culture of parasite larvae. Groups of animals were then dosed on 2 consecutive days with one of the two dose rates of the fungus (250,000 or 500,000 spores/kg liveweight). One (t2) and 5 (t3) days after the second dose of fungus samples were again collected for FEC and culture. The number of larvae recovered from the faecal cultures at t1 and t3 were used as controls to assess the efficacy of the experimental treatment at t2. Average efficacy was 78% with group means ranging from 40 to 93%. Dose rate of fungus appeared to influence efficacy against O. circumcincta but not against H. contortus or T. colubriformis. Overall, there were no differences in the efficacy of the fungus against any of the parasite species or in either host animal. The results of this trial indicate the potential use of this fungus as a broad spectrum anti-parasite agent for use in both goats and sheep.

Determination of radioactivity levels and heavy metal concentrations in seawater, sediment and anchovy (Engraulis encrasicolus) from the Black Sea in Rize, Turkey.

PubMed

Baltas, Hasan; Kiris, Erkan; Sirin, Murat

2017-03-15

Seawater, sediment and fish (anchovy) samples consumed in the Rize province of the Eastern Black Sea region of Turkey were collected from five different stations. The radioactivity levels ( 226 Ra, 232 Th, 40 K and 137 Cs) were determined in all the samples using a high-purity germanium detector. While 226 Ra, 232 Th and 40 K radionuclides were detected in all samples, the radionuclide concentration of 137 Cs, except for the sediment samples (mean activity is 9±1.4Bqkg -1 ), was not detected for the seawater and fish samples. The total annual effective dose rates from the ingestion of these radionuclides for fish were calculated using the measured activity concentrations in radionuclides and their ingested dose conversion factor. Also, the concentrations of some heavy metals in all the samples were determined. The activity and heavy metal concentration values that were determined for the seawater, sediment and fish samples were compared among the locations themselves and with literature values. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pharmacokinetics of fexofenadine: evaluation of a microdose and assessment of absolute oral bioavailability.

PubMed

Lappin, Graham; Shishikura, Yoko; Jochemsen, Roeline; Weaver, Richard John; Gesson, Charlotte; Houston, Brian; Oosterhuis, Berend; Bjerrum, Ole J; Rowland, Malcolm; Garner, Colin

2010-05-12

A human pharmacokinetic study was performed to assess the ability of a microdose to predict the pharmacokinetics of a therapeutic dose of fexofenadine and to determine its absolute oral bioavailability. Fexofenadine was chosen to represent an unmetabolized transporter substrate (P-gP and OATP). Fexofenadine was administered to 6 healthy male volunteers in a three way cross-over design. A microdose (100microg) of (14)C-drug was administered orally (period 1) and intravenously by 30min infusion (period 2). In period 3 an intravenous tracer dose (100microg) of (14)C-drug was administered simultaneously with an oral unlabelled therapeutic dose (120mg). Plasma was collected from all 3 periods and analysed for both total (14)C content and parent drug by accelerator mass spectrometry (AMS). For period 3, plasma samples were also analysed using HPLC-fluorescence to determine total drug concentration. Urine was collected and analysed for total (14)C. Good concordance between the microdose and therapeutic dose pharmacokinetics was observed. Microdose: CL 13L/h, CL(R) 4.1L/h, V(ss) 54L, t(1/2) 16h; therapeutic dose: CL 16L/h, CL(R) 6.2L/h, V(ss) 64L, t(1/2) 12h. The absolute oral bioavailability of fexofenadine was 0.35 (microdose 0.41, therapeutic dose 0.30). Despite a 1200-fold difference in dose of fexofenadine, the microdose predicted well the pharmacokinetic parameters following a therapeutic dose for this transporter dependent compound.

Plasma pharmacokinetics and milk residues of flunixin and 5-hydroxy flunixin following different routes of administration in dairy cattle.

PubMed

Kissell, L W; Smith, G W; Leavens, T L; Baynes, R E; Wu, H; Riviere, J E

2012-12-01

The objective of this study was to determine if the plasma pharmacokinetics and milk elimination of flunixin (FLU) and 5-hydroxy flunixin (5OH) differ following intramuscular and subcutaneous injection of FLU compared with intravenous injection. Twelve lactating Holstein cows were used in a randomized crossover design study. Cows were organized into 2 groups based on milk production (<20 or >30 kg of milk/d). All cattle were administered 2 doses of 1.1mg of FLU/kg at 12-h intervals by intravenous, intramuscular, and subcutaneous injections. The washout period between routes of administration was 7d. Blood samples were collected from the jugular vein before FLU administration and at various time points up to 36 h after the first dose of FLU. Composite milk samples were collected before FLU administration and twice daily for 5d after the first dose of FLU. Samples were analyzed by ultra-HPLC with mass spectrometric detection. For FLU plasma samples, a difference in terminal half-life was observed among routes of administration. Harmonic mean terminal half-lives for FLU were 3.42, 4.48, and 5.39 h for intravenous, intramuscular, and subcutaneous injection, respectively. The mean bioavailability following intramuscular and subcutaneous dosing was 84.5 and 104.2%, respectively. The decrease in 5OH milk concentration versus time after last dose was analyzed with the nonlinear mixed effects modeling approach and indicated that both the route of administration and rate of milk production were significant covariates. The number of milk samples greater than the tolerance limit for each route of administration was also compared at each time point for statistical significance. Forty-eight hours after the first dose, 5OH milk concentrations were undetectable in all intravenously injected cows; however, one intramuscularly injected and one subcutaneously injected cow had measurable concentrations. These cows had 5OH concentrations above the tolerance limit at the 36-h withdrawal time. The high number of FLU residues identified in cull dairy cows by the United States Department of Agriculture Food Safety Inspection Service is likely related to administration of the drug by an unapproved route. Cattle that received FLU by the approved (intravenous) route consistently eliminated the drug before the approved withdrawal times; however, residues can persist beyond these approved times following intramuscular or subcutaneous administration. Cows producing less than 20 kg of milk/d had altered FLU milk clearance, which may also contribute to violative FLU residues. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Vitamin concentrations in human milk vary with time within feed, circadian rhythm, and single-dose supplementation

USDA-ARS?s Scientific Manuscript database

Importance: Human milk is the subject of many nutrition studies but methods for representative sample collection are not established. Our recently improved, validated methods for analyzing micronutrients in human milk now enable systematic study of factors affecting their concentration. Objective...

Off-Site Radiation Exposure Review Project: Phase 2 soils program

DOE Office of Scientific and Technical Information (OSTI.GOV)

McArthur, R.D.; Miller, F.L. Jr.

1989-12-01

To help estimate population doses of radiation from fallout originating at the Nevada Test Site, soil samples were collected throughout the western United States. Each sample was prepared by drying and ball-milling, then analyzed by gamma-spectrometry to determine the amount of {sup 137}Cs it contained. Most samples were also analyzed by chemical separation and alpha-spectrometry to determine {sup 239 + 240}Pu and by isotope mass spectroscopy to determine the ratios of {sup 240}Pu to {sup 239}Pu and {sup 241}Pu to {sup 239}Pu. The total inventories of cesium and plutonium at 171 sites were computed from the results. This report describesmore » the sample collection, processing, and analysis, presents the analytical results, and assesses the quality of the data. 10 refs., 9 figs., 12 tabs.« less

A group sequential adaptive treatment assignment design for proof of concept and dose selection in headache trials.

PubMed

Hall, David B; Meier, Ulrich; Diener, Hans-Cristoph

2005-06-01

The trial objective was to test whether a new mechanism of action would effectively treat migraine headaches and to select a dose range for further investigation. The motivation for a group sequential, adaptive, placebo-controlled trial design was (1) limited information about where across the range of seven doses to focus attention, (2) a need to limit sample size for a complicated inpatient treatment and (3) a desire to reduce exposure of patients to ineffective treatment. A design based on group sequential and up and down designs was developed and operational characteristics were explored by trial simulation. The primary outcome was headache response at 2 h after treatment. Groups of four treated and two placebo patients were assigned to one dose. Adaptive dose selection was based on response rates of 60% seen with other migraine treatments. If more than 60% of treated patients responded, then the next dose was the next lower dose; otherwise, the dose was increased. A stopping rule of at least five groups at the target dose and at least four groups at that dose with more than 60% response was developed to ensure that a selected dose would be statistically significantly (p=0.05) superior to placebo. Simulations indicated good characteristics in terms of control of type 1 error, sufficient power, modest expected sample size and modest bias in estimation. The trial design is attractive for phase 2 clinical trials when response is acute and simple, ideally binary, placebo comparator is required, and patient accrual is relatively slow allowing for the collection and processing of results as a basis for the adaptive assignment of patients to dose groups. The acute migraine trial based on this design was successful in both proof of concept and dose range selection.

Analysis of Potassium in Bricks--Determining the Dose Rate from {sup 40}K for Thermoluminescence Dating

DOE Office of Scientific and Technical Information (OSTI.GOV)

Musilek, Ladislav; Polach, Tomas; Trojek, Tomas

2008-08-07

Thermoluminescence (TL) dating is based on accumulating the natural radiation dose in the material of a dated artefact (brick, pottery, etc.), and comparing the dose accumulated during the lifetime of the object with the dose rate within the sample collected for TL measurement. Determining the dose rate from natural radionuclides in materials is one of the most important and most difficult parts of the technique. The most important radionuclides present are usually nuclides of the uranium and thorium decay series and {sup 40}K. An analysis of the total potassium concentration enables us to determine the {sup 40}K content effectively, andmore » from this it is possible to calculate the dose rate originating from this radiation source. X-ray fluorescence (XRF) analysis can be used to determine the potassium concentration in bricks rapidly and efficiently. The procedure for analysing potassium, examples of results of dose rate calculation and possible sources of error are described here.« less

Northern Marshall Islands radiological survey: sampling and analysis summary

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robison, W.L.; Conrado, C.L.; Eagle, R.J.

1981-07-23

A radiological survey was conducted in the Northern Marshall Islands to document reamining external gamma exposures from nuclear tests conducted at Enewetak and Bikini Atolls. An additional program was later included to obtain terrestrial and marine samples for radiological dose assessment for current or potential atoll inhabitants. This report is the first of a series summarizing the results from the terrestrial and marine surveys. The sample collection and processing procedures and the general survey methodology are discussed; a summary of the collected samples and radionuclide analyses is presented. Over 5400 samples were collected from the 12 atolls and 2 islandsmore » and prepared for analysis including 3093 soil, 961 vegetation, 153 animal, 965 fish composite samples (average of 30 fish per sample), 101 clam, 50 lagoon water, 15 cistern water, 17 groundwater, and 85 lagoon sediment samples. A complete breakdown by sample type, atoll, and island is given here. The total number of analyses by radionuclide are 8840 for /sup 241/Am, 6569 for /sup 137/Cs, 4535 for /sup 239 +240/Pu, 4431 for /sup 90/Sr, 1146 for /sup 238/Pu, 269 for /sup 241/Pu, and 114 each for /sup 239/Pu and /sup 240/Pu. A complete breakdown by sample category, atoll or island, and radionuclide is also included.« less

Riboflavin and ultraviolet light reduce the infectivity of Babesia microti in whole blood.

PubMed

Tonnetti, Laura; Thorp, Aaron M; Reddy, Heather L; Keil, Shawn D; Goodrich, Raymond P; Leiby, David A

2013-04-01

Babesia microti is the parasite most frequently transmitted by blood transfusion in the United States. Previous work demonstrated the efficacy of riboflavin (RB) and ultraviolet (UV) light to inactivate B.microti in apheresis plasma and platelet units. In this study we investigated the effectiveness of RB and UV light to reduce the levels of B.microti in whole blood (WB). WB units were spiked with B. microti-infected hamster blood. Spearman-Karber methods were used to calculate infectivity of each sample in terms of hamster infectious dose 50% (HID50 ) value. After RB addition, the units were illuminated with 80 J/mLRBC UV light. Two samples were collected: one before illumination and one after illumination. The samples were serially diluted and dilutions injected into a group of five naive hamsters. Four weeks postinoculation (PI), blood was collected from the animals and evaluated by microscopic observation. One pilot study showed a good dose response in the animals and demonstrated that sample infectivity could be calculated in terms of an HID50 . Three additional replicates were performed in the same manner as the pilot study, but with fewer dilutions. Infectivity values were consistent between the experiments and were used to calculate log reduction. The posttreatment reduction of B. microti for all the experiments was more than 5 log. The data collected indicate that use of RB and UV is able to decrease the parasite load in WB units thus reducing the risk of transfusion-transmitted B. microti from blood components containing B. microti-infected RBCs. © 2012 American Association of Blood Banks.

Double strand break induction and kinetics indicate preserved hypersensitivity in keratinocytes to subtherapeutic doses for 7weeks of radiotherapy.

PubMed

Qvarnström, Fredrik; Simonsson, Martin; Nyman, Jan; Hermansson, Ingegerd; Book, Majlis; Johansson, Karl-Axel; Turesson, Ingela

2017-01-01

Previously we reported that hyper-radiosensitivity (HRS) was evidenced by quantifying DNA double strand break (DSB) foci in epidermis biopsies collected after delivering radiotherapeutic one and five dose fractions. The aim of this study was to determine whether HRS was preserved throughout a 7-week radiotherapy treatment, and also to examine the rate of foci decline and foci persistence between dose fractions. 42 patients with prostate cancer received 7-week fractionated radiotherapy treatment (RT) with daily dose fractions of 0.05-1.10Gy to the skin. Before RT, and at several times throughout treatment, skin biopsies (n=452) were collected at 30min, and 2, 3, 24, and 72h after dose fractions. DSB-foci markers, γH2AX and 53BP1, were labelled in epidermal keratinocytes with immunofluorescence and immunohistochemical staining. Foci were counted both with digital image analysis and manually. HRS in keratinocytes was evidenced by the dose-response relationships of DSB foci, observed throughout the treatment course, independent of sampling time and quantification method. Foci observed at 24h after dose fractions indicated considerable DSB persistence. Accordingly, foci significantly accumulated after 5 consecutive dose fractions. For doses below 0.3Gy, persistent foci could be observed even at 72h after damage induction. A comparison of γH2AX and 53BP1 quantifications in double-stained biopsies showed similar HRS dose-response relationships. These results represented the first evidence of preserved HRS, assessed by γH2AX- and 53BP1-labelled DSB foci, throughout a 7-week treatment course with daily repeated subtherapeutic dose fractions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A survey of cyclic and linear siloxanes in indoor dust and their implications for human exposures in twelve countries.

PubMed

Tran, Tri Manh; Abualnaja, Khalid O; Asimakopoulos, Alexandros G; Covaci, Adrian; Gevao, Bondi; Johnson-Restrepo, Boris; Kumosani, Taha A; Malarvannan, Govindan; Minh, Tu Binh; Moon, Hyo-Bang; Nakata, Haruhiko; Sinha, Ravindra K; Kannan, Kurunthachalam

2015-05-01

Siloxanes are used widely in a variety of consumer products, including cosmetics, personal care products, medical and electrical devices, cookware, and building materials. Nevertheless, little is known on the occurrence of siloxanes in indoor dust. In this survey, five cyclic (D3-D7) and 11 linear (L4-L14) siloxanes were determined in 310 indoor dust samples collected from 12 countries. Dust samples collected from Greece contained the highest concentrations of total cyclic siloxanes (TCSi), ranging from 118 to 25,100ng/g (median: 1380), and total linear siloxanes (TLSi), ranging from 129 to 4990ng/g (median: 772). The median total siloxane (TSi) concentrations in dust samples from 12 countries were in the following decreasing order: Greece (2970ng/g), Kuwait (2400), South Korea (1810), Japan (1500), the USA (1220), China (1070), Romania (538), Colombia (230), Vietnam (206), Saudi Arabia (132), India (116), and Pakistan (68.3). TLSi concentrations as high as 42,800ng/g (Kuwait) and TCSi concentrations as high as 25,000ng/g (Greece) were found in indoor dust samples. Among the 16 siloxanes determined, decamethylcyclopentasiloxane (D5) was found at the highest concentration in dust samples from all countries, except for Japan and South Korea, with a predominance of L11; Kuwait, with L10; and Pakistan and Romania, with L12. The composition profiles of 16 siloxanes in dust samples varied by country. TCSi accounted for a major proportion of TSi concentrations in dust collected from Colombia (90%), India (80%) and Saudi Arabia (70%), whereas TLSi predominated in samples collected from Japan (89%), Kuwait (85%), and South Korea (78%). Based on the measured median TSi concentrations in indoor dust, we estimated human exposure doses through indoor dust ingestion for various age groups. The exposure doses ranged from 0.27 to 11.9ng/kg-bw/d for toddlers and 0.06 to 2.48ng/kg-bw/d for adults. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Single-Dose, Open-Label Study of the Pharmacokinetics, Safety, and Tolerability of Lisdexamfetamine Dimesylate in Individuals With Normal and Impaired Renal Function

PubMed Central

Ermer, James; Corcoran, Mary; Lasseter, Kenneth; Marbury, Thomas; Yan, Brian

2016-01-01

Background: Lisdexamfetamine (LDX) and d-amphetamine pharmacokinetics were assessed in individuals with normal and impaired renal function after a single LDX dose; LDX and d-amphetamine dialyzability was also examined. Methods: Adults (N = 40; 8/group) were enrolled in 1 of 5 renal function groups [normal function, mild impairment, moderate impairment, severe impairment/end-stage renal disease (ESRD) not requiring hemodialysis, and ESRD requiring hemodialysis] as estimated by glomerular filtration rate (GFR). Participants with normal and mild to severe renal impairment received 30 mg LDX; blood samples were collected predose and serially for 96 hours. Participants with ESRD requiring hemodialysis received 30 mg LDX predialysis and postdialysis separated by a washout period of 7–14 days. Predialysis blood samples were collected predose, serially for 72 hours, and from the dialyzer during hemodialysis; postdialysis blood samples were collected predose and serially for 48 hours. Pharmacokinetic end points included maximum plasma concentration (Cmax) and area under the plasma concentration versus time curve from time 0 to infinity (AUC0–∞) or to last assessment (AUClast). Results: Mean LDX Cmax, AUClast, and AUC0–∞ in participants with mild to severe renal impairment did not differ from those with normal renal function; participants with ESRD had higher mean Cmax and AUClast than those with normal renal function. d-amphetamine exposure (AUClast and AUC0–∞) increased and Cmax decreased as renal impairment increased. Almost no LDX and little d-amphetamine were recovered in the dialyzate. Conclusions: There seems to be prolonged d-amphetamine exposure after 30 mg LDX as renal impairment increases. In individuals with severe renal impairment (GFR: 15 ≤ 30 mL·min−1·1.73 m−2), the maximum LDX dose is 50 mg/d; in patients with ESRD (GFR: <15 mL·min−1·1.73 m−2), the maximum LDX dose is 30 mg/d. Neither LDX nor d-amphetamine is dialyzable. PMID:26926668

Benchmark studies of induced radioactivity produced in LHC materials, Part II: Remanent dose rates.

PubMed

Brugger, M; Khater, H; Mayer, S; Prinz, A; Roesler, S; Ulrici, L; Vincke, H

2005-01-01

A new method to estimate remanent dose rates, to be used with the Monte Carlo code FLUKA, was benchmarked against measurements from an experiment that was performed at the CERN-EU high-energy reference field facility. An extensive collection of samples of different materials were placed downstream of, and laterally to, a copper target, intercepting a positively charged mixed hadron beam with a momentum of 120 GeV c(-1). Emphasis was put on the reduction of uncertainties by taking measures such as careful monitoring of the irradiation parameters, using different instruments to measure dose rates, adopting detailed elemental analyses of the irradiated materials and making detailed simulations of the irradiation experiment. The measured and calculated dose rates are in good agreement.

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

PubMed

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.

Determination of radon and radium concentrations in drinking water samples around the city of Kutahya.

PubMed

Sahin, Latife; Cetinkaya, Hakan; Murat Saç, Müslim; Içhedef, Mutlu

2013-08-01

The concentration of radium and radon has been determined in drinking water samples collected from various locations of Kutahya city, Turkey. The water samples are taken from public water sources and tap water, with the collector chamber method used to measure the radon and radium concentration. The radon concentration ranges between 0.1 and 48.6±1.7 Bq l(-1), while the radium concentration varies from a minimum detectable activity of <0.02-0.7±0.2 Bq l(-1) in Kutahya city. In addition to the radon and radium levels, parameters such as pH, conductivity and temperature of the water, humidity, pressure, elevation and the coordinates of the sampling points have also been measured and recorded. The annual effective dose from radon and radium due to typical water usage has been calculated. The resulting contribution to the annual effective dose due to radon ingestion varies between 0.3 and 124.2 μSv y(-1); the contribution to the annual effective dose due to radium ingestion varies between 0 and 143.3 μSv y(-1); the dose contribution to the stomach due to radon ingestion varies between 0.03 and 14.9 μSv y(-1). The dose contribution due to radon inhalation ranges between 0.3 and 122.5 μSv y(-1), assuming a typical transfer of radon in water to the air. For the overwhelming majority of the Kutahya population, it is determined that the average radiation exposure from drinking water is less than 73.6 µSv y(-1).

Population Pharmacokinetic Model-Based Evaluation of Standard Dosing Regimens for Cefuroxime Used in Coronary Artery Bypass Graft Surgery with Cardiopulmonary Bypass.

PubMed

Alqahtani, Saeed A; Alsultan, Abdullah S; Alqattan, Hussain M; Eldemerdash, Ahmed; Albacker, Turki B

2018-04-01

The purpose of this study was to investigate the population pharmacokinetics (PK) of cefuroxime in patients undergoing coronary artery bypass graft (CABG) surgery. In this observational pharmacokinetic study, multiple blood samples were collected over a 48-h interval of intravenous cefuroxime administration. The samples were analyzed by using a validated high-performance liquid chromatography (HPLC) method. Population pharmacokinetic models were developed using Monolix (version 4.4) software. Pharmacokinetic-pharmacodynamic (PD) simulations were performed to explore the ability of different dosage regimens to achieve the pharmacodynamic targets. A total of 468 blood samples from 78 patients were analyzed. The PK for cefuroxime were best described by a two-compartment model with between-subject variability on clearance, the volume of distribution of the central compartment, and the volume of distribution of the peripheral compartment. The clearance of cefuroxime was related to creatinine clearance (CL CR ). Dosing simulations showed that standard dosing regimens of 1.5 g could achieve the PK-PD target of the percentage of the time that the free concentration is maintained above the MIC during a dosing interval ( fT MIC ) of 65% for an MIC of 8 mg/liter in patients with a CL CR of 30, 60, or 90 ml/min, whereas this dosing regimen failed to achieve the PK-PD target in patients with a CL CR of ≥125 ml/min. In conclusion, administration of standard doses of 1.5 g three times daily provided adequate antibiotic prophylaxis in patients undergoing CABG surgery. Lower doses failed to achieve the PK-PD target. Patients with high CL CR values required either higher doses or shorter intervals of cefuroxime dosing. On the other hand, lower doses (1 g three times daily) produced adequate target attainment for patients with low CL CR values (≤30 ml/min). Copyright © 2018 American Society for Microbiology.

Pharmacokinetics after oral and intravenous administration of a single dose of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis).

PubMed

Souza, Marcy J; Sanchez-Migallon Guzman, David; Paul-Murphy, Joanne R; Cox, Sherry K

2012-08-01

To determine pharmacokinetics after IV and oral administration of a single dose of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). 9 healthy adult Hispaniolan Amazon parrots (3 males, 5 females, and 1 of unknown sex). Tramadol (5 mg/kg, IV) was administered to the parrots. Blood samples were collected from -5 to 720 minutes after administration. After a 3-week washout period, tramadol (10 and 30 mg/kg) was orally administered to parrots. Blood samples were collected from -5 to 1,440 minutes after administration. Three formulations of oral suspension (crushed tablets in a commercially available suspension agent, crushed tablets in sterile water, and chemical-grade powder in sterile water) were evaluated. Plasma concentrations of tramadol and its major metabolites were measured via high-performance liquid chromatography. Mean plasma tramadol concentrations were > 100 ng/mL for approximately 2 to 4 hours after IV administration of tramadol. Plasma concentrations after oral administration of tramadol at a dose of 10 mg/kg were < 40 ng/mL for the entire time period, but oral administration at a dose of 30 mg/kg resulted in mean plasma concentrations > 100 ng/mL for approximately 6 hours after administration. Oral administration of the suspension consisting of the chemical-grade powder resulted in higher plasma tramadol concentrations than concentrations obtained after oral administration of the other 2 formulations; however, concentrations differed significantly only at 120 and 240 minutes after administration. Oral administration of tramadol at a dose of 30 mg/kg resulted in plasma concentrations (> 100 ng/mL) that have been associated with analgesia in Hispaniolan Amazon parrots.

Chronic consumption of a low calorie, high polyphenol cranberry beverage attenuates inflammation and improves glucoregulation and HDL cholesterol in healthy overweight humans: a randomized controlled trial.

PubMed

Chew, Boon; Mathison, Bridget; Kimble, Lindsey; McKay, Diane; Kaspar, Kerrie; Khoo, Christina; Chen, C-Y Oliver; Blumberg, Jeffrey

2018-02-23

We studied the health benefits of low calorie cranberry beverage consumption on glucoregulation, oxidative damage, inflammation, and lipid metabolism in overweight but otherwise healthy humans. 78 overweight or obese men and women (30-70 years; BMI 27-35 kg/m 2 ) with abdominal adiposity (waist: hip > 0.8 for women and > 0.9 for men; waist: height ≥ 0.5) consumed 450 mL placebo or low calorie, high polyphenol cranberry extract beverage (CEB) daily for 8 week in a randomized, double-blind, placebo-controlled, parallel design trial. Blood and urine samples were collected after overnight fast at baseline and after 8 weeks of daily beverage consumption. Blood and urine samples were also collected during 3 oral glucose tolerance test (OGTT) challenges: (1) pre-intervention without the test beverages, (2) following a single dose of placebo or CEB at baseline (week 0), and (3) following a single dose of placebo or CEB at 8 week. Compared to placebo, a single CEB dose at baseline lowered endothelin-1 and elevated nitric oxide and the reduced:oxidized glutathione ratio (P < 0.05). Interferon-γ was elevated (P < 0.05) after a single CEB dose at baseline; however, after 8 week of CEB intervention, fasting C-reactive protein was lower (P < 0.05). CEB consumption for 8 week also reduced serum insulin and increased HDL cholesterol compared to placebo (P < 0.05). An acute dose of low calorie, high polyphenol cranberry beverage improved antioxidant status, while 8 week daily consumption reduced cardiovascular disease risk factors by improving glucoregulation, downregulating inflammatory biomarkers, and increasing HDL cholesterol.

Range of therapeutic prothipendyl and prothipendyl sulfoxide concentrations in clinical blood samples.

PubMed

Krämer, Michael; Heese, Peter; Banger, Markus; Madea, Burkhard; Hess, Cornelius

2018-06-01

Due to a lack of reference blood concentrations in the literature, the forensic evaluation of prothipendyl findings in blood samples is difficult. Interpretations with regard to the assessment of blood concentrations as well as an estimation of the ingested prothipendyl amounts were often vague. To describe a concentration range in clinical samples, prothipendyl and prothipendyl sulfoxide concentrations were determined in serum samples of 50 psychiatric patients receiving 40 mg, 80 mg, or 160 mg doses of prothipendyl. The analyses of prothipendyl and prothipendyl sulfoxide were carried out using validated methods of high performance liquid chromatography coupled to triple quadrupole mass spectrometry (LC-QQQ-MS), respectively. 40 mg doses caused average prothipendyl serum concentrations of 18.0 ng/mL (1 hour after intake) and 7.9 ng/mL (10.5 hours after intake), while 80 mg doses caused averages of 42.6 ng/mL and 15.2 ng/mL at the mentioned times of sampling. Irrespective of the given dose, prothipendyl concentrations below 30 ng/mL were observed in 80% of the patient samples taken 1 hour after ingestion as well as in 90% of the samples collected 10.5 hours after administration. Serum concentrations of the Phase I metabolite prothipendyl sulfoxide averaged 4.3 ng/mL (1 hour after intake) and 3.6 ng/mL (10.5 hours after intake). Possible drug-drug interactions regarding absorption and metabolism of prothipendyl are discussed. Results of the herein presented study are useful for the interpretation of analytical prothipendyl findings in forensic toxicology. The utility of the described concentration range is demonstrated by discussing two death cases involving prothipendyl findings. Copyright © 2017 John Wiley & Sons, Ltd.

Concentration of 3H in ground water and estimation of committed effective dose due to ground water ingestion in some places in the Maharashtra state, India.

PubMed

Reddy, P J; Bhade, S P D; Kolekar, R V; Singh, Rajvir; Pradeepkumar, K S

2014-01-01

The measurement of tritium in environmental samples requires highest possible sensitivity. In the present study, the authors have optimised the counting window for the analysis of (3)H in environmental samples using the recently installed Ultra Low Level Quantulus 1220 Liquid Scintillation Counting at BARC to improve the detection limit of the system. The optimised counting window corresponding to the highest figure of merit of 883.8 was found to be 20-162 channels. Different brands of packaged drinking waters were analysed to select a blank that would define the system background. The minimum detectable activity (MDA) achieved was 1.5 Bq l(-1) for a total counting time of 500 min. The concentration of tritium in well and bore well water samples collected from the villages of Pune, villages located at 1.8 km from Tarapur Atomic Power Station, Kolhapur and Ratnagiri, was analysed. The activity concentration ranged from 0.55 to 3.66 Bq l(-1). The associated age-dependant dose from water ingestion in the study area was estimated. The effective committed dose recorded for different age classes is negligible compared with World Health Organization and US Environmental Protection Agency dose guidelines.

Thyroid Hormones and Thyroid Disease in Relation to Perchlorate Dose and Residence Near a Superfund Site

PubMed Central

Gold, Ellen B.; Blount, Benjamin C.; Rasor, Marianne O’Neill; Lee, Jennifer S.; Alwis, Udeni; Srivastav, Anup; Kim, Kyoungmi

2013-01-01

Background Perchlorate is a widely occurring contaminant, which can competitively inhibit iodide uptake and thus thyroid hormone production. The health effects of chronic low dose perchlorate exposure are largely unknown. Objectives In a community-based study, we compared thyroid function and disease in women with differing likelihoods of prior and current perchlorate exposure. Methods Residential blocks were randomly selected from areas: 1) with potential perchlorate exposure via drinking water; 2) with potential exposure to environmental contaminants; and 3) neighboring but without such exposures. Eligibility included having lived in the area for ≥6 months and aged 20–50 years during 1988–1996 (during documented drinking water well contamination). We interviewed 814 women and collected blood samples (assayed for thyroid stimulating hormone [TSH] and free thyroxine [fT4]) from 431 interviewed women. Daily urine samples were assayed for perchlorate and iodide for 178 premenopausal women with blood samples. We performed multivariable regression analyses comparing thyroid function and disease by residential area and by urinary perchlorate dose adjusted for urinary iodide levels. Results Residential location and current perchlorate dose were not associated with thyroid function or disease. Conclusions No persistent effect of perchlorate on thyroid function or disease was found several years after contaminated wells were capped. PMID:22968349

An overview on GSF activities at the Semipalatinsk Test Site, Kazakhstan.

PubMed

Semioshkina, Natalia; Voigt, Gabrielle

2006-02-01

The Semipalatinsk Test Site (STS) in Kazakhstan was one of the major sites used by the former USSR for testing nuclear weapons for more than 40 years. Since the early 1990s, agricultural activities have been re-established there by neighbouring collective and private farms. Therefore, it has become important to evaluate the radiological situation and the current and future risk to people living on and using the contaminated area. During the last eight years, GSF has participated in many international projects performed on the STS to evaluate the radiological situation. A large number of soil, vegetation and food samples has been collected and analysed. Internal dose is one of the main components of the total dose when deriving risk factors for a population living within the test site. Internal doses, based on food monitoring and whole body measurements, were calculated for adults and were in the range of 13-500 microSv/y due to radiocaesium and radiostrontium.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ugur Cevik; Nevzat Damla; Bahadir Koz

A radiological characterization of soil samples around the Afsin-Elbistan coal-fired thermal power plant in the Mediterranean region of Turkey was carried out. Moreover, activity concentrations and chemical analyses of coal samples used in this power plant and fly ash and slag samples originating from coal combustion were measured. For this purpose, coal, fly ash, slag, and soil samples were collected from this region. The analysis shows that the samples include relevant natural radionuclides such as {sup 226}Ra, {sup 232}Th and {sup 40}K. The mean activity concentrations of {sup 226}Ra, {sup 232}Th, and {sup 40}K were 167, 44, and 404 Bq.kg{supmore » -1}, respectively. Obtained values shows that the average radium equivalent activity, air-absorbed dose rate, annual effective dose, and external hazard index for all samples are 258 Bq.kg{sup -1}, 121 nGy.h{sup -1}, 148 {mu}Sv.y{sup -1}, and 0.7, respectively. The environmental effect of natural radionuclides caused by coal-fired power plants was considered to be negligible because the Ra{sub eq} values of the measured samples are generally lower than the limit value of 370 Bq.kg{sup -1}, equivalent to a gamma dose of 1.5 mSv.y{sup -1}. A comparison of the concentrations obtained in this work with other parts of the world indicates that the radioactivity content of the samples is not significantly different. 20 refs., 1 fig., 5 tabs.« less

PHARMACOKINETICS OF TRAMADOL HYDROCHLORIDE AND ITS METABOLITE O-DESMETHYLTRAMADOL FOLLOWING A SINGLE, ORALLY ADMINISTERED DOSE IN CALIFORNIA SEA LIONS (ZALOPHUS CALIFORNIANUS).

PubMed

Boonstra, Jennifer L; Barbosa, Lorraine; Van Bonn, William G; Johnson, Shawn P; Gulland, Frances M D; Cox, Sherry K; Martin-Jimenez, Tomas

2015-09-01

Tramadol is a synthetic, centrally acting, opiate-like analgesic that is structurally related to codeine and morphine. The objective of this study was to determine the pharmacokinetics of tramadol hydrochloride and its major active metabolite O-desmethyltramadol (M1) in the California sea lion (Zalophus californianus). A single dose of tramadol was administered orally in fish at 2 mg/kg to a total of 15 wild California sea lions admitted for rehabilitation. Twenty-four total blood samples were collected post drug administration at 10, 20, 30, and 45 min and at 1, 3, 5, 6, 8, 12, and 24 hr. Blood plasma was separated and stored at -80°C until analysis with high-performance liquid chromatography was performed to determine levels of tramadol and M1, the major active metabolite. The results indicate that the plasma levels of parent tramadol are low or negligible during the first 30-45 min and then reach the predicted mean maximum plasma concentration of 358 ng/ml at 1.52 hr. The M1 metabolite was not detectable in 21 of 24 plasma samples, below the level of quantification of 5 ng/ml in one sample, and detectable at 11 and 17 ng/ml in two of the samples. This study suggests that a 2 mg/kg dose would need to be administered every 6-8 hr to maintain concentrations of tramadol above the minimum human analgesic level for mild to moderate pain. Based on dosing simulations, a dose of 4 mg/kg q8 hr or q12 hr, on average, may represent an adequate compromise, but further studies are needed using a larger sample size. Pharmacodynamic studies are warranted to determine if tramadol provides analgesic effects in this species. The potential for tramadol toxicosis at any dose also has not been determined in this species.

Health risk assessment of inorganic arsenic intake of Ronphibun residents via duplicate diet study.

PubMed

Saipan, Piyawat; Ruangwises, Suthep

2009-06-01

To assess health risk from exposure to inorganic arsenic via duplicate portion sampling method in Ronphibun residents. A hundred and forty samples (140 subject-days) were collected from participants in Ronphibun sub-district. Inorganic arsenic in duplicate diet sample was determined by acid digestion and hydride generation-atomic absorption spectrometry. Deterministic risk assessment is referenced throughout the present paper using United States Environmental Protection Agency (U.S. EPA) guidelines. The average daily dose and lifetime average daily dose of inorganic arsenic via duplicate diet were 0.0021 mg/kg/d and 0.00084 mg/kg/d, respectively. The risk estimates in terms of hazard quotient was 6.98 and cancer risk was 1.26 x 10(-3). The results of deterministic risk characterization both hazard quotient and cancer risk from exposure inorganic arsenic in duplicate diets were greater than safety risk levels of hazard quotient (1) and cancer risk (1 x 10(-4)).

Usefulness of an injectable anaesthetic protocol for semen collection through urethral catheterisation in domestic cats.

PubMed

Pisu, Maria Carmela; Ponzio, Patrizia; Rovella, Chiara; Baravalle, Michela; Veronesi, Maria Cristina

2017-10-01

Objectives Although less often requested in comparison with dogs, the collection of semen in cats can be necessary for artificial insemination, for semen evaluation in tom cats used for breeding and for semen storage. Urethral catheterisation after pharmacological induction with medetomidine has proved to be useful for the collection of semen in domestic cats. However, most of the previously used protocols require the administration of high doses of medetomidine that can increase the risk of side effects, especially on the cardiovascular system. In routine clinical practice, one safe and useful injectable anaesthetic protocol for short-term clinical investigations or surgery in cats involves premedication with low intramuscular doses of dexmedetomidine with methadone, followed by intravenous propofol bolus injection. We aimed to assess the usefulness of this injectable anaesthetic protocol for semen collection, via urethral catheterisation, in domestic cats. Methods The study was performed on 38 purebred, adult cats, during the breeding season, and semen was collected via urethral catheterisation using an injectable anaesthesia protocol with methadone (0.2 mg/kg) and dexmedetomidine (5 µg/kg) premedication, followed by induction with propofol. Results The anaesthetic protocol used in the present study allowed the collection of large-volume semen samples, characterised by good parameters and without side effects. Conclusions and relevance The results from the present study suggest that the injectable anaesthetic protocol using methadone and dexmedetomidine premedication, followed by induction with propofol, could be suitable and safe for the collection of a good-quality semen sample, via urethral catheterisation, in domestic cats. It can therefore be used as an alternative to previous medetomidine-based sedation protocols.

Estimated collective effective dose to the population from nuclear medicine examinations in Slovenia

PubMed Central

Skrk, Damijan; Zontar, Dejan

2013-01-01

Background A national survey of patient exposure from nuclear medicine diagnostic procedures was performed by Slovenian Radiation Protection Administration in order to estimate their contribution to the collective effective dose to the population of Slovenia. Methods A set of 36 examinations with the highest contributions to the collective effective dose was identified. Data about frequencies and average administered activities of radioisotopes used for those examinations were collected from all nuclear medicine departments in Slovenia. A collective effective dose to the population and an effective dose per capita were estimated from the collected data using dose conversion factors. Results The total collective effective dose to the population from nuclear medicine diagnostic procedures in 2011 was estimated to 102 manSv, giving an effective dose per capita of 0.05 mSv. Conclusions The comparison of results of this study with studies performed in other countries indicates that the nuclear medicine providers in Slovenia are well aware of the importance of patient protection measures and of optimisation of procedures. PMID:24133396

Estimation of absorbed radiation dose rates in wild rodents inhabiting a site severely contaminated by the Fukushima Dai-ichi nuclear power plant accident.

PubMed

Kubota, Yoshihisa; Takahashi, Hiroyuki; Watanabe, Yoshito; Fuma, Shoichi; Kawaguchi, Isao; Aoki, Masanari; Kubota, Masahide; Furuhata, Yoshiaki; Shigemura, Yusaku; Yamada, Fumio; Ishikawa, Takahiro; Obara, Satoshi; Yoshida, Satoshi

2015-04-01

The dose rates of radiation absorbed by wild rodents inhabiting a site severely contaminated by the Fukushima Dai-ichi Nuclear Power Plant accident were estimated. The large Japanese field mouse (Apodemus speciosus), also called the wood mouse, was the major rodent species captured in the sampling area, although other species of rodents, such as small field mice (Apodemus argenteus) and Japanese grass voles (Microtus montebelli), were also collected. The external exposure of rodents calculated from the activity concentrations of radiocesium ((134)Cs and (137)Cs) in litter and soil samples using the ERICA (Environmental Risk from Ionizing Contaminants: Assessment and Management) tool under the assumption that radionuclides existed as the infinite plane isotropic source was almost the same as those measured directly with glass dosimeters embedded in rodent abdomens. Our findings suggest that the ERICA tool is useful for estimating external dose rates to small animals inhabiting forest floors; however, the estimated dose rates showed large standard deviations. This could be an indication of the inhomogeneous distribution of radionuclides in the sampled litter and soil. There was a 50-fold difference between minimum and maximum whole-body activity concentrations measured in rodents at the time of capture. The radionuclides retained in rodents after capture decreased exponentially over time. Regression equations indicated that the biological half-life of radiocesium after capture was 3.31 d. At the time of capture, the lowest activity concentration was measured in the lung and was approximately half of the highest concentration measured in the mixture of muscle and bone. The average internal absorbed dose rate was markedly smaller than the average external dose rate (<10% of the total absorbed dose rate). The average total absorbed dose rate to wild rodents inhabiting the sampling area was estimated to be approximately 52 μGy h(-1) (1.2 mGy d(-1)), even 3 years after the accident. This dose rate exceeds 0.1-1 mGy d(-1) derived consideration reference level for Reference rat proposed by the International Commission on Radiological Protection (ICRP). Copyright © 2015 Elsevier Ltd. All rights reserved.

Radionuclide transfer to wildlife at a 'Reference site' in the Chernobyl Exclusion Zone and resultant radiation exposures.

PubMed

Beresford, N A; Barnett, C L; Gashchak, S; Maksimenko, A; Guliaichenko, E; Wood, M D; Izquierdo, M

2018-02-27

This study addresses a significant data deficiency in the developing environmental protection framework of the International Commission on Radiological Protection, namely a lack of radionuclide transfer data for some of the Reference Animals and Plants (RAPs). It is also the first study that has sampled such a wide range of species (invertebrates, plants, amphibians and small mammals) from a single terrestrial site in the Chernobyl Exclusion Zone (CEZ). Samples were collected in 2014 from the 0.4 km 2 sampling site, located 5 km west of the Chernobyl Nuclear Power complex. We report radionuclide ( 137 Cs, 90 Sr, 241 Am and Pu-isotopes) and stable element concentrations in wildlife and soil samples and use these to determine whole organism-soil concentration ratios and absorbed dose rates. Increasingly, stable element analyses are used to provide transfer parameters for radiological models. The study described here found that for both Cs and Sr the transfer of the stable element tended to be lower than that of the radionuclide; this is the first time that this has been demonstrated for Sr, though it is in agreement with limited evidence previously reported for Cs. Studies reporting radiation effects on wildlife in the CEZ generally relate observations to ambient dose rates determined using handheld dose meters. For the first time, we demonstrate that ambient dose rates may underestimate the actual dose rate for some organisms by more than an order of magnitude. When reporting effects studies from the CEZ, it has previously been suggested that the area has comparatively low natural background dose rates. However, on the basis of data reported here, dose rates to wildlife from natural background radionuclides within the CEZ are similar to those in many areas of Europe. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Comparison of lacosamide concentrations in cerebrospinal fluid and serum in patients with epilepsy.

PubMed

May, Theodor W; Brandt, Christian; Helmer, Renate; Bien, Christian G; Cawello, Willi

2015-07-01

This study was carried out to estimate the exposure of the central nervous system (CNS) to the antiepileptic drug (AED) lacosamide, under steady state conditions, in patients with epilepsy who take oral lacosamide alongside up to three other AEDs. Twenty-seven serum and cerebral spinal fluid (CSF) samples were collected from 21 patients receiving lacosamide for the treatment of epilepsy (50-600 mg/day over two or three doses). This included 23 time-matched pairs of serum and CSF samples from 19 patients. The concentration of lacosamide in each sample was determined using high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Linear regression was used to characterize the relationship between the CSF-to-serum ratio of lacosamide concentration and the time since dosing, the daily lacosamide dose, or the daily dose normalized by volume of distribution (Vd , approximated to total body water), and between the drug concentrations in each compartment (CSF vs. serum). Concentrations of lacosamide in CSF (mean ± standard deviation [SD] 7.37 ± 3.73 μg/ml, range 1.24-14.95, n = 27) and serum (mean ± SD 8.16 ± 3.82 μg/ml, range 2.29-15.45, n = 27) samples showed a good correlation over the dose range investigated. The mean CSF-to-serum ratio of lacosamide concentrations was 0.897 ± 0.193 (range 0.492-1.254, n = 23 time-matched pairs) and was independent of lacosamide dose. Drug concentrations in the CSF are often used to indicate those in the brain interstitial fluid. In patients with epilepsy who follow a stable oral AED dosing regimen, lacosamide concentration in CSF is approximately 85% of that found in serum, suggesting that serum may be a valuable indicator of lacosamide concentration in the CNS. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Lack of effect of ezogabine/retigabine on the pharmacokinetics of digoxin in healthy individuals: results from a drug–drug interaction study

PubMed Central

Tompson, Debra J; Crean, Christopher S; Buraglio, Mauro; Arumugham, Thangam

2014-01-01

Introduction The potential for ezogabine/retigabine (EZG/RTG) and its N-acetyl metabolite (NAMR) to inhibit the transporter protein P-glycoprotein-(P-gp)-mediated digoxin transport was tested in vitro. EZG/RTG did not inhibit P-gp. However, NAMR inhibited P-gp in a concentration-dependent manner. Based on these in vitro results, NAMR had the potential to inhibit P-gp at therapeutic doses of EZG/RTG (600–1,200 mg/day). As digoxin has a narrow therapeutic index, inhibition of digoxin clearance may have an impact on its safety. Methods An open-label, single-center, two session, fixed-sequence study was conducted to assess the effect of co-administration of therapeutic doses of EZG/RTG on digoxin pharmacokinetics in healthy adults. In session 1, subjects received a single dose of digoxin 0.25 mg. In session 2, EZG/RTG was up-titrated over 6 weeks. Digoxin 0.25 mg was co-administered at EZG/RTG steady-state doses of 600, 900, and, based on tolerability, 1,050/1,200 mg/day. Blood samples were collected over 144 hours for determination of digoxin, EZG/RTG, and NAMR concentrations. Urine samples were collected over 48 hours for determination of digoxin concentrations. Results Of 30 subjects enrolled, 29 were included in the pharmacokinetic analysis. Compared with digoxin alone, co-administration with EZG/RTG led to small increases in the digoxin plasma area under the concentration–time curve (AUC)0–120 at doses of 600, 900, and 1,050/1,200 mg (geometric mean ratio 1.08, 90% confidence interval [CI] 1.01–1.15; 1.18, 90% CI 1.10–1.27; 1.13, 90% CI 1.05–1.21, respectively). Safety was consistent with previous repeat-dose studies of EZG/RTG in healthy subjects. Conclusion Co-administration of EZG/RTG across the therapeutic range resulted in small, non-dose-dependent and non-clinically relevant increases in digoxin systemic exposure, suggesting that digoxin dose adjustment is not necessary. PMID:25342921

Collection and processing of plant, animal and soil samples from Bikini, Enewetak and Rongelap Atolls

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stuart, M.L.

1995-09-01

The United States used the Marshall Islands for its nuclear weapons program testing site from 1946 to 1958. The BRAVO test was detonated at Bikini Atoll on March 1, 1954. Due to shifting wind conditions at the time of the nuclear detonation, many of the surrounding Atolls became contaminated with fallout (radionuclides carried by the wind currents). Lawrence Livermore National Laboratory`s (LLNL) Marshall Islands Project has been responsible for the collecting, processing, and analyzing of food crops, vegetation, soil, water, animals, and marine species to characterize the radionuclides in the environment, and to estimate dose at atolls that may havemore » been contaminated. Tropical agriculture experiments reducing the uptake of {sup 137}Cs have been conducted on Bikini Atoll. The Marshall Islands field team and laboratory processing team play an important role in the overall scheme of the Marshall Islands Dose Assessment and Radioecology Project. This report gives a general description of the Marshall Islands field sampling and laboratory processing procedures currently used by our staff.« less

The Northern Marshall Islands Radiological Survey: data and dose assessments.

PubMed

Robison, W L; Noshkin, V E; Conrado, C L; Eagle, R J; Brunk, J L; Jokela, T A; Mount, M E; Phillips, W A; Stoker, A C; Stuart, M L; Wong, K M

1997-07-01

Fallout from atmospheric nuclear tests, especially from those conducted at the Pacific Proving Grounds between 1946 and 1958, contaminated areas of the Northern Marshall Islands. A radiological survey at some Northern Marshall Islands was conducted from September through November 1978 to evaluate the extent of residual radioactive contamination. The atolls included in the Northern Marshall Islands Radiological Survey (NMIRS) were Likiep, Ailuk, Utirik, Wotho, Ujelang, Taka, Rongelap, Rongerik, Bikar, Ailinginae, and Mejit and Jemo Islands. The original test sites, Bikini and Enewetak Atolls, were also visited on the survey. An aerial survey was conducted to determine the external gamma exposure rate. Terrestrial (soil, food crops, animals, and native vegetation), cistern and well water samples, and marine (sediment, seawater, fish and clams) samples were collected to evaluate radionuclide concentrations in the atoll environment. Samples were processed and analyzed for 137Cs, 90Sr, 239+240Pu and 241Am. The dose from the ingestion pathway was calculated using the radionuclide concentration data and a diet model for local food, marine, and water consumption. The ingestion pathway contributes 70% to 90% of the estimated dose. Approximately 95% of the dose is from 137Cs. 90Sr is the second most significant radionuclide via ingestion. External gamma exposure from 137Cs accounts for about 10% to 30% of the dose. 239+240Pu and 241Am are the major contributors to dose via the inhalation pathway; however, inhalation accounts for only about 1% of the total estimated dose, based on surface soil levels and resuspension studies. All doses are computed for concentrations decay corrected to 1996. The maximum annual effective dose from manmade radionuclides at these atolls ranges from .02 mSv y(-1) to 2.1 mSv y(-1). The background dose in the Marshall Islands is estimated to be 2.4 mSv y(-1). The combined dose from both background and bomb related radionuclides ranges from slightly over 2.4 mSv y(-1) to 4.5 mSv y(-1). The 50-y integral dose ranges from 0.5 to 65 mSv.

Randomized clinical trial: pharmacokinetics and safety of multimatrix mesalamine for treatment of pediatric ulcerative colitis

PubMed Central

Cuffari, Carmen; Pierce, David; Korczowski, Bartosz; Fyderek, Krzysztof; Van Heusen, Heather; Hossack, Stuart; Wan, Hong; Edwards, Alena YZ; Martin, Patrick

2016-01-01

Background Limited data are available on mesalamine (5-aminosalicylic acid; 5-ASA) use in pediatric ulcerative colitis (UC). Aim To evaluate pharmacokinetic and safety profiles of 5-ASA and metabolite acetyl-5-ASA (Ac-5-ASA) after once-daily, oral administration of multimatrix mesalamine to children and adolescents with UC. Methods Participants (5–17 years of age; 18–82 kg, stratified by weight) with UC received multi-matrix mesalamine 30, 60, or 100 mg/kg/day once daily (to 4,800 mg/day) for 7 days. Blood samples were collected pre-dose on days 5 and 6. On days 7 and 8, blood and urine samples were collected and safety was evaluated. 5-ASA and Ac-5-ASA plasma and urine concentrations were analyzed by non-compartmental methods and used to develop a population pharmacokinetic model. Results Fifty-two subjects (21 [30 mg/kg]; 22 [60 mg/kg]; 9 [100 mg/kg]) were randomized. On day 7, systemic exposures of 5-ASA and Ac-5-ASA exhibited a dose-proportional increase between 30 and 60 mg/kg/day cohorts. For 30, 60, and 100 mg/kg/day doses, mean percentages of 5-ASA absorbed were 29.4%, 27.0%, and 22.1%, respectively. Simulated steady-state exposures and variabilities for 5-ASA and Ac-5-ASA (coefficient of variation approximately 50% and 40%–45%, respectively) were similar to those observed previously in adults at comparable doses. Treatment-emergent adverse events were reported by ten subjects. Events were similar among different doses and age groups with no new safety signals identified. Conclusion Children and adolescents with UC receiving multimatrix mesalamine demonstrated 5-ASA and Ac-5-ASA pharmacokinetic profiles similar to historical adult data. Multimatrix mesalamine was well tolerated across all dose and age groups. ClinicalTrials.gov Identifier: NCT01130844. PMID:26893546

Pharmacokinetics of the cyclosporine-ketoconazole interaction in dogs.

PubMed

D'mello, A; Venkataramanan, R; Satake, M; Todo, S; Takaya, S; Ptachcinski, R J; Burckart, G J; Starzl, T E

1989-06-01

Numerous clinical reports have documented an increase in trough blood concentrations of cyclosporine in transplant recipients treated concomitantly with ketoconazole. The objective of this study was to elucidate the mechanism(s) underlying the cyclosporine-ketoconazole interaction using a choledochoureterostomy dog model. Five male beagle dogs received a 4 mg/kg, i.v. bolus dose of cyclosporine either alone or on day seven of a 10-day, 13 mg/kg/day, oral dosing regimen of ketoconazole. Blood samples were collected prior to and at predetermined times for 60 hrs after the cyclosporine dose, while the bile/urine mixture was collected quantitatively for 96 hours after the cyclosporine dose. Ketoconazole decreased the systemic clearance of cyclosporine from 7.0 ml/min/kg to 2.5 ml/min/kg. The terminal disposition rate constant was also decreased significantly from 0.0794 to 0.0354 hrs-1. Ketoconazole caused no significant changes in cyclosporine steady state volume of distribution, or plasma unbound fraction. Ketoconazole did not significantly alter the excretion of cyclosporine and various cyclosporine metabolites in the bile/urine mixture. Inhibition of hepatic drug metabolizing enzymes appears to be the primary reason for the ketoconazole induced elevation in cyclosporine concentration.

PHARMACOKINETICS OF THE CYCLOSPORINE-KETOCONAZOLE INTERACTION IN DOGS

PubMed Central

D'mello, A.; Venkataramanan, R.; Satake, M.; Todo, S.; Takaya, S.; Ptachcinski, R. J.; Burckart, G.J.; Starzl, T.E.

2010-01-01

Numerous clinical reports have documented an increase in trough blood concentrations of cyclosporine in transplant recipients treated concomitantly with ketoconazole. The objective of this study was to elucidate the mechanism(s) underlying the cyclosporine-ketoconazole interaction using a choledochoureterostomy dog model. Five male beagle dogs received a 4 mg/kg, i.v. bolus dose of cyclosporine either alone or on day seven of a 10-day, 13 mg/kg/day, oral dosing regimen of ketoconazole. Blood samples were collected prior to and at predetermined times for 60 hrs after the cyclosporine dose, while the bile/urine mixture was collected quantitatively for 96 hours after the cyclosporine dose. Ketoconazole decreased the systemic clearance of cyclosporine from 7.0 ml/min/kg to 2.5 ml/min/kg. The terminal disposition rate constant was also decreased significantly from 0.0794 to 0.0354 hrs−1. Ketoconazole caused no significant changes in cyclosporine steady state volume of distribution, or plasma unbound fraction. Ketoconazole did not significantly alter the excretion of cyclosporine and various cyclosporine metabolites in the bile/urine mixture. Inhibition of hepatic drug metabolizing enzymes appears to be the primary reason for the ketoconazole induced elevation in cyclosporine concentration. PMID:2781141

PB-210 concentrations in cigarettes tobaccos and radiation doses to the smokers.

PubMed

Tahir, S N A; Alaamer, A S

2008-01-01

Cigarette smoking is a source of radiation exposure due to the concentrations of natural radionuclides in the tobacco leaves. From the health point of view, measurement of (210)Pb and (210)Po contents in cigarette tobacco is important to assess the radiological effects associated with the tobacco smoking for the smokers. In the present study, activity concentrations of (210)Pb, which is a (210)Po precursor in the (238)U-decay series, were measured in cigarette tobaccos. Samples of nine different commonly sold brands of cigarette tobaccos were analysed by employing a planar high purity germanium (HPGe) low background detector. Activity concentrations of (210)Pb were measured from its gamma peak at 47 keV. Mean activity concentration of (210)Pb was measured to be 13 +/- 4 Bq kg(-1) from all samples analysed. The annual committed effective dose for a smoker and the collective committed effective dose corresponding to annual cigarettes production were estimated to be 64 +/- 20 microSv and 0.6 x 10(2) man-Sv, respectively.

Bioavailability of suppository acetaminophen in healthy and hospitalized ill dogs.

PubMed

Sikina, E R; Bach, J F; Lin, Z; Gehring, R; KuKanich, B

2018-05-13

To determine the plasma pharmacokinetics of suppository acetaminophen (APAP) in healthy dogs and clinically ill dogs. This prospective study used six healthy client-owned and 20 clinically ill hospitalized dogs. The healthy dogs were randomized by coin flip to receive APAP orally or as a suppository in crossover study design. Blood samples were collected up to 10 hr after APAP dosing. The hospitalized dogs were administered APAP as a suppository, and blood collected at 2 and 6 hr after dosing. Plasma samples were analyzed by ultra-performance liquid chromatography with triple quadrupole mass spectrometry. In healthy dogs, oral APAP maximal concentration (C MAX =2.69 μg/ml) was reached quickly (T MAX =1.04 hr) and eliminated rapidly (T1/2 = 1.81 hr). Suppository APAP was rapidly, but variably absorbed (C MAX =0.52 μg/ml T MAX =0.67 hr) and eliminated (T 1/2  = 3.21 hr). The relative (to oral) fraction of the suppository dose absorbed was 30% (range <1%-67%). In hospitalized ill dogs, the suppository APAP mean plasma concentration at 2 hr and 6 hr was 1.317 μg/ml and 0.283 μg/ml. Nonlinear mixed-effects modeling did not identify significant covariates affecting variability and was similar to noncompartmental results. Results supported that oral and suppository acetaminophen in healthy and clinical dogs did not reach or sustain concentrations associated with efficacy. Further studies performed on different doses are needed. © 2018 John Wiley & Sons Ltd.

Measurement of the terrestrial and anthropogenic radionuclide concentrations in Bafra Kizilirmak delta (bird sanctuary) in Turkey.

PubMed

Mutuk, Halil; Gümüs, Hasan; Turhan, Seref

2014-01-01

In this study, the activity concentrations of terrestrial and anthropogenic radionuclides in the soil samples collected from Bafra Kızılırmak Delta were measured by using gamma spectrometry with an NaI(Tl) detector. The average values of activity concentrations of (238)U, (232)Th and (40)K were found to be 37.2±2.8, 33.7±3.1 and 413.0±59.8 Bq kg(-1), respectively. (137)Cs was also measured in some samples. It has a mean value of 13.8±1.0 Bq kg(-1). From the activity concentrations, the absorbed gamma dose rates in outdoor and the corresponding annual effective dose rates and external hazard index (Hex) were estimated.

Effect of γ irradiation on fungal load and aflatoxins reduction in red chillies

NASA Astrophysics Data System (ADS)

Iqbal, Shahzad Zafar; Bhatti, Ijaz Ahmad; Asi, Muhammad Rafique; Zuber, Mohammad; Shahid, Muhammad; Parveen, Ishrat

2013-01-01

Chillies are a very important cash crop of Pakistan. The effects of gamma irradiation on microbial load, aflatoxin B1 (AFB1) and total aflatoxins have been studied in chillies samples, collected from different districts of Punjab, Pakistan. Aflatoxins were analyzed using HPLC equipped with a fluorescence detector. The results revealed that among the Aspergillus species isolated, those belonging to section parasiticus were predominant. Gamma radiations of doses 2, 4 and 6 kGy were employed on fungi and chilli samples. The results have demonstrated that the dose of 6 kGy reduced the fungal load by 5 logs. Furthermore, 6 kGy reduced the level of AFB1 and total AFs in ground and whole chillies by 1-2 logs (α < 0.05).

GHSI EMERGENCY RADIONUCLIDE BIOASSAY LABORATORY NETWORK: SUMMARY OF A RECENT EXERCISE.

PubMed

Li, Chunsheng; Ansari, Armin; Bartizel, Christine; Battisti, Paolo; Franck, Didier; Gerstmann, Udo; Giardina, Isabella; Guichet, Claude; Hammond, Derek; Hartmann, Martina; Jones, Robert L; Kim, Eunjoo; Ko, Raymond; Morhard, Ryan; Quayle, Deborah; Sadi, Baki; Saunders, David; Paquet, Francois

2016-11-01

The Global Health Security Initiative (GHSI) established a laboratory network within the GHSI community to develop their collective surge capacity for radionuclide bioassay in response to a radiological or nuclear emergency. A recent exercise was conducted to test the participating laboratories for their capabilities in screening and in vitro assay of biological samples, performing internal dose assessment and providing advice on medical intervention, if necessary, using a urine sample spiked with a single radionuclide, 241 Am. The laboratories were required to submit their reports according to the exercise schedule and using pre-formatted templates. Generally, the participating laboratories were found to be capable with respect to rapidly screening samples for radionuclide contamination, measuring the radionuclide in the samples, assessing the intake and radiation dose, and providing advice on medical intervention. However, gaps in bioassay measurement and dose assessment have been identified. The network may take steps to ensure that procedures and practices within this network be harmonised and a follow-up exercise be organised on a larger scale, with potential participation of laboratories from the networks coordinated by the International Atomic Energy Agency and the World Health Organization. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Elimination of coliforms and Salmonella spp. in sheep meat by gamma irradiation treatment

PubMed Central

Henriques, Luciana Salles Vasconcelos; da Costa Henry, Fábio; Barbosa, João Batista; Ladeira, Silvania Alves; de Faria Pereira, Silvia Menezes; da Silva Antonio, Isabela Maria; Teixeira, Gina Nunes; Martins, Meire Lelis Leal; de Carvalho Vital, Helio; dos Prazeres Rodrigues, Dália; dos Reis, Eliane Moura Falavina

2013-01-01

This study aimed at evaluating the bacteriological effects of the treatment of sheep meat contaminated with total coliforms, coliforms at 45 °C and Salmonella spp. by using irradiation at doses of 3 kGy and 5 kGy. Thirty sheep meat samples were collected from animals located in Rio de Janeiro State, Brazil, and then grouped in three lots including 10 samples: non-irradiated (control); irradiated with 3 kGy; and irradiated with 5 kGy. Exposure to gamma radiation in a 137Cs source-driven irradiating facility was perfomed at the Nuclear Defense Section of the Brazilian Army Technological Center (CTEx) in Rio de Janeiro. The samples were kept under freezing temperature (−18 °C) until the analyses, which occurred in two and four months after irradiation. The results were interpreted by comparison with the standards of the current legislation and demonstrated that non-irradiated samples were outside the parameters established by law for all groups of bacteria studied. Gamma irradiation was effective in inactivating those microorganisms at both doses tested and the optimal dose was achieved at 3 kGy. The results have shown not only the need for sanitary conditions improvements in slaughter and processing of sheep meat but also the irradiation effectiveness to eliminate coliform bacteria and Salmonella spp. PMID:24688504

STUDY OF NATURAL RADIOACTIVITY (226Ra, 232Th AND 40K) IN SOIL SAMPLES FOR THE ASSESSMENT OF AVERAGE EFFECTIVE DOSE AND RADIATION HAZARDS.

PubMed

Bangotra, Pargin; Mehra, Rohit; Kaur, Kirandeep; Jakhu, Rajan

2016-10-01

The activity concentration of 226 Ra (radium), 232 Th (thorium) and 40 K (potassium) has been measured in the soil samples collected from Mansa and Muktsar districts of Punjab (India) using NaI (Tikl) gamma detector. The concentration of three radionuclides ( 226 Ra, 232 Th and 40 K) in the studied area has been varied from 18±4 to 46±5, 53±7 to 98±8 and 248±54 to 756±110 Bq kg -1 , respectively. Radium equivalent activities (Ra eq ) have been calculated in soil samples for the assessment of the radiation hazards arising due to the use of these soil samples. The absorbed dose rate of 226 Ra, 232 Th and 40 K in studied area has been varied from 8 to 21, 33 to 61 and 9 to 25 nGy h -1 , respectively. The corresponding indoor and outdoor annual effective dose in studied area was 0.38 and 0.09 mSv, respectively. The external and internal hazard has been also calculated for the assessment of radiation hazards in the studied area. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Prediction of delivery of organic aerosols onto air-liquid interface cells in vitro using an electrostatic precipitator.

PubMed

Yu, Zechen; Jang, Myoseon; Sabo-Attwood, Tara; Robinson, Sarah E; Jiang, Huanhuan

2017-08-01

To better characterize biological responses to atmospheric organic aerosols, the efficient delivery of aerosol to in vitro lung cells is necessary. In this study, chamber generated secondary organic aerosol (SOA) entered the commercialized exposure chamber (CULTEX® Radial Flow System Compact) where it interfaced with an electrostatic precipitator (ESP) (CULTEX® Electrical Deposition Device) and then deposited on a particle collection plate. This plate contained human lung cells (BEAS-2B) that were cultured on a membrane insert to produce an air-liquid interface (ALI). To augment in vitro assessment using the ESP exposure device, the particle dose was predicted for various sampling parameters such as particle size, ESP deposition voltage, and sampling flowrate. The dose model was evaluated against the experimental measured mass of collected airborne particles. The high flowrate used in this study increased aerosol dose but failed to achieve cell stability. For example, RNA in the ALI BEAS-2B cells in vitro was stable at 0.15L/minute but decayed at high flowrates. The ESP device and the resulting model were applied to in vitro studies (i.e., viability and IL-8 expression) of toluene SOA using ALI BEAS-2B cells with a flowrate of 0.15L/minute, and no cellular RNA decay occurred. Copyright © 2017. Published by Elsevier Ltd.

The pharmacokinetics of a single oral or rectal dose of concurrently administered isoniazid, rifampin, pyrazinamide, and ethambutol in Asian elephants (Elephas maximus).

PubMed

P Brock, A; Isaza, R; Egelund, E F; Hunter, R P; Peloquin, C A

2014-10-01

Tuberculosis, caused by Mycobacterium tuberculosis, is a disease of concern in captive Asian elephants (Elephas maximus). Treatment for tuberculosis in elephants utilizes multidrug protocols combining isoniazid, rifampin, pyrazinamide, and/or ethambutol. In this study, a single, coformulated dose of isoniazid 5 mg/kg, rifampin 10 mg/kg, pyrazinamide 30 mg/kg, and ethambutol 30 mg/kg was administered orally to six Asian elephants, and rectally to five elephants using a cross-over design. Blood samples were collected serially over 24 h. Pyrazinamide and ethambutol concentrations were determined using validated gas chromatography assays. Isoniazid and rifampin concentrations were determined using validated high-performance liquid chromatography assays. Rectal isoniazid produced an earlier Tmax compared with oral administration. Oral isoniazid resulted in a comparatively lower Cmax , but higher AUC values compared with rectal isoniazid. Oral rifampin and oral ethambutol were well absorbed while rectal rifampin was not. Oral pyrazinamide produced comparatively higher Cmax and AUC values compared with rectal pyrazinamide. Results of this study indicate that currently recommended therapeutic monitoring sample collection times for rectal isoniazid and oral rifampin do not provide an accurate assessment of exposure for these drugs. This study demonstrates notable individual variability, indicating that dosing of these medications requires individual monitoring and provides additional information to guide the clinician when treating elephants. © 2014 John Wiley & Sons Ltd.

The Daily Consumption of Cola Can Determine Hypocalcemia: A Case Report of Postsurgical Hypoparathyroidism-Related Hypocalcemia Refractory to Supplemental Therapy with High Doses of Oral Calcium.

PubMed

Guarnotta, Valentina; Riela, Serena; Massaro, Marina; Bonventre, Sebastiano; Inviati, Angela; Ciresi, Alessandro; Pizzolanti, Giuseppe; Benvenga, Salvatore; Giordano, Carla

2017-01-01

The consumption of soft drinks is a crucial factor in determining persistent hypocalcemia. The aim of the study is to evaluate the biochemical mechanisms inducing hypocalcemia in a female patient with usual high consumption of cola drink and persistent hypocalcemia, who failed to respond to high doses of calcium and calcitriol supplementation. At baseline and after pentagastrin injection, gastric secretion (Gs) and duodenal secretion (Ds) samples were collected and calcium and total phosphorus (P tot ) concentrations were evaluated. At the same time, blood calcium, P tot , sodium, potassium, chloride, magnesium concentrations, and vitamin D were sampled. After intake of cola (1 L) over 180 min, Gs and Ds and blood were collected and characterized in order to analyze the amount of calcium and P tot or sodium, potassium, magnesium, and chloride ions, respectively. A strong pH decrease was observed after cola intake with an increase in phosphorus concentration. Consequently, a decrease in calcium concentration in Gs and Ds was observed. A decrease in calcium concentration was also observed in blood. In conclusion, we confirm that in patients with postsurgical hypoparathyroidism, the intake of large amounts of cola containing high amounts of phosphoric acid reduces calcium absorption efficiency despite the high doses of calcium therapy.

Disposition of the anti-ulcer medications ranitidine, cimetidine, and omeprazole following administration of multiple doses to exercised Thoroughbred horses.

PubMed

Knych, H K; Stanley, S D; Arthur, R M; McKemie, D S

2017-01-01

The use of anti-ulcer medications, such as cimetidine, ranitidine, and omeprazole, is common in performance horses. The use of these drugs is regulated in performance horses, and as such a withdrawal time is necessary prior to competition to avoid a medication violation. To the authors' knowledge, there are no reports in the literature describing repeated oral administrations of these drugs in the horse to determine a regulatory threshold and related withdrawal time recommendations. Therefore, the objective of the current study was to describe the disposition and elimination pharmacokinetics of these anti-ulcer medications following oral administration to provide data upon which appropriate regulatory recommendations can be established. Nine exercised Thoroughbred horses were administered 20 mg/kg BID of cimetidine or 8 mg/kg BID of ranitidine, both for seven doses or 2.28 g of omeprazole SID for four doses. Blood samples were collected, serum drug concentrations were determined, and elimination pharmacokinetic parameters were calculated. The serum elimination half-life was 7.05 ± 1.02, 7.43 ± 0.851 and 3.94 ± 1.04 h for cimetidine, ranitidine, and omeprazole, respectively. Serum cimetidine and ranitidine concentrations were above the LOQ and omeprazole and omeprazole sulfide below the LOQ in all horses studied upon termination of sample collection. © 2016 John Wiley & Sons Ltd.

Radon in harvested rainwater at the household level, Palestine.

PubMed

Al-Khatib, Issam A; Al Zabadi, Hamzeh; Saffarini, Ghassan

2017-04-01

The main objective of this study was to assess Radon concentration in the harvested rainwater (HRW) at the household level in Yatta area, Palestine. HRW is mainly used for drinking as it is the major source of water for domestic uses due to water scarcity. Ninety HRW samples from the household cisterns were collected from six localities (a town and five villages) and Radon concentrations were measured. The samples were randomly collected from different households to represent the Yatta area. Fifteen samples were collected from each locality at the same day. RAD7 device was used for analysis and each sample was measured in duplicate. Radon concentrations ranged from 0.037 to 0.26 Bq/L with a mean ± standard deviation of 0.14 ± 0.06 Bq/L. The estimated annual effective radiation doses for babies, children and adults were all far below the maximum limit of 5 mSvy -1 set by the National Council on Radiation Protection and Measurements. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pharmacokinetics and tolerability of intravenous ibuprofen injection in healthy Chinese volunteers: a randomized, open-label, single- and multiple-dose study
.

PubMed

Zhou, Huili; Xu, Wei; Wu, Guolan; Wu, Lihua; Shentu, Jianzhong; Pan, Zhengfei; Hu, Shuai; Liu, Yang

2016-11-01

Recently a formulation of intravenous (IV) ibuprofen was developed in China for management of mild to moderate pain in patients who could not take oral medications or where intravenous administration was preferable. The aim of this study was to evaluate the pharmacokinetic properties and tolerability of single and multiple doses of ibuprofen injection in healthy Chinese volunteers. This open-label, single- and multiple-dose study was conducted in healthy Chinese volunteers. In the single-dose phase, subjects were randomized to receive a single dose of ibuprofen injection 0.2, 0.4, or 0.8 g administered as a 30-minute IV infusion with a 1-week washout between periods. Blood samples were collected at regular intervals from 0 to 12.5 hours after drug administration and were analyzed using a validated LC-MS/MS method. In the multiple-dose phase, subjects received 0.4 g ibuprofen every 6 hours for 9 doses. Blood samples were obtained before the 7^th, 8^th, and 9^th administration to determine the C_min at steady state; on the 9^th intravenous administration, blood samples were also collected for 12.5 hours after drug administration. Pharmacokinetic parameters were estimated using a noncompartmental model. Tolerability was determined using clinical evaluation and monitoring of adverse events (AEs). A total of 12 healthy male (n = 6) and female (n = 6) Chinese volunteers were enrolled and completed the trial. After IV administration of single dose, the mean (SD) C_max value increased from 35.77 (6.98) to 117.12 (19.78) µg/mL, and the mean (SD) AUC_0-t value increased from 67.63 (10.30) to 230.50 (33.55) µg×h/mL in the range of 0.2-g to 0.8-g dose. The terminal half-life in plasma was ~ 2.0 hours. After IV administration of 9 doses of ibuprofen 400 mg every 6 hours, the mean (SD) C_max was 66.49 (8.49) µg/mL, the AUC_0-t was 135.65 (26.91) µg×h/mL, the t_1/2 was 2.14 (0.34) hours, the Cl/F was 3.34 (0.68) L/h, and the Vz/F was 10.32 (2.69) L, which were comparable with those after single dosing. The accumulation index was 1.17 (0.06), and the fluctuation was 304.0 (57.7) %. Results of the t-tests of C_max and AUC found no significant differences between the male and female groups. No serious AEs were reported, and there were no discontinuations due to AEs. The pharmacokinetics of ibuprofen exhibited dose-related kinetics from the 0.2- to the 0.8-g dose. After multiple doses, the pharmacokinetic parameters of ibuprofen were consistent with those after single doses. There was no accumulation in ibuprofen exposure in healthy Chinese between multiple doses and single dose. At the doses studied, ibuprofen appeared to be well tolerated in these healthy volunteers.
.

Minimal to no transfer of certolizumab pegol into breast milk: results from CRADLE, a prospective, postmarketing, multicentre, pharmacokinetic study.

PubMed

Clowse, Megan Eb; Förger, Frauke; Hwang, Caroline; Thorp, John; Dolhain, Radboud Jem; van Tubergen, Astrid; Shaughnessy, Laura; Simpson, Jeff; Teil, Marie; Toublanc, Nathalie; Wang, Maggie; Hale, Thomas W

2017-11-01

Women with chronic inflammatory diseases face uncertainty regarding the safety of biologics during breast feeding. CRADLE was the first industry-sponsored study to evaluate certolizumab pegol (CZP) concentrations in human breast milk and estimate average daily infant dose (ADID) of maternal CZP. CRADLE (NCT02154425) was a pharmacokinetic study of lactating mothers receiving CZP. After ≥3 CZP doses, breast milk samples were collected across one dosing period (14 days for 200 mg every 2 weeks [Q2W]; 28 days for 400 mg every 4 weeks [Q4W]). Optimal analytical methods were developed to determine CZP and polyethylene glycol (PEG) levels in breast milk. ADID and relative infant dose (RID) were estimated. Safety events in mothers and infants were assessed. 19 CZP-treated mothers were screened; 17 entered the sampling period: 16 on 200 mg Q2W, 1 on 400 mg Q4W. 77/137 (56%) breast milk samples had no measurable CZP. For 4/17 mothers, all samples were below the lower limit of quantification (LLOQ). Estimated ADID was 0-0.0104 mg/kg/day; median RID: 0.15%. PEG was undetectable in 134/137 samples (results could not be determined in three samples). Infants of CZP-exposed mothers had a safety profile consistent with that of unexposed similar-age infants. When quantifiable, CZP concentrations were <3× LLOQ (<1% plasma concentration observed with therapeutic dose), indicating no/minimal CZP transfer from plasma to breast milk. RID was 0.15% of maternal dose; <10% is considered unlikely to be of clinical concern. No PEG transfer was observed. CZP absorption by infants via breast milk is unlikely due to its low oral bioavailability and Fc--free molecular structure. These findings are reassuring and support continuation of CZP treatment during breast feeding. NCT02154425; Results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Vitamin Concentrations in Human Milk Vary with Time within Feed, Circadian Rhythm, and Single-Dose Supplementation.

PubMed

Hampel, Daniela; Shahab-Ferdows, Setareh; Islam, M Munirul; Peerson, Janet M; Allen, Lindsay H

2017-04-01

Background: Human milk is the subject of many studies, but procedures for representative sample collection have not been established. Our improved methods for milk micronutrient analysis now enable systematic study of factors that affect its concentrations. Objective: We evaluated the effects of sample collection protocols, variations in circadian rhythms, subject variability, and acute maternal micronutrient supplementation on milk vitamin concentrations. Methods: In the BMQ (Breast-Milk-Quality) study, we recruited 18 healthy women (aged 18-26 y) in Dhaka, Bangladesh, at 2-4 mo of lactation for a 3-d supplementation study. On day 1, no supplements were given; on days 2 and 3, participants consumed ∼1 time and 2 times, respectively, the US-Canadian Recommended Dietary Allowances for vitamins at breakfast (0800-0859). Milk was collected during every feeding from the same breast over 24 h. Milk expressed in the first 2 min (aliquot I) was collected separately from the remainder (aliquot II); a third aliquot (aliquot III) was saved by combining aliquots I and II. Thiamin, riboflavin, niacin, and vitamins B-6, B-12, A, and E and fat were measured in each sample. Results: Significant but small differences (14-18%) between aliquots were found for all vitamins except for vitamins B-6 and B-12. Circadian variance was significant except for fat-adjusted vitamins A and E, with a higher contribution to total variance with supplementation. Between-subject variability accounted for most of the total variance. Afternoon and evening samples best reflected daily vitamin concentrations for all study days. Acute supplementation effects were found for thiamin, riboflavin, and vitamins B-6 and A at 2-4 h postdosing, with 0.1-6.17% passing into milk. Supplementation was reflected in fasting, 24-h postdose samples for riboflavin and vitamin B-6. Maximum amounts of dose-responding vitamins in 1 feeding ranged from 4.7% to 21.8% (day 2) and 8.2% to 35.0% (day 3) of Adequate Intake. Conclusions: In the milk of Bangladeshi mothers, differences in vitamin concentrations between aliquots within feedings and by circadian variance were significant but small. Afternoon and evening collection provided the most-representative samples. Supplementation acutely affects some breast-milk micronutrient concentrations. This trial was registered at clinicaltrials.gov as NCT02756026.

Vitamin Concentrations in Human Milk Vary with Time within Feed, Circadian Rhythm, and Single-Dose Supplementation1234

PubMed Central

Shahab-Ferdows, Setareh; Peerson, Janet M; Allen, Lindsay H

2017-01-01

Background: Human milk is the subject of many studies, but procedures for representative sample collection have not been established. Our improved methods for milk micronutrient analysis now enable systematic study of factors that affect its concentrations. Objective: We evaluated the effects of sample collection protocols, variations in circadian rhythms, subject variability, and acute maternal micronutrient supplementation on milk vitamin concentrations. Methods: In the BMQ (Breast-Milk-Quality) study, we recruited 18 healthy women (aged 18–26 y) in Dhaka, Bangladesh, at 2–4 mo of lactation for a 3-d supplementation study. On day 1, no supplements were given; on days 2 and 3, participants consumed ∼1 time and 2 times, respectively, the US-Canadian Recommended Dietary Allowances for vitamins at breakfast (0800–0859). Milk was collected during every feeding from the same breast over 24 h. Milk expressed in the first 2 min (aliquot I) was collected separately from the remainder (aliquot II); a third aliquot (aliquot III) was saved by combining aliquots I and II. Thiamin, riboflavin, niacin, and vitamins B-6, B-12, A, and E and fat were measured in each sample. Results: Significant but small differences (14–18%) between aliquots were found for all vitamins except for vitamins B-6 and B-12. Circadian variance was significant except for fat-adjusted vitamins A and E, with a higher contribution to total variance with supplementation. Between-subject variability accounted for most of the total variance. Afternoon and evening samples best reflected daily vitamin concentrations for all study days. Acute supplementation effects were found for thiamin, riboflavin, and vitamins B-6 and A at 2–4 h postdosing, with 0.1–6.17% passing into milk. Supplementation was reflected in fasting, 24-h postdose samples for riboflavin and vitamin B-6. Maximum amounts of dose-responding vitamins in 1 feeding ranged from 4.7% to 21.8% (day 2) and 8.2% to 35.0% (day 3) of Adequate Intake. Conclusions: In the milk of Bangladeshi mothers, differences in vitamin concentrations between aliquots within feedings and by circadian variance were significant but small. Afternoon and evening collection provided the most-representative samples. Supplementation acutely affects some breast-milk micronutrient concentrations. This trial was registered at clinicaltrials.gov as NCT02756026. PMID:28202638

An overview of the ecological half-life of the 137Cs radioisotope and a determination of radioactivity levels in sediment samples after Chernobyl in the Eastern Black Sea, Turkey

NASA Astrophysics Data System (ADS)

Baltas, Hasan; Sirin, Murat; Dalgic, Goktug; Cevik, Ugur

2018-01-01

A study which determined the activity concentration of 137Cs in sediments contaminated by effluents from the Chernobyl accident which had collected along the coast of the Eastern Black Sea region in Turkey was carried out in 1993. Marine sediment samples were collected in 2015 from the same fifteen sampling points, and the activity concentrations of 226Ra, 232Th, 40K and 137Cs were determined for the sediment samples. The activity concentrations ranged from 10.94-25.95, 12.14-33.05, 265.74-459.89 and 2.08-37.45 Bq kg- 1 for 226Ra, 232Th, 40K and 137Cs respectively. The results showed that there was a steep decline in 137Cs within the sediment at most of the sampling sites from the Eastern Black Sea region during the 22-year period, except for two sites at which the measured levels were much higher. This may be the result of the combined effects of radioactive contaminant entry into this area from rivers, environmental changes and nuclear testing between 1993 and 2015. Furthermore, the ecological half-life (EHL) of the 137Cs radionuclide was estimated for the sediment samples, and radiological hazard parameters such as the absorbed dose rate in air (D), the annual effective dose equivalent (AEDE) and the excess lifetime cancer risk (ELCR) were calculated and compared with the international recommended values. It was shown that these sediments do not present any significant health risk for humans in this area.

Application of Raman spectroscopy for on-line monitoring of low dose blend uniformity.

PubMed

Hausman, Debra S; Cambron, R Thomas; Sakr, Adel

2005-07-14

On-line Raman spectroscopy was used to evaluate the effect of blending time on low dose, 1%, blend uniformity of azimilide dihydrochloride. An 8 qt blender was used for the experiments and instrumented with a Raman probe through the I-bar port. The blender was slowed to 6.75 rpm to better illustrate the blending process (normal speed is 25 rpm). Uniformity was reached after 20 min of blending at 6.75 rpm (135 revolutions or 5.4 min at 25 rpm). On-line Raman analysis of blend uniformity provided more benefits than traditional thief sampling and off-line analysis. On-line Raman spectroscopy enabled generating data rich blend profiles, due to the ability to collect a large number of samples during the blending process (sampling every 20s). In addition, the Raman blend profile was rapidly generated, compared to the lengthy time to complete a blend profile with thief sampling and off-line analysis. The on-line Raman blend uniformity results were also significantly correlated (p-value < 0.05) to the HPLC uniformity results of thief samples.

Natural radioactivity in various water samples and radiation dose estimations in Bolu province, Turkey.

PubMed

Gorur, F Korkmaz; Camgoz, H

2014-10-01

The level of natural radioactivity for Bolu province of north-western Turkey was assessed in this study. There is no information about radioactivity measurement reported in water samples in the Bolu province so far. For this reason, gross α and β activities of 55 different water samples collected from tap, spring, mineral, river and lake waters in Bolu were determined. The mean activity concentrations were 68.11 mBq L(-1), 169.44 mBq L(-1) for gross α and β in tap water. For all samples the gross β activity is always higher than the gross α activity. All value of the gross α were lower than the limit value of 500 mBq L(-1) while two spring and one mineral water samples were found to have gross β activity concentrations of greater than 1000 mBq L(-1). The associated age-dependent dose from all water ingestion in Bolu was estimated. The total dose for adults had an average value exceeds the WHO recommended limit value. The risk levels from the direct ingestion of the natural radionuclides in tap and mineral water in Bolu were determinated. The mean (210)Po and (228)Ra risk the value of tap and mineral waters slightly exceeds what some consider on acceptable risk of 10(-4) or less. Copyright © 2014 Elsevier Ltd. All rights reserved.

Pragmatic pharmacology: population pharmacokinetic analysis of fentanyl using remnant samples from children after cardiac surgery

PubMed Central

Van Driest, Sara L.; Marshall, Matthew D.; Hachey, Brian; Beck, Cole; Crum, Kim; Owen, Jill; Smith, Andrew H.; Kannankeril, Prince J.; Woodworth, Alison; Caprioli, Richard M.

2016-01-01

Aims One barrier contributing to the lack of pharmacokinetic (PK) data in paediatric populations is the need for serial sampling. Analysis of clinically obtained specimens and data may overcome this barrier. To add evidence for the feasibility of this approach, we sought to determine PK parameters for fentanyl in children after cardiac surgery using specimens and data generated in the course of clinical care, without collecting additional blood samples. Methods We measured fentanyl concentrations in plasma from leftover clinically‐obtained specimens in 130 paediatric cardiac surgery patients and successfully generated a PK dataset using drug dosing data extracted from electronic medical records. Using a population PK approach, we estimated PK parameters for this population, assessed model goodness‐of‐fit and internal model validation, and performed subset data analyses. Through simulation studies, we compared predicted fentanyl concentrations using model‐driven weight‐adjusted per kg vs. fixed per kg fentanyl dosing. Results Fentanyl clearance for a 6.4 kg child, the median weight in our cohort, is 5.7 l h–1 (2.2–9.2 l h–1), similar to values found in prior formal PK studies. Model assessment and subset analyses indicated the model adequately fit the data. Of the covariates studied, only weight significantly impacted fentanyl kinetics, but substantial inter‐individual variability remained. In simulation studies, model‐driven weight‐adjusted per kg fentanyl dosing led to more consistent therapeutic fentanyl concentrations than fixed per kg dosing. Conclusions We show here that population PK modelling using sparse remnant samples and electronic medical records data provides a powerful tool for assessment of drug kinetics and generation of individualized dosing regimens. PMID:26861166

Moclobemide excretion in human breast milk.

PubMed Central

Pons, G; Schoerlin, M P; Tam, Y K; Moran, C; Pfefen, J P; Francoual, C; Pedarriosse, A M; Chavinie, J; Olive, G

1990-01-01

1. Six lactating white women, aged 24-36 years, received a single oral dose of 300 mg moclobemide, between 09.00 h and 11.00 h, 3 to 5 days after the delivery of a full term neonate. 2. Complete milk collections were obtained before, 3, 6, 9, 12 and 24 h after drug administration by means of a breast pump. Venous blood samples were drawn before, and 0.5, 1, 3, 4.5, 6, 9, 12, 24 h post-dosing. 3. Moclobemide, and its major metabolite (Ro 12-8095) were measured in milk and plasma samples using h.p.l.c. The active metabolite (Ro 12-5637) could only be detected in plasma. 4. Moclobemide and its metabolites were not detectable in 24 h plasma samples. Cmax, tmax and t1/2 for moclobemide were (mean +/- s.d.) 2.70 +/- 1.24 mg l-1, 2.03 +/- 1.19 h and 2.26 +/- 0.26 h, respectively. 5. The concentrations of moclobemide and Ro 12-8095 in milk were highest at 3 h after drug administration and the drug and metabolite were not detectable after 12 h. Ro 12-5637 was not detected in any milk sample. The percentages of the dose excreted as moclobemide and Ro 12-8095 were (mean +/- s.d.) 0.057 +/- 0.020% and 0.031 +/- 0.011%, respectively. An average 3.5 kg breast-fed neonate would therefore be exposed to only a 0.05 mg kg-1 moclobemide dose (approximately 1% of the maternal dose on the mg kg-1 basis). The low amount of moclobemide excreted into breast milk is unlikely to be hazardous to suckling infants. PMID:2297459

Single-Grain OSL Dating of Early Middle Palaeolithic Deposits at Cuesta de la Bajada, Ebro Basin, Spain

NASA Astrophysics Data System (ADS)

Arnold, L. J.; Demuro, M.; Santonja, M.; Perez-Gonzalez, A.

2012-12-01

The open-air site of Cuesta de la Bajada comprises a 2-2.5 m-thick sequence of fluvial-lacustrine sediments inset into the +50-60 m terrace deposits preserved along the south-eastern margins of the Alfambra river valley, Teruel, Spain. The main archaeological horizons lie ~20 m above the present-day river level and consists of an upward-fining sequence of massive fluvial silts and fine sands with dispersed gravels, detritic marls and shales that collectively overlie a series of planar bedded fluvial gravels. These units have yielded ~3000 lithic artefacts displaying reduction techniques characteristic of an early Middle Palaeolithic techno-complex, as well as a multitude of faunal remains indicative of a late Middle Pleistocene origin. The paucity of open-air Palaeolithic sites in the interior eastern sector of the Iberian Peninsula, and the relatively low number of documented early Middle Palaeolithic archives in this region, means that Cuesta de la Bajada is of key importance for understanding the coexistence/transition of Iberian Acheulean and Mousterian techno-complexes during the Middle Pleistocene period. Establishing reliable absolute chronologies at Cuesta de la Bajada remains essential for understanding the regional significance of this site. In an attempt to redress the existing chronological uncertainty we are undertaking an interdisciplinary dating study of the Middle Palaeolithic deposits using OSL dating, ESR/U-series dating of teeth and ESR dating of sedimentary quartz. Here we present results obtained using quartz single-grain OSL dating of 4 samples collected from a 7 m vertical profile bracketing the archaeological horizons. 2 samples were collected from the archaeology-bearing silt and fine sand horizons, while the remaining samples were obtained from well-bedded fine-sands and silts 3.5 m above and 3 m below the main excavation. The measured quartz grains are characterised by relatively bright OSL signals and typically display dose-response curves with very high saturation limits. The latter offers the advantage of extending the age range over which single-grain techniques can be applied in this Middle Pleistocene context. Dose-recovery tests performed at high doses of 470 Gy yielded accurate equivalent dose (De) results with low overdispersion, providing reasonable confidence in the chosen measurement conditions. 3 of the samples display single-grain De distributions with low levels of dispersion indicating that the sediments were adequately bleached prior to burial and remained undisturbed thereafter. The fourth sample displays higher De dispersion and a younger subpopulation of grains, which could be explained by beta-dose heterogeneity associated with interspersed gravels within the basal archaeological horizon. We apply various statistical age models to derive final chronologies and compare the resultant single-grain ages with those obtained using different absolute dating methods. We also report on experiments performed using 'synthetic multi-grain aliquots' created from the single-grain De datasets, and discuss their implications for the reliability of multi-grain OSL dating techniques in this context.

Single-grain OSL dating of Early Middle Palaeolithic deposits at Cuesta de la Bajada, Ebro Basin, Spain

NASA Astrophysics Data System (ADS)

Arnold, Lee; Demuro, Martina; Santonja, Manuel; Perez-Gonzalez, Alfredo; Pares, Josep

2013-04-01

The open-air site of Cuesta de la Bajada comprises a 2-2.5 m-thick sequence of fluvial-lacustrine sediments inset into the +50-60 m terrace deposits preserved along the south-eastern margins of the Alfambra river valley, Teruel, Spain. The main archaeological horizons lie ~20 m above the present-day river level and consists of an upward-fining sequence of massive fluvial silts and fine sands with dispersed gravels, detritic marls and shales that collectively overlie a series of planar bedded fluvial gravels. These units have yielded ~3000 lithic artefacts displaying reduction techniques characteristic of an early Middle Palaeolithic techno-complex, as well as a multitude of faunal remains indicative of a late Middle Pleistocene origin. The paucity of open-air Palaeolithic sites in the interior eastern sector of the Iberian Peninsula, and the relatively low number of documented early Middle Palaeolithic archives in this region, means that Cuesta de la Bajada is of key importance for understanding the coexistence/transition of Iberian Acheulean and Mousterian techno-complexes during the Middle Pleistocene period. Establishing reliable absolute chronologies at Cuesta de la Bajada remains essential for understanding the regional significance of this site. In an attempt to redress the existing chronological uncertainty we are undertaking an interdisciplinary dating study of the Middle Palaeolithic deposits using OSL dating, ESR/U-series dating of teeth and ESR dating of sedimentary quartz. Here we present results obtained using quartz single-grain OSL dating of 4 samples collected from a 7 m vertical profile bracketing the archaeological horizons. 2 samples were collected from the archaeology-bearing silt and fine sand horizons, while the remaining samples were obtained from well-bedded fine-sands and silts 3.5 m above and 3 m below the main excavation. The measured quartz grains are characterised by relatively bright OSL signals and typically display dose-response curves with very high saturation limits. The latter offers the advantage of extending the age range over which single-grain techniques can be applied in this Middle Pleistocene context. Dose-recovery tests performed at high doses of 470 Gy yielded accurate equivalent dose (De) results with low overdispersion, providing reasonable confidence in the chosen measurement conditions. Three of the samples display single-grain De distributions with low levels of dispersion indicating that the sediments were adequately bleached prior to burial and remained undisturbed thereafter. The fourth sample displays higher De dispersion and a younger subpopulation of grains, which could be explained by beta-dose heterogeneity associated with interspersed gravels within the basal archaeological horizon. We apply various statistical age models to derive final chronologies and compare the resultant single-grain ages with those obtained using different absolute dating methods. We also report on experiments performed using 'synthetic multi-grain aliquots' created from the single-grain De datasets, and discuss their implications for the reliability of multi-grain OSL dating techniques in this context.

Occupational exposure to acrylamide in closed system production plants: air levels and biomonitoring.

PubMed

Moorman, William J; Reutman, Susan S; Shaw, Peter B; Blade, Leo Michael; Marlow, David; Vesper, Hubert; Clark, John C; Schrader, Steven M

2012-01-01

The aim of this study was to evaluate biomarkers of acrylamide exposure, including hemoglobin adducts and urinary metabolites in acrylamide production workers. Biomarkers are integrated measures of the internal dose, and it is total acrylamide dose from all routes and sources that may present health risks. Workers from three companies were studied. Workers potentially exposed to acrylamide monomer wore personal breathing-zone air samplers. Air samples and surface-wipe samples were collected and analyzed for acrylamide. General-area air samples were collected in chemical processing units and control rooms. Hemoglobin adducts were isolated from ethylenediamine teraacetic acid (EDTA)-whole blood, and adducts of acrylamide and glycidamide, at the N-terminal valines of hemoglobin, were cleaved from the protein chain by use of a modified Edman reaction. Full work-shift, personal breathing zone, and general-area air samples were collected and analyzed for particulate and acrylamide monomer vapor. The highest general-area concentration of acrylamide vapor was 350 μg/cm(3) in monomer production. Personal breathing zone and general-area concentrations of acrylamide vapor were found to be highest in monomer production operations, and lower levels were in the polymer production operations. Adduct levels varied widely among workers, with the highest in workers in the monomer and polymer production areas. The acrylamide adduct range was 15-1884 pmol/g; glycidamide adducts ranged from 17.8 to 1376 p/mol/g. The highest acrylamide and glycidamide adduct levels were found among monomer production process operators. The primary urinary metabolite N-acetyl-S-(2-carbamoylethyl) cysteine (NACEC) ranged from the limit of detection to 15.4 μg/ml. Correlation of workplace exposure and sentinel health effects is needed to determine and control safe levels of exposure for regulatory standards.

Urinary excretion of radionuclides from Marshallese exposed to fallout from the 1954 Bravo nuclear test.

PubMed

Harris, Payne S; Simon, Steven L; Ibrahim, Shawki A

2010-08-01

Soon after the Bravo nuclear test at Bikini Atoll in the Marshall Islands on 1 March 1954, urine samples were collected for analysis of excreted radioactivity from native residents exposed to radioactive fallout on two atolls as well as from U.S. military personnel on a third atoll. The earliest acquired samples, obtained by the Los Alamos Scientific Laboratory (LASL), were assayed for various radionuclides and provided the first known measurements of (131)I in urine following exposure to fallout from a nuclear test. Over the course of 1954, many additional samples were collected by the LASL, as well as by the Atomic Energy Commission New York Operations Office's Health and Safety Laboratory and the Naval Radiological Defense Laboratory. Collectively, the groups sampled included Marshallese exposed on Rongelap and Ailinginae Atolls, American military weather observers temporarily resident on Rongerik Atoll, and sailors from the Japanese fishing vessel, the Lucky Dragon. While the bioassay measurement data and individual urine volumes have been crucial to various attempts to assess intakes of radioactivity and the related internal radiation doses among the Marshallese, those data have never been published in any peer-reviewed journal, but have been restricted to agency memoranda, laboratory reports, and summaries in some publications and book chapters. Reconstructions of internal doses to Marshallese in 1954 and in later years have depended on these data and, hence, they have considerable historical importance as well as importance to ongoing health risk projections for Marshallese. This paper presents much of the original data on urine volumes and radioactivity from the various assays of urine for radionuclides, and compares estimates of (131)I intakes made in 1954, 1985, 1987, and 2008.

URINARY EXCRETION OF RADIONUCLIDES FROM MARSHALLESE EXPOSED TO FALLOUT FROM THE 1954 BRAVO NUCLEAR TEST

PubMed Central

Harris, Payne S.; Simon, Steven L.; Ibrahim, Shawki A.

2014-01-01

Soon after the Bravo nuclear test at Bikini Atoll in the Marshall Islands on 1 March 1954, urine samples were collected for analysis of excreted radioactivity from native residents exposed to radioactive fallout on two atolls as well as from U.S. military personnel on a third atoll. The earliest acquired samples, obtained by the Los Alamos Scientific Laboratory (LASL), were assayed for various radionuclides and provided the first known measurements of 131I in urine following exposure to fallout from a nuclear test. Over the course of 1954, many additional samples were collected by the LASL, as well as by the Atomic Energy Commission New York Operations Office’s Health and Safety Laboratory and the Naval Radiological Defense Laboratory. Collectively, the groups sampled included Marshallese exposed on Rongelap and Ailinginae Atolls, American military weather observers temporarily resident on Rongerik Atoll, and sailors from the Japanese fishing vessel, the Lucky Dragon. While the bioassay measurement data and individual urine volumes have been crucial to various attempts to assess intakes of radioactivity and the related internal radiation doses among the Marshallese, those data have never been published in any peer-reviewed journal, but have been restricted to agency memoranda, laboratory reports, and summaries in some publications and book chapters. Reconstructions of internal doses to Marshallese in 1954 and in later years have depended on these data and, hence, they have considerable historical importance as well as importance to ongoing health risk projections for Marshallese. This paper presents much of the original data on urine volumes and radioactivity from the various assays of urine for radionuclides, and compares estimates of 131I intakes made in 1954, 1985, 1987, and 2008. PMID:20622553

Measurement of (222)Rn concentration levels in drinking water and the associated health effects in the Southern part of West Bank - Palestine.

PubMed

Thabayneh, Khalil M

2015-09-01

Radon concentration and annual effective doses were measured in drinking water in the Southern Part of West Bank - Palestine, by using both passive and active techniques. 184 samples were collected from various sources i.e. tap water, groundwater, rain waters and mineral waters. It is found that the annual effective dose resulting from inhalation and ingestion of radon emanated from all types of drinking water is negligible compared to the total annual effective dose from indoor radon in the region. Results reveal that there is no significant public health risk from radon ingested and inhalation with drinking water in the study region. Copyright © 2015. Published by Elsevier Ltd.

Biological Sterilization of Returned Mars Samples

NASA Technical Reports Server (NTRS)

Allen, C. C.; Albert, F. G.; Combie, J.; Bodnar, R. J.; Hamilton, V. E.; Jolliff, B. L.; Kuebler, K.; Wang, A.; Lindstrom, D. J.; Morris, P. A.

1999-01-01

Martian rock and soil, collected by robotic spacecraft, will be returned to terrestrial laboratories early in the next century. Current plans call for the samples to be immediately placed into biological containment and tested for signs of present or past life and biological hazards. It is recommended that "Controlled distribution of unsterilized materials from Mars should occur only if rigorous analyses determine that the materials do not constitute a biological hazard. If any portion of the sample is removed from containment prior to completion of these analyses it should first be sterilized." While sterilization of Mars samples may not be required, an acceptable method must be available before the samples are returned to Earth. The sterilization method should be capable of destroying a wide range of organisms with minimal effects on the geologic samples. A variety of biological sterilization techniques and materials are currently in use, including dry heat, high pressure steam, gases, plasmas and ionizing radiation. Gamma radiation is routinely used to inactivate viruses and destroy bacteria in medical research. Many commercial sterilizers use Co-60 , which emits gamma photons of 1.17 and 1.33 MeV. Absorbed doses of approximately 1 Mrad (10(exp 8) ergs/g) destroy most bacteria. This study investigates the effects of lethal doses of Co-60 gamma radiation on materials similar to those anticipated to be returned from Mars. The goals are to determine the gamma dose required to kill microorganisms in rock and soil samples and to determine the effects of gamma sterilization on the samples' isotopic, chemical and physical properties. Additional information is contained in the original extended abstract.

Orthotopic tumorgrafts in nude mice as a model to evaluate calcitriol effects in breast cancer.

PubMed

Fonseca-Filho, V C N; Katayama, M L H; Lyra, E C; Maria, D A; Basso, R A; Nonogaki, S; Guerra, J M; Maistro, S; Góes, J C G S; Folgueira, M A A K

2017-11-01

Calcitriol antiproliferative effects were observed in xenografts of breast cancer cell lines, however they were not yet investigated in tumorgrafts, consisting of freshly collected breast cancer samples xenografted into animals. To establish a tumorgraft model, from freshly collected breast cancer samples, which were directly implanted in nude mice, to study calcitriol effects. Breast cancer samples collected from 12 patients were orthotopically implanted into nude mice. Animals were treated with weekly intratumoral injections of calcitriol 3 μg/Kg, which was previously shown to induce peak serum calcitriol levels in the predicted therapeutic range. Success engraftment rate was 25%. Tumorgrafts were established from aggressive (HER2 positive or histological grade 3) highly proliferative samples and original tumor characteristics were preserved. Calcitriol highly induced its target gene, CYP24A1, indicating that the genomic vitamin D pathway is active in tumorgrafts. However, no differences in the expression of proliferation and apoptosis markers (BrdU incorporation, Ki67, CDKN1A, CDKN1B, BCL2 expression) were observed in these highly proliferative tumor samples. Tumorgrafts seem a promising model to explore other calcitriol doses and regimens, considering the heterogeneity of the disease and microenvironment interactions.

A pilot study assessing pharmacokinetics and tolerability of oral and intravenous baclofen in healthy adult volunteers.

PubMed

Agarwal, Suresh K; Kriel, Robert L; Cloyd, James C; Coles, Lisa D; Scherkenbach, Lisa A; Tobin, Michael H; Krach, Linda E

2015-01-01

Our objective was to characterize baclofen pharmacokinetics and safety given orally and intravenously. Twelve healthy subjects were enrolled in a randomized, open-label, crossover study and received single doses of baclofen: 3 or 5 mg given intravenously and 5 or 10 mg taken orally with a 48-hour washout. Blood samples for baclofen analysis were collected pre-dose and at regular intervals up to 24 hours post-dose. Clinical response was assessed by sedation scores, ataxia, and nystagmus. Mean absolute bioavailability of oral baclofen was 74%. Dose-adjusted areas under the curve between the oral and intravenous arms were statistically different (P = .0024), whereas area under the curve variability was similar (coefficient of variation: 18%-24%). Adverse effects were mild in severity and not related to either dose or route of administration. Three- and 5-mg intravenous doses of baclofen were well tolerated. Seventy-four percent oral bioavailability indicates that smaller doses of intravenous baclofen are needed to attain comparable total drug exposures. © The Author(s) 2014.

Air pathway effects of nuclear materials production at the Hanford Site, 1983 to 1992

DOE Office of Scientific and Technical Information (OSTI.GOV)

Patton, G.W.; Cooper, A.T.

1993-10-01

This report describes the air pathway effects of Hanford Site operations from 1983 to 1992 on the local environment by summarizing the air concentrations of selected radionuclides at both onsite and offsite locations, comparing trends in environment concentrations to changing facility emissions, and briefly describing trends in the radiological dose to the hypothetical maximally exposed member of the public. The years 1983 to 1992 represent the last Hanford Site plutonium production campaign, and this report deals mainly with the air pathway effects from the 200 Areas, in which the major contributors to radiological emissions were located. An additional purpose formore » report was to review the environmental data for a long period of time to provide insight not available in an annual report format. The sampling and analytical systems used by the Surface Environmental Surveillance Project (SESP) to collect air samples during the period of this report were sufficiently sensitive to observe locally elevated concentrations of selected radionuclides near onsite source of emission as well as observing elevated levels, compared to distant locations, of some radionuclides at the down wind perimeter. The US DOE Derived Concentration Guides (DCGs) for airborne radionuclides were not exceeded for any air sample collected during 1983 to 1992, with annual average concentrations of all radionuclides at the downwind perimeter being considerably below the DCG values. Air emissions at the Hanford Site during the period of this report were dominated by releases from the PUREX Plant, with {sup 85}Kr being the major release on a curie basis and {sup 129}I being the major release on a radiological dose basis. The estimated potential radiological dose from Hanford Site point source emissions to the hypothetical maximally exposed individual (MEI) ranged from 0. 02 to 0.22 mrem/yr (effective dose equivalent), which is well below the DOE radiation limit to the public of 100 mrem/yr.« less

Radiation-Induced Changes in Serum Lipidome of Head and Neck Cancer Patients

PubMed Central

Jelonek, Karol; Pietrowska, Monika; Ros, Malgorzata; Zagdanski, Adam; Suchwalko, Agnieszka; Polanska, Joanna; Marczyk, Michal; Rutkowski, Tomasz; Skladowski, Krzysztof; Clench, Malcolm R.; Widlak, Piotr

2014-01-01

Cancer radiotherapy (RT) induces response of the whole patient’s body that could be detected at the blood level. We aimed to identify changes induced in serum lipidome during RT and characterize their association with doses and volumes of irradiated tissue. Sixty-six patients treated with conformal RT because of head and neck cancer were enrolled in the study. Blood samples were collected before, during and about one month after the end of RT. Lipid extracts were analyzed using MALDI-oa-ToF mass spectrometry in positive ionization mode. The major changes were observed when pre-treatment and within-treatment samples were compared. Levels of several identified phosphatidylcholines, including (PC34), (PC36) and (PC38) variants, and lysophosphatidylcholines, including (LPC16) and (LPC18) variants, were first significantly decreased and then increased in post-treatment samples. Intensities of changes were correlated with doses of radiation received by patients. Of note, such correlations were more frequent when low-to-medium doses of radiation delivered during conformal RT to large volumes of normal tissues were analyzed. Additionally, some radiation-induced changes in serum lipidome were associated with toxicity of the treatment. Obtained results indicated the involvement of choline-related signaling and potential biological importance of exposure to clinically low/medium doses of radiation in patient’s body response to radiation. PMID:24747595

In vivo gamma-rays induced initial DNA damage and the effect of famotidine in mouse leukocytes as assayed by the alkaline comet assay.

PubMed

Mozdarani, Hossein; Nasirian, Borzo; Haeri, S Abolghasem

2007-03-01

Ionizing radiation induces a variety of lesions in DNA, each of which can be used as a bio-indicator for biological dosimetry or the study of the radioprotective effects of substances. To assess gamma ray-induced DNA damage in vivo in mouse leukocytes at various doses and the effect of famotidine, blood was collected from Balb/c male mice after irradiation with 4 Gy gamma-rays at different time intervals post-irradiation. To assess the response, mice were irradiated with doses of gamma-rays at 1 to 4 Grays. Famotidine was injected intra-peritoneally (i.p) at a dose of 5 mg/kg at various time intervals before irradiation. Four slides were prepared from each sample and alkaline comet assay was performed using standard protocols. Results obtained show that radiation significantly increases DNA damage in leukocytes in a dose dependent manner (p < 0.01) when using appropriate sampling time after irradiation, because increasing sampling time after irradiation resulted in a time dependent disappearance of DNA damage. Treatment with only 5 mg/kg famotidine before 4 Gy irradiation led to almost 50% reduction in DNA damage when compared with those animals which received radiation alone. The radioprotective capability of famotidine might be attributed to radical scavenging properties and an anti-oxidation mechanism.

A PILOT STUDY USING AN ACCELEROMETER TO EVALUATE A CAREGIVER'S INTERPRETATION OF AN INFANT OR TODDLER'S ACTIVITY LEVEL AS RECORDED IN A TIME ACTIVITY DIARY

EPA Science Inventory

Linking a young child's activity pattern data with samples that are collected during an exposure assessment is important in evaluating uptake dose rates associated with environmental contaminant exposures. A pilot study (N=9) was performed to test how well categorical activity-le...

Development of an objective dose distribution analysis method for OSL dating and pilot studies for planetary applications

NASA Astrophysics Data System (ADS)

Lepper, Kenneth Errol

Scope and method of study. Part I: In its simplest expression a luminescence age is the natural absorbed radiation dose (De) divided by the in-situ dose rate. The experimental techniques of Optically Stimulated Luminescence (OSL) dating have evolved to the point were hundreds of Des, and therefore depositional ages can be quickly and conveniently determined for a single sediment sample. The first major objective of this research was to develop an objective analysis method for analyzing dose distribution data and selecting an age-representative dose (Dp). The analytical method was developed based on dose data sets collected from 3 eolian and 3 fluvial sediment samples from Central Oklahoma. Findings and conclusions. Part I: An objective method of presenting the dose distribution data, and a mathematically rigorous means of determining the Dp, as well as a statistically meaningful definition of the uncertainty in Dp have been proposed. The concept of experimental error deconvolution was introduced. In addition a set of distribution shape parameters to facilitate comparison among samples have been defined. These analytical techniques hold the potential to greatly enhance the accuracy and utility of OSL dating for young fluvial sediments. Scope and method of study. Part II: The second major objective of this research was to propose the application of luminescence dating to sediments on Mars. A set of fundamental luminescence dating properties was evaluated for a martian surface materials analog and a polar deposit contextual analog. Findings and conclusions. Part II: The luminescence signals measured from the analogs were found to have a wide dynamic dose response range with no unusual or prohibitive short-term instabilities and were readily reset by exposure to sunlight. These properties form a stable base for continued investigations toward the development of luminescence dating instruments and procedures for Mars.

Thermally assisted OSL application for equivalent dose estimation; comparison of multiple equivalent dose values as well as saturation levels determined by luminescence and ESR techniques for a sedimentary sample collected from a fault gouge

NASA Astrophysics Data System (ADS)

Şahiner, Eren; Meriç, Niyazi; Polymeris, George S.

2017-02-01

Equivalent dose estimation (De) constitutes the most important part of either trap-charge dating techniques or dosimetry applications. In the present work, multiple, independent equivalent dose estimation approaches were adopted, using both luminescence and ESR techniques; two different minerals were studied, namely quartz as well as feldspathic polymineral samples. The work is divided into three independent parts, depending on the type of signal employed. Firstly, different De estimation approaches were carried out on both polymineral and contaminated quartz, using single aliquot regenerative dose protocols employing conventional OSL and IRSL signals, acquired at different temperatures. Secondly, ESR equivalent dose estimations using the additive dose procedure both at room temperature and at 90 K were discussed. Lastly, for the first time in the literature, a single aliquot regenerative protocol employing a thermally assisted OSL signal originating from Very Deep Traps was applied for natural minerals. Rejection criteria such as recycling and recovery ratios are also presented. The SAR protocol, whenever applied, provided with compatible De estimations with great accuracy, independent on either the type of mineral or the stimulation temperature. Low temperature ESR signals resulting from Al and Ti centers indicate very large De values due to bleaching in-ability, associated with large uncertainty values. Additionally, dose saturation of different approaches was investigated. For the signal arising from Very Deep Traps in quartz saturation is extended almost by one order of magnitude. It is interesting that most of De values yielded using different luminescence signals agree with each other and ESR Ge center has very large D0 values. The results presented above highly support the argument that the stability and the initial ESR signal of the Ge center is highly sample-dependent, without any instability problems for the cases of quartz resulting from fault gouge.

Pathogenesis of highly pathogenic avian influenza A virus (H7N1) infection in chickens inoculated with three different doses.

PubMed

Chaves, Aida J; Busquets, Nuria; Campos, Naiana; Ramis, Antonio; Dolz, Roser; Rivas, Raquel; Valle, Rosa; Abad, F Xavier; Darji, Ayub; Majo, Natalia

2011-04-01

To study the pathogenesis of a H7N1 highly pathogenic avian influenza virus strain, specific pathogen free chickens were inoculated with decreasing concentrations of virus: 10(5.5) median embryo lethal dose (ELD(50)) (G1), 10(3.5) ELD(50) (G2) and 10(1.5) ELD(50) (G3). Disease progression was monitored over a period of 16 days and sequential necropsies and tissue samples were collected for histological and immunohistochemical examination. Viral RNA loads were also quantified in different tissues, blood, oropharyngeal swabs, and cloacal swabs using quantitative real-time reverse transcriptase-polymerase chain reaction (RT-qPCR). Clinical signs of depression, apathy, listlessness, huddling and ruffled feathers were recorded in G1 and a few G2 birds, whilst neurological signs were only observed in chickens inoculated with the highest dose. Gross lesions of haemorrhages were observed in the unfeathered skin of the comb and legs, and skeletal muscle, lung, pancreas and kidneys of birds inoculated with 10(5.5) ELD(50) and 10(3.5) ELD(50) doses. Microscopic lesions and viral antigen were demonstrated in cells of the nasal cavity, lung, heart, skeletal muscle, brain, spinal cord, gastrointestinal tract, pancreas, liver, bone marrow, thymus, bursa of Fabricius, spleen, kidney, adrenal gland and skin. Viral RNA was detected by RT-qPCR in kidney, lung, intestine, and brain samples of G1 and G2 birds. However, in birds infected with the lowest dose, viral RNA was detected only in brain and lung samples in low amounts at 5 and 7 days post infection. Interestingly, viral shedding was observed in oropharyngeal and cloacal swabs with proportionate decrease with the inoculation dose. We conclude that although an adequate infectious dose is critical in reproducing the clinical infection, chickens exposed to lower doses can be infected and shed virus representing a risk for the dissemination of the viral agent.

Impact of the Norepinephrine Prodrug Droxidopa on the QTc Interval in Healthy Individuals.

PubMed

White, William B; Hewitt, L Arthur; Mehdirad, Ali A

2018-03-01

A double-blind, 4-period crossover study (NCT01327066) was conducted to assess the effect of the novel norepinephrine prodrug droxidopa on the QT interval in in healthy subjects. Subjects were randomized to receive a single dose of droxidopa 600 mg (maximal dose) and 2000 mg (supratherapeutic dose) compared with the positive control, moxifloxacin 400 mg, and placebo, each separated by a 3-day washout period. Patients were monitored by continuous Holter monitoring, and electrocardiograms (ECGs) were extracted 0.5-23 hours after dosing. Blood samples for pharmacokinetic analysis were collected before dosing and after ECG data collection. The primary end point was the time-matched placebo-adjusted change from baseline in the individually corrected QT (QTcI). The time-averaged QTcI mean placebo-corrected changes from baseline for droxidopa 600 and 2000 mg were 0.1 milliseconds (90%CI, -0.9 to 1.0 milliseconds) and 0.3 milliseconds (90%CI, -0.6 to 1.3 milliseconds), respectively, and 9 milliseconds (90%CI, 8.4-10.3 milliseconds) for moxifloxacin. This study found no effect of either dose of droxidopa on cardiac repolarization using QTcI. Analysis of the pharmacokinetic/pharmacodynamic relationship and cardiac repolarization showed no association with droxidopa exposure. There were no clinically relevant effects of droxidopa on heart rate, atrioventricular conduction, or cardiac depolarization identified. No morphologic ECG changes were observed. © 2017 The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

Impact of the Norepinephrine Prodrug Droxidopa on the QTc Interval in Healthy Individuals

PubMed Central

Hewitt, L. Arthur; Mehdirad, Ali A.

2017-01-01

Abstract A double‐blind, 4‐period crossover study (NCT01327066) was conducted to assess the effect of the novel norepinephrine prodrug droxidopa on the QT interval in in healthy subjects. Subjects were randomized to receive a single dose of droxidopa 600 mg (maximal dose) and 2000 mg (supratherapeutic dose) compared with the positive control, moxifloxacin 400 mg, and placebo, each separated by a 3‐day washout period. Patients were monitored by continuous Holter monitoring, and electrocardiograms (ECGs) were extracted 0.5–23 hours after dosing. Blood samples for pharmacokinetic analysis were collected before dosing and after ECG data collection. The primary end point was the time‐matched placebo‐adjusted change from baseline in the individually corrected QT (QTcI). The time‐averaged QTcI mean placebo‐corrected changes from baseline for droxidopa 600 and 2000 mg were 0.1 milliseconds (90%CI, ‐0.9 to 1.0 milliseconds) and 0.3 milliseconds (90%CI, ‐0.6 to 1.3 milliseconds), respectively, and 9 milliseconds (90%CI, 8.4–10.3 milliseconds) for moxifloxacin. This study found no effect of either dose of droxidopa on cardiac repolarization using QTcI. Analysis of the pharmacokinetic/pharmacodynamic relationship and cardiac repolarization showed no association with droxidopa exposure. There were no clinically relevant effects of droxidopa on heart rate, atrioventricular conduction, or cardiac depolarization identified. No morphologic ECG changes were observed. PMID:29024579

Single-dose safety and pharmacokinetic evaluation of fluorocoxib A: pilot study of novel cyclooxygenase-2-targeted optical imaging agent in a canine model

NASA Astrophysics Data System (ADS)

Cekanova, Maria; Uddin, Md. Jashim; Legendre, Alfred M.; Galyon, Gina; Bartges, Joseph W.; Callens, Amanda; Martin-Jimenez, Tomas; Marnett, Lawrence J.

2012-11-01

We evaluated preclinical single-dose safety, pharmacokinetic properties, and specific uptake of the new optical imaging agent fluorocoxib A in dogs. Fluorocoxib A, N-[(5-carboxy-X-rhodaminyl)but-4-yl]-2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetamide, selectively binds and inhibits the cyclooxygenase-2 (COX-2) enzyme, which is overexpressed in many cancers. Safety pilot studies were performed in research dogs following intravenous (i.v.) administration of 0.1 and 1 mg/kg fluorocoxib A. Blood and urine samples collected three days after administration of each dose of fluorocoxib A revealed no evidence of toxicity, and no clinically relevant adverse events were noted on physical examination of exposed dogs over that time period. Pharmacokinetic parameters were assessed in additional research dogs from plasma collected at several time points after i.v. administration of fluorocoxib A using high-performance liquid chromatography analysis. The pharmacokinetic studies using 1 mg/kg showed a peak of fluorocoxib A (92±28 ng/ml) in plasma collected at 0.5 h. Tumor specific uptake of fluorocoxib A was demonstrated using a dog diagnosed with colorectal cancer expressing COX-2. Our data support the safe single-dose administration and in vivo efficacy of fluorocoxib A, suggesting a high potential for successful translation to clinical use as an imaging agent for improved tumor detection in humans.

Determinants of routine immunization costing in Benin and Ghana in 2011.

PubMed

Ahanhanzo, Césaire Damien; Huang, Xiao Xian; Le Gargasson, Jean-Bernard; Sossou, Justin; Nyonator, Frank; Colombini, Anais; Gessner, Bradford D

2015-05-07

Existing tools to evaluate costs do not always capture the heterogeneity of costs at the facility level. This study seeks to address this issue through an analysis of determinants of health facility immunization costs. A statistical analysis on facility routine delivery and vaccine costs was conducted using ordinary least squares regression. Explanatory variables included the number of doses administered; proportion of time spent by facility staff on immunization; average staff wage; whether the health facility had enough staff; presence of cold chain equipment; distance to a vaccine collection point; and, facility ownership. Data were drawn from representative samples of primary care facilities in Benin and Ghana (46 and 50 facilities, respectively) collected as part of the EPIC studies. Weighted average RI immunization facility cost was US$ 16,459 in Ghana and US$ 14,994 in Benin. The regression found total doses administered to be positively and significantly associated with facility cost in both countries. A 10% increase in doses resulted in a 4% increase in cost in Ghana, and a 7.5% increase in Benin. In Ghana, the proportion of immunization time, presence of cold chain, and sufficiency of staff were positively and significantly associated with total cost. In Benin, facility cost was negatively and significantly related to distance to the vaccine collection point. In the pooled sample, facilities in capital cities were associated with significantly higher costs. This study provides evidence on the importance of the level of scale in determining facility immunization cost, as well as the role of availability of health workers and time they spend on immunization in Ghana and Benin. This type of analysis can provide insights into the costs of scaling up immunization services, and can assist with development of more efficient immunization strategies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Determination of naturally occurring radionuclides in soil samples of Ayranci, Turkey

NASA Astrophysics Data System (ADS)

Agar, Osman; Eke, Canel; Boztosun, Ismail; Emin Korkmaz, M.

2015-04-01

The specific activity, radiation hazard index and the annual effective dose of the naturally occurring radioactive elements (238U, 232Th and 40K) were determined in soil samples collected from 12 different locations in Ayranci region by using a NaI(Tl) gamma-ray spectrometer. The measured activity concentrations of the natural radionuclides in studied soil samples were compared with the corresponding results of different countries and the internationally reported values. From the analysis, it is found that these materials may be safely used as construction materials and do not pose significant radiation hazards.

Distribution, variability, and predictors of urinary bisphenol A levels in 50 North Carolina adults over a six-week monitoring period.

PubMed

Morgan, Marsha K; Nash, Maliha; Barr, Dana Boyd; Starr, James M; Scott Clifton, M; Sobus, Jon R

2018-03-01

Bisphenol A (BPA) is commonly manufactured to make polycarbonate plastics and epoxy resins for use in consumer products and packaged goods. BPA has been found in several different types of environmental media (e.g., food, dust, and air). Many cross-sectional studies have frequently detected BPA concentrations in adult urine samples. However, limited data are available on the temporal variability and important predictors of urinary BPA concentrations in adults. In this work, the major objectives were to: 1) quantify BPA levels in duplicate-diet solid food, drinking water, hard floor surface wipe, and urine samples (first-morning void [FMV], bedtime, and 24-h) collected from adults over a six-week monitoring period; 2) determine the temporal variability of urinary BPA levels using concentration, specific gravity (SG) adjusted, creatinine (CR) adjusted, and excretion rate values, and; 3) examine associations between available study factors and urinary BPA concentrations. In 2009-2011, a convenience sample of 50 adults was recruited from residential settings in North Carolina. The participants completed diaries and collected samples during weeks 1, 2, and/or 6 of a six-week monitoring period. BPA was detected in 38%, 4%, and 99% of the solid food (n=775), drinking water (n=50), and surface wipe samples (n=138), respectively. Total BPA (free plus conjugated) was detected in 98% of the 2477 urine samples. Median urinary BPA levels were 2.07ng/mL, 2.20ng/mL-SG, 2.29ng/mg, and 2.31ng/min for concentration, SG-adjusted, CR-adjusted, and excretion rate values, respectively. The intraclass correlation coefficient (ICC) estimates for BPA showed poor reproducibility (≤0.35) for all urine sample types and methods over a day, week, and six weeks. CR-adjusted bedtime voids collected over six-weeks required the fewest, realistic number of samples (n=11) to obtain a reliable biomarker estimate (ICC=0.80). Results of linear mixed-effects models showed that sex, race, season, and CR-level were all significant predictors (p<0.05) of the adults' urinary BPA concentrations. BPA levels in the solid food and surface wipe samples did not contribute significantly to the participants' urinary BPA concentrations. However, a significant positive relationship was observed between solid food intake and urine-based estimates of BPA dose, when aggregated over 24-h periods. Ingestion of BPA via solid food explained only about 20% of the total dose (at the median of the dose distribution), suggesting that these adults were likely exposed to other major unknown (non-dietary) sources of BPA in their everyday environments. Published by Elsevier Ltd.

Optimization-based image reconstruction from sparse-view data in offset-detector CBCT

NASA Astrophysics Data System (ADS)

Bian, Junguo; Wang, Jiong; Han, Xiao; Sidky, Emil Y.; Shao, Lingxiong; Pan, Xiaochuan

2013-01-01

The field of view (FOV) of a cone-beam computed tomography (CBCT) unit in a single-photon emission computed tomography (SPECT)/CBCT system can be increased by offsetting the CBCT detector. Analytic-based algorithms have been developed for image reconstruction from data collected at a large number of densely sampled views in offset-detector CBCT. However, the radiation dose involved in a large number of projections can be of a health concern to the imaged subject. CBCT-imaging dose can be reduced by lowering the number of projections. As analytic-based algorithms are unlikely to reconstruct accurate images from sparse-view data, we investigate and characterize in the work optimization-based algorithms, including an adaptive steepest descent-weighted projection onto convex sets (ASD-WPOCS) algorithms, for image reconstruction from sparse-view data collected in offset-detector CBCT. Using simulated data and real data collected from a physical pelvis phantom and patient, we verify and characterize properties of the algorithms under study. Results of our study suggest that optimization-based algorithms such as ASD-WPOCS may be developed for yielding images of potential utility from a number of projections substantially smaller than those used currently in clinical SPECT/CBCT imaging, thus leading to a dose reduction in CBCT imaging.

Assessment of Natural Radioactivity Levels and Potential Radiological Risks of Common Building Materials Used in Bangladeshi Dwellings.

PubMed

Asaduzzaman, Khandoker; Mannan, Farhana; Khandaker, Mayeen Uddin; Farook, Mohideen Salihu; Elkezza, Aeman; Amin, Yusoff Bin Mohd; Sharma, Sailesh; Abu Kassim, Hasan Bin

2015-01-01

The concentrations of primordial radionuclides (226Ra, 232Th and 40K) in commonly used building materials (brick, cement and sand), the raw materials of cement and the by-products of coal-fired power plants (fly ash) collected from various manufacturers and suppliers in Bangladesh were determined via gamma-ray spectrometry using an HPGe detector. The results showed that the mean concentrations of 226Ra, 232Th and 40K in all studied samples slightly exceeded the typical world average values of 50 Bq kg(-1), 50 Bq kg(-1) and 500 Bq kg(-1), respectively. The activity concentrations (especially 226Ra) of fly-ash-containing cement in this study were found to be higher than those of fly-ash-free cement. To evaluate the potential radiological risk to individuals associated with these building materials, various radiological hazard indicators were calculated. The radium equivalent activity values for all samples were found to be lower than the recommended limit for building materials of 370 Bq kg(-1), with the exception of the fly ash. For most samples, the values of the alpha index and the radiological hazard (external and internal) indices were found to be within the safe limit of 1. The mean indoor absorbed dose rate was observed to be higher than the population-weighted world average of 84 nGy h(-1), and the corresponding annual effective dose for most samples fell below the recommended upper dose limit of 1 mSv y(-1). For all investigated materials, the values of the gamma index were found to be greater than 0.5 but less than 1, indicating that the gamma dose contribution from the studied building materials exceeds the exemption dose criterion of 0.3 mSv y(-1) but complies with the upper dose principle of 1 mSv y(-1).

Assessment of Natural Radioactivity Levels and Potential Radiological Risks of Common Building Materials Used in Bangladeshi Dwellings

PubMed Central

Asaduzzaman, Khandoker; Mannan, Farhana; Khandaker, Mayeen Uddin; Farook, Mohideen Salihu; Elkezza, Aeman; Amin, Yusoff Bin Mohd; Sharma, Sailesh; Abu Kassim, Hasan Bin

2015-01-01

The concentrations of primordial radionuclides (226Ra, 232Th and 40K) in commonly used building materials (brick, cement and sand), the raw materials of cement and the by-products of coal-fired power plants (fly ash) collected from various manufacturers and suppliers in Bangladesh were determined via gamma-ray spectrometry using an HPGe detector. The results showed that the mean concentrations of 226Ra, 232Th and 40K in all studied samples slightly exceeded the typical world average values of 50 Bq kg−1, 50 Bq kg−1 and 500 Bq kg−1, respectively. The activity concentrations (especially 226Ra) of fly-ash-containing cement in this study were found to be higher than those of fly-ash-free cement. To evaluate the potential radiological risk to individuals associated with these building materials, various radiological hazard indicators were calculated. The radium equivalent activity values for all samples were found to be lower than the recommended limit for building materials of 370 Bq kg-1, with the exception of the fly ash. For most samples, the values of the alpha index and the radiological hazard (external and internal) indices were found to be within the safe limit of 1. The mean indoor absorbed dose rate was observed to be higher than the population-weighted world average of 84 nGy h–1, and the corresponding annual effective dose for most samples fell below the recommended upper dose limit of 1 mSv y–1. For all investigated materials, the values of the gamma index were found to be greater than 0.5 but less than 1, indicating that the gamma dose contribution from the studied building materials exceeds the exemption dose criterion of 0.3 mSv y-1 but complies with the upper dose principle of 1 mSv y−1. PMID:26473957

Acetaminophen and meloxicam inhibit platelet aggregation and coagulation in blood samples from humans.

PubMed

Martini, Angela K; Rodriguez, Cassandra M; Cap, Andrew P; Martini, Wenjun Z; Dubick, Michael A

2014-12-01

Acetaminophen (Ace) and meloxicam (Mel) are the two types of analgesic and antipyretic medications. This study investigated the dose responses of acetaminophen and meloxicam on platelet aggregation and coagulation function in human blood samples. Blood samples were collected from six healthy humans and processed to make platelet-adjusted (100 × 10 cells/μl) blood samples. Acetaminophen (Tylenol, Q-PAP, 100 mg/ml) was added at the doses of 0 μg/ml (control), 214 μg/ml (the standard dose, 1 ×), 4 ×, 8 ×, 10 ×, 12 ×, 16 ×, and 20 ×. Similarly, meloxicam (Metacam, 5 mg/ml) was added at doses of 0 μg/ml (control), 2.85 μg/ml (the standard dose, 1 ×), 4 ×, 8 ×, 10 ×, 12 ×, 16 ×, and 20 ×. Fifteen minutes after the addition of acetaminophen and/or meloxicam, platelet aggregation was stimulated with collagen (2 μg/ml) or arachidonic acid (0.5 mmol/l) and assessed using a Chrono-Log 700 aggregometer. Coagulation function was assessed by prothrombin time (PT), activated partial thromboplastin time (aPTT), and using Rotem thrombelastogram. A robust inhibition by acetaminophen and/or meloxicam was observed in arachidonic acid-stimulated platelet aggregation starting at 1 × dose. Collagen-stimulated platelet aggregation was inhibited by ACE starting at 1 × (78 ± 10% of control), and by meloxicam starting at 4 × (72 ± 5% of control, both P < 0.05). The inhibitions by acetaminophen and meloxicam combined were similar to those by acetaminophen or meloxicam. aPTT was prolonged by meloxicam starting at 4 ×. No changes were observed in PT or any of Rotem measurements by acetaminophen and/or meloxicam. Acetaminophen and meloxicam compromised platelet aggregation and aPTT. Further effort is warranted to characterize the effects of acetaminophen and meloxicam on bleeding in vivo.

Pharmacokinetic Properties and Tolerability of Cycloserine Following Oral Administration in Healthy Chinese Volunteers: A Randomized, Open-Label, Single- and Multiple-Dose 3-Way Crossover Study.

PubMed

Zhou, Huili; Wu, Guolan; Hu, Xingjiang; Zhu, Meixiang; Zhai, You; Liu, Jian; Shentu, Jianzhong; Wu, Lihua

2015-06-01

A new generic formulation of cycloserine has been developed in China but the pharmacokinetic properties of cycloserine in the Chinese population have not been reported. The aim of our study was to evaluate the pharmacokinetic properties and tolerability of single and multiple oral administrations of cycloserine capsules in healthy Chinese volunteers. This open-label, single- and multiple-dose 3-way crossover study was conducted in healthy Chinese volunteers. Subjects were randomized to receive a single dose of cycloserine (250, 500, or 1000 mg) in separate trial periods, with a 1-week washout between periods. Those allocated to the 250-mg dose continued into the multiple-dose phase, in which they received 250 mg BID for 5 consecutive days. During the single-dose phase, blood samples were collected at regular intervals from 0 to 72 hours after drug administration and the concentrations of cycloserine were determined using LC-MS/MS. During the multiple-dose phase, blood samples were obtained before drug administration on Days 4, 5, and 6 to determine the Cmin at steady state. On Day 6, blood samples were also collected from 0 to 72 hours after drug administration. Pharmacokinetic parameters were estimated using noncompartmental methods. Tolerability was determined using clinical evaluation and monitoring of adverse events. The study enrolled 12 healthy Chinese volunteers (6 men: mean [SD] age = 23.0 [2.6] years, weight = 60.2 [6.2] kg, height = 170.0 [3.0] cm, and body mass index = 20.7 [1.7]; 6 women: mean [SD] age = 25.3 [1.4] years, weight = 51.5 [3.3] kg, height = 160.0 [4.0] cm, and body mass index = 20.1 [0.9]). After administration of a single dose, cycloserine was rapidly absorbed, reaching peak plasma concentrations approximately 0.84 hours after oral administration, and t½ in plasma was about 13.0 hours. The geometric mean (SD) Cmax value increased in proportion to cycloserine dose, from 19.42 (5.89) to 84.76 (21.74) mg/L, and the geometric mean (SD) AUC0-72h value increased from 264.16 (133.37) to 1153.87 (522.16) mg·h/L in the range of a 250- to 1000-mg dose. After administration of multiple doses of cycloserine 250 mg BID, the mean (SD) t½ was 13.56 (4.38) hours, the apparent total clearance of the drug from plasma after oral administration was 1.02 (0.42) L/h, and the apparent volume of distribution was 18.22 (5.25) L, which were comparable with those after single dosing. The accumulation index was 2.19 (0.51), and the fluctuation was 1.05 (0.35). Results of the t tests of Cmax and AUC found no significant differences between the male and female groups. No serious adverse events were reported, and there were no discontinuations due to adverse events. The pharmacokinetic properties of cycloserine were linear at doses from 250 mg to 1000 mg. After multiple doses, the pharmacokinetic properties of cycloserine were consistent with those after single doses. At the doses studied, cycloserine appears to be well tolerated in these healthy volunteers. Chinese Clinical Trials registration: ChiCTR-TTRCC-13003982. Copyright © 2015. Published by Elsevier Inc.

Annual radiological environmental operating report, Browns Ferry Nuclear Plant, 1987

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1988-04-01

This report describes the environmental radiological monitoring programs conducted by TVA in the vicinity of Browns Ferry Nuclear Plant in 1987. The program includes the collection of samples from the environment and the determination of the concentrations of radioactive materials in the samples. Samples are taken from stations in the general area of the plant and from areas not influenced by plant operations. Station locations are selected after careful consideration of the weather patterns and projected radiation doses to the various areas around the plant. Material sampled includes air, water, milk, foods, vegetation, soil, fish, sediment, and direct radiation levels.more » Results from stations near the plant are compared with concentrations from control stations and with preoperational measurements to determine potential impacts of plant operations. The vast majority of the exposures calculated from environmental samples were contributed by naturally occurring radioactive materials or from materials commonly found in the environment as a result of atmospheric nuclear weapons fallout. Small amounts of Co-60 were found in sediment samples downstreams from the plant. This activity in stream sediment would result in no measurable increase over background in the dose to the general public. 3 refs., 2 figs., 34 tabs.« less

Browns Ferry Nuclear Plant annual radiological environmental operating report, 1990

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1991-04-01

This report describes the environmental radiological monitoring program conducted by TVA in the vicinity of Browns Ferry Nuclear Plant in 1990. The program includes the collection of samples from the environment and the determination of the concentrations of radioactive materials in the samples. Samples are taken from stations in the general area of the plant and from areas not influenced by plant operations. Station locations are selected after careful consideration of the weather patterns and projected radiation doses to the various areas around the plant. Material sampled includes air, water, milk, foods, vegetation, soil, fish, sediment, and direct radiation levels.more » Results from stations near the plant are compared with concentrations from control stations and with preoperational measurements to determine potential impacts of plant operations. The vast majority of the exposures calculated from environmental samples were contributed by naturally occurring radioactive materials or from materials commonly found in the environment as a result of atmospheric nuclear weapons fallout. Small amounts of Co-60 were found in sediment samples downstream from the plant. This activity in stream sediment would result in no measurable increase over background in the dose to the general public. 4 refs., 2 figs., 2 tabs.« less

Annual radiological environmental operating report, Browns Ferry Nuclear Plant, 1989

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1990-04-01

This report describes the environmental radiological monitoring program conducted by TVA in the vicinity of Browns Ferry Nuclear Plant (BFN) in 1989. The program includes the collection of samples from the environment and the determination of the concentrations of radioactive materials in the samples. Samples are taken from stations in the general area of the plant and from areas not influenced by plant operations. Station locations are selected after careful consideration of the weather patterns and projected radiation doses to the various areas around the plant. Material sampled includes air, water, milk, foods, vegetation, soil, fish, sediment, and direct radiationmore » levels. Results from stations near the plant are compared with concentrations from control stations and with preoperational measurements to determine potential impacts if plant operations. The vast majority of the exposures calculated from environmental samples were contributed by naturally occurring radioactive materials or from materials commonly found in the environment as a result of atmospheric nuclear weapons fallout. Small amounts of Co-60 were found in sediment samples downstream from the plant. This activity in river sediment would result in no measurable increase over background in the dose to the general public. 4 refs., 2 figs., 2 tabs.« less

Annual radiological environmental operating report, Browns Ferry Nuclear Plant, 1988

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1989-04-01

This report describes the environmental radiological monitoring program conducted by TVA in the vicinity of Browns Ferry Nuclear Plant in 1988. The program includes the collection of samples from the environment and the determination of the concentrations of radioactive materials in the samples. Samples are taken from stations in the general area of the plant and from areas not influenced by plant operations. Station locations are selected after careful consideration of the weather patterns and projected radiation doses to the various areas around the plant. Material sampled includes air, water, milk, foods, vegetation, soil, fish, sediment, and direct radiation levels.more » Results from stations near the plant are compared with concentrations from control stations and with preoperational measurements to determine potential impacts of plant operations. The vast majority of the exposures calculated from environmental samples were contributed by naturally occurring radioactive materials or from materials commonly found in the environment as a result of atmospheric nuclear weapons fallout. Small amounts of Co-60 were found in sediment samples downstream from the plant. This activity in stream sediment would result in no measurable increase over background in the dose to the general public. 3 refs., 2 figs., 2 tabs.« less

[Erythropoietin influence on oxygen transport function of blood and prooxidant/antioxidant balance in rabbits under lipopolysaccharide injection].

PubMed

Zinchuk, V V; Shul'ga, E V; Guliaĭ, I E

2010-01-01

We aimed to study the erythropoietin influence on oxygen transport function of blood and prooxidant/antioxidant balance in rabbits under lipopolysaccharide injection. Recombinant human erythropoietin-alpha was administered intraperitoneally in the dose 1000 U/kg 30 minutes before intravenous injection of 500 mkg/kg lipopolysaccharide from E. coli. After 12 hours, blood samples were collected for the assessment of oxygen transport function of blood; nitrate/nitrite levels and tissue samples were collected for measurement of conjugated dienes, malondialdehyde, alpha-tocopherol and catalase. Erythropoietin improves parameters of oxygen transport function of blood, increases hemoglobin-oxygen affinity through the NO-dependent mechanism, reduces activity of free radical processes, and increases antioxidant protection under lipopolysaccharide injection.

Maintenance treatment for opioid dependence with slow-release oral morphine: a randomized cross-over, non-inferiority study versus methadone

PubMed Central

Beck, Thilo; Haasen, Christian; Verthein, Uwe; Walcher, Stephan; Schuler, Christoph; Backmund, Markus; Ruckes, Christian; Reimer, Jens

2014-01-01

Aims To compare the efficacy of slow-release oral morphine (SROM) and methadone as maintenance medication for opioid dependence in patients previously treated with methadone. Design Prospective, multiple-dose, open label, randomized, non-inferiority, cross-over study over two 11-week periods. Methadone treatment was switched to SROM with flexible dosing and vice versa according to period and sequence of treatment. Setting Fourteen out-patient addiction treatment centres in Switzerland and Germany. Participants Adults with opioid dependence in methadone maintenance programmes (dose ≥50 mg/day) for ≥26 weeks. Measurements The efficacy end-point was the proportion of heroin-positive urine samples per patient and period of treatment. Each week, two urine samples were collected, randomly selected and analysed for 6-monoacetyl-morphine and 6-acetylcodeine. Non-inferiority was concluded if the two-sided 95% confidence interval (CI) in the difference of proportions of positive urine samples was below the predefined boundary of 10%. Findings One hundred and fifty-seven patients fulfilled criteria to form the per protocol population. The proportion of heroin-positive urine samples under SROM treatment (0.20) was non-inferior to the proportion under methadone treatment (0.15) (least-squares mean difference 0.05; 95% CI = 0.02, 0.08; P > 0.01). The 95% CI fell within the 10% non-inferiority margin, confirming the non-inferiority of SROM to methadone. A dose-dependent effect was shown for SROM (i.e. decreasing proportions of heroin-positive urine samples with increasing SROM doses). Retention in treatment showed no significant differences between treatments (period 1/period 2: SROM: 88.7%/82.1%, methadone: 91.1%/88.0%; period 1: P = 0.50, period 2: P = 0.19). Overall, safety outcomes were similar between the two groups. Conclusions Slow-release oral morphine appears to be at least as effective as methadone in treating people with opioid use disorder. PMID:24304412

Weekly dose of Iron-Folate Supplementation with Vitamin-C in the workplace can prevent anaemia in women employees

PubMed Central

Joseph, Bobby; Ramesh, Naveen

2013-01-01

Objective: To assess if a weekly dose of iron and folic acid along with vitamin C, in the workplace would reduce the prevalence of anaemia. Methodology: A multi-pronged intervention was carried out to reduce the prevalence of anaemia among workers of 7 apparel manufacturing factories using a regime consisting of a supervised single dose of albendazole (400mg) followed by a weekly dose of dried ferrous sulphate (150mg), folic acid (0.5mg) and vitamin C (100mg). Workers were provided information on the causes of anaemia and its prevention. The total duration of the intervention was 16 weeks. Haemoglobin levels of a randomly selected sample of workers were tested before and after the intervention using a computerized non-cyan-meth-haemoglobin method. Results: Of the 10810 workers who were enrolled a sample of 515 workers was randomly selected for the blood investigations. At the end of the intervention (18 weeks after the first blood sample was collected) only 361 out of the 515 who had been enrolled a little more than 16 weeks earlier still remained in the factories and among women 279 out of 385 enrolled were still working in the factories. In the 385 unmatched samples the number of anaemic women had reduced from 141 before the intervention to 79 after - mean haemoglobin increasing from 12.2 to 13.0 (p < 0.001) and in the 279 paired samples prevalence of anaemia had reduced from 105 to 58 - mean haemoglobin increasing from 12.1 to 13.0 (p < 0.001). Conclusions: Our results demonstrated that in resource poor regions, where prevalence of anaemia is high, the workplace may be considered an ideal location to give a weekly supervised dose of iron, folic acid and vitamin C to effectively tackle the problem and probably improve worker efficiency. PMID:24353506

Radioactivity Levels and Gamma-Ray Dose Rate in Soil Samples from Kohistan (Pakistan) Using Gamma-Ray Spectrometry

NASA Astrophysics Data System (ADS)

Hasan, M. Khan; Ismail, M.; K., Khan; Akhter, P.

2011-01-01

The analysis of naturally occurring radionuclides (226Ra, 232Th and 40K) and an anthropogenic radionuclide 137Cs is carried out in some soil samples collected from Kohistan district of N.W.F.P. (Pakistan), using gamma-ray spectrometry. The gamma spectrometry is operated using a high purity Germanium (HPGe) detector coupled with a computer based high resolution multi channel analyzer. The specific activity in soil ranges from 24.72 to 78.48Bq·kg-1 for 226Ra, 21.73 to 75.28Bq·kg-1 for 232Th, 7.06 to 14.9Bq·kg-1 for 137Cs and 298.46 to 570.77Bq·kg-1 for 40K with the mean values of 42.11, 43.27, 9.5 and 418.27Bq·kg-1, respectively. The radium equivalent activity in all the soil samples is lower than the safe limit set in the OECD report (370Bq·kg-1). Man-made radionuclide 137Cs is also present in detectable amount in all soil samples. Presence of 137Cs indicates that the samples in this remote area also receive some fallout from nuclear accident in Chernobyl power plant in 1986. The internal and external hazard indices have the mean values of 0.48 and 0.37 respectively. Absorbed dose rates and effective dose equivalents are also determined for the samples. The concentration of radionuclides found in the soil samples during the present study is nominal and does not pose any potential health hazard to the general public.

Laser-based irradiation apparatus and methods for monitoring the dose-rate response of semiconductor devices

DOEpatents

Horn, Kevin M [Albuquerque, NM

2006-03-28

A scanned, pulsed, focused laser irradiation apparatus can measure and image the photocurrent collection resulting from a dose-rate equivalent exposure to infrared laser light across an entire silicon die. Comparisons of dose-rate response images or time-delay images from before, during, and after accelerated aging of a device, or from periodic sampling of devices from fielded operational systems allows precise identification of those specific age-affected circuit structures within a device that merit further quantitative analysis with targeted materials or electrical testing techniques. Another embodiment of the invention comprises a broad-beam, dose rate-equivalent exposure apparatus. The broad-beam laser irradiation apparatus can determine if aging has affected the device's overall functionality. This embodiment can be combined with the synchronized introduction of external electrical transients into a device under test to simulate the electrical effects of the surrounding circuitry's response to a radiation exposure.

Pharmacokinetic Studies in Neonates: The Utility of an Opportunistic Sampling Design.

PubMed

Leroux, Stéphanie; Turner, Mark A; Guellec, Chantal Barin-Le; Hill, Helen; van den Anker, Johannes N; Kearns, Gregory L; Jacqz-Aigrain, Evelyne; Zhao, Wei

2015-12-01

The use of an opportunistic (also called scavenged) sampling strategy in a prospective pharmacokinetic study combined with population pharmacokinetic modelling has been proposed as an alternative strategy to conventional methods for accomplishing pharmacokinetic studies in neonates. However, the reliability of this approach in this particular paediatric population has not been evaluated. The objective of the present study was to evaluate the performance of an opportunistic sampling strategy for a population pharmacokinetic estimation, as well as dose prediction, and compare this strategy with a predetermined pharmacokinetic sampling approach. Three population pharmacokinetic models were derived for ciprofloxacin from opportunistic blood samples (SC model), predetermined (i.e. scheduled) samples (TR model) and all samples (full model used to previously characterize ciprofloxacin pharmacokinetics), using NONMEM software. The predictive performance of developed models was evaluated in an independent group of patients. Pharmacokinetic data from 60 newborns were obtained with a total of 430 samples available for analysis; 265 collected at predetermined times and 165 that were scavenged from those obtained as part of clinical care. All datasets were fit using a two-compartment model with first-order elimination. The SC model could identify the most significant covariates and provided reasonable estimates of population pharmacokinetic parameters (clearance and steady-state volume of distribution) compared with the TR and full models. Their predictive performances were further confirmed in an external validation by Bayesian estimation, and showed similar results. Monte Carlo simulation based on area under the concentration-time curve from zero to 24 h (AUC24)/minimum inhibitory concentration (MIC) using either the SC or the TR model gave similar dose prediction for ciprofloxacin. Blood samples scavenged in the course of caring for neonates can be used to estimate ciprofloxacin pharmacokinetic parameters and therapeutic dose requirements.

Effect of antacid on the bioavailabiity of lithium carbonate.

PubMed

Goode, D L; Newton, D W; Ueda, C T; Wilson, J E; Wulf, B G; Kafonek, D

1984-01-01

The effect of an antacid on the bioavailability of lithium carbonate was determined in six healthy men in a crossover study. The volunteers were given single 300-mg doses of lithium carbonate alone and with 30 ml of an antacid containing aluminum and magnesium hydroxides with simethicone. Blood samples were collected at various times for 0-24 hours after each dose. The plasma samples were analyzed for lithium using a spectrophotometer, and bioavailability variables were calculated from plasma lithium concentration-time curves. There were no significant differences in peak plasma lithium concentration, time to peak concentration, area under the concentration-time curve from 0 to 24 hours, first-order absorption rate constant, and first-order elimination rate constant between the two treatments. Concurrent administration of antacids and lithium carbonate should not affect lithium blood concentrations.

Phthalates in dormitory and house dust of northern Chinese cities: Occurrence, human exposure, and risk assessment.

PubMed

Li, Hai-Ling; Song, Wei-Wei; Zhang, Zi-Feng; Ma, Wan-Li; Gao, Chong-Jing; Li, Jia; Huo, Chun-Yan; Mohammed, Mohammed O A; Liu, Li-Yan; Kannan, Kurunthachalam; Li, Yi-Fan

2016-09-15

Phthalates are widely used chemicals in household products, which severely affect human health. However, there were limited studies emphasized on young adults' exposure to phthalates in dormitories. In this study, seven phthalates were extracted from indoor dust that collected in university dormitories in Harbin, Shenyang, and Baoding, in the north of China. Dust samples were also collected in houses in Harbin for comparison. The total concentrations of phthalates in dormitory dust in Harbin and Shenyang samples were significantly higher than those in Baoding samples. The total geometric mean concentration of phthalates in dormitory dust in Harbin was lower than in house dust. Di-(2-ethylhexyl) phthalate (DEHP) was the most abundant phthalate in both dormitory and house dust. The daily intakes of the total phthalates, carcinogenic risk (CR) of DEHP, hazard index (HI) of di-isobutyl phthalate (DiBP), dibutyl phthalate (DBP), and DEHP were estimated, the median values for all students in dormitories were lower than adults who live in the houses. Monte Carlo simulation was applied to predict the human exposure risk of phthalates. HI of DiBP, DBP, and DEHP was predicted according to the reference doses (RfD) provided by the United States Environmental Protection Agency (U.S.EPA) and the reference doses for anti-androgenicity (RfD AA) developed by Kortenkamp and Faust. The results indicated that the risks of some students had exceeded the limitation, however, the measured results were not exceeded the limitation. Risk quotients (RQ) of DEHP were predicted based on China specific No Significant Risk Level (NSRL) and Maximum Allowable Dose Level (MADL). The predicted results of CR and RQ of DEHP suggested that DEHP could pose a health risk through intake of indoor dust. Copyright © 2016 Elsevier B.V. All rights reserved.

Tailored interventions for screening mammography among a sample of initially non-adherent women: when is a booster dose important?

PubMed

Skinner, Celette Sugg; Kobrin, Sarah C; Monahan, Patrick O; Daggy, Joanne; Menon, Usha; Todora, Helen Smith; Champion, Victoria L

2007-01-01

To assess added value of a booster dose of a tailored mammography intervention. Participants, non-adherent at baseline, were randomly assigned to usual care or one of three tailored interventions. Intervention group members (n=657) were further randomly assigned to receive/not receive a booster intervention dose. Electronic record mammography data were collected following initial intervention and at 6 and 15 months post-booster. Booster had no effect among women not screened after first intervention dose (n=337). Among women screened after initial dose (n=320), booster predicted re-screening at 6 but not 15 months. A boosterxrace interaction showed a booster effect at 6 months for African Americans (OR=4.66, p=.0005) but not Caucasians (OR=0.74, p=.44). Findings suggest if a first-dose intervention does not facilitate screening, neither will a booster dose. However, among women for whom a first dose is effective, boosters can facilitate timely repeat adherence, especially among African Americans. At 6 months booster recipients were less likely to be off-schedule but, by 15 months, the groups were similar. Boosters may effect when, but not whether, women continue screening.

Evaluation of Gamma Radiation-Induced Biochemical Changes in Skin for Dose Assesment: A Study on Small Experimental Animals.

PubMed

Kumar Soni, Sandeep; Basu, Mitra; Agrawal, Priyanka; Bhatnagar, Aseem; Chhillar, Neelam

2018-05-24

Researchers have been evaluating several approaches to assess acute radiation injury/toxicity markers owing to radiation exposure. Keeping in mind this background, we assumed that whole-body irradiation in single fraction in graded doses can affect the antioxidant profile in skin that could be used as an acute radiation injury/toxicity marker. Sprague-Dawley rats were treated with CO-60 gamma radiation (dose: 1-5 Gy; dose rate: 0.85 Gy/minute). Skin samples were collected (before and after radiation up to 72 hours) and analyzed for glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation (LPx). Intra-group comparison showed significant differences in GSH, GPx, SOD, and CAT, and they declined in a dose-dependent manner from 1 to 5 Gy (P value0.05). This study suggests that skin antioxidants were sensitive toward radiation even at a low radiation dose, which can be used as a predictor of radiation injury and altered in a dose-dependent manner. These biochemical parameters may have wider application in the evaluation of radiation-induced skin injury and dose assessment. (Disaster Med Public Health Preparedness. 2018;page 1 of 6).

Albendazole Stimulates the Excretion of Strongyloides stercoralis Larvae in Stool Specimens and Enhances Sensitivity for Diagnosis of Strongyloidiasis▿

PubMed Central

Anamnart, Witthaya; Pattanawongsa, Attarat; Intapan, Pewpan Maleewong; Maleewong, Wanchai

2010-01-01

We succeeded in stimulation of excretion of Strongyloides stercoralis larvae in stool by oral administration of a single dose of 400 mg albendazole to strongyloidiasis patients. This result overcame the false-negative results of stool examination due to low larval numbers. Stool samples were collected from 152 asymptomatic strongyloidiasis patients in the morning, prior to eating. After breakfast, they were given a dose of 400 mg albendazole, and stool samples were collected the following morning. Agar plate culture (APC), modified formalin-ether concentration technique (MFECT), and direct-smear (DS) methods were used to examine stool specimens within 3 h after defecation. The results before and after albendazole was taken were compared. All APCs that were positive became negative after albendazole administration, while MFECT showed a 1.4- to 18.0-fold increase in larval numbers in 97.4% (148/152) of the samples. The DSs were positive in 3 out of 3 smears at a larval number of ≥45 larvae per g (lpg) of stool, and in 1or 2 out of 3 smears at a larval number between 35 and 44 lpg. At a larval number of <35 lpg, the DS became negative. Interestingly 90.5% (19/21) of the samples that were negative by all methods before albendazole administration became positive by MFECT after the treatment. Thus, MFECT can be effectively used for diagnosis of strongyloidiasis with prior administration of albendazole to the subject. PMID:20844212

The Prevalence of PCR-Confirmed Pertussis Cases in Palestine From Archived Nasopharyngeal Samples.

PubMed

Dumaidi, Kamal; Al-Jawabreh, Amer

2018-05-01

Pertussis caused by Bordetella pertussis is a vaccine-preventable disease causing whooping cough in humans of all ages. This study reports infection rate of pertussis in Palestine between the years 2004-2008 from archived nasopharyngeal samples collected from clinically- suspected cases. A convenience archived DNA samples collected from 267 clinically-suspected pertussis cases were investigated for B. pertussis. Laboratory diagnosis was done by examining all DNA samples using polymerase chain reaction (PCR). Approximately 49% (130/267) were confirmed by PCR. A pertussis peak was shown to occur in 2008 with 77% (100/130) of PCR-confirmed cases isolated in that year. PCR-confirmed cases existed in all Palestinian districts with highest rate in Ramallah, Bethlehem, Jenin and Al-Khalil. Half of the PCR-confirmed cases (68/130) were less than 2 months old. The positivity rate among who had three doses of vaccine (at 2, 4 and 6 months) was 38%, and became 50% with the fourth dose at 12 months. The prevalence of pertussis was found to be significantly high among infants less than 2 months old. Active pertussis surveillance using rapid PCR assays is essential, as it is helpful in prompt diagnosis and treatment of patients with pertussis. © 2018 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Low-angle X-ray scattering properties of irradiated spices

NASA Astrophysics Data System (ADS)

Almeida, A. P. G.; Braz, D.; Barroso, R. C.; Lopes, R. T.

2007-09-01

The scattering of X-rays at low angles (LAXS) is a technique dominated by the coherent scattering process. One characteristic observation of low-angle coherent scattering is the so-called molecular interference effect, being characterized by the presence of one or more peaks in the forward direction of scattering. In the present study, LAXS profiles from five different spices are carefully measured in order to establish characteristic scattering signatures. Samples of Ceylon cinnamon, cumin, nutmeg, paprika and black pepper were bought in local market in Rio de Janeiro, Brazil. The LAXS patterns were obtained using a Shimadzu DRX 6000 diffractometer in reflection geometry. Coherent scattering patterns are measured for the samples for θ=5-35°. The data were collected in 0.05° increments every 3 s. In order to evaluate the possible molecular structure changes caused to the irradiation procedure, the signatures obtained for control (non-irradiated) spices were compared with spice samples irradiated with different doses varying from 3 to 40 kGy. The LAXS patterns of all samples were obtained after 30, 60, 90, 120 days to evaluate the effect of storage period. Scattering profiles from spices irradiated with different irradiation doses were obtained and the results compared. For each spice, there is no considerable deviation in shape in function of the irradiation dose. It indicates that the molecular structure of each analyzed spices is preserved considering the dose range chosen. The results show that the molecular structure was found to be stable during storage at the ambient temperature for up to 4 months.

Relationship of soil terrestrial radionuclide concentrations and the excess of lifetime cancer risk in western Mazandaran Province, Iran.

PubMed

Abbaspour, M; Moattar, F; Okhovatian, A; Kharrat Sadeghi, M

2010-12-01

The main goal of this study is to lay out the map of the soil radionuclide activity concentrations and the terrestrial outdoor gamma dose rates in the western Mazandaran Province of Iran, and to present an evaluation scheme. Mazandaran Province was selected due to its special geographical characteristics, high population density and the long terrestrial and aquatic borders with the neighbouring countries possessing nuclear facilities. A total of 54 topsoil samples were collected, ranging from the Nour to Ramsar regions, and were based on geological conditions, vegetation coverage and the sampling standards outlined by the International Atomic Energy Agency. The excess lifetime cancer risks (ELCRs) were evaluated and the coordinates of sampling locations were determined by the global positioning system. The average terrestrial outdoor gamma dose rate was 612.38 ± 3707.93 nGy h(-1), at 1 m above the ground. The annual effective gamma dose at the western part of Mazandaran Province was 750 μSv, and the ELCR was 0.26 × 10(-2). Soil samples were analysed by gamma spectrometry with a high-purity germanium detector. The average (226)Ra, (232)Th, (40)K and (137)Cs activities were 1188.50 ± 7838.40, 64.92 ± 162.26, 545.10 ± 139.42 and 10.41 ± 7.86 Bq kg(-1), respectively. The average soil radionuclide concentrations at the western part of Mazandaran Province were higher than the worldwide range. The excess lifetime risks of cancer and the annual effective gamma doses were also higher than the global average.

Initial formal toxicity evaluation of APC-2, a novel fluorescent tracer agent for real-time measurement of glomerular filtration rate in preparation for a first-in-man clinical trial

NASA Astrophysics Data System (ADS)

Bugaj, Joseph E.; Dorshow, Richard B.

2014-03-01

The fluorescent tracer agent 2,5-bis[N-(1-carboxy-2-hydroxy)]carbamoyl-3,6-diaminopyrazine, designated APC-2, has been developed with properties and attributes necessary for use as a direct measure of glomerular filtration rate (GFR). Comparison to known standard exogenous GFR agents in animal models has demonstrated an excellent correlation. A clinical trial to demonstrate this same correlation in humans is in preparation. A battery of formal toxicity tests necessary for regulatory clearance to proceed with a clinical trial has been recently completed on this new fluorescent tracer agent. These include single dose toxicity studies in rats and dogs to determine overall toxicity and toxicokinetics of the compound. Blood compatibility, mutation assay, chromosomal aberration assay, and several other assays were also completed. Toxicity assessments were based on mortality, clinical signs, body weight, food consumption and anatomical pathology. Blood samples were collected to assess pharmacokinetic parameters including half-life, area under the curve, and clearance. Urine samples were collected to assess distribution. Doses of up to 200-300 times the estimated human dose were administered. No test-article related effects were noted on body weight, food consumption, ophthalmic observations and no abnormal pathology was seen in either macroscopic or microscopic evaluations of any organs or tissues. All animals survived to scheduled sacrifice. Transient discoloration of skin and urine was noted at the higher dose levels in both species as expected from a highly fluorescent compound and was not considered pathological. Thus initial toxicology studies of this new fluorescent tracer agent APC-2 have resulted in no demonstrable pathological test article concerns.

A Study of the Focal Adhesion Kinase Inhibitor GSK2256098 in Patients with Recurrent Glioblastoma with Evaluation of Tumor Penetration of [11C]GSK2256098.

PubMed

Brown, Nicholas F; Williams, Matthew; Arkenau, Hendrik-Tobias; Fleming, Ronald A; Tolson, Jerry; Yan, Li; Zhang, Jianping; Swartz, Lisa; Singh, Rajendra; Auger, Kurt R; Lenox, Laurie; Cox, David; Lewis, Yvonne; Plisson, Christophe; Searle, Graham; Saleem, Azeem; Blagden, Sarah; Mulholland, Paul

2018-05-17

GSK2256098 is a novel oral focal adhesion kinase inhibitor. Preclinical studies demonstrate growth inhibition in glioblastoma cell lines. However, rodent studies indicate limited blood-brain barrier penetration. In this expansion cohort within a phase I study, the safety, tolerability, pharmacokinetics and clinical activity of GSK2256098 were evaluated in patients with recurrent glioblastoma. Biodistribution and kinetics of [11C]GSK2256098 were assessed in a sub-study using positron-emission tomography (PET). Patients were treated with GSK2256098 until disease progression or withdrawal due to adverse events (AEs). Serial pharmacokinetic samples were collected on Day 1. On a single day between Days 9-20, patients received a microdose of intravenous [11C]GSK2256098 and scanned with PET over 90 minutes with parallel PK sample collection. Response was assessed by MRI every six weeks. Thirteen patients were treated in three dose cohorts (1000 mg, 750 mg, 500 mg; all dosed twice-daily). The maximum tolerated dose was 1000 mg twice-daily. Dose-limiting toxicities were related to cerebral edema. Treatment-related AEs (>25%) were diarrhea, fatigue and nausea. Eight patients participated in the PET sub-study, with [11C]GSK2256098 VT estimates of 0.9 in tumor tissue, 0.5 in surrounding T2 enhancing areas, and 0.4 in normal brain,. Best response of stable disease was observed in three patients, including one patient on treatment for 11.3 months. GSK2256098 was tolerable in patients with relapsed glioblastoma. GSK2256098 crossed the blood-brain barrier at low levels into normal brain, but at markedly higher levels into tumor, consistent with tumor-associated blood-brain barrier disruption. Additional clinical trials of GSK2256098 are ongoing.

SU-E-J-85: Leave-One-Out Perturbation (LOOP) Fitting Algorithm for Absolute Dose Film Calibration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chu, A; Ahmad, M; Chen, Z

2014-06-01

Purpose: To introduce an outliers-recognition fitting routine for film dosimetry. It cannot only be flexible with any linear and non-linear regression but also can provide information for the minimal number of sampling points, critical sampling distributions and evaluating analytical functions for absolute film-dose calibration. Methods: The technique, leave-one-out (LOO) cross validation, is often used for statistical analyses on model performance. We used LOO analyses with perturbed bootstrap fitting called leave-one-out perturbation (LOOP) for film-dose calibration . Given a threshold, the LOO process detects unfit points (“outliers”) compared to other cohorts, and a bootstrap fitting process follows to seek any possibilitiesmore » of using perturbations for further improvement. After that outliers were reconfirmed by a traditional t-test statistics and eliminated, then another LOOP feedback resulted in the final. An over-sampled film-dose- calibration dataset was collected as a reference (dose range: 0-800cGy), and various simulated conditions for outliers and sampling distributions were derived from the reference. Comparisons over the various conditions were made, and the performance of fitting functions, polynomial and rational functions, were evaluated. Results: (1) LOOP can prove its sensitive outlier-recognition by its statistical correlation to an exceptional better goodness-of-fit as outliers being left-out. (2) With sufficient statistical information, the LOOP can correct outliers under some low-sampling conditions that other “robust fits”, e.g. Least Absolute Residuals, cannot. (3) Complete cross-validated analyses of LOOP indicate that the function of rational type demonstrates a much superior performance compared to the polynomial. Even with 5 data points including one outlier, using LOOP with rational function can restore more than a 95% value back to its reference values, while the polynomial fitting completely failed under the same conditions. Conclusion: LOOP can cooperate with any fitting routine functioning as a “robust fit”. In addition, it can be set as a benchmark for film-dose calibration fitting performance.« less

Daily radionuclide ingestion and internal radiation doses in Aomori prefecture, Japan.

PubMed

Ohtsuka, Yoshihito; Kakiuchi, Hideki; Akata, Naofumi; Takaku, Yuichi; Hisamatsu, Shun'ichi

2013-10-01

To assess internal annual dose in the general public in Aomori Prefecture, Japan, 80 duplicate cooked diet samples, equivalent to the food consumed over a 400-d period by one person, were collected from 100 volunteers in Aomori City and the village of Rokkasho during 2006–2010 and were analyzed for 11 radionuclides. To obtain average rates of ingestion of radionuclides, the volunteers were selected from among office, fisheries, agricultural, and livestock farm workers. Committed effective doses from ingestion of the diet over a 1-y period were calculated from the analytical results and from International Commission on Radiological Protection dose coefficients; for 40K, an internal effective dose rate from the literature was used. Fisheries workers had significantly higher combined internal annual dose than the other workers, possibly because of high rates of ingestion of marine products known to have high 210Po concentrations. The average internal dose rate, weighted by the numbers of households in each worker group in Aomori Prefecture, was estimated at 0.47 mSv y-1. Polonium-210 contributed 49% of this value. The sum of committed effective dose rates for 210Po, 210Pb, 228Ra, and 14C and the effective dose rate of 40K accounted for approximately 99% of the average internal dose rate.

Using smartphone as a motion detector to collect time-microenvironment data for estimating the inhalation dose.

PubMed

Hoi, Tran Xuan; Phuong, Huynh Truc; Van Hung, Nguyen

2016-09-01

During the production of iodine-131 from neutron irradiated tellurium dioxide by the dry distillation, a considerable amount of (131)I vapor is dispersed to the indoor air. People who routinely work at the production area may result in a significant risk of exposure to chronic intake by inhaled (131)I. This study aims to estimate the inhalation dose for individuals manipulating the (131)I at a radioisotope production. By using an application installed on smartphones, we collected the time-microenvironment data spent by a radiation group during work days in 2015. Simultaneously, we used a portable air sampler combined with radioiodine cartridges for grabbing the indoor air samples and then the daily averaged (131)I concentration was calculated. Finally, the time-microenvironment data jointed with the concentration to estimate the inhalation dose for the workers. The result showed that most of the workers had the annual internal dose in 1÷6mSv. We concluded that using smartphone as a motion detector is a possible and reliable way instead of the questionnaires, diary or GPS-based method. It is, however, only suitable for monitoring on fixed indoor environments and limited the targeted people. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluating cytochrome P450 in birds by monooxygenases and immunohistochemistry: possible nonlethal assessment by skin immunohistochemistry

USGS Publications Warehouse

Melancon, M.J.; Kutay, A.L.; Woodin, Bruce R.; Stegeman, John J.

2000-01-01

Six month old Lesser Scaup and nestling Tree Swallows were injected intraperitoneally with beta-naphthoflavone (BNF) or vehicle. Nestling Tree Swallows were also collected from five sites with differing levels of contaminants. Liver samples were taken and stored at -80C until microsome preparation and monooxygenase (MO) assay. Skin and heart samples were placed in buffered formalin until immunohistochemical (IMHC) analysis for cytochrome P4501A (CYP1A). Scaup treated with BNF at 20 or 100 mg/kg body weight showed approximately 20- to 65-fold increases in four MOs. Responses of two of the four MOs were as high at 20 mg/kg as at 100mg/kg. There was no IMHC response in the vehicle-injected ducks, while in skin the IMHC response was the same for both dose levels of BNF and in heart there was response in two of four samples at 20 mg/kg and in all five samples at 100mg/kg. Tree Swallows injected with BNF at 100, but not at 20 mg/kg showed significant increases (ca.5-fold) in two MO activities. There was no IMHC response in control swallows. In skin and heart there were IMHC responses in one of five swallows at 20 mg/kg and four of five swallows at 100mg/kg. There was poor correlation between individual skin IMHC responses and MO activities and PCB concentrations in 47 field-collected Tree Swallow samples, but 14 of the 16 skin samples with positive IMHC responses were from the location with the highest MO activities and PCB concentrations. Although present data do not allow construction of significant dose response curves, the responses in skin make it well worth continuing study on this potential nonlethal technique for biomonitoring contaminant exposure of birds.

A comparative study of removal of fluoride from contaminated water using shale collected from different coal mines in India.

PubMed

Biswas, Gargi; Dutta, Manjari; Dutta, Susmita; Adhikari, Kalyan

2016-05-01

Low-cost water defluoridation technique is one of the most important issues throughout the world. In the present study, shale, a coal mine waste, is employed as novel and low-cost adsorbent to abate fluoride from simulated solution. Shale samples were collected from Mahabir colliery (MBS) and Sonepur Bazari colliery (SBS) of Raniganj coalfield in West Bengal, India, and used to remove fluoride. To increase the adsorption efficiency, shale samples were heat activated at a higher temperature and samples obtained at 550 °C are denoted as heat-activated Mahabir colliery shale (HAMBS550) and heat-activated Sonepur Bazari colliery shale (HASBS550), respectively. To prove the fluoride adsorption onto different shale samples and ascertain its mechanism, natural shale samples, heat-activated shale samples, and their fluoride-loaded forms were characterized using scanning electron microscopy, energy dispersive X-ray analysis, X-ray diffraction study, and Fourier transform infrared spectroscopy. The effect of different parameters such as pH, adsorbent dose, size of particles, and initial concentration of fluoride was investigated during fluoride removal in a batch contactor. Lower pH shows better adsorption in batch study, but it is acidic in nature and not suitable for direct consumption. However, increase of pH of the solution from 3.2 to 6.8 and 7.2 during fluoride removal process with HAMBS550 and HASBS550, respectively, confirms the applicability of the treated water for domestic purposes. HAMBS550 and HASBS550 show maximum removal of 88.3 and 88.5 %, respectively, at initial fluoride concentration of 10 mg/L, pH 3, and adsorbent dose of 70 g/L.

Ultra-wide Range Gamma Detector System for Search and Locate Operations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Odell, D. Mackenzie Odell; Harpring, Larry J.; Moore, Frank S. Jr.

2005-10-26

Collecting debris samples following a nuclear event requires that operations be conducted from a considerable stand-off distance. An ultra-wide range gamma detector system has been constructed to accomplish both long range radiation search and close range hot sample collection functions. Constructed and tested on a REMOTEC Andros platform, the system has demonstrated reliable operation over six orders of magnitude of gamma dose from 100's of uR/hr to over 100 R/hr. Functional elements include a remotely controlled variable collimator assembly, a NaI(Tl)/photomultiplier tube detector, a proprietary digital radiation instrument, a coaxially mounted video camera, a digital compass, and both local andmore » remote control computers with a user interface designed for long range operations. Long range sensitivity and target location, as well as close range sample selection performance are presented.« less

Air concentrations of PBDEs on in-flight airplanes and assessment of flight crew inhalation exposure.

PubMed

Allen, Joseph G; Sumner, Ann Louise; Nishioka, Marcia G; Vallarino, Jose; Turner, Douglas J; Saltman, Hannah K; Spengler, John D

2013-07-01

To address the knowledge gaps regarding inhalation exposure of flight crew to polybrominated diphenyl ethers (PBDEs) on airplanes, we measured PBDE concentrations in air samples collected in the cabin air at cruising altitudes and used Bayesian Decision Analysis (BDA) to evaluate the likelihood of inhalation exposure to result in the average daily dose (ADD) of a member of the flight crew to exceed EPA Reference Doses (RfDs), accounting for all other aircraft and non-aircraft exposures. A total of 59 air samples were collected from different aircraft and analyzed for four PBDE congeners-BDE 47, 99, 100 and 209 (a subset were also analyzed for BDE 183). For congeners with a published RfD, high estimates of ADD were calculated for all non-aircraft exposure pathways and non-inhalation exposure onboard aircraft; inhalation exposure limits were then derived based on the difference between the RfD and ADDs for all other exposure pathways. The 95th percentile measured concentrations of PBDEs in aircraft air were <1% of the derived inhalation exposure limits. Likelihood probabilities of 95th percentile exposure concentrations >1% of the defined exposure limit were zero for all congeners with published RfDs.

Selenium metabolites in urine of cancer patients receiving L-selenomethionine at high doses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuehnelt, Doris; Juresa, Dijana; Francesconi, Kevin A.

2007-04-15

We investigated, with quantitative HPLC/mass spectrometry, the selenium metabolites in urine from five cancer patients receiving high doses of L-selenomethionine over an extended period (2 x 4000 {mu}g Se/day for 7 days, then 4000 {mu}g Se/day for 21 days) as an adjunct to their normal cancer chemotherapy. Urine samples were collected at day 0 (all 5 patients), and at 2-3 additional collection times ranging from 1 to 33 days. The background selenium concentrations ranged from 12 to 55 {mu}g Se/L and increased to 870 to 4420 {mu}g Se/L for the five patients during the study. All five patients had appreciablemore » levels of selenosugars in their background urine sample, and the concentrations increased dramatically after selenium intake. Trimethylselenonium ion (TMSe), on the other hand, was generally present as only a trace metabolite in background urine, and, although the concentration of TMSe increased following selenium exposure, it became a less significant proportion relative to selenosugars. These data refute the currently accepted role of TMSe as the preferred excretion metabolite when selenium exposure is high.« less

Fractionation of radioactivity in the milk of goats administered UC-aflatoxin B1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goto, T.; Hsieh, D.P.

A detailed fractionation of radioactivity in the milk of goats administered UC-aflatoxin B1 at low doses was performed. The milk collected in the first 24 h following dosing contained radioactivity equivalent to 0.45-1.1% of the dose given. The radioactivity in each sample was partitioned into 4 fractions: ether, protein, dichloromethane, and water-alcohol. Over 80% of the radioactivity was detected in the dichloromethane fraction, of which over 95% was attributable to aflatoxin M1. No aflatoxin B1 or other known aflatoxin metabolites were detected in any fraction. The results indicate that the major metabolite of aflatoxin B1 in goat milk is aflatoxinmore » M1 and that other metabolites, including conjugates, are of minor significance.« less

Implementation of a cryo-electron tomography tilt-scheme optimized for high resolution subtomogram averaging.

PubMed

Hagen, Wim J H; Wan, William; Briggs, John A G

2017-02-01

Cryo-electron tomography (cryoET) allows 3D structural information to be obtained from cells and other biological samples in their close-to-native state. In combination with subtomogram averaging, detailed structures of repeating features can be resolved. CryoET data is collected as a series of images of the sample from different tilt angles; this is performed by physically rotating the sample in the microscope between each image. The angles at which the images are collected, and the order in which they are collected, together are called the tilt-scheme. Here we describe a "dose-symmetric tilt-scheme" that begins at low tilt and then alternates between increasingly positive and negative tilts. This tilt-scheme maximizes the amount of high-resolution information maintained in the tomogram for subsequent subtomogram averaging, and may also be advantageous for other applications. We describe implementation of the tilt-scheme in combination with further data-collection refinements including setting thresholds on acceptable drift and improving focus accuracy. Requirements for microscope set-up are introduced, and a macro is provided which automates the application of the tilt-scheme within SerialEM. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Study on the abuse of amantadine in tissues of broiler chickens by HPLC-MS/MS.

PubMed

You, X; Yang, S; Zhao, J; Zhang, Y; Zhao, L; Cheng, Y; Hou, C; Xu, Z

2017-10-01

To evaluate the residual target tissues for better monitoring of amantadine abuse in broiler chickens, 22-day-old commercial Arbor Acres broiler chickens were, respectively, fed with 10, 20, and 40 mg/kg of amantadine for five consecutive days. Plasma, breast, and liver tissue samples from the chickens were collected 0, 4, 16, 24, 48, 96, 144, and 312 h after amantadine withdrawal. The high-performance liquid chromatography-tandem mass spectrometry method was used to detect the concentrations of amantadine. The highest concentration was found in the chicken liver and it took the longest time for amantadine to vanish by metabolism. In the high-dose group, amantadine residues were still detected 312 h after amantadine withdrawal. As the amantadine dose increased, amantadine residues in the chicken liver were more slowly to disappear than in other tissues. Even if approximately the same concentration of amantadine residues was found in chicken breast and plasma samples, it took a shorter time before the residues were eliminated. In the medium- and high-dose groups, the concentrations of amantadine residues in chicken liver samples were substantially higher than those in chicken breast and plasma samples, and it took more time to eliminate them. Therefore, the chicken liver can be used as a target tissue to detect illegal use of amantadine. © 2017 John Wiley & Sons Ltd.

1H NMR based pharmacometabolomics analysis of urine identifies metabolic phenotype of clopidogrel high on treatment platelets reactivity in coronary artery disease patients.

PubMed

Amin, Arwa M; Sheau Chin, Lim; Teh, Chin-Hoe; Mostafa, Hamza; Mohamed Noor, Dzul Azri; Sk Abdul Kader, Muhamad Ali; Kah Hay, Yuen; Ibrahim, Baharudin

2017-11-30

Clopidogrel high on treatment platelets reactivity (HTPR) has burdened achieving optimum therapeutic outcome. Although there are known genetic and non-genetic factors associated with clopidogrel HTPR, which explain in part clopidogrel HTPR, yet, great portion remains unknown, often hindering personalizing antiplatelet therapy. Nuclear magnetic resonance ( 1 H NMR) pharmacometabolomics analysis is useful technique to phenotype drug response. We investigated using 1 H NMR analysis to phenotype clopidogrel HTPR in urine. Urine samples were collected from 71 coronary artery disease (CAD) patients who were planned for interventional angiographic procedure prior to taking 600mg clopidogrel loading dose (LD) and 6h post LD. Patients' platelets function testing was assessed with the VerifyNow ® P2Y12 assay at 6h after LD. Urine samples were analysed using 1 H NMR. Multivariate statistical analysis was used to identify metabolites associated with clopidogrel HTPR. In pre-dose samples, 16 metabolites were associated with clopidogrel HTPR. However, 18 metabolites were associated with clopidogrel HTPR in post-dose samples. The pathway analysis of the identified biomarkers reflected that multifactorial conditions are associated with clopidogrel HTPR. It also revealed the implicated role of gut microbiota in clopidogrel HTPR. Pharmacometabolomics not only discovered novel biomarkers of clopidogrel HTPR but also revealed implicated pathways and conditions. Copyright © 2017 Elsevier B.V. All rights reserved.

Radon Concentration And Dose Assessment In Well Water Samples From Karbala Governorate Of Iraq

NASA Astrophysics Data System (ADS)

Al-Alawy, I. T.; Hasan, A. A.

2018-05-01

There are numerous studies around the world about radon concentrations and their risks to the health of human beings. One of the most important social characteristics is the use of water wells for irrigation, which is a major source of water pollution with radon gas. In the present study, six well water samples have been collected from different locations in Karbala governorate to investigate radon concentration level using CR-39 technique. The maximum value 4.112±2.0Bq/L was in Al-Hurr (Al-Qarih Al-Easariah) region, and the lowest concentration of radon was in Hay Ramadan region which is 2.156±1.4Bq/L, with an average value 2.84±1.65Bq/L. The highest result of annual effective dose (AED) was in Al-Hurr (Al-Qarih Al-Easariah) region which is equal to 15.00±3.9μSv/y, while the minimum was recorded in Hay Ramadan 7.86±2.8μSv/y, with an average value 10.35±3.1μSv/y. The current results have shown that the radon concentrations in well water samples are lower than the recommended limit 11.1Bq/L and the annual effective dose in these samples are lower than the permissible international limit 1mSv/y.

Pharmacokinetic and Tolerability Assessment of a Pediatric Oral Formulation of Pentoxifylline in Kawasaki Disease☆

PubMed Central

Best, Brookie M.; Burns, Jane C.; DeVincenzo, John; Phelps, Stephanie J.; Blumer, Jeffrey L.; Wilson, John T.; Capparelli, Edmund V.; Connor, James D.

2003-01-01

Background: In infants and children, treatment of Kawasaki disease (KD) with high-dose intravenous immunoglobulin (IVIG) and acetylsalicylic acid ([ASA] aspirin) diminishes inflammatory response and reduces the risk for coronary artery abnormalities. However, patients with high serum concentrations of tumor necrosis factor (TNF)-alpha, which is associated with vascular damage, may develop coronary artery lesions even with treatment. The hemorheologic agent pentoxifylline blocks the production of TNF-alpha and may be an appropriate adjunctive therapy to IVIG and ASA. Objective: The objective of this study was to assess the pharmacokinetic characteristics and tolerability of a new oral syrup formulation of pentoxifylline as an adjunct to IVIG and ASA in the treatment of KD in children. Methods: Hospitalized boys and girls aged 6 months to 5 years and who were diagnosed with KD within the first 10 days of illness were eligible. Patients were assigned to 1 of 4 pentoxifylline treatment groups, by dose level (dose levels 1, 2, 3, and 4: 10, 15, 20, and 25 mg/kg daily, respectively, divided into 3 doses). Six plasma samples collected at the time the first dose was administered, and 4 samples collected after administration of the last dose on study day 6, were assessed by high-performance liquid chromatography using noncompartmental and 1-compartment pharmacokinetic analyses for pentoxifylline and its active metabolite (M-1). TNF-alpha levels on days 1 and 6 were assessed using electroimmunoassay. Results: Fourteen boys and 10 girls were enrolled. The mean age, body weight, and illness day at study entry were 34.5 months, 13.8 kg, and 6, respectively. Pentoxifylline exhibited nonlinear kinetic characteristics, with median area under the plasma concentration–time curve from time 0 to infinity(AUC0–∞) values of 622, 3428, 8416, and 10,347 ng/mL · h for dose levels 1 to 4, respectively, on study day 1. Pentoxifylline noncompartmental oral clearance and volume of distribution were significantly lower, and dose-normalized AUC0–∞ was significantly higher, for dose level 3 than dose level 1. M-1 parameters were not significantly different between dose levels. No accumulation of pentoxifylline or M-1 was noted. Fifteen of 24 patients (63%) reported mild to moderate adverse events that may or may not have been treatment related. Frequency and severity did not differ significantly between dose levels. Conclusions: In the children in this study, pentoxifylline was well tolerated at the doses studied. No notable differences in clinical outcomes were observed between dose levels, and dose levels 3 and 4 (20 and 25 mg/kg daily, respectively) resulted in similar exposure to both pentoxifylline and M-1. Future efficacy and tolerability studies should use a daily dose of 20 mg/kg of pentoxifylline in acute KD. PMID:24944359

Posology and Field Efficacy Study with Novobiocin for Intramammary Infusion in Nonlactating Dairy Cows

PubMed Central

Swenson, G. H.

1979-01-01

Four dose levels of novobiocin (50, 200, 400, 600 mg) were compared with no drug for the intramammary treatment of Staphylococcus aureus, Streptococcus agalactiae and other streptococcal infections present in the udder of dairy cows at the initiation of the dry period. Treatment success was evaluated by comparing the microbiological status of duplicate pretreatment quarter milk samples collected at drying off with the microbiological status of duplicate quarter milk samples collected four to ten days postcalving. Infection status of 1318 cows in 75 herds in five geographic locations was determined. Treatment effects on infected cows were evaluated by least squares analysis of variance with treatment, herd, lactation number, days dry and milk production at drying off considered as variables. The dose of 400 mg novobiocin per quarter was demonstrated to be significantly more effective (P < 0.05) than no drug and significantly better than (P < 0.05) or equal to the other doses for curing infections caused by S. aureus, S. agalactiae and other streptococci. A significant reduction (P < 0.05) in the overall rate of new udder infections acquired during the dry period was observed in cows treated with ≥ 200 mg novobiocin at drying off. The data supported the conclusion that the cow rather than the quarter is the appropriate experimental unit in the evaluation of intramammary mastitis treatments. Herd and lactation number were the most significant variables affecting cures. PMID:548166

Effects of garlic oil and two of its major organosulfur compounds, diallyl disulfide and diallyl trisulfide, on intestinal damage in rats injected with endotoxin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chiang, Y.-H.; Jen, L.-N.; Su, H.-Y.

Garlic and its active components are known to possess antioxidant and antiinflammatory effects. The present study investigated the effects of garlic oil and its organosulfur compounds on endotoxin-induced intestinal mucosal damage. Wistar rats received by gavage 50 or 200 mg/kg body weight garlic oil (GO), 0.5 mmol/kg body weight diallyl disulfide or diallyl trisulfide, or the vehicle (corn oil; 2 ml/kg body weight) every other day for 2 weeks before being injected with endotoxin (i.p., 5 mg/kg body weight). Control rats were administered with corn oil and were injected with sterile saline. Samples for the measurement of proinflammatory cytokines weremore » collected 3 h after injection, and all other samples were collected 18 h after injection. The low dose of GO suppressed endotoxin-induced inducible nitric oxide synthase (iNOS) activity, ulceration, and apoptosis in the intestinal mucosa (P < 0.05). The high dose of GO significantly lowered the peripheral level of nitrate/nitrite and endotoxin-induced iNOS activity in the intestinal mucosa (P < 0.05) but worsened intestinal mucosal damage accompanied by elevated peripheral proinflammatory cytokines. Diallyl trisulfide but not diallyl disulfide showed similar toxic effect as that of high-dose GO. These results suggest the preventive effect and possible toxicity of garlic oil and its organosulfur compounds in endotoxin-induced systemic inflammation and intestinal damage.« less

Quercetin dose affects the fate of hepatic ischemia and reperfusion injury in rats: An experimental research.

PubMed

Uylaş, Mustafa Ufuk; Şahin, Adnan; Şahintürk, Varol; Alataş, İbrahim Özkan

2018-05-01

Quercetin found in fruits and vegetables has an antioxidative effect. We aimed to investigate the protective effects of quercetin according to different doses on hepatic and ischemia-reperfusion (I/R) injury. Fifty mature male Sprague-Dawley rats were randomly divided into five groups (n = 10 for each). All the animal groups underwent laparotomy. Group 1 rats served as a sham-operated group. Groups 2-5 underwent 1 h hepatic ischemia and were followed by 2 h reperfusion. Group 3-5 animals received an additional intraperitoneal dose of 25, 50 or 100 mg/kg quercetin respectively before I/R operation. Blood samples were collected for determining serum aspartate transaminase (AST), alanine transaminase (ALT) and malondialdehyde (MDA) levels. Also, liver tissue samples were taken for measuring of liver MDA concentration and for histopathology assessment. The highest levels of biochemical parameters were observed in group 2. In quercetin-treated groups, serum AST, ALT, MDA levels, and tissue MDA concentration were decreased as inversely with increasing quercetin dose. Microscopic evaluation revealed that most conspicuous histological improvement was observed in 50 mg/kg quercetin co-treated rats. 25 and 100 mg/kg quercetin co-treatment could not protect completely against hepatic I/R injury. Quercetin can be effective in preventing of hepatic I/R injury when the correct dose was used. Copyright © 2018. Published by Elsevier Ltd.

PROPOSALS FOR THE ESTABLISHMENT OF NATIONAL DIAGNOSTIC REFERENCE LEVELS FOR RADIOGRAPHY FOR ADULT PATIENTS BASED ON REGIONAL DOSE SURVEYS IN RUSSIAN FEDERATION.

PubMed

Vodovatov, A V; Balonov, M I; Golikov, V Yu; Shatsky, I G; Chipiga, L A; Bernhardsson, C

2017-04-01

In 2009-2014, dose surveys aimed to collect adult patient data and parameters of most common radiographic examinations were performed in six Russian regions. Typical patient doses were estimated for the selected examinations both in entrance surface dose and in effective dose. 75%-percentiles of typical patient effective dose distributions were proposed as preliminary regional diagnostic reference levels (DRLs) for radiography. Differences between the 75%-percentiles of regional typical patient dose distributions did not exceed 30-50% for the examinations with standardized clinical protocols (skull, chest and thoracic spine) and a factor of 1.5 for other examinations. Two different approaches for establishing national DRLs were evaluated: as a 75%-percentile of a pooled regional sample of patient typical doses (pooled method) and as a median of 75%-percentiles of regional typical patient dose distributions (median method). Differences between pooled and median methods for effective dose did not exceed 20%. It was proposed to establish Russian national DRLs in effective dose using a pooled method. In addition, the local authorities were granted an opportunity to establish regional DRLs if the local radiological practice and typical patient dose distributions are significantly different. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Use of FTA filter paper for the molecular detection of Newcastle disease virus.

PubMed

Perozo, Francisco; Villegas, Pedro; Estevez, Carlos; Alvarado, Iván; Purvis, Linda B

2006-04-01

The feasibility of using Flinders Technology Associates filter papers (FTA cards) to collect allantoic fluid and chicken tissue samples for Newcastle disease virus (NDV) molecular detection was evaluated. Trizol RNA extraction and one-step reverse transcriptase-polymerase chain reaction (RT-PCR) were used. FTA cards allowed NDV identification from allantoic fluid with a titre of 10(5.8) median embryo lethal doses/ml. The inactivated virus remained stable on the cards for 15 days. NDV was detected from FTA imprints of the trachea, lung, caecal tonsil and cloacal faeces of experimentally infected birds. RT-PCR detection from FTA cards was confirmed by homologous frozen-tissue RT-PCR and virus isolation. Direct nucleotide sequence of the amplified F gene allowed prediction of NDV virulence. No virus isolation was possible from the FTA inactivated samples, indicating viral inactivation upon contact. The FTA cards are suitable for collecting and transporting NDV-positive samples, providing a reliable source of RNA for molecular characterization and a hazard-free sample.

Identification and characterization of metabolites of ASP015K, a novel oral Janus kinase inhibitor, in rats, chimeric mice with humanized liver, and humans.

PubMed

Nakada, Naoyuki; Oda, Kazuo

2015-01-01

1. Here, we elucidated the structure of metabolites of novel oral Janus kinase inhibitor ASP015K in rats and humans and evaluated the predictability of human metabolites using chimeric mice with humanized liver (PXB mice). 2. Rat biological samples collected after oral dosing of (14)C-labelled ASP015K were examined using a liquid chromatography-radiometric detector and mass spectrometer (LC-RAD/MS). The molecular weight of metabolites in human and the liver chimeric mouse biological samples collected after oral dosing of non-labelled ASP015K was also investigated via LC-MS. Metabolites were also isolated from rat bile samples and analyzed using nuclear magnetic resonance. 3. Metabolic pathways of ASP015K in rats and humans were found to be glucuronide conjugation, methyl conjugation, sulfate conjugation, glutathione conjugation, hydroxylation of the adamantane ring and N-oxidation of the 1H-pyrrolo[2,3-b]pyridine ring. The main metabolite of ASP015K in rats was the glucuronide conjugate, while the main metabolite in humans was the sulfate conjugate. Given that human metabolites were produced by human hepatocytes in chimeric mice with humanized liver, this human model mouse was believed to be useful in predicting the human metabolic profile of various drug candidates.

Trends in anemia management among US hemodialysis patients.

PubMed

Coladonato, Joseph A; Frankenfield, Diane L; Reddan, Donal N; Klassen, Preston S; Szczech, Lynda A; Johnson, Curtis A; Owen, William F

2002-05-01

This study was undertaken to describe the relationship between hematocrit (Hct) and changes in the prescribed dose of erythropoietin (EPO) as well as selected patient and process care measures across annual national samples of hemodialysis patients from 1994 to 1998. This study uses the cohorts identified in the ESRD Core Indicators Project, random samples of 6181, 6241, 6364, 6634, and 7660 patients, stratified by ESRD Networks drawn for each year from 1994 to 1998. Patient demographic and clinical information was collected from October to December for each year. Surrogates of iron stores and patterns of iron and EPO administration were profiled from 1996 to 1998. Multivariable stepwise linear regression analyses were performed to adjust for potential confounding variables and to identify independent variables associated with Hct and EPO dose. Mean Hct and EPO dose increased each year from 31.1 +/- 5.2% to 34.1 +/- 3.7% and from 58.2 +/- 41.8 U/kg to 68.2 +/- 55.0 U/kg, respectively (P = 0.0001). Increasing Hct was positively associated with male gender, more years on dialysis, older age, higher urea reduction ratio and transferrin saturation, prescription of intravenous iron, and lower ferritin and EPO dose in multivariable models (all P = 0.0001). Male gender, older age, diabetes, higher Hct, and increasing weight, urea reduction ration, and transferrin saturation were associated with lower EPO doses (all P < 0.01). Conversely, intravenous EPO and iron were associated with higher prescribed EPO doses (all P = 0.0001). Although increasing Hct is associated with decreasing EPO dose at the patient level, the increase in Hct seen across years among the cohorts of hemodialysis patients in the United States has been associated with increasing doses of EPO at the population level.

Effect of aminocaproic acid on clot strength and clot lysis of canine blood determined by use of an in vitro model of hyperfibrinolysis.

PubMed

Brown, Jamie C; Brainard, Benjamin M; Fletcher, Daniel J; Nie, Ben; Arnold, Robert D; Schmiedt, Chad W

2016-11-01

OBJECTIVE To determine pharmacodynamic and pharmacokinetic profiles of aminocaproic acid (ACA) by use of a thromboelastography (TEG)-based in vitro model of hyperfibrinolysis and high-performance liquid chromatography-mass spectrometry. ANIMALS 5 healthy adult dogs. PROCEDURES A single dose of injectable ACA (20, 50, or 100 mg/kg) or an ACA tablet (approximately 100 mg/kg) was administered orally. Blood samples were collected at 0, 15, 30, 45, 60, 90, 120, and 240 minutes after ACA administration for pharmacokinetic analysis. Samples were obtained at 0, 60, and 240 minutes for pharmacodynamic analysis by use of a TEG model of hyperfibrinolysis. RESULTS No adverse effects were detected. In the hyperfibrinolysis model, after all doses, a significantly higher TEG maximum amplitude (clot strength), compared with baseline, was detected at 60 and 240 minutes. Additionally, the percentage of fibrinolysis was reduced from the baseline value at 60 and 240 minutes, with the greatest reduction at 60 minutes. At 240 minutes, there was significantly less fibrinolysis for the 100 mg/kg dose than the 20 mg/kg dose. Maximum plasma ACA concentration was dose dependent. There was no significant difference in pharmacokinetic parameters between 100 mg/kg formulations. CONCLUSIONS AND CLINICAL RELEVANCE In an in vitro model of hyperfibrinolysis, ACA inhibited fibrinolysis at all doses tested. At 240 minutes after administration, the 100 mg/kg dose inhibited fibrinolysis more effectively than did the 20 mg/kg dose. Thus, ACA may be useful for in vivo prevention of fibrinolysis in dogs. IMPACT FOR HUMAN MEDICINE These data may improve research models of hyperfibrinolytic diseases.

Enhancing Cytogenetic Biological Dosimetry Capabilities of the Philippines for Nuclear Incident Preparedness.

PubMed

Asaad, Celia O; Caraos, Gloriamaris L; Robles, Gerardo Jose M; Asa, Anie Day D C; Cobar, Maria Lucia C; Asaad, Al-Ahmadgaid

2016-01-01

The utility of a biological dosimeter based on the analysis of dicentrics is invaluable in the event of a radiological emergency wherein the estimated absorbed dose of an exposed individual is crucial in the proper medical management of patients. The technique is also used for routine monitoring of occupationally exposed workers to determine radiation exposure. An in vitro irradiation study of human peripheral blood lymphocytes was conducted to establish a dose-response curve for radiation-induced dicentric aberrations. Blood samples were collected from volunteer donors and together with optically stimulated luminescence (OSL) dosimeters and were irradiated at 0, 0.1, 0.25, 0.5, 0.75, 1, 2, 4, and 6 Gy using a cobalt-60 radiotherapy unit. Blood samples were cultured for 48 h, and the metaphase chromosomes were prepared following the procedure of the International Atomic Energy Agency's Emergency Preparedness and Response - Biodosimetry 2011 manual. At least 100 metaphases were scored for dicentric aberrations at each dose point. The data were analyzed using R language program. The results indicated that the distribution of dicentric cells followed a Poisson distribution and the dose-response curve was established using the estimated model, Y dic = 0.0003 (±0.0003) +0.0336 (±0.0115) × D + 0.0236 (±0.0054) × D 2 . In this study, the reliability of the dose-response curve in estimating the absorbed dose was also validated for 2 and 4 Gy using OSL dosimeters. The data were fitted into the constructed curve. The result of the validation study showed that the obtained estimate for the absorbed exposure doses was close to the true exposure doses.

Persistence and bioaccumulation of oxyfluorfen residues in onion.

PubMed

Sondhia, Shobha

2010-03-01

A field study was conducted to determine persistence and bioaccumulation of oxyflorfen residues in onion crop at two growth stages. Oxyfluorfen (23.5% EC) was sprayed at 250 and 500 g ai/ha on the crop (variety, N53). Mature onion and soil samples were collected at harvest. Green onion were collected at 55 days from each treated and control plot and analyzed for oxyfluorfen residues by a validated high-performance liquid chromatography method with an accepted recovery of 78-92% at the minimum detectable concentration of 0.003 microg g(-1). Analysis showed 0.015 and 0.005 microg g(-1) residues of oxyfluorfen at 250 g a.i. ha(-1) rate in green and mature onion samples, respectively; however, at 500 g a.i.ha(-1) rates, 0.025 and 0.011 microg g(-1) of oxyfluorfen residues were detected in green and mature onion samples, respectively. Soil samples collected at harvest showed 0.003 and 0.003 microg g(-1) of oxyfluorfen residues at the doses 250 and 500 g a.i. ha(-1), respectively. From the study, a pre-harvest interval of 118 days for onion crop after the herbicide application is suggested.

Effect of clindamycin prophylaxis on the colonic microflora in patients undergoing colorectal surgery.

PubMed Central

Kager, L; Liljeqvist, L; Malmborg, A S; Nord, C E

1981-01-01

Clindamycin was given intravenously to 15 patients undergoing colorectal surgery in an initial dose of 600 mg, given at induction of anesthesia followed by 6 doses of 600 mg at 8-h intervals. Series of serum samples and fecal specimens were taken for analysis of clindamycin concentrations. Tissue samples from the gut wall were taken at surgery. The highest serum concentrations observed occurred 30 min after administration of clindamycin and varied between 6.8 and 37.9 microgram/ml (mean, 14.8 +/- 2.0 [standard error] microgram/ml). The clindamycin concentrations in the tissue samples were between 1.8 and 13.0 microgram/g. Clindamycin concentration in the fecal samples varied between 2.1 and 460 microgram/g. Fecal samples were also collected during the investigation period for cultivation of aerobic and anaerobic bacteria. Among the aerobic bacteria, enterococci and streptococci decreased during the prophylaxis period. Anaerobic bacteria also decreased significantly during the same period. After the clindamycin administration period, enterococci, streptococci and anaerobic bacteria proliferated. No anaerobic strains resistant to clindamycin were isolated. Postoperative infections due to Streptococcus faecalis and different enterobacteria such as Escherichia coli, Enterobacter cloacae, Citrobacter freundii, and Klebsiella occurred in five patients. PMID:7325640

Effect of clindamycin prophylaxis on the colonic microflora in patients undergoing colorectal surgery.

PubMed

Kager, L; Liljeqvist, L; Malmborg, A S; Nord, C E

1981-12-01

Clindamycin was given intravenously to 15 patients undergoing colorectal surgery in an initial dose of 600 mg, given at induction of anesthesia followed by 6 doses of 600 mg at 8-h intervals. Series of serum samples and fecal specimens were taken for analysis of clindamycin concentrations. Tissue samples from the gut wall were taken at surgery. The highest serum concentrations observed occurred 30 min after administration of clindamycin and varied between 6.8 and 37.9 microgram/ml (mean, 14.8 +/- 2.0 [standard error] microgram/ml). The clindamycin concentrations in the tissue samples were between 1.8 and 13.0 microgram/g. Clindamycin concentration in the fecal samples varied between 2.1 and 460 microgram/g. Fecal samples were also collected during the investigation period for cultivation of aerobic and anaerobic bacteria. Among the aerobic bacteria, enterococci and streptococci decreased during the prophylaxis period. Anaerobic bacteria also decreased significantly during the same period. After the clindamycin administration period, enterococci, streptococci and anaerobic bacteria proliferated. No anaerobic strains resistant to clindamycin were isolated. Postoperative infections due to Streptococcus faecalis and different enterobacteria such as Escherichia coli, Enterobacter cloacae, Citrobacter freundii, and Klebsiella occurred in five patients.

Method of Analysis by the U.S. Geological Survey California District Sacramento Laboratory?Determination of Trihalomethane Formation Potential, Method Validation, and Quality-Control Practices

USGS Publications Warehouse

Crepeau, Kathryn L.; Fram, Miranda S.; Bush, Noel

2004-01-01

An analytical method for the determination of the trihalomethane formation potential of water samples has been developed. The trihalomethane formation potential is measured by dosing samples with chlorine under specified conditions of pH, temperature, incubation time, darkness, and residual-free chlorine, and then analyzing the resulting trihalomethanes by purge and trap/gas chromatography equipped with an electron capture detector. Detailed explanations of the method and quality-control practices are provided. Method validation experiments showed that the trihalomethane formation potential varies as a function of time between sample collection and analysis, residual-free chlorine concentration, method of sample dilution, and the concentration of bromide in the sample.

Thermoradiation inactivation of naturally occurring organisms in soil

NASA Technical Reports Server (NTRS)

Reynolds, M. C.; Lindell, K. F.; David, T. J.

1973-01-01

Samples of soil collected from Kennedy Space Center near spacecraft assembly facilities were found to contain microorganisms very resistant to conventional sterilization techniques. The inactivation behavior of the naturally occurring spores in soil was investigated using dry heat and ionizing radiation, first separately, then in combination. Dry heat inactivation rates of spores were determined for 105 and 125 C. Radiation inactivation rates were determined for dose rates of 660 and 76 krad/hr at 25 C. Simultaneous combinations of heat and radiation were then investigated at 105, 110, 115, 120, and 125 C. Combined treatment was found to be highly synergistic requiring greatly reduced radiation doses to accomplish sterilization.

Optically stimulated luminescence dating of Holocene alluvial fans, East Anatolian Fault System, Turkey

NASA Astrophysics Data System (ADS)

Dogan, Tamer; Cetin, Hasan; Yegingil, Zehra; Topaksu, Mustafa; Yüksel, Mehmet; Duygun, Fırat; Nur, Necmettin; Yegingil, İlhami

2015-07-01

In this study, the optically stimulated luminescence dating technique was used to determine the time of deposition of alluvial sediment samples from the Türkoğlu-Antakya segment of the East Anatolian Fault System (EAFS) in Turkey. The double-single aliquot regenerative dose protocol on fine grain samples was used to estimate equivalent doses (De). Annual dose rate was computed using elemental concentration of uranium (U) and thorium (Th) determined by using thick-source alpha counting and potassium (K) concentrations using X-ray fluorescence and/or atomic absorption spectroscopy. The environmental dose was measured in situ using α-Al2O3:C chips inside plastic tubes for a year. The two different bulk sediment samples collected from the Islahiye trench yielded ages of 4.54 ± 0.28 and 2.91 ± 0.23 ka. We also obtained a 2.60 ± 0.18 ka age for the alluvial deposit in the Kıranyurdu trench and 2.31 ± 0.14 ka age for an excavation area called Malzeme Ocağı. These ages were consistent with the corresponding calibrated Carbon-14 (14C) ages of the region. The differences between the determined ages were insufficient to clearly distinguish the disturbance event from the effects of bioturbation, biological mixing, or other sources of De variation in the region. They provide a record of alluvial aggradation in the region and may determine undocumented historical earthquake events.

Use of FTA sampling cards for molecular detection of avian influenza virus in wild birds.

PubMed

Keeler, Shamus P; Ferro, Pamela J; Brown, Justin D; Fang, Xingwang; El-Attrache, John; Poulson, Rebecca; Jackwood, Mark W; Stallknecht, David E

2012-03-01

Current avian influenza (AI) virus surveillance programs involving wild birds rely on sample collection methods that require refrigeration or low temperature freezing to maintain sample integrity for virus isolation and/or reverse-transcriptase (RT) PCR. Maintaining the cold chain is critical for the success of these diagnostic assays but is not always possible under field conditions. The aim of this study was to test the utility of Finders Technology Associates (FTA) cards for reliable detection of AI virus from cloacal and oropharyngeal swabs of wild birds. The minimum detectable titer was determined, and the effect of room temperature storage was evaluated experimentally using multiple egg-propagated stock viruses (n = 6). Using real time RT-PCR, we compared results from paired cloacal swab and samples collected on FTA cards from both experimentally infected mallards (Anasplatyrhynchos) and hunter-harvested waterfowl sampled along the Texas Gulf Coast. Based on the laboratory trials, the average minimal detectable viral titer was determined to be 1 x 10(4.7) median embryo infectious dose (EID50)/ml (range: 1 x 10(4.3) to 1 x 10(5.4) EID50/ml), and viral RNA was consistently detectable on the FTA cards for a minimum of 20 days and up to 30 days for most subtypes at room temperature (23 C) storage. Real-time RT-PCR of samples collected using the FTA cards showed fair to good agreement in live birds when compared with both real-time RT-PCR and virus isolation of swabs. AI virus detection rates in samples from several wild bird species were higher when samples were collected using the FTA cards compared with cloacal swabs. These results suggest that FTA cards can be used as an alternative sample collection method when traditional surveillance methods are not possible, especially in avian populations that have historically received limited testing or situations in which field conditions limit the ability to properly store or ship swab samples.

Bioavailability of sulforaphane from two broccoli sprout beverages: Results of a short term, cross-over clinical trial in Qidong, China

PubMed Central

Egner, Patricia A.; Chen, Jian Guo; Wang, Jin Bing; Wu, Yan; Sun, Yan; Lu, Jian Hua; Zhu, Jian; Zhang, Yong Hui; Chen, Yong Sheng; Friesen, Marlin D.; Jacobson, Lisa P.; Muñoz, Alvaro; Ng, Derek; Qian, Geng Sun; Zhu, Yuan Rong; Chen, Tao Yang; Botting, Nigel P.; Zhang, Qingzhi; Fahey, Jed W.; Talalay, Paul; Groopman, John D; Kensler, Thomas W.

2011-01-01

One of several challenges in design of clinical chemoprevention trials is the selection of the dose, formulation and dose schedule of the intervention agent. Therefore, a cross-over clinical trial was undertaken to compare the bioavailability and tolerability of sulforaphane from two of broccoli sprout-derived beverages: one glucoraphanin-rich (GRR) and the other sulforaphane-rich (SFR). Sulforaphane was generated from glucoraphanin contained in GRR by gut microflora or formed by treatment of GRR with myrosinase from daikon (Raphanus sativus) sprouts to provide SFR. Fifty healthy, eligible participants were requested to refrain from crucifer consumption and randomized into two treatment arms. The study design was as follows: 5-day run-in period, 7-day administration of beverages, 5-day washout period, and 7-day administration of the opposite intervention. Isotope dilution mass spectrometry was used to measure levels of glucoraphanin, sulforaphane and sulforaphane thiol conjugates in urine samples collected daily throughout the study. Bioavailability, as measured by urinary excretion of sulforaphane and its metabolites (in approximately 12 hour collections after dosing), was substantially greater with the SFR (mean = 70%) than with GRR (mean = 5%) beverages. Interindividual variability in excretion was considerably lower with SFR than GRR beverage. Elimination rates were considerably slower with GRR allowing for achievement of steady state dosing as opposed to bolus dosing with SFR. Optimal dosing formulations in future studies should consider blends of sulforaphane and glucoraphanin as SFR and GRR mixtures to achieve peak concentrations for activation of some targets and prolonged inhibition of others implicated in the protective actions of sulforaphane. PMID:21372038

Metabolism of isotretinoin. Biliary excretion of isotretinoin glucuronide in the rat.

PubMed

Meloche, S; Besner, J G

1986-01-01

The biliary metabolites of isotretinoin were examined after iv administration of 4-20-mg/kg doses to vitamin A-normal bile duct-cannulated rats. Analysis of bile by reverse phase high performance liquid chromatography showed that injection of isotretinoin is followed by a rapid excretion of metabolites in bile. Isotretinoin glucuronide was identified as the major metabolite in bile. A specific high performance liquid chromatography method based on the assay of generated isotretinoin in beta-glucuronidase-treated bile was developed for the determination of isotretinoin glucuronide in bile samples. The excretion rate of isotretinoin glucuronide increased rapidly to reach a maximum 55 min after dosing and then declined exponentially. After 330 min of collection, biliary excretion of isotretinoin glucuronide was almost complete, and the metabolite accounted for 34.8-37.9% of the dose. These results indicate that conjugation with glucuronic acid represents a major pathway for the metabolism of pharmacological doses of isotretinoin. The maximum excretion rate of isotretinoin glucuronide in bile increased in a linear manner with the dose of isotretinoin, and no delay was observed after the larger doses. These data suggest that glucuronidation and biliary excretion are not saturated at high pharmacological doses of isotretinoin.

Vitamin D in corticosteroid-naïve and corticosteroid-treated Duchenne muscular dystrophy: what dose achieves optimal 25(OH) vitamin D levels?

PubMed

Alshaikh, Nahla; Brunklaus, Andreas; Davis, Tracey; Robb, Stephanie A; Quinlivan, Ros; Munot, Pinki; Sarkozy, Anna; Muntoni, Francesco; Manzur, Adnan Y

2016-10-01

Assessment of the efficacy of vitamin D replenishment and maintenance doses required to attain optimal levels in boys with Duchenne muscular dystrophy (DMD). 25(OH)-vitamin D levels and concurrent vitamin D dosage were collected from retrospective case-note review of boys with DMD at the Dubowitz Neuromuscular Centre. Vitamin D levels were stratified as deficient at <25 nmol/L, insufficient at 25-49 nmol/L, adequate at 50-75 nmol/L and optimal at >75 nmol/L. 617 vitamin D samples were available from 197 boys (range 2-18 years)-69% from individuals on corticosteroids. Vitamin D-naïve boys (154 samples) showed deficiency in 28%, insufficiency in 42%, adequate levels in 24% and optimal levels in 6%. The vitamin D-supplemented group (463 samples) was tested while on different maintenance/replenishment doses. Three-month replenishment of daily 3000 IU (23 samples) or 6000 IU (37 samples) achieved optimal levels in 52% and 84%, respectively. 182 samples taken on 400 IU revealed deficiency in 19 (10%), insufficiency in 84 (47%), adequate levels in 67 (37%) and optimal levels in 11 (6%). 97 samples taken on 800 IU showed deficiency in 2 (2%), insufficiency in 17 (17%), adequate levels in 56 (58%) and optimal levels in 22 (23%). 81 samples were on 1000 IU and 14 samples on 1500 IU, with optimal levels in 35 (43%) and 9 (64%), respectively. No toxic level was seen (highest level 230 nmol/L). The prevalence of vitamin D deficiency and insufficiency in DMD is high. A 2-month replenishment regimen of 6000 IU and maintenance regimen of 1000-1500 IU/day was associated with optimal vitamin D levels. These data have important implications for optimising vitamin D dosing in DMD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Radiation dose to Malaysian infants from natural radionuclides via consumption of powdered milk

NASA Astrophysics Data System (ADS)

Uwatse, Onosohwo Bemigho; Olatunji, Michael Adekunle; Khandaker, Mayeen Uddin; Amin, Yusoff Mohd.

2015-04-01

Milk is the basic food stuff for the infants because they generally consume more milk on a daily basis as its minerals and proteins are essential for their growth and development, therefore, it is very important to assess the natural radioactivity levels and the associated dose in the widely consumed powered infant's milk. As a result, 14 brands of infant's powdered milk were collected from different supermarkets around Selangor, Malaysia and analysed for 226Ra, 232Th and 40K activities. The obtained mean activity of 226Ra, 232Th and 40K are 3.05±1.84, 2.55±2.48 and 99.1±69.5 Bqkg-1, respectively. Among the analysed milk samples, the brand from Philippines (Lactogen) showed low level of radioactivity while Singaporean brand (S26 SMA Gold) showed the highest. The estimated mean annual effective doses due to the ingestion of natural radionuclides in the sampled milk are 635 and 111 µSv for infant ≤ 1y and infant 1-2y, respectively. The obtained dose value does not yet pose any significant radiological hazards to the population under investigation comparing with the 1.0 mSvy-1 recommended by ICRP for all ages.

Pharmacokinetics of Compounded Intravenous and Oral Gabapentin in Hispaniolan Amazon Parrots ( Amazona ventralis ).

PubMed

Baine, Katherine; Jones, Michael P; Cox, Sherry; Martín-Jiménez, Tomás

2015-09-01

Neuropathic pain is a manifestation of chronic pain that arises with damage to the somatosensory system. Pharmacologic treatment recommendations for alleviation of neuropathic pain are often multimodal, and the few reports communicating treatment of suspected neuropathic pain in avian patients describe the use of gabapentin as part of the therapeutic regimen. To determine the pharmacokinetics of gabapentin in Hispaniolan Amazon parrots ( Amazona ventralis ), compounded gabapentin suspensions were administered at 30 mg/kg IV to 2 birds, 10 mg/kg PO to 3 birds, and 30 mg/kg PO to 3 birds. Blood samples were collected immediately before and at 9 different time points after drug administration. Plasma samples were analyzed for gabapentin concentration, and pharmacokinetic parameters were calculated with both a nonlinear mixed-effect approach and a noncompartmental analysis. The best compartmental, oral model was used to simulate the concentration-time profiles resulting from different dosing scenarios. Mild sedation was observed in both study birds after intravenous injection. Computer simulation of different dosing scenarios with the mean parameter estimates showed that 15 mg/kg every 8 hours would be a starting point for oral dosing in Hispaniolan Amazon parrots based on effective plasma concentrations reported for human patients; however, additional studies need to be performed to establish a therapeutic dose.

Effect of a single gemfibrozil dose on the pharmacokinetics of rosuvastatin in bile and plasma in healthy volunteers.

PubMed

Bergman, Ebba; Matsson, Elin M; Hedeland, Mikael; Bondesson, Ulf; Knutson, Lars; Lennernäs, Hans

2010-09-01

The effect of a single intrajejunal dose of gemfibrozil (600 mg) on the plasma pharmacokinetics and biliary excretion of a single intrajejunal dose of rosuvastatin (20 mg) was investigated by using a multichannel catheter positioned in the distal duodenum-proximal jejunum in 8 healthy volunteers. Bile and plasma samples were collected every 20 minutes for 200 minutes, with additional plasma samples being drawn for up to 48 hours. Gemfibrozil did not affect the bioavailability of rosuvastatin, although it increased the apparent absorption phase during the initial 200 minutes (AUC(plasma,200min)) by 1.56-fold (95% confidence interval, 1.14-2.15). The interaction was less pronounced in this single-dose study than in a previous report when gemfibrozil was administered repeatedly; nevertheless, the interaction coincided with the highest exposure to gemfibrozil. The plausible reason why the interaction in this investigation was only minor is the low exposure to gemfibrozil (and its metabolites), suggesting that the total plasma concentration of gemfibrozil needs to be above 20 µM to affect the disposition of rosuvastatin. This study demonstrates the value of monitoring the plasma pharmacokinetics of the inhibitor, and not only the drug under investigation, to improve the mechanistic interpretation.

Four Week Oral Toxicity Study of WR242511 in Dogs. Volume 1

DTIC Science & Technology

1994-06-03

fecal samples were collected for internal parasites examinations. All dogs had been previously vaccinated against canine distemper , infectious...every two weeks. Certified Canine Diet No. 5007 (PMI Feeds Inc., St. Louis, MO), approximately 400 g, was provided daily from arrival until termination... canine hepatitis, leptospirosis, parainfluenza, parvo, oral papilloma, and rabies by the animal supplier. For approximately three weeks prior to dosing

Metabolism, distribution and elimination of lisdexamfetamine dimesylate: open-label, single-centre, phase I study in healthy adult volunteers.

PubMed

Krishnan, Suma M; Pennick, Michael; Stark, Jeffrey G

2008-01-01

Attention-deficit/hyperactivity disorder (ADHD) in children often persists into adulthood and is potentially associated with significant social and occupational impairments. It is important to understand the effects of pharmacological treatments of ADHD in adults. This study aimed to assess the absorption, metabolism and elimination of lisdexamfetamine dimesylate in normal, healthy adult subjects following a single oral dose. A secondary objective was to assess the safety and tolerability of treatment. In an open-label, single-centre study, six healthy adult volunteers aged 22-52 years received a single oral 70 mg dose of (14)C-radiolabelled lisdexamfetamine dimesylate in solution following a 10-hour fast. Blood samples drawn pre-dose and at time points up to 120 hours post-dose were used for plasma pharmacokinetic analysis of the active d-amphetamine and the intact parent compound lisdexamfetamine dimesylate. Recovery of radioactivity was determined by liquid scintillation counting of blood samples (whole blood and plasma), urine samples and faecal samples collected pre-dose and at designated time points up to 120 hours post-dose. Urine samples were also analysed for the presence of amphetamine-derived metabolites. Safety was assessed by adverse event reporting, changes in physical findings, vital sign measurements, ECG measurements, and clinical laboratory test results. For intact lisdexamfetamine dimesylate, the median time to reach maximum plasma drug concentration (t(max)) was 1.00 hour, and the mean maximum plasma drug concentration (C(max)) was 58.2 +/- 28.1 ng/mL. Intact lisdexamfetamine dimesylate exhibited modest systemic exposure (area under the drug concentration-time curve from time 0 to infinity [AUC(infinity)] 67.04 +/- 18.94 ng . h/mL), and rapid elimination (mean apparent terminal elimination half-life [t((1/2)beta)] 0.47 hours). For d-amphetamine, the median t(max) was 3.00 hours, and the mean C(max) was 80.3 +/- 11.8 ng/mL. The AUC(infinity) of d-amphetamine was 1342 +/- 216.9 ng . h/mL, and elimination occurred as a first-order process. The t((1/2)beta) of d-amphetamine was 10.39 hours. Peaks consistent with amphetamine and hippuric acid were identified in urine samples by high-performance liquid chromatography radioactive profiling. Relative to dose administered, 41.5% was recovered in urine as d-amphetamine, 24.8% as hippuric acid and 2.2% as intact lisdexamfetamine dimesylate. Less than 0.3% of the administered dose was recovered in the faeces. During the 0- to 48-hour urine samples, no unexpected adverse events or clinically significant laboratory, ECG or physical examination findings related to the study medication were observed. Following a single 70 mg oral dose, lisdexamfetamine dimesylate was quickly absorbed, extensively metabolized to d-amphetamine and its derivatives, and rapidly eliminated. Systemic exposure to d-amphetamine was approximately 20-fold higher than systemic exposure to intact lisdexamfetamine dimesylate in healthy adults. Lisdexamfetamine dimesylate, administered as a single 70 mg dose, was generally well tolerated in this study.

Elimination of 7-aminoclonazepam in urine after a single dose of clonazepam.

PubMed

Negrusz, Adam; Bowen, Andrew M; Moore, Christine M; Dowd, Sheila M; Strong, Mary Jane; Janicak, Philip G

2003-08-01

The objective of this paper was to determine how long after administration of benzodiazepine clonazepam (CLO), its major metabolite 7-aminoclonazepam (7-ACLO) could be detected in urine collected from 10 healthy volunteers who received a single 3-mg dose of Klonopin (clonazepam). Such data would be of great importance to law enforcement agencies trying to determine the best time interval for urine collection from a victim of drug-facilitated sexual assault in order to reveal drug use. A highly sensitive NCI-GC-MS method for the simultaneous quantitation of CLO and its major metabolite 7-ACLO in urine was developed and validated. The following urine samples were collected from each volunteer: one before CLO administration, and 6 h, and 1, 3, 5, 8, 10, 14, 21 and 28 days after. All urine samples (1 mL) were extracted following addition of the internal standard (D(5)-diazepam) and enzymatic hydrolysis ( beta-glucuronidase) using solid-phase extraction columns. Standard curves for CLO (500-4000 pg x mL(-1)) and 7-ACLO (50-2000 pg x mL(-1)) were prepared by spiking aliquots of negative urine. The urine from every subject was still positive for 7-ACLO 14 days after administration of the drug. Eight of the ten volunteers had measurable amounts of the metabolite 21 days after administration. One volunteer was still positive 28 days after administration. Six of the volunteers had urine concentrations of 7-ACLO that peaked at 1 day after administration. One volunteer had the highest concentration of 7-ACLO at 3 days, two volunteers at 5 days, and one at 8 days. The range of concentrations detected was from 73.0 pg x mL(-1) to 183.2 ng x mL(-1). CLO was not detected in any of the samples.

A randomized controlled trial [corrected] administration of tetanus toxoid (TT) versus tetanus and reduced diphtheria (Td) in pregnant women.

PubMed

Salama, Maha M; Hady, Osama A W; Ashour, Wael; Mostafa, Amal; El Alkamy, Sahar; El Sayed, Nehad; El Yazeed, Remon Abu

2009-07-01

The present study was designed as a randomized clinical trial to compare the immunogenicity, reactogenicity, and efficacy of tetanus toxoid (TT) and the combined tetanus and reduced diphtheria (Td) in pregnant women in four rural communities in Egypt. The pregnant women in each four villages received either TT or Td randomly. Both TT and Td vaccines are manufactured by the Egyptian Company for Biological Products & Vaccines (VACSERA) in Egypt. A total of 131 pregnant women were enrolled during the time of antenatal care visit (at 20 weeks gestational age of pregnancy) in one of four health units in Abu Homos district, Beheira Governorate, Egypt. Unimmunized women received two random doses of either TT or Td 8 weeks apart during their pregnancy. Outpatient follow-up for adverse reactions occurred at the third day after each vaccine dose as either local effects such as pain, redness, and swelling or systematic effects such as fever, malaise, and headache or body aches which was served as primary safety endpoint. Blood was collected three times from each woman for determination of antibody titer against tetanus and diphtheria by using enzyme-linked immunosorbent assay technique. The first sample was collected immediately before the first dose, the second before the second dose, and the third sample 1 week after delivery. Active surveillance home visits to all study participants were done twice: the first home visit during the first week after delivery and the second 1 month after labor to report the health status of the mother and the baby. A total of 122 pregnant women received two ordinary doses with interdose intervals within the allowable range and three blood samples were collected in each protocol analysis (62 in the TT group and 60 in the Td group). There was no statistically significant difference between groups in the percentage of reporting a primary safety endpoint (fever, malaise, body ache, headache) or local reactions at the site of injection as redness and swelling, at third day after each dose. While in the Td group, after doses I and II, there was significant reporting pain at injection site as compared with TT group, home visits clinical examination revealed that the mothers and children were normal on in both groups. However, in the TT group, some children suffered from physiological jaundice. In all women in the two groups, protective immunity for tetanus was acquired, which reflected in neutralization of antibodies at titer (>0.10 IU/ml) after complete vaccination; however, the tetanus geometric mean titers postdoses I and II were significantly higher in TT vaccines group (P < 0.001). The postvaccination seroprotection titer (>0.10 IU/ml) in diphtheria was significantly higher in Td group than the TT group; diphtheria geometric mean titers of postdose II were significantly higher in Td vaccines as compared to the other group (P < 0.0001). From this results, we can conclude that the use of Td vaccine improves immunogenicity for both tetanus and diphtheria more than the use of TT vaccine alone and we can recommend to replace TT in immunization of pregnant women.

Using dried blood spot sampling to improve data quality and reduce animal use in mouse pharmacokinetic studies.

PubMed

Wickremsinhe, Enaksha R; Perkins, Everett J

2015-03-01

Traditional pharmacokinetic analysis in nonclinical studies is based on the concentration of a test compound in plasma and requires approximately 100 to 200 μL blood collected per time point. However, the total blood volume of mice limits the number of samples that can be collected from an individual animal-often to a single collection per mouse-thus necessitating dosing multiple mice to generate a pharmacokinetic profile in a sparse-sampling design. Compared with traditional methods, dried blood spot (DBS) analysis requires smaller volumes of blood (15 to 20 μL), thus supporting serial blood sampling and the generation of a complete pharmacokinetic profile from a single mouse. Here we compare plasma-derived data with DBS-derived data, explain how to adopt DBS sampling to support discovery mouse studies, and describe how to generate pharmacokinetic and pharmacodynamic data from a single mouse. Executing novel study designs that use DBS enhances the ability to identify and streamline better drug candidates during drug discovery. Implementing DBS sampling can reduce the number of mice needed in a drug discovery program. In addition, the simplicity of DBS sampling and the smaller numbers of mice needed translate to decreased study costs. Overall, DBS sampling is consistent with 3Rs principles by achieving reductions in the number of animals used, decreased restraint-associated stress, improved data quality, direct comparison of interanimal variability, and the generation of multiple endpoints from a single study.

Using Dried Blood Spot Sampling to Improve Data Quality and Reduce Animal Use in Mouse Pharmacokinetic Studies

PubMed Central

Wickremsinhe, Enaksha R; Perkins, Everett J

2015-01-01

Traditional pharmacokinetic analysis in nonclinical studies is based on the concentration of a test compound in plasma and requires approximately 100 to 200 µL blood collected per time point. However, the total blood volume of mice limits the number of samples that can be collected from an individual animal—often to a single collection per mouse—thus necessitating dosing multiple mice to generate a pharmacokinetic profile in a sparse-sampling design. Compared with traditional methods, dried blood spot (DBS) analysis requires smaller volumes of blood (15 to 20 µL), thus supporting serial blood sampling and the generation of a complete pharmacokinetic profile from a single mouse. Here we compare plasma-derived data with DBS-derived data, explain how to adopt DBS sampling to support discovery mouse studies, and describe how to generate pharmacokinetic and pharmacodynamic data from a single mouse. Executing novel study designs that use DBS enhances the ability to identify and streamline better drug candidates during drug discovery. Implementing DBS sampling can reduce the number of mice needed in a drug discovery program. In addition, the simplicity of DBS sampling and the smaller numbers of mice needed translate to decreased study costs. Overall, DBS sampling is consistent with 3Rs principles by achieving reductions in the number of animals used, decreased restraint-associated stress, improved data quality, direct comparison of interanimal variability, and the generation of multiple endpoints from a single study. PMID:25836959

Determination of GHB in human hair by HPLC-MS/MS: Development and validation of a method and application to a study group and three possible single exposure cases.

PubMed

Bertol, Elisabetta; Mari, Francesco; Vaiano, Fabio; Romano, Guido; Zaami, Simona; Baglìo, Giovanni; Busardò, Francesco Paolo

2015-05-01

Gamma-hydroxybutyrate (GHB) over the last two decades has generated increased notoriety as a euphoric and disinhibiting drug of abuse in cases of drug-related sexual assault and for this reason it is considered a 'date rape' drug. The first aim of this paper was to develop and fully validate a method for the detection of GHB in human hair by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) after liquid-liquid extraction (LLE). The second aim was the application of the method to hair samples of 30 GHB-free users in order to determine the basal level. The results obtained showed no significant differences in endogenous concentrations (p = 0.556) between hair samples of the three groups (black, blonde, and dyed hair) and the age and sex of the subjects did not affect the endogenous levels. Another 12 healthy volunteers, with no previous history of GHB use, were selected and a single dose (25 mg/Kg) was orally administered to all of them and hair samples were collected before the administration of the single dose and other two samples were collected one month and two months later, respectively. The segmental analysis of the latter two samples allowed us to calculate two ratios: 4.45:1 (95% C.I. 3.52-5.63) and 3.35:1 (95% C.I. 2.14-5.18), respectively, which can be recommended as reasonable values for a positive identification of GHB intake. Finally the method was applied to three real cases where a GHB single exposure probably occurred. Copyright © 2014 John Wiley & Sons, Ltd.

Effects of chlorhexidine preprocedural rinse on bacteremia in periodontal patients: a randomized clinical trial

PubMed Central

Balejo, Rodrigo Dalla Pria; Cortelli, José Roberto; Costa, Fernando Oliveira; Cyrino, Renata Magalhães; Aquino, Davi Romeiro; Cogo-Müller, Karina; Miranda, Taís Browne; Moura, Sara Porto; Cortelli, Sheila Cavalca

2017-01-01

Abstract Objective: Single dose of systemic antibiotics and short-term use of mouthwashes reduce bacteremia. However, the effects of a single dose of preprocedural rinse are still controversial. This study evaluated, in periodontally diseased patients, the effects of a pre-procedural mouth rinse on induced bacteremia. Material and Methods: Systemically healthy individuals with gingivitis (n=27) or periodontitis (n = 27) were randomly allocated through a sealed envelope system to: 0.12% chlorhexidine pre-procedural rinse (13 gingivitis and 13 periodontitis patients) or no rinse before dental scaling (14 gingivitis and 15 periodontitis patients). Periodontal probing depth, clinical attachment level, plaque, and gingival indices were measured and subgingival samples were collected. Blood samples were collected before dental scaling, 2 and 6 minutes after scaling. Total bacterial load and levels of P. gingivalis were determined in oral and blood samples by real-time polymerase chain reaction, while aerobic and anaerobic counts were determined by culture in blood samples. The primary outcome was the antimicrobial effect of the pre-procedural rinse. Data was compared by Mann-Whitney and Signal tests (p<0.05). Results: In all sampling times, polymerase chain reaction revealed higher blood bacterial levels than culture (p<0.0001), while gingivitis patients presented lower bacterial levels in blood than periodontitis patients (p<0.0001). Individuals who experienced bacteremia showed worse mean clinical attachment level (3.4 mm vs. 1.1 mm) and more subgingival bacteria (p<0.005). The pre-procedural rinse did not reduce induced bacteremia. Conclusions: Bacteremia was influenced by periodontal parameters. In periodontally diseased patients, pre-procedural rinsing showed a discrete effect on bacteremia control. PMID:29211279

Hematocrit-Independent Quantitation of Stimulants in Dried Blood Spots: Pipet versus Microfluidic-Based Volumetric Sampling Coupled with Automated Flow-Through Desorption and Online Solid Phase Extraction-LC-MS/MS Bioanalysis.

PubMed

Verplaetse, Ruth; Henion, Jack

2016-07-05

A workflow overcoming microsample collection issues and hematocrit (HCT)-related bias would facilitate more widespread use of dried blood spots (DBS). This report describes comparative results between the use of a pipet and a microfluidic-based sampling device for the creation of volumetric DBS. Both approaches were successfully coupled to HCT-independent, fully automated sample preparation and online liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) analysis allowing detection of five stimulants in finger prick blood. Reproducible, selective, accurate, and precise responses meeting generally accepted regulated bioanalysis guidelines were observed over the range of 5-1000 ng/mL whole blood. The applied heated flow-through solvent desorption of the entire spot and online solid phase extraction (SPE) procedure were unaffected by the blood's HCT value within the tested range of 28.0-61.5% HCT. Enhanced stability for mephedrone on DBS compared to liquid whole blood was observed. Finger prick blood samples were collected using both volumetric sampling approaches over a time course of 25 h after intake of a single oral dose of phentermine. A pharmacokinetic curve for the incurred phentermine was successfully produced using the described validated method. These results suggest that either volumetric sample collection method may be amenable to field-use followed by fully automated, HCT-independent DBS-SPE-LC-MS/MS bioanalysis for the quantitation of these representative controlled substances. Analytical data from DBS prepared with a pipet and microfluidic-based sampling devices were comparable, but the latter is easier to operate, making this approach more suitable for sample collection by unskilled persons.

Persistence of azoxystrobin in/on grapes and soil in different grapes growing areas of India.

PubMed

Gajbhiye, Vijay Tularam; Gupta, Suman; Mukherjee, Irani; Singh, Shashi Bala; Singh, Neera; Dureja, Prem; Kumar, Yogesh

2011-01-01

Persistence of azoxystrobin was studied in/on grapes when applied @ 150 g ai ha⁻¹ (recommended dose) and 300 g ai ha⁻¹ (double the recommended dose) in three grapes growing states of India, namely Karnataka, Maharashtra and Tamil Nadu, in the year 2006-2007. A total of five sprays were given at an interval of about 15 days. Grapes and soil samples were collected after 5th spray, extracted and analysed by gas chromatography using electron capture detector. Half life of azoxystrobin on grapes varied from 5.4 to 11.2 days. Residues of azoxystrobin were much below the prescribed MRL (0.5 mg kg⁻¹) after 21 days. The dissipation of azoxystrobin in soil followed first order rate kinetics with an average half life of 8.1 days at the recommended dose of application.

SU-C-201-03: Ionization Chamber Collection Efficiency in Pulsed Radiation Fields of High Pulse Dose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gotz, M; Karsch, L; Pawelke, J

Purpose: To investigate the reduction of collection efficiency of ionization chambers (IC) by volume recombination and its correction in pulsed fields of very high pulse dose. Methods: Measurements of the collection efficiency of a plane-parallel advanced Markus IC (PTW 34045, 1mm electrode spacing, 300V nominal voltage) were obtained for collection voltages of 100V and 300V by irradiation with a pulsed electron beam (20MeV) of varied pulse dose up to approximately 600mGy (0.8nC liberated charge). A reference measurement was performed with a Faraday cup behind the chamber. It was calibrated for the liberated charge in the IC by a linear fitmore » of IC measurement to reference measurement at low pulse doses. The results were compared to the commonly used two voltage approximation (TVA) and to established theories for volume recombination, with and without considering a fraction of free electrons. In addition, an equation system describing the charge transport and reactions in the chamber was solved numerically. Results: At 100V collection voltage and moderate pulse doses the established theories accurately predict the observed collection efficiency, but at extreme pulse doses a fraction of free electrons needs to be considered. At 300V the observed collection efficiency deviates distinctly from that predicted by any of the established theories, even at low pulse doses. However, the numeric solution of the equation system is able to reproduce the measured collection efficiency across the entire dose range of both voltages with a single set of parameters. Conclusion: At high electric fields (3000V/cm here) the existing theoretical descriptions of collection efficiency, including the TVA, are inadequate to predict pulse dose dependency. Even at low pulse doses they might underestimate collection efficiency. The presented, more accurate numeric solution, which considers additional effects like electric shielding by the charges, might provide a valuable tool for future investigations. This project was funded by the German ministry of research and education (BMBF) under grant number: 03Z1N511 and by the state of Saxony under grant number: B 209.« less

Radiological conditions at Naen, Yugui, Lomiulal, Kabelle and Mellu Islands in the northern half of Rongelap Atoll

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robison, W.L.; Conrado, C.L.

1996-03-01

The data presented in the following tables is the total available for each northern island; they include both the data from the 1978 Northern Marshall Island Radiological Survey (NMIRS) and trips to Rongelap Atoll from 1986 through 1989. In one table we present the number of vegetation samples collected in the 1978 NMIRS and from 1986 through 1989. Again the majority of the {sup 137}Cs data is from the 1986-1989 trips. We have not made additional analyses of {sup 239+240}Pu, {sup 241}Am and {sup 90}Sr because the concentrations are very low and these radionuclides contribute less than 5% of anmore » already very small dose. In another table we show the number of soil samples collected at each island in 1978 and the number collected since 1986. Most of the data are from 1986 through 1989. The major exception is {sup 90}Sr where all of the data are from the 1978 NMIRS. We have done some additional Pu analyses of surface soils (0-5 cm depth) in the northern islands. A significant amount of new data for {sup 137}Cs and {sup 241}Am have been generated from the samples collected from 1986 through 1989. The data are presented in the form of summary tables, graphics, detailed appendices and aerial photographs of the islands with the sample locations marked. The identified sample locations from the 1978 NMIRS will be added later.« less

Single and Multiple Dose Pharmacokinetics of Maraviroc in Saliva, Semen, and Rectal Tissue of Healthy HIV-negative Men

PubMed Central

Patterson, Kristine B.; Malone, Stephanie A.; Shaheen, Nicholas J.; Asher Prince, Heather M.; Dumond, Julie B.; Spacek, Melissa B.; Heidt, Paris E.; Cohen, Myron S.; Kashuba, Angela D. M.

2011-01-01

Background. Antiretroviral pharmacology in seminal plasma (SP) and rectal tissue (RT) may provide insight into antiretroviral resistance and the prevention of sexual transmission of human immunodeficiency virus (HIV). Saliva may be of utility for noninvasively measuring adherence. Methods. A pharmacokinetic study was performed in 12 HIV-negative men receiving maraviroc 300 mg twice daily for 8 days. Seven time-matched pairs of blood plasma (BP) and saliva samples were collected over 12 h on day 1 (PK1) and days 7 and 8 (PK2). One RT sample from each subject was collected during PK1 and PK2. Two SP samples were collected from each subject during PK1, and 6 SP samples were collected from each subject during PK2. Results. SP AUCs were ∼50% lower than BP. However, protein binding in SP ranged from 4% to 25%, resulting in protein-free concentrations >2-fold higher than BP. RT AUCs were 7.5- to 26-fold higher than BP. Maraviroc saliva AUCs were ∼70% lower than BP, but saliva concentrations correlated with BP (r2 = 0.58). Conclusions. More pharmacologically available maraviroc was found in SP than BP. High RT concentrations are promising for preventing rectal HIV acquisition. Saliva correlation with BP suggests that this may be useful for monitoring adherence. Clinical Trials Registration. NCT00775294. PMID:21502084

Intraosseous samples can be used for creatinine measurements--an experimental study in the anaesthetised pig.

PubMed

Strandberg, Gunnar; Lipcsey, Miklós; Eriksson, Mats; Larsson, Anders

2014-01-01

Intraosseous (IO) access is a valuable tool in prehospital locations and in emergency departments when other forms of vascular access are unavailable. Creatinine is often used for dose adjustment of drugs that may be administered through intraosseous cannulae. We aimed to study the possibility of analysing creatinine in intraosseous samples and study the accuracy and precision of such measurements. Eight pigs with endotoxin induced septic shock were sampled hourly for six hours and analysed for plasma creatinine. Samples were collected from arterial, venous, and IO cannulae. There was an increase in creatinine values during the later part of the experiment. The coefficients of variation between the three sampling sites were less than 10% at all sampling times. Based on our findings intraosseous samples can be used for creatinine determination in emergency settings.

Inadequacy of Plasma Acyclovir Levels at Delivery in Patients with Genital Herpes Receiving Oral Acyclovir Suppressive Therapy in Late Pregnancy

PubMed Central

Leung, Daniel T.; Henning, Paul A.; Wagner, Emily C.; Blasig, Audrey; Wald, Anna; Sacks, Stephen L.; Corey, Lawrence; Money, Deborah M.

2009-01-01

Objective: Acyclovir therapy in late pregnancy among women with recurrent genital herpes is effective in decreasing genital lesion frequency and subclinical viral shedding rates at delivery, thereby decreasing the need for caesarean delivery. Despite good adherence and increased dosing schedules, breakthrough lesions and viral shedding are still observed in some women at or near delivery. Anecdotal data suggests that low levels of HSV replication at delivery may result in transmission to the neonate. Therefore, defining optimal acyclovir dosing during labor and delivery is warranted. Our objectives were to determine actual acyclovir levels at delivery, and explore associations between acyclovir levels, duration of labour and time since last acyclovir dose. Methods: Twenty-seven patients were prescribed oral acyclovir 400 mg three times daily from 36 weeks gestation. Cord blood (venous and arterial) and maternal venous blood samples were collected at delivery, and acyclovir levels measured using capillary electrophoresis. Correlations between duration of labour and time since last acyclovir dose with acyclovir blood levels were calculated. Results: Acyclovir levels were below the published mean steady-state trough value (180 ng/ml) in 52% of venous cord, 55% of arterial cord, and 36% of maternal samples. There was a significant inverse correlation between time since last dose and venous cord (rs19=−0.57, p<0.015), arterial cord (rs16=−0.63, p<0.01), and maternal acyclovir levels (r10=−0.69, p<0.03). Conclusions: Oral dosing of acyclovir in late pregnancy may result in insufficient levels at delivery to prevent viral shedding. Alternative approaches should evaluate dosing through labor, perhaps intravenously, and its effect on viral shedding. PMID:20085679

Intra-patient variability of thromboelastographic parameters following in vivo and ex vivo administration of recombinant activated factor VII in haemophilia patients. A multi-centre, randomised trial.

PubMed

Kenet, G; Stenmo, C B; Blemings, A; Wegert, W; Goudemand, J; Krause, M; Schramm, W; Kirchmaier, C; Martinowitz, U

2010-02-01

Thromboelastography methods have been used to predict or monitor treatment of haemophilia patients with recombinant activated factor VII (rFVIIa). However, neither of the two thromboelastographic methods (ROTEM and TEG) has as yet been validated. This multi-centre, randomised trial compared both methods in terms of intra- and inter- patient variability following in vivo and ex vivo rFVIIa administration to haemophilia A and B patients with and without inhibitors. Patients ((3)16 years old) received the same intravenous rFVIIa dose (45, 90 or 180 microg/kg) twice, 1-12 weeks apart. Blood samples were collected pre-dose and 15, 60, 120 and 240 minutes post-dose for ROTEM and TEG analysis. Pre-dose samples were also spiked ex vivo with rFVIIa (0.6, 1.2 or 2.4 microg/ml), to correspond to the three in vivo doses. Twenty-six haemophilia A and four haemophilia B patients were enrolled. A significant treatment effect was observed with in vivo rFVIIa (p<0.05) with more pronounced effects in inhibitor (n=14) versus non-inhibitor (n=16) patients. There was a strong positive correlation between ROTEM and TEG parameters. Intra- and inter-patient variation was large for all thromboelastography parameters at all time points and rFVIIa doses. Intra-patient variation was generally lower for non-inhibitor than inhibitor patients, and lower following ex vivo spiking versus in vivo rFVIIa administration. In conclusion, there was a clear effect of rFVIIa on all thromboelastography parameters, but the large intra- and inter-patient variability following in vivo rFVIIa administration renders the use of our method unsuitable for dose-response prediction for haemophilia patients in the clinical setting.

Radiological conditions at the Southern Islands of Rongelap Atoll

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robison, W.L.; Conrado, C.L.

1996-03-01

The data presented in the following tables is the total available for each southern island; they include both the data from the 1978 Northern Marshall Island Radiological Survey (NMIRS) and trips to Rongelap Atoll from 1986 through 1991. There are additional samples that were taken at Rongelap Island in 1990 and 1991, and the data are unavailable for this report. In one table we present the number of vegetation samples collected in the 1978 NMIRS and from 1986 through 1991. Again, the majority of the {sup 137}Cs is from the 1986-1991 trips. We have not made additional analyses of {supmore » 239+240}Pu, {sup 241}Am and {sup 90}Sr because the concentrations are very low and these radionuclides contribute less than 5% of an already very small dose. In another table we show the number of soil samples collected at each island in 1978 and the number collected since 1986. Most of the data are from 1986 through 1991. The major exception is {sup 90}Sr where all of the data are from the 1978 NMIRS. We have done some additional Pu analyses of soils from Rongelap Eniaetok, and Borukka Island but none of the other southern islands. A significant amount of new data for {sup 137}Cs and {sup 241}Am have been generated from the samples collected from 1986 through 1991. The data are presented in the form of summary tables, graphics, detailed appendices and aerial photographs of the islands with the sample locations marked. The identified sample locations from the 1978 NMIRS will be added later.« less

Ultra-high-performance liquid chromatography tandem mass spectrometry determination of GHB, GHB-glucuronide in plasma and cerebrospinal fluid of narcoleptic patients under sodium oxybate treatment.

PubMed

Tittarelli, Roberta; Pichini, Simona; Pedersen, Daniel S; Pacifici, Roberta; Moresco, Monica; Pizza, Fabio; Busardò, Francesco Paolo; Plazzi, Giuseppe

2017-05-01

Sodium oxybate (Xyrem ® ), the sodium salt of γ- hydroxybutyric acid (GHB), is a first-line treatment of the symptoms induced by type 1 narcolepsy (NT1) and it is highly effective in improving sleep architecture, decreasing excessive daytime sleepiness and the frequency of cataplexy attacks. Using an ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) validated method, GHB was determined together with its glucuronide (GHB-gluc), in plasma and cerebrospinal fluid (CSF) samples of NT1 patients under sodium oxybate treatment. To characterize the plasma pharmacokinetics of GHB, three subjects with NT1 were administered at time 0 and 4h with 1.25, 1.5 and 3.55g Xyrem ® , respectively and had their blood samples collected at 7 time points throughout an 8-h session. CSF specimens, collected for orexin A measurement from the same three subjects 6h after their second administration, were also tested. The results obtained suggested that GHB plasma values increased disproportionally with the rising doses, (C max0-4 : 12.53, 32.95 and 69.62μg/mL; C max4-8 : 44.93, 75.03 and 111.93μg/mL for total Xyrem ® dose of 2.5, 3 and 7g respectively) indicating non-linear dose-response. GHB-Gluc was present only in traces in all plasma samples from treated patients, not changing with increasing Xyrem ® doses. GHB values of 5.62, 6.10 and 17.74μg/mL for 2, 3 and 7g Xyrem ® were found in CSF with a significant difference from control values. GHB-Gluc was found in negligible concentrations with no differences to those of control individuals. In conclusion this simple and fast UHPLC-MS/MS method proved useful for pharmacokinetic studies and therapeutic drug monitoring of GHB in narcoleptic patients treated with sodium oxybate. Copyright © 2017 Elsevier B.V. All rights reserved.

Estimation of annual effective dose due to natural radioactive elements in ingestion of foodstuffs in tin mining area of Jos-Plateau, Nigeria.

PubMed

Jibiri, N N; Farai, I P; Alausa, S K

2007-01-01

Soils and food crops from a former tin mining location in a high background radiation area on the Jos-Plateau, Nigeria were collected and analyzed by gamma spectrometry to measure their contents of 40K, 238U and 232Th. As well as collecting samples, in situ dose rates on farms were measured using a precalibrated survey meter. Activity concentrations determined in food crops were compared with the local food derivatives or diets to investigate the possible removal or addition of radionuclides during food preparation by cooking or other means. Potassium-40 was found to contribute the highest activity in all the food products. The activity concentration of 40K, 238U and 232Th in local prepared diets ranged between 60 and 494 Bq kg-1, between BDL and 48 Bq kg-1 and between BDL and 17 Bq kg-1, respectively. The internal effective dose to individuals from the consumption of the food types was estimated on the basis of the measured radionuclide contents in the food crops. It ranged between 0.2 microSv y-1 (beans) and 2164 microSv y-1 (yam) while the annual external gamma effective dose in the farms due to soil radioactivity ranged between 228 microSv and 4065 microSv.

The Marshall Islands Data Management Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stoker, A.C.; Conrado, C.L.

1995-09-01

This report is a resource document of the methods and procedures used currently in the Data Management Program of the Marshall Islands Dose Assessment and Radioecology Project. Since 1973, over 60,000 environmental samples have been collected. Our program includes relational database design, programming and maintenance; sample and information management; sample tracking; quality control; and data entry, evaluation and reduction. The usefulness of scientific databases involves careful planning in order to fulfill the requirements of any large research program. Compilation of scientific results requires consolidation of information from several databases, and incorporation of new information as it is generated. The successmore » in combining and organizing all radionuclide analysis, sample information and statistical results into a readily accessible form, is critical to our project.« less

Effect of gamma radiation on the ripening and levels of bioactive amines in bananas cv. Prata

NASA Astrophysics Data System (ADS)

Gloria, Maria Beatriz A.; Adão, Regina C.

2013-06-01

Green Prata bananas at the full three-quarter stage were exposed to gamma radiation at doses of 0.0 (control), 1.0, 1.5 and 2.0 kGy and stored at 16±1 °C and 85% relative humidity. Samples were collected periodically and analyzed for peel color, pulp-to-peel ratio and levels of starch, soluble sugars and bioactive amines. Degradation of starch and formation of fructose and glucose followed first- and zero-order kinetics, respectively. Higher irradiation doses caused increased inhibitory effect on starch degradation and glucose formation. However, doses of 1.5 and 2.0 kGy caused browning of the peel, making the fruit unacceptable. Irradiation at 1.0 kGy was the most promising dose: it did not affect peel color, the pulp-to-peel ratio or the levels of the amines spermidine, serotonin and putrescine. However, it slowed down starch degradation and the formation and accumulation of fructose and glucose, delaying the ripening of the fruit for 7 days.

Spatial distribution of uranium and basic water quality parameter in the capital of Bihar and consequent ingestion dose.

PubMed

Kumar, Deepak; Singh, Anshuman; Jha, Rishi Kumar

2018-04-21

Investigation of presence of Uranium (U) in groundwater/drinking water is an active are of research due to its chemical and radiological toxicity as well as long-term health effects. The current study had the objective of estimating U as a naturally occurring radioactive element in groundwater samples and assessment of ingestion dose, when groundwater is the source of drinking water. The random sampling method was chosen for the collection of samples based on population density. The estimation of U was done using LED fluorimeter. Statistical tools were applied to analyze the data and its spatial distribution. The U concentrations in three blocks of urban Patna were well below the permissible limits suggested by different health agencies of the world. A correlation test was performed to analyze the association of U with other physiochemical parameters of water samples. It was found that the sulfate, chloride, calcium, hardness, alkalinity, TDS, salinity, and ORP were positively correlated, whereas fluoride, phosphate, magnesium, dissolved oxygen, and pH were negatively correlated with U concentrations. The ingestion dose due to U, occurring in groundwater, was found to vary from 0.2-27.0 μSv y -1 with a mean of 4.2 μSv y - 1 , which was well below the recommended limit of 0.1 mSv (WHO WHO Chron 38:104-108, 2012).Therefore, the water in this region is fit for drinking purposes.

Comparison of the transplacental pharmacokinetics of cortisol and triamcinolone acetonide in the rhesus monkey

DOE Office of Scientific and Technical Information (OSTI.GOV)

Slikker, W. Jr.; Althaus, Z.R.; Rowland, J.M.

1982-11-01

The late gestational age rhesus monkey was used to study the transplacental pharmacokinetics of radiolabeled triamcinolone acetonide (TAC) and cortisol. Tritiated-TAC and (/sup 14/C)cortisol were administered simultaneously via the maternal radial vein were administered simultaneously via the maternal radial vein and blood samples were serially drawn from catheters implanted in both the maternal femoral artery and fetal umbilical vein and artery. High-performance liquid chromatography of the processed blood samples revealed that from 93 to 100% of the /sup 3/H in the fetal circulation was parent TAC, whereas only 14 to 49% of the /sup 14/C was cortisol during the 40-minmore » period after dose administration. Fetal tissue samples taken at 3 hr after dose administration showed that 75 to 96% of the /sup 3/H present was TAC, whereas no cortisol was observed. TAC demonstrated dose-independent kinetics. Samples collected from the umbilical vein of the in situ placenta after fetectomy revealed that cortisol was extensively converted to cortisone by the placenta, whereas TAC was refractory to placental metabolism. This placental conversion of cortisol to cortisone and the further metabolism and conjugation of cortisol by the fetoplacental unit resulted in a fetal to maternal plasma cortisol ratio of 0.2. In contrast, the lack of placental or fetoplacental metabolism of TAC resulted in a fetal to maternal plasma TAC ratio of 0.6.« less

Effects of oral megestrol acetate administration on the hypothalamic-pituitary-adrenal axis of male bottlenose dolphins (Tursiops truncatus).

PubMed

Houser, Dorian S; Champagne, Cory D; Jensen, Eric D; Smith, Cynthia R; Cotte, Lara S; Meegan, Jenny M; Booth, Rebecca K; Wasser, Samuel K

2017-07-15

OBJECTIVE To evaluate the impact of oral megestrol acetate (MA) administration on adrenal function in male bottlenose dolphins (Tursiops truncatus). DESIGN Serial cross-sectional study. ANIMALS 8 adult male dolphins, all of which were receiving MA at various daily doses (range, 0 to 60 mg, PO) for the control of reproductive behavior. PROCEDURES Blood samples were collected every 2 weeks for 1 year from dolphins trained to voluntarily provide them. Cortisol, ACTH, and other hormone concentrations were measured in serum or plasma via radioimmunoassay or ELISA. Fecal samples, also provided by dolphins voluntarily, were assayed for glucocorticoid metabolite concentrations. Effects of daily MA dose on hormone concentrations were evaluated. RESULTS Daily MA doses as low as 10 mg strongly suppressed cortisol secretion in nearly all dolphins, and except for a single measurement, no dolphin had measurable serum concentrations at doses ≥ 20 mg. Variations in serum cortisol concentration were unrelated to season but were directly related to ACTH concentrations, suggesting primary effects upstream of the adrenal gland. Cessation of MA administration resulted in almost immediate restoration of measurable serum cortisol concentrations, although concentrations continued to rise in a few dolphins over the following weeks to months. CONCLUSIONS AND CLINICAL RELEVANCE Caution should be exercised when administering MA to control reproductive behavior in male dolphins. Because the hypothalamic-pituitary-adrenal axis appeared to be sensitive to even small doses of MA in dolphins, duration of treatment may be the most critical consideration.

51Cr-EDTA absorption blood test: an easy method for assessing small intestinal permeability in dogs.

PubMed

Frias, Rafael; Sankari, Satu; Westermarck, Elias

2004-01-01

The 51Cr-EDTA test is a valuable clinical tool for screening intestinal diseases in dogs. The test is performed by calculating the percentage of recovery from urine of a PO-ingested dose of 51Cr-EDTA after 6 or 24 hours. Careful urine collection is a practical limitation of this test in dogs, and our goal was to develop a simpler test that measures 51Cr-EDTA in blood. A 51Cr-EDTA absorption test was simultaneously performed on urine and serum 43 times in healthy Beagle Dogs. Timed blood samples were withdrawn, and urine was collected during a 6-hour period. Percentages of the ingested dose were then calculated in urine and serum. The mean +/- standard deviation (range) percentage in urine after 6 hours was 14.07 +/- 8.72% (3.81-34.18%), whereas results in serum from samples taken at 2, 3, 4, 5, and 6 hours were 0.49 +/- 0.45% (0.02-2.13%), 0.75 +/- 0.52% (0.03-1.89%), 0.82 +/- 0.57% (0.13-2.21%), 0.70 +/- 0.53% (0.12-1.99%), and 0.47 +/- 0.44% (0.11-1.79%), respectively. The results for blood specimens showed good concordance with those for urine, especially for the samples taken at 4 hours (r = 0.89). Moreover, the correlation between urine and blood was better when the sum of the percentages of the recovered analyte from various blood samples was compared with urine. The correlation coefficient when summing 4 blood samples was excellent (r = 0.97) and remained excellent when summing only 2 blood samples taken at 3 and 5 hours (r = 0.95) or at 3 and 4 hours (r = 0.94). We conclude that a serum 51Cr-EDTA test determined by summing successive blood samples provides an easier means of estimating small intestinal permeability in dogs and gives results comparable to those of the 6-hour urine test.

Effect of chronic pyridostigmine bromide treatment on cardiovascular and behavioral parameters in mice.

PubMed

Bernatova, Iveta; Dubovicky, Michal; Price, William A; Grubbs, Robert D; Lucot, James B; Morris, Mariana

2003-03-01

Experiments were performed to determine the effect of chronic low-dose pyridostigmine bromide (PB) treatment on blood acetylcholinesterase (AChE), cardiovascular (CV) function, and behavior in C57BL/6J male mice. Chronic carotid arterial catheters were used for long-term CV measurements and for collection of blood samples. Separate groups of mice were used for behavioral open field tests. PB was administered subcutaneously using osmotic minipumps at 1 and 3 mg/kg/day for 7 days. Blood pressure and heart rate (HR) were measured continuously for 24 h before treatment and on Days 3 and 7 after minipump insertion. Blood samples were collected on the same days. Mean arterial pressure (MAP) of the control group was 108+/-2 and 104+/-2 mm Hg during the dark and light periods, respectively. HR was 510+/-18 and 493+/-19 beats/min during the dark and light periods, respectively. PB treatment had no effect on MAP or HR in either dark or light period. Basal AChE activity was 0.42+/-0.1 micromol/min/ml, with no changes observed with PB at 1 mg/kg/day. The higher PB dose (3 mg/kg/day) decreased blood AChE activity by 85% on Day 7. Despite the reduction in blood AChE activity, there were no alterations in open field behaviors (locomotor activity, rearing, distance traveled, rest time, number of entries, and pokes). In conclusion, chronic low-dose PB exposure decreased blood AChE activity but had no effect on CV function or behavior in mice.

Multiple Low-Dose Challenges in a Rhesus Macaque AIDS Vaccine Trial Result in an Evolving Host Response That Affects Protective Outcome

PubMed Central

Selinger, Christian; Strbo, Natasa; Gonzalez, Louis; Aicher, Lauri; Weiss, Jeffrey M.; Law, G. Lynn; Palermo, Robert E.; Vaccari, Monica; Franchini, Genoveffa; Podack, Eckhard R.

2014-01-01

Using whole-blood transcriptional profiling, we investigated differences in the host response to vaccination and challenge in a rhesus macaque AIDS vaccine trial. Samples were collected from animals prior to and after vaccination with live, irradiated vaccine cells secreting the modified endoplasmic reticulum chaperone gp96-Ig loaded with simian immunodeficiency virus (SIV) peptides, either alone or in combination with a SIV-gp120 protein boost. Additional samples were collected following multiple low-dose rectal challenges with SIVmac251. Animals in the boosted group had a 73% reduced risk of infection. Surprisingly, few changes in gene expression were observed during the vaccination phase. Focusing on postchallenge comparisons, in particular for protected animals, we identified a host response signature of protection comprised of strong interferon signaling after the first challenge, which then largely abated after further challenges. We also identified a host response signature, comprised of early macrophage-mediated inflammatory responses, in animals with undetectable viral loads 5 days after the first challenge but with unusually high viral titers after subsequent challenges. Statistical analysis showed that prime-boost vaccination significantly lowered the probability of infection in a time-consistent manner throughout several challenges. Given that humoral responses in the prime-boost group were highly significant prechallenge correlates of protection, the strong innate signaling after the first challenge suggests that interferon signaling may enhance vaccine-induced antibody responses and is an important contributor to protection from infection during repeated low-dose exposure to SIV. PMID:25274805

Distribution of natural and anthropogenic radionuclides in beach sand samples from Mediterranean Coast of Turkey

NASA Astrophysics Data System (ADS)

Özmen, S. F.; Cesur, A.; Boztosun, I.; Yavuz, M.

2014-10-01

Following Fukushima Dai-ichi Nuclear Power Plant accident, a huge amount of radionuclides were released in atmosphere and ocean. It's impact on the environment is of great concern to the good of the public at large. In this regard environmental radioactivity monitoring such as external dose rate and radioactivity measurements in environmental samples has been carried out. For this purpose, several beach sand samples were collected from south coast of the Turkey in September 2011 and radioactivity concentrations of 226Ra (238U), 228Ac (232Th), 40K, 134Cs and 137Cs were determined by gamma spectrometry using a high-purity Germanium detector. The measured activity concentrations in beach sand samples ranged from 4.0±0.5 to 21.5±1.8 Bq/kg, 1.8±0.4 to 27.9±2.4 Bq/kg, 19.0±2.2 to 590.3±28.6 Bq/kg and 0.1±0.0 to 1.0±0.1 Bq/kg for 226Ra, 232Th, 40K and 137Cs, respectively. However there was no sign of 134Cs in the sample spectrum after Fukushima Dai-ichi Nuclear Power Plant accident. Hence we can safely conclude that there was no significant material transfer from Fukushima to Turkey. The other activities are in good agreement with the published results of neighboring areas. The absorbed gamma dose rate (D) and the annual effective dose (AED) of beach sand samples were below the world wide average implying that the radiation hazard is insignificant. The data presented in this study would also be very useful to determine the possible future effects of the nuclear power plant to the environment.

Pulmonary deposition modeling with airborne fiber exposure data: a study of workers manufacturing refractory ceramic fibers.

PubMed

Lentz, Thomas J; Rice, Carol H; Succop, Paul A; Lockey, James E; Dement, John M; LeMasters, Grace K

2003-04-01

Increasing production of refractory ceramic fiber (RCF), a synthetic vitreous material with industrial applications (e.g., kiln insulation), has created interest in potential respiratory effects of exposure to airborne fibers during manufacturing. An ongoing study of RCF manufacturing workers in the United States has indicated an association between cumulative fiber exposure and pleural plaques. Fiber sizing data, obtained from electron microscopy analyses of 118 air samples collected in three independent studies over a 20-year period (1976-1995), were used with a computer deposition model to estimate pulmonary dose of fibers of specified dimensions for 652 former and current RCF production workers. Separate dose correction factors reflecting differences in fiber dimensions in six uniform job title groups were used with data on airborne fiber concentration and employment duration to calculate cumulative dose estimates for each worker. From review of the literature, critical dimensions (diameter <0.4 microm, length <10 microm) were defined for fibers that may translocate to the parietal pleura. Each of three continuous exposure/dose metrics analyzed in separate logistic regression models was significantly related to plaques, even after adjusting for possible past asbestos exposure: cumulative fiber exposure, chi(2) = 15.2 (p < 0.01); cumulative pulmonary dose (all fibers), chi(2) = 14.6 (p < 0.01); cumulative pulmonary dose (critical dimension fibers), chi(2) = 12.4 (p < 0.01). Odds ratios (ORs) were calculated for levels of each metric. Increasing ORs were statistically significant for the two highest dose levels of critical dimension fibers (level three, OR = 11, 95%CI = [1.4, 98]; level four, OR = 25, 95%CI = [3.2, 190]). Similar associations existed for all metrics after adjustment for possible asbestos exposure. It was concluded that development of pleural plaques follows exposure- and dose-response patterns, and that airborne fibers in RCF manufacturing facilities include those with critical dimensions associated with pleural plaque formation. Analysis of additional air samples may improve estimates of the dose-response relationship.

Comparing probabilistic and descriptive analyses of time–dose–toxicity relationship for determining no-observed-adverse-effect level in drug development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Glatard, Anaïs; Berges, Aliénor; Sahota, Tarjinder

The no-observed-adverse-effect level (NOAEL) of a drug defined from animal studies is important for inferring a maximal safe dose in human. However, several issues are associated with its concept, determination and application. It is confined to the actual doses used in the study; becomes lower with increasing sample size or dose levels; and reflects the risk level seen in the experiment rather than what may be relevant for human. We explored a pharmacometric approach in an attempt to address these issues. We first used simulation to examine the behaviour of the NOAEL values as determined by current common practice; andmore » then fitted the probability of toxicity as a function of treatment duration and dose to data collected from all applicable toxicology studies of a test compound. Our investigation was in the context of an irreversible toxicity that is detected at the end of the study. Simulations illustrated NOAEL's dependency on experimental factors such as dose and sample size, as well as the underlying uncertainty. Modelling the probability as a continuous function of treatment duration and dose simultaneously to data from multiple studies allowed the estimation of the dose, along with its confidence interval, for a maximal risk level that might be deemed as acceptable for human. The model-based data integration also reconciled between-study inconsistency and explicitly provided maximised estimation confidence. Such alternative NOAEL determination method should be explored for its more efficient data use, more quantifiable insight to toxic doses, and the potential for more relevant animal-to-human translation. - Highlights: • Simulations revealed issues with NOAEL concept, determination and application. • Probabilistic modelling was used to address these issues. • The model integrated time-dose-toxicity data from multiple studies. • The approach uses data efficiently and may allow more meaningful human translation.« less

Impact of Peptide Transporter 1 on the Intestinal Absorption and Pharmacokinetics of Valacyclovir after Oral Dose Escalation in Wild-Type and PepT1 Knockout Mice

PubMed Central

Yang, Bei; Hu, Yongjun

2013-01-01

The primary objective of this study was to determine the in vivo absorption properties of valacyclovir, including the potential for saturable proton-coupled oligopeptide transporter 1 (PepT1)-mediated intestinal uptake, after escalating oral doses of prodrug within the clinical dose range. A secondary aim was to characterize the role of PepT1 on the tissue distribution of its active metabolite, acyclovir. [3H]Valacyclovir was administered to wild-type (WT) and PepT1 knockout (KO) mice by oral gavage at doses of 10, 25, 50, and 100 nmol/g. Serial blood samples were collected over 180 minutes, and tissue distribution studies were performed 20 minutes after a 25-nmol/g oral dose of valacyclovir. We found that the Cmax and area under the curve (AUC)0–180 of acyclovir were 4- to 6-fold and 2- to 3-fold lower, respectively, in KO mice for all four oral doses of valacyclovir. The time to peak concentration of acyclovir was 3- to 10-fold longer in KO compared with WT mice. There was dose proportionality in the Cmax and AUC0–180 of acyclovir in WT and KO mice over the valacyclovir oral dose range of 10–100 nmol/g (i.e., linear absorption kinetics). No differences were observed in the peripheral tissue distribution of acyclovir once these tissues were adjusted for differences in perfusing drug concentrations in the systemic circulation. In contrast, some differences were observed between genotypes in the concentrations of acyclovir in the distal intestine. Collectively, the findings demonstrate a critical role of intestinal PepT1 in improving the rate and extent of oral absorption for valacyclovir. Moreover, this study provides definitive evidence for the rational development of a PepT1-targeted prodrug strategy. PMID:23924683

A Phase I Dose-Escalation Study of Danusertib (PHA-739358) Administered as a 24-hour Infusion With and Without G-CSF in a 14-day Cycle in Patients with Advanced Solid Tumors

PubMed Central

Cohen, Roger B.; Jones, Suzanne F.; Aggarwal, Charu; von Mehren, Margaret; Cheng, Jonathan; Spigel, David R.; Greco, F. Anthony; Mariani, Mariangela; Rocchetti, Maurizio; Ceruti, Roberta; Comis, Silvia; Laffranchi, Bernard; Moll, Jurgen; Burris, Howard A.

2009-01-01

Purpose This study was conducted to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of the intravenous pan-aurora kinase inhibitor PHA-739358, danusertib, in patients with advanced solid tumors. Experimental Design In Part 1, patients received escalating doses of danusertib (24-h infusion every 14 days) without filgrastim (G-CSF). Febrile neutropenia was the dose-limiting toxicity without G-CSF. Further dose escalation was performed in part 2 with G-CSF. Blood samples were collected for danusertib pharmacokinetics and pharmacodynamics. Skin biopsies were collected to assess histone H3 phosphorylation (pH3). Results Fifty-six patients were treated, 40 in part 1 and 16 in part 2. Febrile neutropenia was the dose limiting toxicity in Part 1 without G-CSF. Most other adverse events were grade 1–2, occurring at doses ≥360 mg/m2 with similar incidence in parts 1 and 2. The MTD without G-CSF is 500 mg/m2. The recommended phase 2 dose (RP2D) in Part 2 with G-CSF is 750 mg/m2. Danusertib demonstrated dose-proportional pharmacokinetics in parts 1 and 2 with a median half-life of 18–26 hours. pH3 modulation in skin biopsies was observed at ≥500 mg/m2. One patient with refractory small cell lung cancer (1000 mg/m2 with G-CSF) had an objective response lasting 23 weeks. One patient with refractory ovarian cancer had 27% tumor regression and 30% CA125 decline. Conclusions Danusertib was well tolerated with target inhibition in skin at ≥500 mg/m2. Preliminary evidence of anti-tumor activity, including a PR and several occurrences of prolonged stable disease (SD), was seen across a variety of advanced refractory cancers. Phase II studies are ongoing. PMID:19825950

Viral etiology of mumps-like illnesses in suspected mumps cases reported in Catalonia, Spain

PubMed Central

Barrabeig, Irene; Costa, Josep; Rovira, Ariadna; Marcos, M Angeles; Isanta, Ricard; López-Adalid, Rubén; Cervilla, Ana; Torner, Nuria; Domínguez, Angela

2014-01-01

We investigated the etiology of reported sporadic suspected mumps cases with a negative RT-PCR result for the mumps virus in the Barcelona-South region in 2007–2011. Samples from mumps virus-negative patients presenting unilateral or bilateral parotitis or other salivary gland swelling were tested for Epstein-Barr virus (EBV) by real-time PCR and for respiratory viruses by two multiplex-PCR-based assays to detect parainfluenza virus (PIV) 1–4, influenza virus (InV) A, B and C, respiratory syncytial virus (RSV), enterovirus, coronavirus 229E, coronavirus OC43, and rhinovirus. 101 samples were analyzed in persons aged 8 months to 50 years. Oral samples were collected on the first day of glandular swelling in 53 patients (52.5%), and on the first two days in 74 patients (73.3%). Viruses were detected in 52 (51.5%) of samples: one virus (25 EBV, 8 PIV3, 4 adenovirus, 4 PIV2, 1 PIV1, 1 InVA, and 1 enterovirus) was detected in 44 patients (84.6%), two viruses in 7 patients, and three viruses in one patient. In 58 patients (57.5%) whose sample was collected in the first 2 days after onset of parotitis and had received two doses of MMR vaccine and in 15 patients (14.8%) whose sample was collected on the first day, it is very likely that the cause was not the mumps virus. This would mean that 72.3% (73/101) of the reported sporadic suspected mumps cases were not mumps cases. The timing of oral-sample collection is crucial to correctly interpret the negative results for mumps virus RNA, especially when suspected cases occur in vaccinated persons. PMID:25483547

X RAY SENSITIVITY OF CONIDIA OF COLLECTOTRICHUM COCCODES (WALLR.) HUGHES (in Italian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Loprieno, N.; Nannarone, A.

1963-01-01

Conidia collected from 6-day-old cultures of Colletotrichum coccodes were washed, resuspended in distilled water, and exposed to various doses of x radiation. Samples of the conidia were then seeded on complete media and survival was evaluated after 3 days by counting the number of colonies. Results demonstrate a very high sensitivity of this fungus to the lethal effects of x rays. (C.H.)

Comparison of lateral flow assay, kidney inhibition swab, and liquid chromatography-tandem mass spectrometry for the detection of penicillin G residues in sow urine

USDA-ARS?s Scientific Manuscript database

Sows (n=126) were administered penicillin G procaine at 5x the label dose for 3 consecutive days. Eighteen sows were slaughtered on each withdrawal days, 5, 10, 15, 20, 25, 32, or 39 d after treatment. Urine samples were collected at slaughter and were frozen at -80 °C until screening as positive ...

Radiation hardness study of semi-insulating GaAs detectors against 5 MeV electrons

NASA Astrophysics Data System (ADS)

Šagátová, A.; Zaťko, B.; Nečas, V.; Sedlačková, K.; Boháček, P.; Fülöp, M.; Pavlovič, M.

2018-01-01

A radiation hardness study of Semi-Insulating (SI) GaAs detectors against 5 MeV electrons is described in this paper. The influence of two parameters, the accumulative absorbed dose (from 1 to 200 kGy) and the applied dose rate (20, 40 or 80 kGy/h), on detector spectrometric properties were studied. The accumulative dose has influenced all evaluated spectrometric properties and also negatively affected the detector CCE (Charge Collection Efficiency). We have observed its systematic reduction from an initial 79% before irradiation down to about 51% at maximum dose of 200 kGy. Relative energy resolution was also influenced by electron irradiation. Its degradation was obvious in the range of doses from 24 up to a maximum dose of 200 kGy, where an increase from 19% up to 31% at 200 V reverse voltage was noticed. On the other hand, a global increase of detection efficiency with accumulative absorbed dose was observed for all samples. Concerning the actual detector degradation we can assume that the tested SI GaAs detectors will be able to operate up to a dose of 300 kGy at least, when irradiated by 5 MeV electrons. The second investigated parameter of irradiation, the dose rate of chosen ranges, did not greatly alter the spectrometric properties of studied detectors.

Serum, tissue and body fluid concentrations of tigecycline after a single 100 mg dose.

PubMed

Rodvold, Keith A; Gotfried, Mark H; Cwik, Michael; Korth-Bradley, Joan M; Dukart, Gary; Ellis-Grosse, Evelyn J

2006-12-01

The purpose of this study was to determine the tissue and corresponding serum concentration of tigecycline at selected time points in gall bladder, bile, colon, bone, synovial fluid (SF), lung and CSF in subjects undergoing surgical or medical procedures. One hundred and four adult subjects (aged 24-83 years; 64 women, 40 men) received a single intravenous (i.v.) dose of tigecycline (100 mg infused over 30 min). Subjects were randomly assigned to one of four collection times at 4, 8, 12 and 24 h after the start of the infusion. For CSF, samples were collected at approximately 1.5 and 24 h after the start of the infusion. All subjects had serum samples collected before the administration of tigecycline, at the end of the infusion and at the time corresponding to tissue or body fluid collection. Drug concentrations in serum, tissues and body fluids were determined by LC/MS/MS. The area under the mean concentration-time curve from 0 to 24 h (AUC(0-24)) was determined for the comparison of systemic exposure between tissue or body fluid to serum. The mean serum concentrations of tigecycline were similar to those previously published. Tissue penetration, expressed as the ratio of AUC(0-24) in tissue or body fluid to serum, was 537 for bile, 23 for gall bladder, 2.6 for colon, 2.0 for lung, 0.41 for bone, 0.31 for SF and 0.11 for CSF. A single 100 mg dose of intravenous tigecycline produced considerably higher tissue/fluid concentrations in bile, gall bladder, colon and lung compared with simultaneous serum concentrations. On average, the systemic exposure of tigecycline in bone, SF and CSF ranged from 11% to 41% of serum concentrations. The results in bone are inconsistent with previous radiolabelled studies in animals and it is unclear if tight binding to bone (versus low bone uptake) or poor extraction of tigecycline for LC/MS/MS detection or both may have contributed to the differences we observed in humans.

Distribution of Cr and Pb in artificial sea water and their sorption in marine sediments: an example from experimental mesocosms.

PubMed

Maccotta, A; Cosentino, Claudia; Coccioni, R; Frontalini, F; Scopelliti, G; Caruso, A

2016-12-01

The uptake of two heavy metals (chromium and lead) in sediments in experimental mesocosms under exposure to different metal concentrations was evaluated by monitoring their concentrations over time both in seawater and in sediment. Two separate experiments under laboratory-controlled conditions were carried out for the two metals. Sediments were collected from a protected natural area characterized by low anthropic influence and were placed in mesocosms that were housed in aquaria each with seawater at a different metal concentration. At pre-established time intervals, seawater and sediment samples were collected from each mesocosm for chemical analyses. Quantification of chromium and lead concentration in seawater and sediment samples was carried out by atomic absorption spectrometer with graphite furnace. Low doses of chromium and lead (<1 mg L -1 ) do not entail an uptake in sediments and waters. At doses ≥1 mg L -1 , evolution of concentrations over time shows significant differences between these two metals: (i) chromium absorption from seawater is twice faster than lead; (ii) lead accumulates in considerable amount in sediments. The different behaviour of the two investigated heavy metals could be ascribed to different interactions existing between metal ions and different components of sediment.

Arsenic speciation in hair and nails of acute promyelocytic leukemia (APL) patients undergoing arsenic trioxide treatment.

PubMed

Chen, Baowei; Cao, Fenglin; Lu, Xiufen; Shen, Shengwen; Zhou, Jin; Le, X Chris

2018-07-01

Arsenic in hair and nails has been used to assess chronic exposure of humans to environmental arsenic. However, it remains to be seen whether it is appropriate to evaluate acute exposure to sub-lethal doses of arsenic typically used in therapeutics. In this study, hair, fingernail and toenail samples were collected from nine acute promyelocytic leukemia (APL) patients who were administered intravenously the daily dose of 10 mg arsenic trioxide (7.5 mg arsenic) for up to 54 days. These hair and nail samples were analyzed for arsenic species using high performance liquid chromatography separation and inductively coupled plasma mass spectrometry detection (HPLC-ICPMS). Inorganic arsenite was the predominant form among water-extractable arsenicals. Dimethylarsinic acid (DMA V ), monomethylarsonic acid (MMA V ), monomethylarsonous acid (MMA III ), monomethylmonothioarsonic acid (MMMTA V ), and dimethylmonothioarsinic acid (DMMTA V ) were also detected in both hair and nail samples. This is the first report of the detection of MMA III and MMMTA V as metabolites of arsenic in hair and nails of APL patients. Copyright © 2018 Elsevier B.V. All rights reserved.

RADIOACTIVITY DOSAGE OF ORNAMENTAL GRANITIC ROCKS BASED ON CHEMICAL, MINERALOGICAL AND LITHOLOGICAL DATA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Salas, H.T.; Nalini, H.A. Jr.; Mendes, J.C.

2004-10-03

One hundred samples of granitic rock were collected from granite traders in Belo Horizonte. Autoradiography, optical microscopy, diffractometry, and chemical analysis (X-ray spectrometry, X-ray fluorescence, neutron activation, gravimetry and electron probe microanalysis) were used to determine the mineral assemblages and lithotypes. Autoradiographic results for several samples showed the presence of monazite, allanite and zircon. Chemical analysis revealed concentrations of uranium of {le} 30ppm, and thorium {le} 130ppm. Higher concentrations generally correlated with high concentrations of light rare earths in silica-rich rocks of granitic composition. Calculations were made of radioactive doses for floor tiles in a standard room for samples withmore » total concentration of uranium and thorium greater than 60ppm. On the basis of calculations of {sup 232}Th, {sup 40}K and {sup 226}Ra from Th, K and U analysis, the doses calculated were between 0.11 and 0.34 mSv/year, which are much lower than the acceptable international exposure standard of 1.0 mSv/year.« less

Is more better than less? An analysis of children's mental health services.

PubMed Central

Foster, E M

2000-01-01

OBJECTIVE: To assess the dose-response relationship for outpatient therapy received by children and adolescents-that is, to determine the impact of added outpatient visits on key mental health outcomes (functioning and symptomatology). DATA SOURCES/STUDY SETTING: The results presented involve analyses of data from the Fort Bragg Demonstration and are based on a sample of 301 individuals using outpatient services. STUDY DESIGN: This article provides estimates of the impact of outpatient therapy based on comparisons of individuals receiving differing treatment doses. Those comparisons involve standard multiple regression analyses as well as instrumental variables estimation. The latter provides a means of adjusting comparisons for unobserved or unmeasured differences among individuals receiving differing doses, differences that would otherwise be confounded with the impact of treatment dose. DATA COLLECTION/EXTRACTION METHODS: Using structured diagnostic interviews and behavior checklists completed by the child and his or her caretaker, detailed data on psychopathology, symptomatology, and psychosocial functioning were collected on individuals included in these analyses. Information on the use of mental health services was taken from insurance claims and a management information system. Services data were used to describe the use of outpatient therapy within the year following entry into the study. PRINCIPAL FINDINGS/CONCLUSIONS: Instrumental variables estimation indicates that added outpatient therapy improves functioning among children and adolescents. The effect is statistically significant and of moderate practical magnitude. These results imply that conventional analyses of the dose-response relationship may understate the impact of additional treatment on functioning. This finding is robust to choice of functional form, length of time over which outcomes are measured, and model specification. Dose does not appear to influence symptomatology. PMID:11130814

Exposure of infants to budesonide through breast milk of asthmatic mothers.

PubMed

Fält, Anette; Bengtsson, Thomas; Kennedy, Britt-Marie; Gyllenberg, Ann; Lindberg, Bengt; Thorsson, Lars; Stråndgarden, Kerstin

2007-10-01

Maintenance treatment with inhaled corticosteroids is often required for asthmatic nursing women. Data on the transfer of inhaled corticosteroids from plasma to breast milk and the subsequent exposure of the breast-feeding infant has been unavailable. We sought to assess budesonide concentrations in milk and plasma of asthmatic nursing women receiving maintenance treatment with the Pulmicort Turbuhaler and estimate the exposure of their breast-fed infants. Milk and plasma samples were collected up to 8 hours after dosing from 8 mothers receiving budesonide maintenance treatment (200 or 400 microg twice daily). Pharmacokinetic parameters were calculated from budesonide milk and plasma concentrations. Infant exposure was estimated based on average milk budesonide concentrations. A single blood sample was obtained from 5 infants close to expected infant maximum concentration. Budesonide concentrations in milk reflected those in maternal plasma, supporting passive diffusion of budesonide between plasma and milk, and was always lower than that in plasma. The mean milk/plasma ratio was 0.46. The estimated daily infant dose was 0.3% of the daily maternal dose for both dose levels, and the average plasma concentration in infants was estimated to be 1/600th of the concentrations observed in maternal plasma, assuming complete infant oral bioavailability. Budesonide concentrations in infant plasma samples were all less than the limit of quantification. Maintenance treatment with inhaled budesonide (200 or 400 microg twice daily) in asthmatic nursing women results in negligible systemic exposure to budesonide in breast-fed infants. These data support continued use of inhaled budesonide during breast-feeding.

An evaluation of cold chain system for vaccines in Bangalore.

PubMed

Sudarshan, M K; Sundar, M; Girish, N; Narendra, S; Patel, N G

1994-01-01

The cold chain plays a major role in the universal immunization programme which helps in preventing against six major killer diseases in children. We collected 144 study samples randomly from different parts of Bangalore to know the training status of personnel, refrigeration facilities, storage, monitoring and potency of vaccines. It was observed that 6.6% of general practitioners were trained under Universal Immunization Programme, monitoring was not satisfactory, and two of the OPV samples from medical practitioners had an unsatisfactory titre dose. Comprehensive orientation/training on cold chain is essential for medical practitioners and other professionals.

Enhancement of Structured Reporting - an Integration Reporting Module with Radiation Dose Collection Supporting.

PubMed

Lee, Ming-Che; Chuang, Kei-Shih; Hsu, Tien-Cheng; Lee, Chien-Ding

2016-11-01

Collection of radiation dose derived from radiological examination is necessary not only for radiation protection, but also for fulfillment of structured reports. However, the material regarding of radiation dose cannot be directly utilized by the Radiological Information System (RIS) since it is generated and only stored in the Picture Archiving and Communication System (PACS). In this paper, an integration reporting module is proposed to facilitate handling of dose information and structured reporting by providing two functionalities. First, a gateway is established to automatically collect the related information from PACS for further analyzing and monitoring the accumulated radiation. Second, the designated structured reporting patterns with corresponding radiation dose measurements can be acquired by radiologists as necessary. In the design, the radiation dose collection gateway and the well-established pattern are collocated to achieve that there is no need to do manual entry for structured reporting, thus increasing productivity and medical quality.

Method to determine the position-dependant metal correction factor for dose-rate equivalent laser testing of semiconductor devices

DOEpatents

Horn, Kevin M.

2013-07-09

A method reconstructs the charge collection from regions beneath opaque metallization of a semiconductor device, as determined from focused laser charge collection response images, and thereby derives a dose-rate dependent correction factor for subsequent broad-area, dose-rate equivalent, laser measurements. The position- and dose-rate dependencies of the charge-collection magnitude of the device are determined empirically and can be combined with a digital reconstruction methodology to derive an accurate metal-correction factor that permits subsequent absolute dose-rate response measurements to be derived from laser measurements alone. Broad-area laser dose-rate testing can thereby be used to accurately determine the peak transient current, dose-rate response of semiconductor devices to penetrating electron, gamma- and x-ray irradiation.

Investigation of a mumps outbreak among university students with two measles-mumps-rubella (MMR) vaccinations, Virginia, September-December 2006.

PubMed

Rota, J S; Turner, J C; Yost-Daljev, M K; Freeman, M; Toney, D M; Meisel, E; Williams, N; Sowers, S B; Lowe, L; Rota, P A; Nicolai, L A; Peake, L; Bellini, W J

2009-10-01

Following the clinical diagnosis of the first case of mumps on September 22, 2006 at the University of Virginia (UVA), 52 suspected cases were identified through active surveillance for mumps by the end of December 2006. Samples were collected from 47 students who presented with parotitis despite a documented history of two doses of measles, mumps, and rubella (MMR) vaccine. Six of 47 serum samples (13%) were positive for mumps IgM, and 46/47 specimens were positive for mumps IgG. Endpoint titration of acute phase serum samples from laboratory-confirmed cases did not provide evidence that elevated serum IgG is a consistent marker for infection among cases due to secondary vaccine failure. Buccal swab samples from 39 of the 47 students were tested by real-time reverse transcription-polymerase chain reaction (RT-PCR) and/or viral culture. Mumps virus or mumps RNA was detected in 12 of 39 buccal samples (31%). Genetic analysis of the virus from the outbreak at UVA indicated that the outbreak was not linked to the large mumps outbreak in the Midwestern US that occurred earlier in 2006. Our findings support the use of viral detection to improve laboratory diagnosis of mumps among persons who have received two doses of MMR.

Detailed deposition density maps constructed by large-scale soil sampling for gamma-ray emitting radioactive nuclides from the Fukushima Dai-ichi Nuclear Power Plant accident.

PubMed

Saito, Kimiaki; Tanihata, Isao; Fujiwara, Mamoru; Saito, Takashi; Shimoura, Susumu; Otsuka, Takaharu; Onda, Yuichi; Hoshi, Masaharu; Ikeuchi, Yoshihiro; Takahashi, Fumiaki; Kinouchi, Nobuyuki; Saegusa, Jun; Seki, Akiyuki; Takemiya, Hiroshi; Shibata, Tokushi

2015-01-01

Soil deposition density maps of gamma-ray emitting radioactive nuclides from the Fukushima Dai-ichi Nuclear Power Plant (NPP) accident were constructed on the basis of results from large-scale soil sampling. In total 10,915 soil samples were collected at 2168 locations. Gamma rays emitted from the samples were measured by Ge detectors and analyzed using a reliable unified method. The determined radioactivity was corrected to that of June 14, 2011 by considering the intrinsic decay constant of each nuclide. Finally the deposition maps were created for (134)Cs, (137)Cs, (131)I, (129m)Te and (110m)Ag. The radioactivity ratio of (134)Cs-(137)Cs was almost constant at 0.91 regardless of the locations of soil sampling. The radioactivity ratios of (131)I and (129m)Te-(137)Cs were relatively high in the regions south of the Fukushima NPP site. Effective doses for 50 y after the accident were evaluated for external and inhalation exposures due to the observed radioactive nuclides. The radiation doses from radioactive cesium were found to be much higher than those from the other radioactive nuclides. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

[The Dose Effect of Isocenter Selection during IMRT Dose Verification with the 2D Chamber Array].

PubMed

Xie, Chuanbin; Cong, Xiaohu; Xu, Shouping; Dai, Xiangkun; Wang, Yunlai; Han, Lu; Gong, Hanshun; Ju, Zhongjian; Ge, Ruigang; Ma, Lin

2015-03-01

To investigate the dose effect of isocenter difference during IMRT dose verification with the 2D chamber array. The samples collected from 10 patients were respectively designed for IMRT plans, the isocenter of which was independently defined as P(o), P(x) and P(y). P(o) was fixed on the target center and the other points shifted 8cm from the target center in the orientation of x/y. The PTW729 was used for 2D dose verification in the 3 groups which beams of plans were set to 0 degrees. The γ-analysis passing rates for the whole plan and each beam were gotten using the different standards in the 3 groups, The results showed the mean passing rate of γ-analysis was highest in the P(o) group, and the mean passing rate of the whole plan was better than that of each beam. In addition, it became worse with the increase of dose leakage between the leaves in P(y) group. Therefore, the determination of isocenter has a visible effect for IMRT dose verification of the 2D chamber array, The isocenter of the planning design should be close to the geometric center of target.

Pharmacokinetics After Single Ascending Dose, Food Effect, and Safety of Sacubitril/Valsartan (LCZ696), an Angiotensin Receptor and Neprilysin Inhibitor, in Healthy Japanese Subjects.

PubMed

Akahori, Mizuki; Ayalasomayajula, Surya; Langenickel, Thomas; Pal, Parasar; Zhou, Wei; Sunkara, Gangadhar

2017-06-01

LCZ696 (sacubitril/valsartan) is a novel angiotensin receptor neprilysin inhibitor (ARNI) that has been developed for treatment of heart failure patients with reduced ejection fraction and approved in the US, Europe, and many other countries. This randomized, placebo-controlled study was conducted in healthy Japanese male subjects (N = 50) to assess the pharmacokinetics and safety of single ascending oral doses (20-600 mg) of LCZ696. Food effect was also evaluated following administration of 200 mg dose. Plasma and urine samples from 40 subjects receiving LCZ696 were collected to assess pharmacokinetics of LCZ696 analytes (sacubitril, sacubitrilat, and valsartan). Following single oral dose administration of LCZ696, sacubitril and valsartan rapidly appeared in systemic circulation with a dose-linear increase in the exposure to the LCZ696 analytes. Of the administered dose, approximately 0.85 %, 54.0 %, and 8.19 % of sacubitril, sacubitrilat, and valsartan, respectively, were recovered in urine. Food reduced AUC of sacubitril, sacubitrilat, and valsartan by 21, 8, and 40 %, respectively, and C max by 72, 27, and 51 %, respectively. Single oral doses of up to 600 mg of LCZ696 were safe and generally well tolerated in healthy Japanese male subjects.

Geological sources of fluoride and acceptable intake of fluoride in an endemic fluorosis area, southern Iran.

PubMed

Battaleb-Looie, Sedigheh; Moore, Farid; Jacks, Gunnar; Ketabdari, Mohammad Reza

2012-10-01

The present study is the first attempt to put forward possible source(s) of fluoride in the Dashtestan area, Bushehr Province, southern Iran. In response to reports on the high incidence of dental fluorosis, 35 surface and groundwater samples were collected and analysed for fluoride. The results indicate that dissolved fluoride in the study area is above the maximum permissible limit recommended by the World Health Organization (WHO). An additional 35 soil and rock samples were also collected and analysed for fluoride, and rock samples were subjected to petrographic investigations and X-ray diffraction. The results of these analyses show that the most likely source for fluoride in the groundwater is from clay minerals (chlorite) and micas (muscovite, sericite, and biotite) in the soils and rocks in the area. We also note that due to the high average temperatures all year round and excessive water consumption in the area, the optimum fluoride dose level should be lower than that recommended by the WHO.

Sensitive immunodetection of radiotoxicity after iodine-131 therapy for thyroid cancer using γ-H2AX foci of DNA damage in lymphocytes.

PubMed

Doai, Mariko; Watanabe, Naoto; Takahashi, Tomoko; Taniguchi, Mitsuru; Tonami, Hisao; Iwabuchi, Kuniyoshi; Kayano, Daiki; Fukuoka, Makoto; Kinuya, Seigo

2013-04-01

The purpose of our study was to evaluate the degree of radiotoxicity to lymphocytes in thyroid cancer after iodine-131(I-131) therapy using γ-H2AX foci immunodetection. This study focused on 15 patients who underwent I-131 therapy for differentiated thyroid cancer after surgery. All patients received 3.7 GBq of I-131. Venous blood samples were collected from each patient before therapy and 4 days thereafter. Lymphocytes were isolated from the blood samples and subjected to γ-H2AX immunofluorescence staining. The number (mean ± SD) of foci per lymphocyte nucleus was 0.41 ± 0.51 before and 6.19 ± 1.80 after radioiodine therapy, and this difference was statistically significant (P = 0.001 < 0.05). Absorbed doses estimated for the 15 patients were 0.77 ± 0.31 Gy applying standard line in vitro external radiation doses. γ-H2AX foci immunodetection in lymphocytes may detect radiation-induced DNA damage associated with I-131 therapy for thyroid cancer, and may facilitate estimation of the radiation doses absorbed with this therapy.

Seroprevalence of Measles Antibodies and Predictors for Seropositivity among Chinese Children.

PubMed

Wang, Xiaoqin; Ma, Mei; Hui, Zhaozhao; Terry, Paul D; Zhang, Yue; Su, Rui; Wang, Mingxu; Gu, Wei; Li, Ling

2017-06-06

Background : Supplementary measles immunization has been implemented since 2010 throughout China, yet few studies have reported its effect in the northwest regions. Methods: A cross-sectional study was conducted among children aged 2 to 4 years old ( n = 755) from February to September 2014 in 25 towns of Qian County, Shaanxi Province. Blood samples were analyzed for measles antibodies using enzyme-linked immunosorbent immunoglobulin G (IgG) assays. Socio-demographic factors were assessed by questionnaire. Data on vaccine dose were collected from town medical records. Univariate and logistic regression analyses were used to determine factors associated with measles antibody seropositivity. Results : Measles antibody seroprevalence was 91.13% (95% CI: 89.52-92.83) in our sample. Compared with children whose mother's highest education was primary school, seroprevalence was higher in children whose maternal education was middle school (adjusted OR: 1.4, 95% CI: 0.7-2.8), high school (adjusted OR: 2.4, 95% CI: 1.3-7.7), and college/university (adjusted OR: 2.9, 95% CI: 1.2-9.3). Vaccine dose was positively associated with seropositivity. Conclusions : Measles seroprevalence is high in China and is associated with the mother's education and vaccine dose.

The effect of inorganic precursors on disinfection byproduct formation during UV-chlorine/chloramine drinking water treatment.

PubMed

Lyon, Bonnie A; Dotson, Aaron D; Linden, Karl G; Weinberg, Howard S

2012-10-01

Ultraviolet (UV) disinfection is being increasingly used in drinking water treatment. It is important to understand how its application to different types of water may influence finished water quality, particularly as anthropogenic activity continues to impact the quality of source waters. The objective of this study was to evaluate the effect of inorganic precursors on the formation of regulated and unregulated disinfection byproducts (DBPs) during UV irradiation of surface waters when combined with chlorination or chloramination. Samples were collected from three drinking water utilities supplied by source waters with varying organic and inorganic precursor content. The filtered samples were treated in the laboratory with a range of UV doses delivered from low pressure (LP, UV output at 253.7 nm) and medium pressure (MP, polychromatic UV output 200-400 nm) mercury lamps followed by chlorination or chloramination, in the presence and absence of additional bromide and nitrate. The regulated trihalomethanes and haloacetic acids were not affected by UV pretreatment at disinfection doses (40-186 mJ/cm²). With higher doses (1000 mJ/cm²), trihalomethane formation was increased 30-40%. While most effects on DBPs were only observed with doses much higher than typically used for UV disinfection, there were some effects on unregulated DBPs at lower doses. In nitrate-spiked samples (1-10 mg N/L), chloropicrin formation doubled and increased three- to six-fold with 40 mJ/cm² MP UV followed by chloramination and chlorination, respectively. Bromopicrin formation was increased in samples containing bromide (0.5-1 mg/L) and nitrate (1-10 mg N/L) when pretreated with LP or MP UV (30-60% with 40 mJ/cm² LP UV and four- to ten-fold increase with 40 mJ/cm² MP UV, after subsequent chlorination). The formation of cyanogen chloride doubled and increased three-fold with MP UV doses of 186 and 1000 mJ/cm², respectively, when followed by chloramination in nitrate-spiked samples but remained below the World Health Organization guideline value of 70 μg/L in all cases. MP UV and high LP UV doses (1000 mJ/cm²) increased chloral hydrate formation after subsequent chlorination (20-40% increase for 40 mJ/cm² MP UV). These results indicate the importance of bench-testing DBP implications of UV applications in combination with post-disinfectants as part of the engineering assessment of a UV-chlorine/chloramine multi-barrier disinfection design for drinking water treatment. Copyright © 2012 Elsevier Ltd. All rights reserved.

Investigation of pregnancy-associated malaria by microscopy, rapid diagnostic test and PCR in Bandundu, the Democratic Republic of Congo.

PubMed

Ruh, Emrah; Bateko, Jean Paul; Imir, Turgut; Taylan-Ozkan, Aysegul

2018-01-01

The study was conducted to investigate malaria prevalence among a group of women in the Democratic Republic of Congo (DRC) who received intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP). A total of 250 women from Bandundu city who received two doses of IPTp-SP were enrolled in the survey. Blood samples were collected at the time of delivery and malaria prevalence was determined using microscopy, rapid diagnostic test (RDT), and nested polymerase chain reaction (PCR). Malaria infection was detected in 81 (32.4%), 93 (37.2%), and 92 (36.8%) samples by microscopy, RDT, and PCR, respectively. Among 92 samples, P. falciparum mono-infection (n=87; 94.5%), P. falciparum+P. vivax (n=2; 2.2%) and P. falciparum+P. malariae (n=1; 1.1%) mixed infections, and P. vivax mono-infection (n=2; 2.2%) were detected. Prevalence of malaria was not affected by age and number of pregnancies (p>0.05). Microscopy and RDT, either alone (κ=0.29; p<0.001) or in combination (κ=0.33; p<0.001) showed a fair agreement with PCR. Our findings indicate that two doses of IPTp-SP did not protect the women against malaria in the DRC, and support the World Health Organization (WHO) guidelines that ensure a minimum of three doses of SP in pregnancy.

Vaccine Poliovirus Shedding and Immune Response to Oral Polio Vaccine in HIV-Infected and -Uninfected Zimbabwean Infants

PubMed Central

Troy, Stephanie B.; Musingwini, Georgina; Halpern, Meira S.; Huang, ChunHong; Stranix-Chibanda, Lynda; Kouiavskaia, Diana; Shetty, Avinash K.; Chumakov, Konstantin; Nathoo, Kusum; Maldonado, Yvonne A.

2013-01-01

Background. With prolonged replication, attenuated polioviruses used in oral polio vaccine (OPV) can mutate into vaccine-derived poliovirus (VDPV) and cause poliomyelitis outbreaks. Individuals with primary humoral immunodeficiencies can become chronically infected with vaccine poliovirus, allowing it to mutate into immunodeficiency-associated VDPV (iVDPV). It is unclear if children perinatally infected with the human immunodeficiency virus (HIV), who have humoral as well as cellular immunodeficiencies, might be sources of iVDPV. Methods. We conducted a prospective study collecting stool and blood samples at multiple time points from Zimbabwean infants receiving OPV according to the national schedule. Nucleic acid extracted from stool was analyzed by real-time polymerase chain reaction for OPV serotypes. Results. We analyzed 825 stool samples: 285 samples from 92 HIV-infected children and 540 from 251 HIV-uninfected children. Poliovirus shedding was similar after 0–2 OPV doses but significantly higher in the HIV-infected versus uninfected children after ≥3 OPV doses, particularly within 42 days of an OPV dose, independent of seroconversion status. HIV infection was not associated with prolonged or persistent poliovirus shedding. HIV infection was associated with significantly lower polio seroconversion rates. Conclusions. HIV infection is associated with decreased mucosal and humoral immune responses to OPV but not the prolonged viral shedding required to form iVDPV. PMID:23661792

Assessment of Committed Effective Dose due to consumption of Red Sea coral reef fishes collected from the local market (Sudan).

PubMed

Hassona, Rifaat K; Sam, A K; Osman, O I; Sirelkhatim, D A; LaRosa, J

2008-04-15

An assessment of Committed Effective Dose (CED) due to consumption of Red Sea fish containing (210)Po and (137)Cs was performed for 23 different marine fish samples collected from the local market at Port Sudan. The fish were classified according to their feeding habits into three categories: carnivores, herbivores, and omnivores. Measured activity concentrations of (210)Po were found in the ranges 0.25-6.42 (carnivores), 0.7-5 (omnivores) and 1.5-3.8 (herbivores) Bq/kg fresh weight. In the same study, activity concentrations of Cs-137 were determined to be in the ranges 0.1-0.46 (carnivores), 0.09-0.35 (omnivores) and 0.09-0.32 (herbivores) Bq/kg fresh weight, which were several times lower than those of (210)Po. Appropriate conversion factors were used to derive the CED, which was found to be 0.012, 0.01 and 0.01 (microSv/yr) in carnivores, omnivores and herbivores, respectively, for (137)Cs. This contributes about 0.4% of the total dose exclusively by ingestion of fish. For (210)Po, it was found to be 3.47, 4.81 and 4.14 (microSv/yr) in carnivores, omnivores and herbivores, respectively, which represents 99.6% of the total dose (exclusively by ingestion of fish). The results of CED calculations suggest that the dose received by the Sudanese population from the consumption of marine fish is rather small and that the contribution of (137)Cs is negligible compared to (210)Po.

Mammary tumors and serum hormones in the bitch treated with medroxyprogesterone acetate or progesterone for four years

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frank, D.W.; Kirton, K.T.; Murchison, T.E.

After four years of a long term contraceptive steroid safety study, the incidence and the histologic type of mammary dysplasia produced is similar in beagles treated with medroxyprogesterone acetate (medroxyprogesterone) or progesterone. Serum insulin, thyroid stimulating hormone (TSH), triiodothyronine, growth hormone, prolactin, 17..beta..-estradiol, progesterone, and cortisol were determined by radioimmunoassay on samples collected after 45 months of treatment. Serum growth hormone and insulin concentrations were elevated in a dose related manner in both treatment groups. Triiodothyronine, cortisol, and estradiol-17..beta.. (medroxyprogesterone only) were lowered. TSH and prolactin concentrations were not changed. Pituitary--gonadal hormone interaction in the pathogenesis of mammary neoplasia ofmore » the dog is discussed. Prolonged treatment of the beagle with massive doses of progesterone or medroxyprogesterone results in a dose related incidence of mammary modules.« less

Cadmium induces histopathological injuries and ultrastructural changes in the liver of freshwater turtle (Chinemys reevesii).

PubMed

Huo, Junfeng; Dong, Aiguo; Wang, Yonghui; Lee, Shaochin; Ma, Cungen; Wang, Lan

2017-11-01

The study investigated the histopathological and ultrastructural lesions of liver of freshwater turtle Chinemys reevesii exposed to Cadmium (Cd). The animals were exposed to 0 mg kg -1 (0.85% normal saline (NS)), 7.5 mg kg -1 , 15 mg kg -1 , 30 mg kg -1 Cd chloride separately by intraperitoneal injection. Liver samples were collected for examination of lesions under light and electronic microscopes. Results showed that liver tissues from Cd -treated animals presented various degrees of histopathological lesions. Liver cells showed swollen, degeneration and necrosis with dose-dependent manner. Under electronic microscope, nucleus, mitochondria and rough endoplasmic reticulum presented various degrees of lesions with dose-dependent manner. In conclusion, Cd has significant toxicity on liver tissue of the freshwater turtle, which occurs in a dose-dependent manner. Copyright © 2017 Elsevier Ltd. All rights reserved.

Persistence of Azoxystrobin in/on Grapes and Soil in Different Grapes Growing Areas of India

PubMed Central

Gajbhiye, Vijay Tularam; Gupta, Suman; Mukherjee, Irani; Singh, Shashi Bala; Singh, Neera; Kumar, Yogesh

2010-01-01

Persistence of azoxystrobin was studied in/on grapes when applied @ 150 g ai ha−1 (recommended dose) and 300 g ai ha−1 (double the recommended dose) in three grapes growing states of India, namely Karnataka, Maharashtra and Tamil Nadu, in the year 2006–2007. A total of five sprays were given at an interval of about 15 days. Grapes and soil samples were collected after 5th spray, extracted and analysed by gas chromatography using electron capture detector. Half life of azoxystrobin on grapes varied from 5.4 to 11.2 days. Residues of azoxystrobin were much below the prescribed MRL (0.5 mg kg−1) after 21 days. The dissipation of azoxystrobin in soil followed first order rate kinetics with an average half life of 8.1 days at the recommended dose of application. PMID:21153804

Dose Monitoring in Radiology Departments: Status Quo and Future Perspectives.

PubMed

Boos, J; Meineke, A; Bethge, O T; Antoch, G; Kröpil, P

2016-05-01

The number of computed tomography examinations has continuously increased over the last decades and accounts for a major part of the collective radiation dose from medical investigations. For purposes of quality assurance in modern radiology a systematic monitoring and analysis of dose related data from radiological examinations is mandatory. Various ways of collecting dose data are available today, for example the Digital Imaging and Communication in Medicine - Structured Report (DICOM-SR), optical character recognition and DICOM-modality performed procedure steps (MPPS). The DICOM-SR is part of the DICOM-standard and provides the DICOM-Radiation Dose Structured Report, which is an easily applicable and comprehensive solution to collect radiation dose parameters. This standard simplifies the process of data collection and enables comprehensive dose monitoring. Various commercial dose monitoring software devices with varying characteristics are available today. In this article, we discuss legal obligations, various ways to monitor dose data, current dose monitoring software solutions and future perspectives in regard to the EU Council Directive 2013/59/EURATOM. • Automated, systematic dose monitoring is an important element in quality assurance of radiology departments. • DICOM-RDSR-capable CT scanners facilitate the monitoring of dose data. • A variety of commercial and non-commercial dose monitoring software tools are available today. • Successful dose monitoring requires comprehensive infrastructure for monitoring, analysing and optimizing radiation exposure. Citation Format: • Boos J, Meineke A, Bethge OT et al. Dose Monitoring in Radiology Departments: Status Quo and Future Perspectives. Fortschr Röntgenstr 2016; 188: 443 - 450. © Georg Thieme Verlag KG Stuttgart · New York.

Are There Dangerous Levels of Lead in Local Soil?

NASA Astrophysics Data System (ADS)

Pita, I.

2017-12-01

The purpose of this experiment was to show that comparing random soil samples from areas in New Orleans; the Garden District will have the highest levels of lead in soil. My Independent variable was the soil samples collected from locations in the Garden District area of New Orleans, and other locations throughout New Orleans. The control was the soil samples collected from the local playground in the New Orleans area. My dependent variable was the lead soil test kit, using ppm (parts per million) of lead to show concentration. 400 ppm + in bare soil where children play is considered dangerous hazard levels. 1,000 + ppm in all other areas is considered dangerous hazard levels. The first step to my experiment, I collected soil samples from different locations throughout the Garden District area of New Orleans. The second step to my experiment, I conducted the lead soil testing in a controlled area at home in a well ventilated room, using all the necessary safety equipment needed, I began testing a 24 hour test period and a 48 hour test period. I then collected the data from both test. The results showed that soil samples from the Garden District area compared to the other sample locations had higher lead concentrations in the soil. This backed my hypothesis when comparing soil samples from areas in New Orleans, the Garden District will have the highest lead levels. In conclusion these experiments showed that with the soil samples collected, there were higher concentrations of lead in the soil from the Garden District area compared to the other areas where soil was collected. Reconstruction and renovations, from the devastation that Hurricane Katrina created, are evident of the lead in paint of older homes which now show the lead concentration in the soil. Lead is a lethal element if consumed or inhaled in high doses, which can damage key organs in our body, which can be deadly. Better awareness through social media, television, radio, doctors, studies, pamphlets, environmental agencies, and other forms to address the steps in protecting your family and home for a lead free environment.

Breath biomarkers in toxicology.

PubMed

Pleil, Joachim D

2016-11-01

Exhaled breath has joined blood and urine as a valuable resource for sampling and analyzing biomarkers in human media for assessing exposure, uptake metabolism, and elimination of toxic chemicals. This article focuses current use of exhaled gas, aerosols, and vapor in human breath, the methods for collection, and ultimately the use of the resulting data. Some advantages of breath are the noninvasive and self-administered nature of collection, the essentially inexhaustible supply, and that breath sampling does not produce potentially infectious waste such as needles, wipes, bandages, and glassware. In contrast to blood and urine, breath samples can be collected on demand in rapid succession and so allow toxicokinetic observations of uptake and elimination in any time frame. Furthermore, new technologies now allow capturing condensed breath vapor directly, or just the aerosol fraction alone, to gain access to inorganic species, lung pH, proteins and protein fragments, cellular DNA, and whole microorganisms from the pulmonary microbiome. Future applications are discussed, especially the use of isotopically labeled probes, non-targeted (discovery) analysis, cellular level toxicity testing, and ultimately assessing "crowd breath" of groups of people and the relation to dose of airborne and other environmental chemicals at the population level.

Radiation dose to Malaysian infants from natural radionuclides via consumption of powdered milk

DOE Office of Scientific and Technical Information (OSTI.GOV)

Uwatse, Onosohwo Bemigho; Olatunji, Michael Adekunle; Khandaker, Mayeen Uddin

Milk is the basic food stuff for the infants because they generally consume more milk on a daily basis as its minerals and proteins are essential for their growth and development, therefore, it is very important to assess the natural radioactivity levels and the associated dose in the widely consumed powered infant’s milk. As a result, 14 brands of infant’s powdered milk were collected from different supermarkets around Selangor, Malaysia and analysed for {sup 226}Ra, {sup 232}Th and {sup 40}K activities. The obtained mean activity of {sup 226}Ra, {sup 232}Th and {sup 40}K are 3.05±1.84, 2.55±2.48 and 99.1±69.5 Bqkg{sup −1},more » respectively. Among the analysed milk samples, the brand from Philippines (Lactogen) showed low level of radioactivity while Singaporean brand (S26 SMA Gold) showed the highest. The estimated mean annual effective doses due to the ingestion of natural radionuclides in the sampled milk are 635 and 111 µSv for infant ≤ 1y and infant 1-2y, respectively. The obtained dose value does not yet pose any significant radiological hazards to the population under investigation comparing with the 1.0 mSvy{sup −1} recommended by ICRP for all ages.« less

Absorption and distribution of lycopene in rat colon.

PubMed

Oshima, S; Inakuma, T; Narisawa, T

1999-01-01

Colonic absorption and distribution of lycopene, which inhibited rat colon carcinogenesis in our previous studies, were investigated in Sprague-Dawley rats. Three groups of six rats each with or without a single-barreled colostomy at the mid colon were given a single intragastric or intracolonic dose of 0.2 mL of corn oil containing 12 mg of lycopene. Twenty-four hours later, all rats were sacrificed and the blood and some tissues were collected. The contents of lycopene in the samples were assayed by HPLC. Lycopene was detected in an appreciable amount in the liver, but only in trace amount in the serum of all rats treated with an intracolonic dose of lycopene and in rats with an intragastric dose. After an intragastric lycopene treatment, lycopene was detected in the mucosa of the proximal colon and of the distal colon of the colostomized rats, whose distal colon had been excluded from the fecal stream. A large amount of lycopene was recovered in the feces. None was detected in any sample from the control rats treated with an intragastric or intracolonic dose of plain corn oil. The results suggest that lycopene is absorbed from the colon and also from the small intestine. It might be concluded that both ways of absorption contribute to a comparative amount of lycopene accumulation in the colon mucosa after ingestion of this carotenoid.

In vitro effects of 0 to 120 Grays of irradiation on bone viability and release of growth factors.

PubMed

Sawada, Kosaku; Fujioka-Kobayashi, Masako; Kobayashi, Eizaburo; Brömme, Jens O; Schaller, Benoit; Miron, Richard J

2016-07-04

High dose radiation therapy is commonly used in maxillofacial surgeries to treat a number of head and neck tumors. Despite its widespread use, little information is available regarding the effects of irradiation on bone cell viability and release of growth factors following dose-dependent irradiation. Bone samples were collected from porcine mandibular cortical bone and irradiated at doses of 0, 7.5, 15, 30, 60 and 120 Grays. Thereafter, cell viability was quantified, and the release of growth factors including TGFβ1, BMP2, VEGF, IL1β and RANKL were investigated over time. It was observed that at only 7.5Gy of irradiation, over 85 % of cells were non-vital and by 60 Gy, all cells underwent apoptosis. Furthermore, over a 7-fold decrease in VEGF and a 2-fold decrease in TGFβ1 were observed following irradiation at all tested doses. Little change was observed for BMP2 and IL1β whereas RANKL was significantly increased for all irradiated samples. These results demonstrate the pronounced effects of irradiation on bone-cell vitality and subsequent release of growth factors. Interestingly, the largest observed change in gene expression was the 7-fold decrease in VEGF protein following irradiation. Future research aimed at improving our understanding of bone following irradiation is necessary to further improve future clinical treatments.

Holding effects on coliform enumeration in drinking water samples.

PubMed Central

McDaniels, A E; Bordner, R H; Gartside, P S; Haines, J R; Brenner, K P; Rankin, C C

1985-01-01

Standard procedures for analyzing drinking water stress the need to adhere to the time and temperature conditions recommended for holding samples collected for microbiological testing. The National Drinking Water Laboratory Certification Program requires compliance with these holding limits, but some investigators have reported difficulties in meeting them. Research was conducted by standard analytical methods to determine if changes occurred when samples were held at 5 and 22 degrees C and analyzed at 0, 24, 30, and 48 h. Samples were analyzed for coliforms by the membrane filter and fermentation-tube procedures and for heterotrophs by the pour plate method. A total of 17 treated water samples were collected from a large municipal distribution system from August to December 1981, and 12 samples were collected from January to May 1983. The samples were dosed with coliforms previously isolated from the water system, Enterobacter cloacae in 1981 and Citrobacter freundii in 1983. The coliform counts declined linearly over time, and the rates of decline were significant at both 5 and 22 degrees C. Within 24 h at 22 degrees C, levels of E. cloacae and C. freundii decreased by 47 and 26%, respectively, and at 5 degrees C, E. cloacae numbers declined by 23%. Results from these representative laboratory-grown coliforms reinforced those previously obtained with naturally occurring coliforms under the same experimental conditions. Significantly, some samples with initially unacceptable counts (greater than 4/100 ml) met the safe drinking water limits after storage at 24 h at 5 and 22 degrees C and would have been classified as satisfactory.(ABSTRACT TRUNCATED AT 250 WORDS) Images PMID:4083877

Impact of lower challenge doses of enterotoxigenic Escherichia coli on clinical outcome, intestinal colonization and immune responses in adult volunteers.

PubMed

Chakraborty, Subhra; Harro, Clayton; DeNearing, Barbara; Brubaker, Jessica; Connor, Sean; Maier, Nicole; Dally, Len; Flores, Jorge; Bourgeois, A Louis; Walker, Richard; Sack, David A

2018-04-01

A reliable and effective human challenge model is needed to help down-select the most promising ETEC vaccines currently under development. Such a model would need to reliably induce diarrhea in a high proportion of volunteers using the lowest possible inoculum to maximize safety and sensitivity. Previously we validated a challenge model that utilized a dose of 2x107 CFU of ETEC strain H10407 (LT+, ST+, CFA/I+ and O78+) to induce attack rates for moderate to severe diarrhea (MSD) of ~60-70%. Here we detail efforts to further refine the model in an attempt to determine if a lower challenge dose of H10407 can be used. Thirty subjects were randomized 1:1 to receive an oral administration of H10407 at doses of 106 or 105 CFU in bicarbonate buffer. After challenge, subjects were monitored for signs and symptoms of enteric illness and stool samples were collected to detect shedding of the challenge strain. Systemic and mucosal immune responses were measured using serum, antibody in lymphocyte supernatant and fecal samples. The attack rate was 13.3% (2/15) and 26.7% (4/15) for MSD in the 105 and 106 groups, respectively. Four MSD cases met criteria for early antibiotic treatment. All subjects but one shed the challenge strain in fecal samples. The frequency and magnitude of anti-LT toxin, CFA/I and LPS O78 immune responses were antigen, dose, severity of diarrhea and shedding levels dependent. Notably, although of lower magnitude, there were considerable immune responses in the subjects with no diarrhea. This may indicate that immune responses to asymptomatic infections of ETEC in children in the endemic countries may contribute to protection. Based on this and our prior studies, we conclude that a dose of 2x107 H10407 remains the lowest practical dose for use in future volunteer studies evaluating candidate vaccines and other preventive or therapeutic ETEC interventions. ClinicalTrials.gov NCT00844493.

Impact of lower challenge doses of enterotoxigenic Escherichia coli on clinical outcome, intestinal colonization and immune responses in adult volunteers

PubMed Central

DeNearing, Barbara; Brubaker, Jessica; Connor, Sean; Maier, Nicole; Dally, Len; Flores, Jorge; Bourgeois, A. Louis; Walker, Richard; Sack, David A.

2018-01-01

A reliable and effective human challenge model is needed to help down-select the most promising ETEC vaccines currently under development. Such a model would need to reliably induce diarrhea in a high proportion of volunteers using the lowest possible inoculum to maximize safety and sensitivity. Previously we validated a challenge model that utilized a dose of 2x107 CFU of ETEC strain H10407 (LT+, ST+, CFA/I+ and O78+) to induce attack rates for moderate to severe diarrhea (MSD) of ~60–70%. Here we detail efforts to further refine the model in an attempt to determine if a lower challenge dose of H10407 can be used. Thirty subjects were randomized 1:1 to receive an oral administration of H10407 at doses of 106 or 105 CFU in bicarbonate buffer. After challenge, subjects were monitored for signs and symptoms of enteric illness and stool samples were collected to detect shedding of the challenge strain. Systemic and mucosal immune responses were measured using serum, antibody in lymphocyte supernatant and fecal samples. The attack rate was 13.3% (2/15) and 26.7% (4/15) for MSD in the 105 and 106 groups, respectively. Four MSD cases met criteria for early antibiotic treatment. All subjects but one shed the challenge strain in fecal samples. The frequency and magnitude of anti-LT toxin, CFA/I and LPS O78 immune responses were antigen, dose, severity of diarrhea and shedding levels dependent. Notably, although of lower magnitude, there were considerable immune responses in the subjects with no diarrhea. This may indicate that immune responses to asymptomatic infections of ETEC in children in the endemic countries may contribute to protection. Based on this and our prior studies, we conclude that a dose of 2x107 H10407 remains the lowest practical dose for use in future volunteer studies evaluating candidate vaccines and other preventive or therapeutic ETEC interventions. Trial registration: ClinicalTrials.gov NCT00844493. PMID:29702652

Utility of capillary microsampling for rat pharmacokinetic studies: Comparison of tail-vein bleed to jugular vein cannula sampling.

PubMed

Korfmacher, Walter; Luo, Yongyi; Ho, Stacy; Sun, Wei; Shen, Liduo; Wang, Jie; Wu, Zhongtao; Guo, Yang; Snow, Gregory; O'Shea, Thomas

2015-01-01

Serial sampling methods have been used for rat pharmacokinetic (PK) studies for over 20 years. Currently, it is still common to take 200-250 μL of blood at each timepoint when performing a PK study in rats and using serial sampling. While several techniques have been employed for collecting blood samples from rats, there is only limited published data to compare these methods. Recently, microsampling (≤ 50 μL) techniques have been reported as an alternative process for collecting blood samples from rats. In this report, five compounds were dosed orally into rats. For three proprietary compounds, jugular vein cannula (JVC) sampling was used to collect whole blood and plasma samples and capillary microsampling (CMS) was used to collect blood samples from the tail vein of the same animal. For the two other compounds, marketed drugs fluoxetine and glipizide, JVC sampling was used to collect both whole blood and blood CMS samples while tail-vein sampling from the same rats was also used to collect both whole blood and blood CMS samples. For the three proprietary compounds, the blood AUC as well as the blood concentration-time profile that were obtained from the tail vein were different from those obtained via JVC sampling. For fluoxetine, the blood total exposure (AUC) was not statistically different when comparing tail-vein sampling to JVC sampling, however the blood concentration-time profile that was obtained from the tail vein was different than the one obtained from JVC sampling. For glipizide, the blood AUC and concentration-time profile were not statistically different when comparing the tail-vein sampling to the JVC sampling. For both fluoxetine and glipizide, the blood concentration profiles obtained from CMS were equivalent to the blood concentration profiles obtained from the standard whole blood sampling, collected at the same sampling site. The data in this report provide strong evidence that blood CMS is a valuable small volume blood sampling approach for rats and that it provides results for test compound concentrations that are equivalent to those obtained from traditional whole blood sampling. The data also suggest that for some compounds, the concentration-time profile that is obtained for a test compound based on sampling from a rat tail vein may be different from that obtained from rat JVC sampling. In some cases, this shift in the concentration-time profile will result in different PK parameters for the test compound. Based on these observations, it is recommended that a consistent blood sampling method should be used for serial microsampling in discovery rat PK studies when testing multiple new chemical entities. If the rat tail vein sampling method is selected for PK screening, then conducting a bridging study on the lead compound is recommended to confirm that the rat PK obtained from JVC sampling is comparable to the tail-vein sampling. Copyright © 2015 Elsevier Inc. All rights reserved.

Methylphenidate side effect profile is influenced by genetic variation in the attention-deficit/hyperactivity disorder-associated CES1 gene.

PubMed

Johnson, Katherine A; Barry, Edwina; Lambert, David; Fitzgerald, Michael; McNicholas, Fiona; Kirley, Aiveen; Gill, Michael; Bellgrove, Mark A; Hawi, Ziarih

2013-12-01

A naturalistic, prospective study of the influence of genetic variation on dose prescribed, clinical response, and side effects related to stimulant medication in 77 children with attention-deficit/hyperactivity disorder (ADHD) was undertaken. The influence of genetic variation of the CES1 gene coding for carboxylesterase 1A1 (CES1A1), the major enzyme responsible for the first-pass, stereoselective metabolism of methylphenidate, was investigated. Parent- and teacher-rated behavioral questionnaires were collected at baseline when the children were medication naïve, and again at 6 weeks while they were on medication. Medication dose, prescribed at the discretion of the treating clinician, and side effects, were recorded at week 6. Blood and saliva samples were collected for genotyping. Single nucleotide polymorphisms (SNPs) were selected in the coding, non-coding and the 3' flanking region of the CES1 gene. Genetic association between CES1 variants and ADHD was investigated in an expanded sample of 265 Irish ADHD families. Analyses were conducted using analysis of covariance (ANCOVA) and logistic regression models. None of the CES1 gene variants were associated with the dose of methylphenidate provided or the clinical response recorded at the 6 week time point. An association between two CES1 SNP markers and the occurrence of sadness as a side effect of short-acting methylphenidate was found. The two associated CES1 markers were in linkage disequilibrium and were significantly associated with ADHD in a larger sample of ADHD trios. The associated CES1 markers were also in linkage disequilibrium with two SNP markers of the noradrenaline transporter gene (SLC6A2). This study found an association between two CES1 SNP markers and the occurrence of sadness as a side effect of short-acting methylphenidate. These markers were in linkage disequilibrium together and with two SNP markers of the noradrenaline transporter gene.

Pharmacokinetic Modeling of Intranasal Scopolamine in Plasma Saliva and Urine

NASA Technical Reports Server (NTRS)

Wu, L.; Chow, D. S. L.; Tam, V.; Putcha, L.

2014-01-01

An intranasal gel formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness. The bioavailability and pharmacokinetics (PK) were evaluated under the Food and Drug Administration guidelines for clinical trials for an Investigative New Drug (IND). The aim of this project was to develop a PK model that can predict the relationship between plasma, saliva and urinary scopolamine concentrations using data collected from the IND clinical trial with INSCOP. METHODS: Twelve healthy human subjects were administered three dose levels (0.1, 0.2 and 0.4 mg) of INSCOP. Serial blood, saliva and urine samples were collected between 5 min to 24 h after dosing and scopolamine concentrations measured by using a validated LC-MS-MS assay. Pharmacokinetic Compartmental models, using actual dosing and sampling times, were built using Phoenix (version 1.2). Model discrimination was performed, by minimizing the Akaike Information Criteria (AIC), maximizing the coefficient of determination (r²) and by comparison of the quality of fit plots. RESULTS: The best structural model to describe scopolamine disposition after INSCOP administration (minimal AIC =907.2) consisted of one compartment for plasma, saliva and urine respectively that were inter-connected with different rate constants. The estimated values of PK parameters were compiled in Table 1. The model fitting exercises revealed a nonlinear PK for scopolamine between plasma and saliva compartments for K21, Vmax and Km. CONCLUSION: PK model for INSCOP was developed and for the first time it satisfactorily predicted the PK of scopolamine in plasma, saliva and urine after INSCOP administration. Using non-linear PK yielded the best structural model to describe scopolamine disposition between plasma and saliva compartments, and inclusion of non-linear PK resulted in a significant improved model fitting. The model can be utilized to predict scopolamine plasma concentration using saliva and/or urine data that allows non-invasive assessment of pharmacotherapeutics of scopolamine in space and other remote environments without requiring blood sampling.

Decay of Sabin inactivated poliovirus vaccine (IPV)-boosted poliovirus antibodies.

PubMed

Resik, Sonia; Tejeda, Alina; Fonseca, Magile; Sein, Carolyn; Hung, Lai Heng; Martinez, Yenisleidys; Diaz, Manuel; Okayasu, Hiromasa; Sutter, Roland W

We conducted a follow-on study to a phase I randomized, controlled trial conducted in Cuba, 2012, to assess the persistence of poliovirus antibodies at 21-22 months following booster dose of Sabin-IPV compared to Salk-IPV in adults who had received multiple doses of oral poliovirus vaccine (OPV) during childhood. In 2012, 60 healthy adult males aged 19-23 were randomized to receive one booster dose, of either Sabin-inactivated poliovirus vaccine (Sabin-IPV), adjuvanted Sabin-IPV (aSabin-IPV), or conventional Salk-IPV. In the original study, blood was collected at days 0 (before) and 28 (after vaccination), respectively. In this study, an additional blood sample was collected 21-22 months after vaccination, and tested for neutralizing antibodies to Sabin poliovirus types 1, 2 and 3. We collected sera from 59/60 (98.3%) subjects; 59/59 (100%) remained seropositive to all poliovirus types, 21-22 months after vaccination. The decay curves were very similar among the study groups. Between day 28 and 21-22 months, there was a reduction of ⩾87.4% in median antibody levels for all poliovirus types in all study groups, with no significant differences between the study groups. The decay of poliovirus antibodies over a 21-22-month period was similar regardless of the type of booster vaccine used, suggesting the scientific data of Salk IPV long-term persistence and decay may be broadly applicable to Sabin IPV.

Ocular biodistribution of bevasiranib following a single intravitreal injection to rabbit eyes

PubMed Central

Dejneka, Nadine S.; Wan, Shanhong; Bond, Ottrina S.; Kornbrust, Douglas J.

2008-01-01

Purpose The primary objective of these investigations was to determine the ocular biodistribution of bevasiranib, a small interfering RNA (siRNA) targeting vascular endothelial growth factor A (VEGF-A), following a single intravitreal injection to rabbit eyes. Methods A tissue distribution and pharmacokinetic study was conducted with 3H-bevasiranib prepared in balanced-salt solution (BSS). Single doses of either 0.5 mg/eye or 2.0 mg/eye of 3H-bevasiranib were given by intravitreal injection to Dutch-Belted rabbits (both eyes were treated). Subgroups of rabbits were serially-sacrificed at various times up to 7 days following dosing for collection of tissue samples. The right eye of each rabbit was collected whole, and the left eye was dissected to isolate five ocular tissues. All samples were analyzed by liquid scintillation counting to determine the concentrations of bevasiranib equivalents. An ocular disposition study was also performed with non-radiolabeled bevasiranib, which was administered to Dutch-Belted rabbit eyes via intravitreal injection at a dose of 2.0 mg/eye. Twenty-four hours post-dose, the eyes were enucleated and dissected into eight individual ocular structures that were analyzed for intact bevasiranib using a locked nuleic acid (LNA) noncompetitive hybridization-ligation enzyme-linked immunosorbent assay. Results Following intravitreal injection of 0.5 mg or 2.0 mg radiolabeled bevasiranib to Dutch-Belted rabbits, bevasiranib was detected in the vitreous, iris, retina, retinal pigment epithelium (RPE), and sclera (+choroid). As expected, the highest concentrations were found in the vitreous, and vitreous levels steadily decreased over time, while concentrations of radioactivity in the other ocular tissues increased to maximum values between 24 h and 72 h after dosing. Of these tissues, the highest concentration of radioactivity was detected in the retina. The LNA assay further confirmed the presence of intact bevasiranib in these tissues 24 h following intravitreal injection of non-radiolabeled bevasiranib (2 mg/eye). Conclusions These studies demonstrate distribution of bevasiranib throughout the eye following intravitreal injection, including extensive uptake into the retina. PMID:18523657

Mumps increase in Flanders, Belgium, 2012-2013: results from temporary mandatory notification and a cohort study among university students.

PubMed

Braeye, Toon; Linina, Indra; De Roy, Rikka; Hutse, Veronik; Wauters, Magali; Cox, Pia; Mak, Ruud

2014-07-31

In 2012, an increase in mumps notifications occurred in Belgium, affecting young vaccinated adults. At the end of 2012, a mumps outbreak occurred at the Catholic University of Leuven KU Leuven in Flanders. We investigated the outbreak to estimate incidence, mumps vaccine effectiveness and to detect potential risk factors for the disease. In June 2012, we set up mandatory notification in Flanders and we collected information on circulating genotypes from the National Reference Centre. We conducted a cohort study among KU Leuven students. We defined a case as self-reported parotitis, between September 2012 and March 2013. We distributed web-based questionnaires to a random sample of students. We calculated vaccine effectiveness by comparing the risks in students vaccinated twice with those vaccinated once. We estimated risk ratios (RR) to identify risk factors. From 16th June 2012 to 1st April 2013, 4061 mumps cases were notified to the regional public health office (30% were vaccinated once and 69% were vaccinated twice). All 16 samples collected at the KU Leuven were genotype G5. Of 717 participants of the cohort study, 38 (5%; 95%CI 4-8%) met the case-definition. All reported being vaccinated with at least one dose of mumps-containing vaccine. The incidence of mumps was 5% among those vaccinated twice and 16% among those vaccinated once (vaccine effectiveness of two doses compared to one: 68%, 95%CI -24% to 92%). The risk of mumps was lower among those vaccinated with two doses of mumps-containing vaccine ≤10 years before (RR: 0.33, 95%CI 0.10-1.02) and higher among students working in a bar (RR: 3.6, 95%CI 1.8-7.0). Incomplete protection by two doses of mumps-containing vaccine, possible waning immunity and intense social contacts may have contributed to the occurrence of this outbreak in Flanders. Efforts to maintain high vaccination coverage with two doses remain essential. However, the reasons for low vaccine effectiveness must be further explored and additional immunological research for more immunogenic mumps vaccines is necessary. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Immediate postpartum initiation of etonogestrel-releasing implant: A randomized controlled trial on breastfeeding impact.

PubMed

Braga, Giordana Campos; Ferriolli, Eduardo; Quintana, Silvana Maria; Ferriani, Rui Alberto; Pfrimer, Karina; Vieira, Carolina Sales

2015-12-01

Breast milk volume has never been evaluated when the etonogestrel (ENG) implant was inserted immediately postpartum. Thus, this study evaluated if the immediate postpartum insertion of the ENG implant alters breast milk volume. Twenty-four postpartum women and their newborns (NBs) were randomized into two groups: Implant group (ENG implant inserted within 48 h after delivery) and Control group (absence of contraceptive method). The primary outcome was the amount of breast milk intake by the NBs in the first 6 weeks after delivery. Five and ten grams of deuterium (D(2)O) were orally administered to the postpartum women on the day of randomization (day 0) and on the 29th study day, respectively. Saliva samples were collected from the mother-NB pairs prior to each D(2)O dose administration and after D(2)O ingestion (periodic collection). The amount of breast milk ingested by the NBs was estimated by the amount of deuterium (D(2)O) ingested by the NBs through breastfeeding, using mass spectrometry in the saliva samples. Twenty-four postpartum women and their NB were randomized (12 per group). The median of breast milk intake by NBs following the two D(2)O doses were similar between groups {first D(2)O dose [Implant: 340 mL/day (240-420 mL/day) vs. 330 mL/day (300-530 mL/day), p=.54]; second D(2)O dose [Implant: 845 mL/day (770-980 mL/day) vs. 785 mL/day (680-980 mL/day), p=.63]}. The exclusive breastfeeding rate and NB weight were similar between groups in the first 6 weeks postpartum. ENG implant insertion immediately postpartum does not alter the volume of breast milk intake by NBs. Considering the benefits of immediate postpartum initiation of ENG implant on reducing unintended pregnancy and pregnancy recurrence, especially in vulnerable populations, our study adds safety data on breastfeeding effect of this practice. Copyright © 2015 Elsevier Inc. All rights reserved.

A Population Pharmacokinetic Model for Disposition in Plasma, Saliva and Urine of Scopolamine after Intranasal Administration to Healthy Human Subjects

NASA Technical Reports Server (NTRS)

Wu, L.; Tam, V. H.; Chow, D. S. L.; Putcha, L.

2014-01-01

An intranasal gel formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness. The bioavailability and pharmacokinetics (PK) were evaluated under the Food and Drug Administration guidelines for clinical trials with an Investigative New Drug (IND) protocol. The aim of this project was to develop a PK model that can predict the relationship between plasma, saliva and urinary scopolamine concentrations using data collected from the IND clinical trials with INSCOP. Methods: Twelve healthy human subjects were administered three dose levels (0.1, 0.2 and 0.4 mg) of INSCOP. Serial blood, saliva and urine samples were collected between 5 min and 24 h after dosing and scopolamine concentrations were measured by using a validated LC-MS-MS assay. Pharmacokinetic Compartmental models, using actual dosing and sampling times, were built using Phoenix (version 1.2). Model selection was based on the likelihood ratio test on the difference of criteria (-2LL) and comparison of the quality of fit plots. Results: The best structural model for INSCOP (minimal -2LL= 502.8) was established. It consisted of one compartment each for plasma, saliva and urine, respectively, which were connected with linear transport processes except the nonlinear PK process from plasma to saliva compartment. The best-fit estimates of PK parameters from individual PK compartmental analysis and Population PK model analysis were shown in Tables 1 and 2, respectively. Conclusion: A population PK model that could predict population and individual PK of scopolamine in plasma, saliva and urine after dosing was developed and validated. Incorporating a non-linear transfer from plasma to saliva compartments resulted in a significantly improved model fitting. The model could be used to predict scopolamine plasma concentrations from salivary and urinary drug levels, allowing non-invasive therapeutic monitoring of scopolamine in space and other remote environments.

Dose escalation pharmacokinetics of intranasal scopolamine gel formulation.

PubMed

Wu, Lei; Boyd, Jason L; Daniels, Vernie; Wang, Zuwei; Chow, Diana S-L; Putcha, Lakshmi

2015-02-01

Astronauts experience Space Motion Sickness requiring treatment with an anti-motion sickness medication, scopolamine during space missions. Bioavailability after oral administration of scopolamine is low and variable, and absorption form transdermal patch is slow and prolonged. Intranasal administration achieves faster absorption and higher bioavailability of drugs that are subject to extrahepatic, first pass metabolism after oral dosing. We examined pharmacokinetics of 0.1, 0.2, and 0.4 mg doses of the Investigational New Drug formulation of intranasal scopolamine gel (INSCOP) in 12 healthy subjects using a randomized, double-blind cross-over study design. Subjects received one squirt of 0.1 g of gel containing either 0.1 mg or 0.2 mg/0.1 mL scopolamine or placebo in each nostril. Serial blood samples and total urine voids were collected after dosing and drug concentrations were determined using a modified LC-MS-MS method. Results indicate dose-linear pharmacokinetics of scopolamine with linear increases in Cmax and AUC within the dose range tested. Plasma drug concentrations were significantly lower in females than in males after administration of 0.4 dose. All three doses were well tolerated with no unexpected or serious adverse side effects reported. These results suggest that intranasal scopolamine gel formulation (INSCOP) offers a fast, reliable, and safe alternative for the treatment of motion sickness. © 2014, The American College of Clinical Pharmacology.

Pharmacokinetics of opicapone, a third-generation COMT inhibitor, after single and multiple oral administration: A comparative study in the rat.

PubMed

Gonçalves, Daniela; Alves, Gilberto; Fortuna, Ana; Soares-da-Silva, Patrício; Falcão, Amílcar

2017-05-15

Opicapone is a novel potent, reversible and purely peripheral catechol-O-methyltransferase inhibitor that has been developed to be used as an adjunct to levodopa/aromatic L-amino acid decarboxylase inhibitor therapy for Parkinson's disease. Thus, this study aimed to compare the plasma pharmacokinetics of opicapone and its active metabolite (BIA 9-1079) after the administration of single and multiple oral doses to rats. Wistar rats (n=8 per group) were orally treated with single (30, 60 or 90mg/kg) or multiple (30mg/kg once-daily for seven consecutive days) oral doses of opicapone. Blood samples were collected up to 24h post-dosing through a cannula introduced in the tail vein of rats. After quantifying opicapone and BIA 9-1079 in plasma, a non-compartmental pharmacokinetic analysis was performed. Opicapone was quickly absorbed (time to reach the maximum plasma concentration≤2h) in both dosage regimens and the extent of systemic exposure to opicapone increased approximately in a dose-proportional manner after single-dosing within the studied dose range (30-90mg/kg). Opicapone and BIA 9-1079 showed a relatively short plasma elimination half-life (1.58-4.50h) and a small systemic accumulation after multiple-dosing. Hence, no pharmacokinetic concerns are expected when opicapone is administered with a once-daily dosing regimen. Copyright © 2017 Elsevier Inc. All rights reserved.

Chromosome aberrations in human lymphocytes induced by 250 MeV protons: effects of dose, dose rate and shielding.

PubMed

George, K; Willingham, V; Wu, H; Gridley, D; Nelson, G; Cucinotta, F A

2002-01-01

Although the space radiation environment consists predominantly of energetic protons, astronauts inside a spacecraft are chronically exposed to both primary particles as well as secondary particles that are generated when the primary particles penetrate the spacecraft shielding. Secondary neutrons and secondary charged particles can have an LET value that is greater than the primary protons and, therefore, produce a higher relative biological effectiveness (RBE). Using the accelerator facility at Loma Linda University, we exposed human lymphocytes in vitro to 250 MeV protons with doses ranging from 0 to 60 cGy at three different dose rates: a low dose rate of 7.5 cGy/h, an intermediate dose rate of 30 cGy/h and a high dose rate of 70 cGy/min. The effect of 15 g/cm2 aluminum shielding on the induction of chromosome aberrations was investigated for each dose rate. After exposure, lymphocytes were incubated in growth medium containing phytohemagglutinin (PHA) and chromosome spreads were collected using a chemical-induced premature chromosome condensation (PCC) technique. Aberrations were analyzed using the fluorescence in situ hybridization (FISH) technique with three different colored chromosome-painting probes. The frequency of reciprocal and complex-type chromosome exchanges were compared in shielded and unshielded samples. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

Chromosome aberrations in human lymphocytes induced by 250 MeV protons: effects of dose, dose rate and shielding

NASA Technical Reports Server (NTRS)

George, K.; Willingham, V.; Wu, H.; Gridley, D.; Nelson, G.; Cucinotta, F. A.

2002-01-01

Although the space radiation environment consists predominantly of energetic protons, astronauts inside a spacecraft are chronically exposed to both primary particles as well as secondary particles that are generated when the primary particles penetrate the spacecraft shielding. Secondary neutrons and secondary charged particles can have an LET value that is greater than the primary protons and, therefore, produce a higher relative biological effectiveness (RBE). Using the accelerator facility at Loma Linda University, we exposed human lymphocytes in vitro to 250 MeV protons with doses ranging from 0 to 60 cGy at three different dose rates: a low dose rate of 7.5 cGy/h, an intermediate dose rate of 30 cGy/h and a high dose rate of 70 cGy/min. The effect of 15 g/cm2 aluminum shielding on the induction of chromosome aberrations was investigated for each dose rate. After exposure, lymphocytes were incubated in growth medium containing phytohemagglutinin (PHA) and chromosome spreads were collected using a chemical-induced premature chromosome condensation (PCC) technique. Aberrations were analyzed using the fluorescence in situ hybridization (FISH) technique with three different colored chromosome-painting probes. The frequency of reciprocal and complex-type chromosome exchanges were compared in shielded and unshielded samples. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

SU-F-P-19: Fetal Dose Estimate for a High-Dose Fluoroscopy Guided Intervention Using Modern Data Tools

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moirano, J

Purpose: An accurate dose estimate is necessary for effective patient management after a fetal exposure. In the case of a high-dose exposure, it is critical to use all resources available in order to make the most accurate assessment of the fetal dose. This work will demonstrate a methodology for accurate fetal dose estimation using tools that have recently become available in many clinics, and show examples of best practices for collecting data and performing the fetal dose calculation. Methods: A fetal dose estimate calculation was performed using modern data collection tools to determine parameters for the calculation. The reference pointmore » air kerma as displayed by the fluoroscopic system was checked for accuracy. A cumulative dose incidence map and DICOM header mining were used to determine the displayed reference point air kerma. Corrections for attenuation caused by the patient table and pad were measured and applied in order to determine the peak skin dose. The position and depth of the fetus was determined by ultrasound imaging and consultation with a radiologist. The data collected was used to determine a normalized uterus dose from Monte Carlo simulation data. Fetal dose values from this process were compared to other accepted calculation methods. Results: An accurate high-dose fetal dose estimate was made. Comparison to accepted legacy methods were were within 35% of estimated values. Conclusion: Modern data collection and reporting methods ease the process for estimation of fetal dose from interventional fluoroscopy exposures. Many aspects of the calculation can now be quantified rather than estimated, which should allow for a more accurate estimation of fetal dose.« less

Liquid scintillator tiles for calorimetry

DOE PAGES

Amouzegar, M.; Belloni, A.; Bilki, B.; ...

2016-11-28

Future experiments in high energy and nuclear physics may require large, inexpensive calorimeters that can continue to operate after receiving doses of 50 Mrad or more. Also, the light output of liquid scintillators suffers little degradation under irradiation. However, many challenges exist before liquids can be used in sampling calorimetry, especially regarding developing a packaging that has sufficient efficiency and uniformity of light collection, as well as suitable mechanical properties. We present the results of a study of a scintillator tile based on the EJ-309 liquid scintillator using cosmic rays and test beam on the light collection efficiency and uniformity,more » and some preliminary results on radiation hardness.« less

Liquid scintillator tiles for calorimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Amouzegar, M.; Belloni, A.; Bilki, B.

Future experiments in high energy and nuclear physics may require large, inexpensive calorimeters that can continue to operate after receiving doses of 50 Mrad or more. Also, the light output of liquid scintillators suffers little degradation under irradiation. However, many challenges exist before liquids can be used in sampling calorimetry, especially regarding developing a packaging that has sufficient efficiency and uniformity of light collection, as well as suitable mechanical properties. We present the results of a study of a scintillator tile based on the EJ-309 liquid scintillator using cosmic rays and test beam on the light collection efficiency and uniformity,more » and some preliminary results on radiation hardness.« less

Natural radioactivity in granite stones used as building materials in Iran.

PubMed

Asgharizadeh, F; Abbasi, A; Hochaghani, O; Gooya, E S

2012-04-01

Due to increasing concern about environmental radiological protection, specific radioactivity concentrations of (226)Ra, (232)Th and (40)K in different types of commonly used granite stone samples collected from the Tehran city of Iran have been determined by means of a high-resolution HPGe gamma-spectroscopy system. The activity concentrations of (232)Th, (226)Ra and (40)K in the selected granite samples ranged from 18 to 178, 6 to 160 and 556 to 1539 Bq kg(-1), respectively. The radium equivalent activities (Ra(eq)) are lower than the limit of 370 Bq kg(-1) set by NEA-OECD [Nuclear Energy Agency. Exposure to radiation from natural radioactivity in building materials. Report by NEA Group of Experts. OECD (1979)], except in two samples. The internal hazard indexes have been found well below the acceptable limit in most of the samples. Five samples of investigated commercial granite stones do not satisfy the safety criterion illustrated by UNSCEAR (United Nations Scientific Committee on the Effects of Atomic Radiation. Exposure from natural sources of radiation. Report to the General Assembly (1993). Applying dose criteria recently recommended by the EC [European Commission Report on Radiological Protection Principles Concerning the Natural Radioactivity of Building Materials. Radiation Protection 112 (1999)] for superficial materials, all investigated samples meet the exemption dose limit of 0.3 mSv y(-1).

Microdose study of a P-glycoprotein substrate, fexofenadine, using a non-radioisotope-labelled drug and LC/MS/MS.

PubMed

Yamazaki, A; Kumagai, Y; Yamane, N; Tozuka, Z; Sugiyama, Y; Fujita, T; Yokota, S; Maeda, M

2010-04-01

Fexofenadine is a P-glycoprotein substrate of low bioavailability. It is primarily excreted into faeces as a parent drug via biliary excretion. The predictability from microdose data for the drug absorbed via transporters such as P-glycoprotein is not known. Therefore, this study assessed the predictability of therapeutic-dose pharmacokinetics of fexofenadine from microdosing data using non-radioisotope-labelled drug and liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS). In a single dose, randomized, two-way crossover study, eight subjects received a microdose (100 microg) or a therapeutic dose (60 mg) of fexofenadine. Blood samples were collected until 12 h after dosing, and assayed using LC/MS/MS. Plasma concentration-time curves of fexofenadine between microdose and therapeutic dose were similar. The mean +/- SD of C(max) normalized to 60 mg dose after microdose and therapeutic dose were 379 +/- 147 and 275 +/- 145 ng/mL respectively. The mean AUC(last) normalized to 60 mg dose after microdose and therapeutic dose were 1914 +/- 738 and 1431 +/- 432 ng/h/mL respectively. The mean dose-adjusted C(max) and AUC(last) after microdose were higher compared with those after therapeutic dose. Individual plots of C(max) and AUC(last) normalized to 60 mg dose, were similar for microdose and therapeutic dose. None of the pharmacokinetic parameters were statistically different using anova. Overall, the microdose pharmacokinetics profile was similar to, and hence predictive of, that of the therapeutic dose. For the P-glycoprotein substrate fexofenadine, the predictability of therapeutic-dose pharmacokinetics from microdose data was good. A microdose study using a non-radioisotope-labelled drug and LC/MS/MS is convenient, and has the potential to aid the early selection of drug candidates.

Determination of natural radioactivity by gross alpha and beta measurements in ground water samples.

PubMed

Turhan, S; Ozçitak, E; Taşkin, H; Varinlioğlu, A

2013-06-01

In this study, the activity concentrations of the gross α and β in ground water samples collected from the different drilled wells in Nevşehir province were measured to assess annual effective dose due to the ingestion of the water samples. Nevşehir province is one of the major cities of Cappadocia Region which is a popular tourist destination as it has many areas with unique geological, historic, and cultural features. Sampling and measurements were carried out in the autumn of 2011 and the spring of 2012. The values of the activity concentrations of the gross α and β measured in the water samples ranged from 80 to 380 mBq L(-1) with a mean of 192 mBq L(-1) and 120-3470 mBq L(-1) with a mean of 579 mBq L(-1) respectively. All values of the gross α were lower than the limit value of 500 mBq L(-1) while two ground water samples were found to have gross β activity concentrations of greater than 1000 mBq L(-1). Therefore two water samples were the subject of further radioisotope-specific analysis. The obtained result indicated that the elevated activity concentrations of the gross β in these water samples are dominated by (40)K activity. Annual effective doses ranged from 0.04 to 0.20 mSv y(-1). Copyright © 2013 Elsevier Ltd. All rights reserved.

Ion-recombination correction for different ionization chambers in high dose rate flattening-filter-free photon beams

NASA Astrophysics Data System (ADS)

Lang, Stephanie; Hrbacek, Jan; Leong, Aidan; Klöck, Stephan

2012-05-01

Recently, there has been an increased interest in flattening-filter-free (FFF) linear accelerators. Removal of the filter results in available dose rates up to 24 Gy min-1 (for nominal energy 10 MV in depth of maximum dose, a source-surface distance of 100 cm and a field size of 10×10 cm2). To guarantee accurate relative and reference dosimetry for the FFF beams, we investigated the charge collection efficiency of multiple air-vented and one liquid ionization chamber for dose rates up to 31.9 Gy min-1. For flattened beams, the ion-collection efficiency of all air-vented ionization chambers (except for the PinPoint chamber) was above 0.995. By removing the flattening filter, we found a reduction in collection efficiency of approximately 0.5-0.9% for a 10 MV beam. For FFF beams, the Markus chamber showed the largest collection efficiency of 0.994. The observed collection efficiencies were dependent on dose per pulse, but independent of the pulse repetition frequency. Using the liquid ionization chamber, the ion-collection efficiency for flattened beams was above 0.990 for all dose rates. However, this chamber showed a low collection efficiency of 0.940 for the FFF 10 MV beam at a dose rate of 31.9 Gy min-1. All investigated air-vented ionization chambers can be reliably used for relative dosimetry of FFF beams. The order of correction for reference dosimetry is given in the manuscript. Due to their increased saturation in high dose rate FFF beams, liquid ionization chambers appear to be unsuitable for dosimetry within these contexts.

Antipsychotic doses among community-dwelling persons with Alzheimer disease in Finland.

PubMed

Taipale, Heidi; Koponen, Marjaana; Tanskanen, Antti; Tolppanen, Anna-Maija; Tiihonen, Jari; Hartikainen, Sirpa

2014-08-01

Use of antipsychotics for treatment of behavioral and psychological symptoms of dementia is frequent among persons with Alzheimer disease (AD). Doses used in long-term therapy have not been previously reported. We describe antipsychotic doses used among community-dwelling persons with AD and investigate factors associated with high-dose use. The MEDALZ-2005 (Medication use and Alzheimer disease) cohort is a nationwide sample including all persons with clinically diagnosed AD at the end of year 2005 in Finland (n = 28,093). Data including prescriptions, comorbidities, and hospital discharge diagnoses were collected from nationwide registers. Antipsychotic doses in monotherapy were investigated during 2006 to 2009. Among 8920 antipsychotic users, 4% (n = 336) used antipsychotics with high dose. Typical antipsychotics were more often used with high dose than atypical antipsychotics. High-dose use was associated with younger age (<80 years) (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.36-2.15]), male sex (OR, 1.52; CI, 1.21-1.91), history of psychiatric disorder (OR, 3.25; CI, 2.54-4.15), and inversely associated with Charlson Comorbidity Index score (score 1: OR, 0.74; CI, 0.57-0.97; score ≥2: OR, 0.68; CI, 0.47-0.97). In conclusion, the majority of persons with AD used antipsychotics with low or medium dose. Typical antipsychotics were more often used with high dose than atypical antipsychotics, which indicates a need for precise dosing instructions in the treatment of behavioral and psychological symptoms of dementia. Clinicians should regularly assess dosing levels especially among men and those with history of psychiatric disorder.

A neuropharmacokinetic assessment of bafetinib, a second generation dual BCR-Abl/Lyn tyrosine kinase inhibitor, in patients with recurrent high-grade gliomas.

PubMed

Portnow, Jana; Badie, Behnam; Markel, Susan; Liu, An; D'Apuzzo, Massimo; Frankel, Paul; Jandial, Rahul; Synold, Timothy W

2013-05-01

The primary objective of this study was to use intracerebral microdialysis (ICMD) to determine the neuropharmacokinetics of bafetinib, a dual BCR-Abl/Lyn tyrosine kinase inhibitor that may have activity against gliomas. A microdialysis catheter was placed into either peritumoural or enhancing brain tissue of seven patients at the time of tumour resection or biopsy. Twenty-four hours later, bafetinib was administered, 240 or 360 mg po, repeating the same dose 12 h later. Dialysate samples were continuously collected for 24h, with plasma samples obtained in parallel. One to two weeks after finishing ICMD, patients were allowed to resume taking bafetinib continuously while being observed for toxicity and tumour response. Twenty-six dialysate samples per patient were collected (n=6) and analysed for bafetinib by tandem mass spectrometry. Bafetinib concentrations in the brain were below the lower limit of detection of the assay (0.1 ng/ml) in all samples except one from a single subject that was 0.52 ng/ml. The mean plasma bafetinib maximum concentrations after dose 1 and 2 were 143±99 and 247±73 ng/ml, respectively. Only one patient remained on treatment past two cycles, and no radiographic responses were seen. Bafetinib does not sufficiently cross intact or disrupted blood-brain barrier, and therefore, systemic administration of bafetinib is not recommended when investigating this drug as a treatment for brain tumours. ICMD can be a valuable research tool in early drug development. Lead-in ICMD studies can be performed relatively quickly, requiring only a small number of patients, and without significantly disrupting standard cancer care. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effects of Gamma Irradiation on Bacterial Microflora Associated with Human Amniotic Membrane

PubMed Central

Binte Atique, Fahmida; Ahmed, Kazi Tahsin; Asaduzzaman, S. M.; Hasan, Kazi Nadim

2013-01-01

Human amniotic membrane is considered a promising allograft material for the treatment of ocular surface reconstruction, burns, and other skin defects. In order to avoid the transmission of any diseases, grafts should be perfectly sterile. Twenty-five amniotic sacs were collected to determine the microbiological quality of human amniotic membrane, to analyze the radiation sensitivity pattern of the microorganism, and to detect the radiation decimal reduction dose (D10) values. All the samples were found to be contaminated, and the bioburden was ranged from 3.4 × 102 to 1.2 × 105 cfu/g. Initially, a total fifty bacterial isolates were characterized according to their cultural, morphological, and biochemical characteristics and then tested for the radiation sensitivity in an incremental series of radiation doses from 1 to 10 KGy. The results depict gradual decline in bioburden with incline of radiation doses. Staphylococcus spp. were the most frequently isolated bacterial contaminant in tissue samples (44%). The D10 values of the bacterial isolates were ranged from 0.6 to 1.27 KGy. Streptococcus spp. were found to be the highest radioresistant strain with the radiation sterilization dose (RSD) of 11.4 KGy for a bioburden level of 1000. To compare the differences, D10 values were also calculated by graphical evaluations of the data with two of the representative isolates of each bacterial species which showed no significant variations. Findings of this study indicate that lower radiation dose is quite satisfactory for the sterilization of amniotic membrane grafts. Therefore, these findings would be helpful to predict the efficacy of radiation doses for the processing of amniotic membrane for various purposes. PMID:24063009

Environmental dose rate distribution along the Romanian Black Sea shore

NASA Astrophysics Data System (ADS)

Duliu, Octavian G.; Margineanu, Romul M.; Blebea-Apostu, Ana-Maria; Gomoiu, Claudia; Bercea, Sorin

2013-04-01

The radiometric investigation of the natural radioactivity dose rate distribution along the most important Romanian Black Sea tourist resorts showed values between 34 and 54 nSv/h, lower than the 59 nSv/h, the average background reported for the entire Romanian territory. At the same time we have noticed that the experimental dose rates monotonously increase northward, reaching a maximum in the vicinity of Vadu and Corbu beaches, both on the southern part of the Chituc sandbank. Concurrent gamma ray spectrometric measurements, performed at the Slanic-Prahova Low-Background Radiation Laboratory for sand samples collected from the same location, have shown that the natural radionuclides have a major contribution to background radiation while anthropogenic Cs-137 plays, 26 years after Chernobyl catastrophe, a negligible role. The experimental values of activity concentrations of all radionuclides present in sand samples were used to calculate the corresponding values of dose rates to which, by adding the contribution of cosmic rays, we have obtained values coincident, within experimental uncertainties, with the experimental ones. At the same time, on Chituc sandbank, a transverse profile of dose rate distribution revealed the presence of some local maxima, two to thee times higher then the average ones. Subsequent gamma ray spectrometry showed an increased content of natural radionuclides, most probably due to a local accumulation of heavy minerals, a common occurrence in the vicinity of river deltas, in our case the Danube Delta. In such a way, the monitoring of local dose rate distribution could be very useful not only in attesting the environmental quality of various resorts and beaches, but also, in signaling the presence of heavy minerals, with beneficent economic consequences.

Comparative pharmacokinetics of purified flaxseed and associated mammalian lignans in male Wistar rats.

PubMed

Mukker, Jatinder Kaur; Singh, Ravi Shankar Prasad; Muir, Alister D; Krol, Ed S; Alcorn, Jane

2015-03-14

Consumption of flaxseed lignans is associated with various health benefits; however, little is known about the bioavailability of purified lignans in flaxseed. Data on their bioavailability and hence pharmacokinetics (PK) are necessary to better understand their role in putative health benefits. In the present study, we conducted a comparative PK analysis of the principal lignan of flaxseed, secoisolariciresinol diglucoside (SDG), and its primary metabolites, secoisolariciresinol (SECO), enterodiol (ED) and enterolactone (EL) in rats. Purified lignans were intravenously or orally administered to each male Wistar rat. SDG and its primary metabolites SECO, ED and EL were administered orally at doses of 40, 40, 10 and 10 mg/kg, respectively, and intravenously at doses of 20, 20, 5 and 1 mg/kg, respectively. Blood samples were collected at 0 (pre-dose), 5, 10, 15, 20, 30 and 45 min, and at 1, 2, 4, 6, 8, 12 and 24 h post-dosing, and serum samples were analysed. PK parameters and oral bioavailability of purified lignans were determined by non-compartmental methods. In general, administration of the flaxseed lignans SDG, SECO and ED demonstrated a high systemic clearance, a large volume of distribution and short half-lives, whereas administration of EL at the doses of 1 mg/kg (intravenously) and 10 mg/kg (orally administered) killed the rats within a few hours of dosing, precluding a PK analysis of this lignan. PK parameters of flaxseed lignans exhibited the following order: systemic clearance, SDG < SECO < ED; volume of distribution, SDG < SECO < ED; half-life, SDG < ED < SECO. The percentage of oral bioavailability was 0, 25 and < 1 % for SDG, SECO and ED, respectively.

Pharmacokinetic profile of Mitoguazone (MGBG) in patients with AIDS related non-Hodgkin's lymphoma.

PubMed

Rizzo, J; Levine, A M; Weiss, G R; Pearce, T; Kraynak, M; Mueck, R; Smith, S; Von Hoff, D D; Kuhn, J G

1996-01-01

Mitoguazone is a unique chemotherapeutic agent whose activity is believed to result primarily from the competitive inhibition of S-adenosyl-methionine decarboxylase leading to a disruption in polyamine biosynthesis. Initial clinical trials demonstrated that the dose-limiting toxicities (mucositis and myelosuppression) of Mitoguazone were both dose and schedule dependent. Early pharmacokinetic studies of Mitoguazone in man revealed a prolonged half-life. Concurrent with a recent Phase II trial of Mitoguazone in patients with AIDS related non-Hodgkin's lymphoma, the single dose pharmacokinetics of Mitoguazone were characterized. Twelve patients received 600 mg/m2 of intravenous Mitoguazone over 30 minutes on an intermittent every 2 week schedule. Blood, urine, cerebrospinal fluid (CSF), pleural fluid and tissue samples were collected and analyzed by HPLC. Mitoguazone was cleared from the plasma triexponentially with a harmonic mean terminal half-life of 175 hours and a mean residence time of 192 hours. Peak plasma levels occurred immediately post-infusion, ranged from 6.47 to 42.8 micrograms/ml, and remained (for an extended period) well above the reported concentration for inhibition of polyamine biosynthesis. Plasma clearance averaged 4.73 l/hr/m2 with a relatively large apparent volume of distribution at steady-state of 1012 l/m2 indicating tissue sequestration. Renal excretion of unchanged Mitoguazone accounted for an average of 15.8% of the dose within 48 to 72 hours post-administration. Detectable levels of drug were present in random voided samples eight days post-dose. Mitoguazone levels in CSF ranged from 22 to 186 ng/ml post-dose with CSF/plasma ratios ranging from 0.6% to 7%. The pleural fluid/plasma ratio was approximately 1. Tissue levels of Mitoguazone were highest in the liver followed by lymph node, spleen and the brain.

Mutagenicity and in vivo toxicity of combined particulate and semivolatile organic fractions of gasoline and diesel engine emissions.

PubMed

Seagrave, JeanClare; McDonald, Jacob D; Gigliotti, Andrew P; Nikula, Kristen J; Seilkop, Steven K; Gurevich, Michael; Mauderly, Joe L

2002-12-01

Exposure to engine emissions is associated with adverse health effects. However, little is known about the relative effects of emissions produced by different operating conditions, fuels, or technologies. Rapid screening techniques are needed to compare the biological effects of emissions with different characteristics. Here, we examined a set of engine emission samples using conventional bioassays. The samples included combined particulate material and semivolatile organic compound fractions of emissions collected from normal- and high-emitter gasoline and diesel vehicles collected at 72 degrees F, and from normal-emitter groups collected at 30 degrees F. The relative potency of the samples was determined by statistical analysis of the dose-response curves. All samples induced bacterial mutagenicity, with a 10-fold range of potency among the samples. Responses to intratracheal instillation in rats indicated generally parallel rankings of the samples by multiple endpoints reflecting cytotoxic, inflammatory, and lung parenchymal changes, allowing selection of a more limited set of parameters for future studies. The parameters selected to assess oxidative stress and macrophage function yielded little useful information. Responses to instillation indicated little difference in potency per unit of combined particulate material and semivolatile organic compound mass between normal-emitter gasoline and diesel vehicles, or between emissions collected at different temperatures. However, equivalent masses of emissions from high-emitter vehicles of both types were more potent than those from normal-emitters. While preliminary in terms of assessing contributions of different emissions to health hazards, the results indicate that a subset of this panel of assays will be useful in providing rapid, cost-effective feedback on the biological impact of modified technology.

Glyphosate in Irish adults - A pilot study in 2017.

PubMed

Connolly, Alison; Leahy, Michelle; Jones, Kate; Kenny, Laura; Coggins, Marie A

2018-08-01

Glyphosate is the highest volume herbicide used globally and has recently been classified as a 2 A 'probably carcinogenic to humans' by the International Agency for Research on Cancer (IARC). There is limited data to evaluate the public health impacts from glyphosate exposure. The objective of this study is to conduct an exploratory glyphosate exposure assessment study among Irish adults, who were non-occupational users of glyphosate. A convenient sampling method was used, collecting one first morning void spot urine sample from each participant. A biomonitoring survey involving the collection and analysis of 20 ml spot urine samples from 50 Irish adults was conducted in June 2017. Participants completed a short questionnaire to collect information on demographics, dietary habits and lifestyle. Glyphosate was extracted using solid phase extraction (SPE) and analysed by liquid chromatography tandem mass spectrometry (LC-MC/MS). Of the 50 urine samples analysed, 10 (20%) contained detectable levels of glyphosate (0.80-1.35 µg L -1 ). Exposure concentrations are higher than those reported in comparable studies of European and American adults. Glyphosate was detectable in 20% of the samples collected from Irish adults. The low proportion of detectable glyphosate levels could be due to lower localised use of pesticides, having a small sample size or the higher analytical detection limit used in this study (0.5 µg L -1 ), which could underestimate the true exposure and warrants further investigation. Given the widespread use of glyphosate, further information on population exposure is required to advance our understanding of the relationship between chronic low dose exposure to glyphosate and human health risk. Copyright © 2018 Elsevier Inc. All rights reserved.

Annual radiological environmental operating report, Browns Ferry Nuclear Plant, 1991

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1992-04-01

This report describes the environmental radiological monitoring program conducted by TVA in the vicinity of Browns Ferry Nuclear Plant in 1991. The program includes the collection of samples from the environment and the determination of the concentrations of radioactive materials in the samples. Samples are taken from stations in the general area of the plant and from areas not influenced by plant operations. Station locations are selected after careful consideration of the weather patterns and projected radiation doses to the various areas around the plant. Material sampled includes air, water, milk, foods, vegetation, soil, fish, sediment, and direct radiation levels.more » Results from stations near the plant are compared with concentrations from control stations and with preoperational measurements to determine potential impacts of plant operations.« less

Factors affecting urine reagent strip blood results in dogs and nonhuman primates and interpretation of urinalysis in preclinical toxicology studies: a Multi-Institution Contract Research Organization and BioPharmaceutical Company Perspective.

PubMed

Aulbach, Adam D; Schultze, Eric; Tripathi, Niraj K; Hall, Robert L; Logan, Michael R; Meyer, Denny J

2015-06-01

Urinalysis data in preclinical toxicology studies can be influenced by preanalytic and analytic factors which have the potential to confound interpretation. There is a paucity of information regarding positive reagent strip urinary blood reactions in healthy nonhuman primates (NHP) and Beagle dogs used in preclinical toxicology studies. The objectives were (1) to establish historical control data for reagent strip urinary blood reactions in healthy NHP and Beagle dogs, (2) to determine the incidence of positive urinary blood reactions during predose and dosing phases, and (3) to determine if collection practice was a relevant parameter. Historical control data from 2 institutions in the biopharmaceutical industry were retrospectively analyzed for reagent strip urinary blood reactions in healthy NHP and Beagles. The incidence of positive results between the 2 institutions with different urine collection practices and between males and females was compared. The incidence of positive urinary blood reactions in NHP was comparable between institutions (≤ 14% in males; ≤ 33% in females), while the incidence of positive urinary blood reactions in Beagles was more variable (≤ 77% in males; ≤ 69% in females), and higher in females during the dosing phase. Positive urinary blood results that could potentially be misinterpreted as toxicologically relevant were identified in healthy NHP and Beagles during predose and dosing phases. Different incidences of positive results between the 2 institutions were likely related to collection practices. Strategies to reduce feces and food contamination of collected urine samples should help minimize false-positive urinary blood reactions. © 2015 American Society for Veterinary Clinical Pathology.

Non-invasive evaluation of the haemodynamic effects of high-dose medetomidine in healthy cats for semen collection.

PubMed

Romagnoli, Noemi; Zambelli, Daniele; Cunto, Marco; Lambertini, Carlotta; Ventrella, Domenico; Baron Toaldo, Marco

2016-04-01

This study aimed to assess non-invasively the cardiovascular effects of high-dose medetomidine on healthy male cats undergoing semen collection. Haemodynamic evaluations were assessed on the basis of clinical examination, systolic arterial pressure (SAP) and transthoracic echocardiographic examination. Eight client owned, male domestic shorthair cats were sedated with a bolus of medetomidine intramuscularly (IM; 0.13 mg/kg), and semen collection was performed. A second transthoracic echocardiographic examination and SAP measurement were carried out 15 mins after sedation. At the end of the examination, the patients received a bolus of atipamezole (0.3 mg/kg) IM. The cats were deeply sedated, relaxed and laterally recumbent during the entire procedure. No rhythm abnormalities were observed during the examinations and no significant increase in SAP was recorded. Heart rate dropped from 200 ± 33 to 92 ± 13.1 beats per min after sedation. There was a significant increase in left ventricular dimensions and the left atrial area. The parameters of left ventricular systolic function were reduced, as were systemic and pulmonary cardiac outputs. Peak diastolic wave velocities were significantly reduced, while isovolumic contraction and relaxation time of the left ventricle were prolonged. Aortic valve insufficiency was recorded for all cats, while mitral valve insufficiency was noted in five cats. None of the subjects developed systolic anterior motion of the mitral valve. The protocol allowed us to collect good semen samples in healthy cats. However, high-dose medetomidine induces significant haemodynamic effects on the feline heart, mainly due to a reduced heart rate, an increased cardiac preload and impaired systolic function. The animals recovered from the anaesthesia, after antagonist administration, without showing any clinically relevant consequences. © ISFM and AAFP 2015.

Genotoxicity Assessment of Water Samples from the Sungai Dua River in Pulau Pinang, Malaysia, Using the Allium cepa Test

PubMed Central

Akinboro, Akeem; Mohammed, Kamaruzaman; Rathnasamy, Selestin; Muniandy, Vijay Raj

2011-01-01

Unwanted side effects from a polluted water body may not be limited to the flora and fauna, they may also be transferred to the organisms along the food chain. Four water samples collected immediately and five days after rainfall from two locations inside the polluted Sungai Dua River (SGD) were tested for toxicity using the Allium cepa assay. The samples were analysed for metal content and were both macroscopically and microscopically evaluated. The water samples contained more sodium (Na+) and calcium (Ca2+) than the control tap water, and they showed root growth and mitotic inhibitions (MI) in A. cepa. However, the inhibitory effects were not dose-dependent. No chromosomal aberration (CA) was induced at 100.00% (undiluted water sample). These results suggest the water samples from SGD had weak mitodepressive and genotoxic effects on the A. cepa cells. PMID:24575215

Adaptive control of theophylline therapy: importance of blood sampling times.

PubMed

D'Argenio, D Z; Khakmahd, K

1983-10-01

A two-observation protocol for estimating theophylline clearance during a constant-rate intravenous infusion is used to examine the importance of blood sampling schedules with regard to the information content of resulting concentration data. Guided by a theory for calculating maximally informative sample times, population simulations are used to assess the effect of specific sampling times on the precision of resulting clearance estimates and subsequent predictions of theophylline plasma concentrations. The simulations incorporated noise terms for intersubject variability, dosing errors, sample collection errors, and assay error. Clearance was estimated using Chiou's method, least squares, and a Bayesian estimation procedure. The results of these simulations suggest that clinically significant estimation and prediction errors may result when using the above two-point protocol for estimating theophylline clearance if the time separating the two blood samples is less than one population mean elimination half-life.

Pharmacokinetics and safety of the selective progesterone receptor modulator vilaprisan in healthy postmenopausal women
.

PubMed

Schultze-Mosgau, Marcus-Hillert; Schuett, Barbara; Hafner, Frank-Thorsten; Zollmann, Frank; Kaiser, Andreas; Hoechel, Joachim; Rohde, Beate

2017-01-01

Vilaprisan is a novel, potent, and highly selective progesterone receptor modulator, which might offer a promising option for the treatment of uterine fibroids. In this randomized, placebo-controlled, parallel-group phase 1 study, the pharmacokinetics and safety of vilaprisan were investigated in healthy postmenopausal women. Subjects received a single oral dose of vilaprisan (1, 5, 15, or 30 mg) or placebo and - after a wash-out period - daily doses of the same strength over 28 days. Safety assessments included vital signs, ECGs, clinical laboratory tests, and adverse events. Blood samples for pharmacokinetic (PK) profiles were collected over 14 days after single dose (sd) and multiple dose (md; day 28). Vilaprisan was well tolerated. Mild to moderate adverse events occurred with similar frequency at all dose levels. Following single dose, maximum vilaprisan concentrations were observed 1 - 2 hours post-dose. Terminal half-lives ranged from 31 to 38 hours. Maximum concentrations of vilaprisan (Cmax) and exposure to vilaprisan (AUC) increased roughly dose-proportionally from 3.74 µg/L (1 mg) to 68.6 µg/L (30 mg) and 58.5 µg×h/L to 1,590 µg×h/L, respectively. With daily dosing, accumulation consistent with the long terminal half-life was observed (AUC(0-24)md/AUC(0-24)sd ratios: 1.9 to 3.2). The ratio AUC(0-24)md/AUCsd increased with dose from ~ 1 (1 mg) to 1.5 (30 mg). Exposure to vilaprisan increased roughly dose-proportionally in the dose range studied and accumulated after multiple dosing as expected based on t1/2, indicating linear pharmacokinetics of vilaprisan in the expected therapeutic dose range.
.

EPR Investigation of Gamma-Irradiated Rapana Thomasiana (Gastropoda, Muricidae) Shell

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seletchi, Emilia Dana; Duliu, Octavian G.; Georgescu, Rodica

2007-04-23

The shell of Rapana Thomasiana snail, a carnivorous gastropod collected from the coasts of the Black Sea (Romania) was investigated by using Electron Paramagnetic Resonance (EPR) spectroscopy. The samples in powder form were irradiated with a 60Co gamma-ray source at ambient temperature in the dose range between 1.06 and 11.3 kGy. The measurements showed that the EPR signal intensity enhanced following saturation exponential with the absorbed dose. The estimated EPR parameters: g1 = 1.9976, g2 = 2.0006, g3 = 2.0015, g4 = 2.0030 and g5 = 2.0043 revealed a complex spectrum consisting of CO{sub 2}{sup -}, CO{sub 3}{sup 3-} andmore » CO{sub 3}{sup -} species. A very weak signal at g6 = 2.0057 was associated to SO{sub 2}{sup -} electron center. All EPR signals of gamma-irradiated samples decreased with various rate with the of 100 deg. C isothermal annealing time.« less

Effects of alprazolam on capture stress-related serum cortisol responses in Korean raccoon dogs (Nyctereutes procyonoides koreensis)

PubMed Central

Kim, Sun-A; Lee, So-Yeong; Kimura, Junpei

2011-01-01

The purpose of this study was to evaluate the effect of alprazolam on the stress that Korean raccoon dogs (Nyctereutes procyonoides koreensis) may experience while caught in a live trap by measuring their serum cortisol response. The animals were placed in a live trap with or without being pretreated with oral doses of alprazolam. In both groups, pre-trap blood samples were initially collected without anesthesia before the animals were positioned in the live trap; then post-trap blood samples were collected after the animals had remained in the live trap for 2 h. Changes in cortisol levels were observed using a chemiluminescent immunoassay. The level of cortisol increased in the control group and decreased in the alprazolam-pretreatment group (p < 0.05). In this study, we demonstrated that alprazolam pretreatment reduced stress during live trap capture. PMID:21368571

Effects of alprazolam on capture stress-related serum cortisol responses in Korean raccoon dogs (Nyctereutes procyonoides koreensis).

PubMed

Kim, Sun-A; Lee, So-Yeong; Kimura, Junpei; Shin, Nam-Shik

2011-03-01

The purpose of this study was to evaluate the effect of alprazolam on the stress that Korean raccoon dogs (Nyctereutes procyonoides koreensis) may experience while caught in a live trap by measuring their serum cortisol response. The animals were placed in a live trap with or without being pretreated with oral doses of alprazolam. In both groups, pre-trap blood samples were initially collected without anesthesia before the animals were positioned in the live trap; then post-trap blood samples were collected after the animals had remained in the live trap for 2 h. Changes in cortisol levels were observed using a chemiluminescent immunoassay. The level of cortisol increased in the control group and decreased in the alprazolam-pretreatment group (p < 0.05). In this study, we demonstrated that alprazolam pretreatment reduced stress during live trap capture.

Chemical anesthesia of Northern sea otters (Enhydra lutris): Results of past field studies

USGS Publications Warehouse

Monson, Daniel H.; McCormick, C.; Ballachey, Brenda E.

2001-01-01

Between 1987 and 1997, we chemically immobilized 597 wild sea otters (Enhydra lutris) in Alaska for the collection of biological samples or for surgical instrumentation. One drug-related sea otter fatality occurred during this time. Fentanyl in combination with diazepam produced consistent, smooth inductions with minimal need for supplemental anesthetics during procedures lasting 30-40 min. Antagonism with naltrexone or naloxone was rapid and complete, although we observed narcotic recycling in sea otters treated with naloxone. For surgical procedures, we recommend a fentanyl target dose of 0.33 mg/kg of body mass and diazepam at 0.11 mg/kg. For nonsurgical biological sample collection procedures, we recommend fentanyl at 0.22 mg/kg and diazepam at 0.07 mg/kg. We advise the use of the opioid antagonist naltrexone at a ratio of 2:1 to the total fentanyl administered during processing.

Detection of toxoplasmosis in experimentally infected goats by PCR.

PubMed

Sreekumar, C; Rao, J R; Mishra, A K; Ray, D; Joshi, P; Singh, R K

2004-05-15

PCR was used to diagnose toxoplasmosis in two pairs of Barbari goats infected by oral administration of doses of either 10(4) or 10(5) oocysts of Toxoplasma gondii. Blood and lymph node aspirates were collected from the infected goats and control goat at intervals, and tissues were also collected from a fetus that was aborted and a doe that died during the trial. Both processed and unprocessed samples were used for the PCR, using primers directed to the multicopy B1 gene. None of the blood samples was positive, but a specific signal was obtained from the lymph node aspirates after partial DNA extraction. Direct PCR of the lung, muscle and mesenteric lymph node of the doe and lung tissue of the aborted fetus yielded the target fragment. The simplified PCR protocols, including partial DNA extraction and direct assay of lung tissue, were effective for the diagnosis of toxoplasmosis.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bozkurt, A.; Yorulmaz, N.; Kam, E.

This study aims to assess the environmental radioactivity levels of Harran Plain located within the boundaries of the south-eastern province of Sanliurfa, Turkey. In addition to being at the center of Turkey's major irrigation and development project (South Eastern Anatolian Project, GAP), this 1500 km2 region is famous for its historic attractions. The outdoor gamma dose rates were measured at selected points of the study area using a plastic scintillator. The activity concentrations in the soil samples collected from the study area were determined by gamma spectrometry for the natural radionuclides 238U, 232Th and 40K and the fission product 137Cs.more » The gross alpha and beta activities in the water samples collected from the region was measured using a low-level gamma spectrometry device. A comparison of the measurement results obtained in this study with those of national and world averages are presented in graphical and tabular forms.« less

Concentrations of Radiocesium in Local Foods Collected in Kawauchi Village after the Accident at the Fukushima Dai-ichi Nuclear Power Station

NASA Astrophysics Data System (ADS)

Orita, Makiko; Nakashima, Kanami; Hayashida, Naomi; Endo, Yuuko; Yamashita, Shunichi; Takamura, Noboru

2016-06-01

We evaluated the current concentrations of radiocesium in local foods collected in Kawauchi Village, which is located less than 30 km from Fukushima Daiichi Nuclear Power Station, to minimize public anxiety regarding internal radiation exposure through the consumption of locally produced foods after the 2011 Fukushima accident. The number of samples exceeding the regulatory radiocesium limit (100 Bq/kg for general foods) was five out of 4,080 vegetables (0.1%), 652 of 1,986 (32.8%) among edible wild plants and fungi, and eight of 647 (1.2%) in fruits. Our study confirmed that the internal radiation doses of ingesting these foods are acceptably low compared to the public dose limit, ranging from 24.4 to 42.7 μSv for males and from 21.7 to 43.4 μSv for females, although the potential for radiation exposure still exists. Long-term comprehensive follow-up should take place to clarify trends in radiocesium concentrations in local foods and the committed effective doses found in Fukushima-area residents. By constructing a system that allows residents to access information on radiocesium concentration in foods, a risk communication model between specialists and residents could be developed in the recovery phase after the Fukushima accident.

Concentrations of Radiocesium in Local Foods Collected in Kawauchi Village after the Accident at the Fukushima Dai-ichi Nuclear Power Station

PubMed Central

Orita, Makiko; Nakashima, Kanami; Hayashida, Naomi; Endo, Yuuko; Yamashita, Shunichi; Takamura, Noboru

2016-01-01

We evaluated the current concentrations of radiocesium in local foods collected in Kawauchi Village, which is located less than 30 km from Fukushima Daiichi Nuclear Power Station, to minimize public anxiety regarding internal radiation exposure through the consumption of locally produced foods after the 2011 Fukushima accident. The number of samples exceeding the regulatory radiocesium limit (100 Bq/kg for general foods) was five out of 4,080 vegetables (0.1%), 652 of 1,986 (32.8%) among edible wild plants and fungi, and eight of 647 (1.2%) in fruits. Our study confirmed that the internal radiation doses of ingesting these foods are acceptably low compared to the public dose limit, ranging from 24.4 to 42.7 μSv for males and from 21.7 to 43.4 μSv for females, although the potential for radiation exposure still exists. Long-term comprehensive follow-up should take place to clarify trends in radiocesium concentrations in local foods and the committed effective doses found in Fukushima-area residents. By constructing a system that allows residents to access information on radiocesium concentration in foods, a risk communication model between specialists and residents could be developed in the recovery phase after the Fukushima accident. PMID:27334847

Ascorbic acid interference in the measurement of serum biochemical parameters: in vivo and in vitro studies.

PubMed

Martinello, Flávia; da Silva, Edson Luiz

2006-04-01

To investigate the negative interference of ascorbic acid in serum biochemical tests in relation to the dose of vitamin C intake and to the time of blood collection. Healthy volunteers (n = 18) consumed daily doses of vitamin C (0.25-4.0 g) for 1 week and serum parameters were assayed prior to the experiment and on the eighth day of consumption. Blood samples were collected 4, 12 and 24 h after vitamin C intake. Serum levels of ascorbic acid increased significantly after vitamin C ingestion inhibiting urate and total bilirubin tests 4 and 12 h after intake (P < 0.01). A significant negative interference occurred up to 24 h after consumption of 4 g vitamin C for the urate test. In contrast, ingestion of vitamin C did not show interference in glucose, triglyceride and cholesterol tests. Addition of ascorbic acid to serum inhibited the urate test to a similar extent to that observed after vitamin C intake. However, after ingesting vitamin C, the interference for the bilirubin test was greater than that of the in vitro interference. Commonly taken doses of supplementary vitamin C interfered negatively with the serum urate test based on the Trinder method, and with bilirubin metabolism.

NATURAL RADIOACTIVITY IN SEDIMENTS AND RIVER BANK SOIL OF KALLADA RIVER OF KERALA, SOUTH INDIA AND ASSOCIATED RADIOLOGICAL RISK.

PubMed

Venunathan, N; Kaliprasad, C S; Narayana, Y

2016-10-01

The paper presents the activity concentrations of 232 Th, 226 Ra and 40 K in the sediments and river bank soil samples collected from the Kallada river environs of coastal Kerala. The radiological risks associated with these radionuclides were calculated. The samples were processed following standard procedure, and activity was counted using a high-efficiency 5″ × 5″ NaI (Tl) detector coupled to GSPEC gamma spectroscopy system. The mean values of measured activities of 232 Th, 226 Ra and 40 K in soil samples were found to be 98.1 ± 0.4, 60.3 ± 1.1 and 343.4 ± 1.8 Bq kg -1 , respectively, which results in an average absorbed dose rate of 103 nGy h -1 The corresponding values for sediment samples were found to be 88.0 ± 0.4, 48.6 ± 0.9 and 423.2 ± 2.0 Bq kg -1 , respectively, with a resulting absorbed dose rate of 95 nGy h -1 Radium equivalent activity, annual effective dose equivalent, the external and internal hazard indices were determined and compared with recommended limits. The results of the work provide background data on natural radioactive isotopes, which are useful in the assessment of human radiation exposure from natural environment. The accumulation of information on natural radiation is of great value for radiation protection. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Range of therapeutic metformin concentrations in clinical blood samples and comparison to a forensic case with death due to lactic acidosis.

PubMed

Hess, C; Unger, M; Madea, B; Stratmann, B; Tschoepe, D

2018-05-01

Due to a lack of reference values for blood concentration of metformin in the literature, the forensic evaluation of metformin findings in blood samples is difficult. Interpretations with regard to the assessment of blood concentrations as well as an estimation of the ingested metformin amounts are often vague. Furthermore, post mortem evaluation of death due to lactic acidosis because of metformin is difficult since renal performance or lactate concentrations can not always reliably be determined after death. To describe a concentration range in clinical samples after chronic use of metformin, metformin serum concentrations were determined in serum samples of 95 diabetic patients receiving daily doses of 500mg-3000mg of metformin. The analyses of metformin was carried out using a validated high performance liquid chromatograph coupled to triple quadrupole mass spectrometry (LC-QQQ-MS). On average, metformin concentrations were 1846ng/mL (

Pharmacokinetics and tissue elimination of flunixin in veal calves.

PubMed

Kissell, Lindsey W; Brinson, Patrick D; Gehring, Ronette; Tell, Lisa A; Wetzlich, Scott E; Baynes, Ronald E; Riviere, Jim E; Smith, Geof W

2016-06-01

OBJECTIVE To describe plasma pharmacokinetic parameters and tissue elimination of flunixin in veal calves. ANIMALS 20 unweaned Holstein calves between 3 and 6 weeks old. PROCEDURES Each calf received flunixin (2.2 mg/kg, IV, q 24 h) for 3 days. Blood samples were collected from all calves before the first dose and at predetermined times after the first and last doses. Beginning 24 hours after injection of the last dose, 4 calves were euthanized each day for 5 days. Plasma and tissue samples were analyzed by ultraperformance liquid chromatography. Pharmacokinetic parameters were calculated by compartmental and noncompartmental methods. RESULTS Mean ± SD plasma flunixin elimination half-life, residence time, and clearance were 1.32 ± 0.94 hours, 12.54 ± 10.96 hours, and 64.6 ± 40.7 mL/h/kg, respectively. Mean hepatic and muscle flunixin concentrations decreased to below FDA-established tolerance limits (0.125 and 0.025 μg/mL, respectively) for adult cattle by 3 and 2 days, respectively, after injection of the last dose of flunixin. Detectable flunixin concentrations were present in both the liver and muscle for at least 5 days after injection of the last dose. CONCLUSIONS AND CLINICAL RELEVANCE The labeled slaughter withdrawal interval for flunixin in adult cattle is 4 days. Because administration of flunixin to veal calves represents extralabel drug use, any detectable flunixin concentrations in edible tissues are considered a violation. Results indicated that a slaughter withdrawal interval of several weeks may be necessary to ensure that violative tissue residues of flunixin are not detected in veal calves treated with that drug.

Effects of long-term corticosterone implants on growth and immune function in juvenile alligators, Alligator mississippiensis.

PubMed

Morici, L A; Elsey, R M; Lance, V A

1997-10-01

Sixty juvenile alligators were implanted subcutaneously with slow release pellets of corticosterone or placebo. Alligators were divided into five different groups such that each group received a different dose. A blood sample was taken prior to and 4 days after the implants were in place to measure hormone levels. Additional blood samples were collected at 1 month and 3 months. At 4 days corticosterone levels ranged from 3,400 ng/ml in the group treated with the high dose to 40 ng/ml in the group implanted with the low dose. The extremely high dose caused 40% mortality within 4 weeks. It was evident that the pellets did not release the hormone for the expected 90 days. Circulating levels of corticosterone were back to baseline levels by 3 months. Hormone levels achieved at 4 days were a reliable predictor of subsequent growth. Rate of growth was negatively correlated with plasma corticosterone at 4 days (r2 = 0.711) and at 1 month (r2 = 0.544) posttreatment. Differential white blood cell counts performed after 1 month of treatment showed a clear effect of the implant. Alligators treated with corticosterone had decreased percentages of lymphocytes, eosinophils, and basophils and had a higher heterophil/lymphocyte (H/L) ratio than the placebo group. Furthermore, histological examination of the spleen revealed a significant depletion of lymphoid cells in alligators treated with the highest dose of hormone. The results from this study demonstrate that exogenous corticosterone can mimic the effects of prolonged stress in juvenile alligators.

Effects of Low Doses of Bisphenol A on the Metabolome of Perinatally Exposed CD-1 Mice

PubMed Central

Cabaton, Nicolas J.; Canlet, Cécile; Wadia, Perinaaz R.; Tremblay-Franco, Marie; Gautier, Roselyne; Molina, Jérôme; Sonnenschein, Carlos; Cravedi, Jean-Pierre; Rubin, Beverly S.; Soto, Ana M.

2013-01-01

Background: Bisphenol A (BPA) is a well-known endocrine disruptor used to manufacture polycarbonate plastics and epoxy resins. Exposure of pregnant rodents to low doses of BPA results in pleiotropic effects in their offspring. Objective: We used metabolomics—a method for determining metabolic changes in response to nutritional, pharmacological, or toxic stimuli—to examine metabolic shifts induced in vivo by perinatal exposure to low doses of BPA in CD-1 mice. Methods: Male offspring born to pregnant CD-1 mice that were exposed to vehicle or to 0.025, 0.25, or 25 µg BPA/kg body weight/day, from gestation day 8 through day 16 of lactation, were examined on postnatal day (PND) 2 or PND21. Aqueous extracts of newborns (PND2, whole animal) and of livers, brains, and serum samples from PND21 pups were submitted to 1H nuclear magnetic resonance spectroscopy. Data were analyzed using partial least squares discriminant analysis. Results: Examination of endogenous metabolic fingerprints revealed remarkable discrimination in whole extracts of the four PND2 newborn treatment groups, strongly suggesting changes in the global metabolism. Furthermore, statistical analyses of liver, serum, and brain samples collected on PND21 successfully discriminated among treatment groups. Variations in glucose, pyruvate, some amino acids, and neurotransmitters (γ-aminobutyric acid and glutamate) were identified. Conclusions: Low doses of BPA disrupt global metabolism, including energy metabolism and brain function, in perinatally exposed CD-1 mouse pups. Metabolomics can be used to highlight the effects of low doses of endocrine disruptors by linking perinatal exposure to changes in global metabolism. PMID:23425943

Symptoms, airway responsiveness, and exposure to dust in beech and oak wood workers

PubMed Central

Bohadana, A.; Massin, N.; Wild, P.; Toamain, J.; Engel, S.; Goutet, P.

2000-01-01

OBJECTIVES—To investigate the relation between levels of cumulative exposure to wood dust and respiratory symptoms and the occurrence of bronchial hyperresponsiveness among beech and oak workers.
METHODS—114 Male woodworkers from five furniture factories and 13 male unexposed controls were examined. The unexposed control group was supplemented by 200 male historical controls. Statistical analyses were performed excluding and including the historical controls. Dust concentration was measured by personal sampling methods. Cumulative exposure to dust was calculated for each woodworker by multiplying the duration of the work by the intensity of exposure (years.mg/m3). Bronchial hyperresponsiveness was assessed by the methacholine bronchial challenge test. Subjects were labelled methacholine bronchial challenge positive if forced expiratory volume in 1 second (FEV1) fell by ⩾20%. The linear dose-response slope was calculated as the last dose divided by the total dose given.
RESULTS—443 Dust samples were collected. The median cumulative exposure to dust was 110 years.mg/m3 with lower and upper quartiles at 70 and 160 years.mg/m3 Overall, no declines in FEV1 and forced vital capacity (FVC) were found with increasing exposures. A dose-response relation was found between intensity of exposure on the one hand, and sore throat, increased prevalence of positive methacholine bronchial challenge tests, and steeper dose-response slope, on the other.
CONCLUSION—Exposure to oak and beech dust may lead to the development of sore throat and bronchial hyperresponsiveness.


Keywords: bronchial hyperresponsiveness; wood dust; beech; oak PMID:10810114

An assessment of the radiological scenario around uranium mines in Singhbhum East district, Jharkhand, India.

PubMed

Tripathi, R M; Sahoo, S K; Mohapatra, S; Patra, A C; Lenka, P; Dubey, J S; Jha, V N; Puranik, V D

2012-07-01

The present work deals with the prevalent radiological scenario around uranium-mining sites in the Singhbhum East district of Jharkhand state, India. The concentration of naturally occurring radioactive materials (NORMs) was estimated from 27 soil samples collected around three regions in the study area, namely Bagjata, Turamdih and Jaduguda. The mean activity concentrations of (238)U in Bagjata, Turamdih and Jaduguda regions were found to be 128.6, 95.7 and 49.2 Bq kg(-1), respectively. Similarly for (232)Th and (40)K the activity concentrations were found to be 57.3, 78.4, 68.9 and 530, 425 and 615 Bq kg(-1) in the Bagjata, Turamdih and Jaduguda regions, respectively, which are comparable with other reported values worldwide, except for some high values. The calculated gamma dose rate, obtained from the concentrations of (238)U, (232)Th and (40)K in the samples, was compared with the observed dose rate in air. A good correlation (0.96) was observed between the calculated and the observed gamma dose rate. The annual outdoor effective dose rate was estimated and the values falls between 0.04-0.3, 0.07-0.3 and 0.07-.14 mSv y(-1) with mean values of 0.14, 0.12 and 0.11 mSv y(-1) for the Bagjata, Turamdih and Jaduguda regions, respectively. The terrestrial dose rates in all the three regions are comparable with other reported values worldwide, except for a few high values in Greece, Rio Grande Do Norte (Brazil) and Kalpakkam (India).

Effect of simethicone on lactulose-induced H2 production and gastrointestinal symptoms.

PubMed

Friis, H; Bodé, S; Rumessen, J J; Gudmand-Høyer, E

1991-01-01

The results of studies of the effect of simethicone on abdominal gas-related symptoms have been contradictory. In a randomized, double-blind cross-over study, 10 healthy volunteers were given 30 g lactulose and 600 mg simethicone or placebo. End-expiratory breath samples were collected and analyzed for H2 and gastrointestinal symptoms registered. There were no differences in biochemical parameters or symptom score between simethicone and placebo. In contrast to previous studies, we used a sufficiently large dose of lactulose to produce gastrointestinal symptoms, a higher dose of simethicone and placebo tablets containing the same additives as the simethicone tablets. There was no demonstrable effect of simethicone on symptoms or intestinal gas production caused by carbohydrate malabsorption.

Effect of Terbinafine on Theophylline Pharmacokinetics in Healthy Volunteers

PubMed Central

Trépanier, Eric F.; Nafziger, Anne N.; Amsden, Guy W.

1998-01-01

Twelve healthy volunteers were enrolled in an open-label, randomized, crossover study. Subjects received single doses of theophylline (5 mg/kg) with and without multiple-dose terbinafine, and 11 blood samples were collected over 24 h. The study phases were separated by a 4-week washout period. Theophylline serum data were modeled via noncompartmental analysis. When the control phase (i.e., no terbinafine) was compared to the treatment phase (terbinafine), theophylline exposure (the area under the serum concentration-time curve from time zero to infinity) increased by 16% (P = 0.03), oral clearance decreased by 14% (P = 0.04), and half-life increased by 24% (P = 0.002). No significant changes in other theophylline pharmacokinetic parameters were evident. PMID:9517954

Calcium bioavailability and kinetics of calcium ascorbate and calcium acetate in rats.

PubMed

Cai, Jianwei; Zhang, Qinmin; Wastney, Meryl E; Weaver, Connie M

2004-01-01

The objective was to investigate the bioavailability and mechanism of calcium absorption of calcium ascorbate (ASC) and calcium acetate (AC). A series of studies was performed in adult Sprague-Dawley male rats. In the first study, each group of rats (n = 10/group) was assigned to one of the five test meals labeled with (45)Ca: (i) 25 mg calcium as heated ASC or (ii) unheated ASC, (iii) 25 mg calcium as unheated AC, (iv) 3.6 mg Ca as unheated ASC, or (v) unheated AC. Femur uptake indicated better calcium bioavailability from ASC than AC at both calcium loads. A 5-min heat treatment partly reduced bioavailability of ASC. Kinetic studies were performed to further investigate the mechanism of superior calcium bioavailability from ASC. Two groups of rats (n = 10/group) received oral doses of 25 mg Ca as ASC or AC. Each dose contained 20 micro Ci (45)Ca. Two additional groups of rats (n = 10/group) received an intravenous injection (iv) of 10 micro Ci (45)Ca after receiving an unlabeled oral dose of 25 mg calcium as ASC or AC. Sequential blood samples were collected over 48 hrs. Urine and fecal samples were collected every 12 hrs for 48 hrs and were analyzed for total calcium and (45)Ca content. Total calcium and (45)Ca from serum, urine, and feces were fitted by a compartment kinetics model with saturable and nonsaturable absorption pathways by WinSAAM (Windows-based Simulation Analysis and Modeling). The difference in calcium bioavailability between the two salts was due to differences in saturable rather than passive intestinal absorption and not to endogenous secretion or calcium deposition rate. The higher bioavailability of calcium ascorbate was due to a longer transit time in the small intestine compared with ASC.

Sperm chromatin structure integrity in liquid stored boar semen and its relationships with field fertility.

PubMed

Boe-Hansen, G B; Christensen, P; Vibjerg, D; Nielsen, M B F; Hedeboe, A M

2008-04-01

Extended semen doses from some boars used for AI have been shown to develop high levels of sperm DNA fragmentation during storage. Studies in other animals and humans have shown that if DNA damage is present in a certain percentage of the sperm cells the fertility potential of the semen sample is reduced. The objectives of the present study was to determine the relationship between sperm DNA fragmentation measured using the sperm chromatin structure assay (SCSA) in extended stored semen and field fertility in the boar. Three ejaculates from each of 145 boars were collected. Preparation of the semen doses included dilution with an EDTA extender and storage for up to 72 h post collection. The semen doses were assessed using flow cytometric methods for the percentage of viable sperm (PI/SYBR-14) and sperm DNA fragmentation (SCSA) at 0, 24, 48, and 72 h. A total of 3276 experimental inseminations in Danish breeding herds were conducted. The results showed that for 11 (7.6%) of the boars at least one of the three samples showed a value of DNA fragmentation index (DFI) above 20% within the storage period. Total number of piglets born (litter size) for Hampshire, Landrace and Danish Large White boars was, respectively, 0.5, 0.7 and 0.9 piglets smaller per litter when DFI values were above 2.1% as opposed to below this value. In conclusion the SCSA technique appears to be able to identify individuals with lower fertility with respect to litter size, and could in the future be implemented by the pig industry after a cost-benefit analysis.

Radon Levels Measured at a Touristic Thermal Spa Resort in Montagu (South Africa) and Associated Effective Doses.

PubMed

Botha, R; Newman, R T; Maleka, P P

2016-09-01

Radon activity concentrations (in water and in air) were measured at 13 selected locations at the Avalon Springs thermal spa resort in Montagu (Western Cape, South Africa) to estimate the associated effective dose received by employees and visitors. A RAD-7 detector (DURRIDGE), based on alpha spectrometry, and electret detectors (E-PERM®Radelec) were used for these radon measurements. The primary source of radon was natural thermal waters from the hot spring, which were pumped to various locations on the resort, and consequently a range of radon in-water analyses were performed. Radon in-water activity concentration as a function of time (short term and long term measurements) and spatial distributions (different bathing pools, etc.) were studied. The mean radon in-water activity concentrations were found to be 205 ± 6 Bq L (source), 112 ± 5 Bq L (outdoor pool) and 79 ± 4 Bq L (indoor pool). Radon in-air activity concentrations were found to range between 33 ± 4 Bq m (at the outside bar) to 523 ± 26 Bq m (building enclosing the hot spring's source). The most significant potential radiation exposure identified is that due to inhalation of air rich in radon and its progeny by the resort employees. The annual occupational effective dose due to the inhalation of radon progeny ranges from 0.16 ± 0.01 mSv to 0.40 ± 0.02 mSv. For the water samples collected, the Ra in-water activity concentrations from samples collected were below the lower detection limit (~0.7 Bq L) of the γ-ray detector system used. No significant radiological health risk can be associated with radon and progeny from the hot spring at the Avalon Springs resort.

Pharmacokinetics of ginkgolide B injection in beagle dogs.

PubMed

Song, H; Bu, F; Wei, C; Yuan, G; Liu, X; Wang, B; Guo, R

2012-12-01

A liquid chromatography-mass spectrometry method was developed, validated, and applied to the pharmacokinetic study with doses of 0.68, 2.73 and 10.92 mg/kg of ginkgolide B in beagle dogs after intravenous infusion.An aliquot of blood samples were -collected, separated and quantitatively analyzed by liquid chromatography-mass spectrometry method with mobile phase of acetonitrile-0.02% ammonia solution (33:67, v/v) at a flow rate of 0.8 mL/min on the UltimateTM XB-C18 column (5 μm, 4.6×150 mm).The method was sensitive, accurate and convenient, and can be used for the determination of ginkgolide B in beagle dogs. The Cmax and AUC0-∞ of GB increased with dose escalation, but ANOVA analyses showed that no significant difference was observed in other pharmacokinetic parameters between different doses.An LC/MS method was developed with good sensitivity, reproducibility and specificity. In the pharmacokinetic study of GB in beagle dogs, linear pharmacokinetics was found at doses from 0.62 to 10.92 mg/kg after a single-dose intravenous infusion. Gender differences were not observed in the pharmacokinetics of GB. © Georg Thieme Verlag KG Stuttgart · New York.

Is the Linear No-Threshold Dose-Response Paradigm Still Necessary for the Assessment of Health Effects of Low Dose Radiation?

PubMed Central

2016-01-01

Inevitable human exposure to ionizing radiation from man-made sources has been increased with the proceeding of human civilization and consequently public concerns focus on the possible risk to human health. Moreover, Fukushima nuclear power plant accidents after the 2011 East-Japan earthquake and tsunami has brought the great fear and anxiety for the exposure of radiation at low levels, even much lower levels similar to natural background. Health effects of low dose radiation less than 100 mSv have been debated whether they are beneficial or detrimental because sample sizes were not large enough to allow epidemiological detection of excess effects and there was lack of consistency among the available experimental data. We have reviewed an extensive literature on the low dose radiation effects in both radiation biology and epidemiology, and highlighted some of the controversies therein. This article could provide a reasonable view of utilizing radiation for human life and responding to the public questions about radiation risk. In addition, it suggests the necessity of integrated studies of radiobiology and epidemiology at the national level in order to collect more systematic and profound information about health effects of low dose radiation. PMID:26908982

Radionuclides and radiation doses in heavy mineral sands and other mining operations in Mozambique.

PubMed

Carvalho, Fernando P; Matine, Obete F; Taímo, Suzete; Oliveira, João M; Silva, Lídia; Malta, Margarida

2014-01-01

Sites at the littoral of Mozambique with heavy mineral sands exploited for ilmenite, rutile and zircon and inland mineral deposits exploited for tantalite, uranium and bauxite were surveyed for ambient radiation doses, and samples were collected for the determination of radionuclide concentrations. In heavy mineral sands, (238)U and (232)Th concentrations were 70±2 and 308±9 Bq kg(-1) dry weight (dw), respectively, whereas after separation of minerals, the concentrations in the ilmenite fraction were 2240±64 and 6125±485 Bq kg(-1) (dw), respectively. Tantalite displayed the highest concentrations with 44 738±2474 Bq kg(-1) of (238)U. Radiation exposure of workers in mining facilities is likely to occur at levels above the dose limit for members of the public (1 mSv y(-1)) and therefore radiation doses should be assessed as occupational exposures. Local populations living in these regions in general are not exposed to segregated minerals with high radionuclide concentrations. However, there is intensive artisanal mining and a large number of artisanal miners and their families may be exposed to radiation doses exceeding the dose limit. A radiation protection programme is therefore needed to ensure radiation protection of the public and workers of developing mining projects.

A method for estimating dry forage intake by sheep using polyethylene glycol as a faecal marker measured with NIRS.

PubMed

Hassoun, P; Viudes, G; Autran, P; Bastianelli, D; Bocquier, F

2013-08-01

In experiments based on ruminants' individual dry matter intake (DMI) assessment, several external markers can be used to estimate faecal output when total faeces collection is not possible. However, preparation of the markers to be administered and analytical procedures used for marker content determination are time-consuming thus strongly limiting the number of animals involved in the experiments. In this paper, polyethylene glycol (PEG, molecular weight 6000 da) was tested as a faecal marker. Four trials were conducted on dry, non-lactating ewes kept in digestibility crates that allowed individual measurements. The overall experiment was designed to assess the major factors that could lessen the effectiveness of this method, assuming that the use of grab samples of faeces is sufficient. Trial 1 was designed to test two levels of PEG (20 and 40 g/day) administered in two equal amounts. Trial 2 was designed to test the effect of either a single morning (0800 h) dose (20 g/day) or a twice daily administration (0800 and 1600 h) of the same fractionated dose. Trial 3 was designed to test a 20 g/day dose of PEG administered once daily to ewes fed with hays of different qualities: medium (MH) and low (LH). In trial 4, a lower dose of PEG (10 g/day) was administered once a day to ewes fed with fresh oat-vetch forage. It was demonstrated that PEG could be precisely estimated (average prediction error = 3.47 g/kg) with near-infrared reflectance spectroscopy (NIRS). On the basis of the four trials, it has been proved that PEG administration (20 and 40 g/day) did not significantly affect the DMI of ewes fed dry diets (trials 1, 2 and 3), whereas there was an unexpected increase of DMI for ewes fed exclusively with green feed (trial 4) without DM digestibility modification. Providing PEG as a single dose (0800 h) or split into two equal parts (0800 and 1600 h) did not alter the estimated DMI. Considering the interest of grab sampling, there were clear variations of PEG in faeces with higher concentrations observed at 0800 and 1600 h and lower concentrations at 1400 h. Consequently, with PEG (measured with NIRS) administered once and using the grab sampling procedure (morning collection), it is possible to estimate the DMI of dry feeds with good accuracy. For green feeds, more research is needed as the estimated results are still highly variable.

Local discrepancies in measles vaccination opportunities: results of population-based surveys in Sub-Saharan Africa

PubMed Central

2014-01-01

Background The World Health Organization recommends African children receive two doses of measles containing vaccine (MCV) through routine programs or supplemental immunization activities (SIA). Moreover, children have an additional opportunity to receive MCV through outbreak response immunization (ORI) mass campaigns in certain contexts. Here, we present the results of MCV coverage by dose estimated through surveys conducted after outbreak response in diverse settings in Sub-Saharan Africa. Methods We included 24 household-based surveys conducted in six countries after a non-selective mass vaccination campaign. In the majority (22/24), the survey sample was selected using probability proportional to size cluster-based sampling. Others used Lot Quality Assurance Sampling. Results In total, data were collected on 60,895 children from 2005 to 2011. Routine coverage varied between countries (>95% in Malawi and Kirundo province (Burundi) while <35% in N’Djamena (Chad) in 2005), within a country and over time. SIA coverage was <75% in most settings. ORI coverage ranged from >95% in Malawi to 71.4% [95% CI: 68.9-73.8] in N’Djamena (Chad) in 2005. In five sites, >5% of children remained unvaccinated after several opportunities. Conversely, in Malawi and DRC, over half of the children eligible for the last SIA received a third dose of MCV. Conclusions Control pre-elimination targets were still not reached, contributing to the occurrence of repeated measles outbreak in the Sub-Saharan African countries reported here. Although children receiving a dose of MCV through outbreak response benefit from the intervention, ensuring that programs effectively target hard to reach children remains the cornerstone of measles control. PMID:24559281

[Clinical applications of dosing algorithm in the predication of warfarin maintenance dose].

PubMed

Huang, Sheng-wen; Xiang, Dao-kang; An, Bang-quan; Li, Gui-fang; Huang, Ling; Wu, Hai-li

2011-12-27

To evaluate the feasibility of clinical application for genetic based dosing algorithm in the predication of warfarin maintenance dose in Chinese population. The clinical data were collected and blood samples harvested from a total of 126 patients undergoing heart valve replacement. The genotypes of VKORC1 and CYP2C9 were determined by melting curve analysis after PCR. They were divided randomly into the study and control groups. In the study group, the first three doses of warfarin were prescribed according to the predicted warfarin maintenance dose while warfarin was initiated at 2.5 mg/d in the control group. The warfarin doses were adjusted according to the measured international normalized ratio (INR) values. And all subjects were followed for 50 days after an initiation of warfarin therapy. At the end of a 50-day follow-up period, the proportions of the patients on a stable dose were 82.4% (42/51) and 62.5% (30/48) for the study and control groups respectively. The mean durations of reaching a stable dose of warfarin were (27.5 ± 1.8) and (34.7 ± 1.8) days and the median durations were (24.0 ± 1.7) and (33.0 ± 4.5) days in the study and control groups respectively. Significant differences existed in the durations of reaching a stable dose between the two groups (P = 0.012). Compared with the control group, the hazard ratio (HR) for the duration of reaching a stable dose was 1.786 in the study group (95%CI 1.088 - 2.875, P = 0.026). The predicted dosing algorithm incorporating genetic and non-genetic factors may shorten the duration of achieving efficiently a stable dose of warfarin. And the present study validates the feasibility of its clinical application.

Chemistry, toxicology, and persistence of particulates during and after the 2016 Fort McMurray Wildfires in Alberta, Canada

NASA Astrophysics Data System (ADS)

Kohl, L.; Chan, A. W. H.; Cooke, C. A.; Hustins, S.; Jackson, B.; Wang, S.; Jing, X.; Meng, M.

2017-12-01

The Horse River Fire in May 2016 forced the evacuation of 88,000 Fort McMurray residents, and led to the destruction of over 2000 houses. After re-entry to homes, there is significant concern about exposures to residual fire-derived contaminants in residential houses. Wildfire research, however, provides little guidance on how long ashes and pollutants persist in household dust after major fires. The FACET project studies the chemistry and toxicology of samples of urban and forest ashes and airborne particles collected during the fire, as well as over 500 house dust samples collected in July 2017 (14 months after the fire). Here we present results on the chemical composition of the urban and forest ash samples collected during the fire along with initial results from house dust samples. Wildfire ashes contained elevated concentrations of polycyclic aromatic hydrocarbons (PAH), heavy metals, and dioxin like compounds (DLC). Relative to EPA reference doses, As and Sb constitute the greatest non-carcinogenic health hazard, whereas PAHs Benzo(a)pyrene and Indeno(1,2,3-cd)pyrene are the most relevant carcinogens. Ashes from urban locations contained higher concentrations of heavy metals and DLC than samples collected from forested areas outside of the City of Fort McMurray. Urban samples furthermore had a greater potential for generating oxidative stress than rural samples, as determined by dithiothreitol (DTT) consumption assays. The oxidative potential was positively correlated to Al, Cu, As, and V concentrations. Airborne particulate matter samples from the smoke plume contained consistent concentrations of levoglucosan (99 ± 5 mg g-1), along with other tracers for biomass burning (free lignin monomers, retene). Together these results will serve as proxies for understanding the contribution and the persistence of fire-derived pollutants in house dust in Fort McMurray homes.

Summary of Surface Swipe Sampling for Beryllium on Lead Bricks and Shielding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paik, S Y; Barron, D A

2011-08-03

Approximately 25,000 lbs of lead bricks at Site 300 were assessed by the Site 300 Industrial Hygienis tand Health Physicist for potential contamination of beryllium and radiation for reuse. These lead bricks and shielding had been used as shielding material during explosives tests that included beryllium and depleted uranium. Based on surface swipe sampling that was performed between July 26 and October 11, 2010, specifically for beryllium, the use of a spray encapsulant was found to be an effective means to limit removable surface contamination to levels below the DOE release limit for beryllium, which is 0.2 mcg/100 cm{sup 2}.more » All the surface swipe sampling data for beryllium and a timeline of when the samples were collected (and a brief description) are presented in this report. On December 15, 2010, the lead bricks and shielding were surveyed with an ion chamber and indicated dose rates less than 0.05 mrem per hour on contact. This represents a dose rate consistent with natural background. An additional suevey was performed on February 8, 2011, using a GM survey instrument to estimate total activity on the lead bricks and shielding, confirming safe levels of radioactivity. The vendor is licensed to possess and work with radioactive material.« less

Fast and low-dose computed laminography using compressive sensing based technique

NASA Astrophysics Data System (ADS)

Abbas, Sajid; Park, Miran; Cho, Seungryong

2015-03-01

Computed laminography (CL) is well known for inspecting microstructures in the materials, weldments and soldering defects in high density packed components or multilayer printed circuit boards. The overload problem on x-ray tube and gross failure of the radio-sensitive electronics devices during a scan are among important issues in CL which needs to be addressed. The sparse-view CL can be one of the viable option to overcome such issues. In this work a numerical aluminum welding phantom was simulated to collect sparsely sampled projection data at only 40 views using a conventional CL scanning scheme i.e. oblique scan. A compressive-sensing inspired total-variation (TV) minimization algorithm was utilized to reconstruct the images. It is found that the images reconstructed using sparse view data are visually comparable with the images reconstructed using full scan data set i.e. at 360 views on regular interval. We have quantitatively confirmed that tiny structures such as copper and tungsten slags, and copper flakes in the reconstructed images from sparsely sampled data are comparable with the corresponding structure present in the fully sampled data case. A blurring effect can be seen near the edges of few pores at the bottom of the reconstructed images from sparsely sampled data, despite the overall image quality is reasonable for fast and low-dose NDT.

Calcium kinetics with microgram stable isotope doses and saliva sampling

NASA Technical Reports Server (NTRS)

Smith, S. M.; Wastney, M. E.; Nyquist, L. E.; Shih, C. Y.; Wiesmann, H.; Nillen, J. L.; Lane, H. W.

1996-01-01

Studies of calcium kinetics require administration of tracer doses of calcium and subsequent repeated sampling of biological fluids. This study was designed to develop techniques that would allow estimation of calcium kinetics by using small (micrograms) doses of isotopes instead of the more common large (mg) doses to minimize tracer perturbation of the system and reduce cost, and to explore the use of saliva sampling as an alternative to blood sampling. Subjects received an oral dose (133 micrograms) of 43Ca and an i.v. dose (7.7 micrograms) of 46Ca. Isotopic enrichment in blood, urine, saliva and feces was well above thermal ionization mass spectrometry measurement precision up to 170 h after dosing. Fractional calcium absorptions determined from isotopic ratios in blood, urine and saliva were similar. Compartmental modeling revealed that kinetic parameters determined from serum or saliva data were similar, decreasing the necessity for blood samples. It is concluded from these results that calcium kinetics can be assessed with micrograms doses of stable isotopes, thereby reducing tracer costs and with saliva samples, thereby reducing the amount of blood needed.

A statistical approach to investigating enhancement of polonium-210 in the Eastern Irish Sea arising from discharges from a former phosphate processing plant.

PubMed

Dewar, Alastair; Camplin, William; Barry, Jon; Kennedy, Paul

2014-12-01

Since the cessation of phosphoric acid production (in 1992) and subsequent closure and decommissioning (2004) of the Rhodia Consumer Specialties Limited plant in Whitehaven, the concentration levels of polonium-210 ((210)Po) in local marine materials have declined towards a level more typical of natural background. However, enhanced concentrations of (210)Po and lead-210 ((210)Pb), due to this historic industrial activity (plant discharges and ingrowth of (210)Po from (210)Pb), have been observed in fish and shellfish samples collected from this area over the last 20 years. The results of this monitoring, and assessments of the dose from these radionuclides, to high-rate aquatic food consumers are published annually in the Radioactivity in Food and the Environment (RIFE) report series. The RIFE assessment uses a simple approach to determine whether and by how much activity is enhanced above the normal background. As a potential tool to improve the assessment of enhanced concentrations of (210)Po in routine dose assessments, a formal statistical test, where the null hypothesis is that the Whitehaven area is contaminated with (210)Po, was applied to sample data. This statistical, modified "green", test has been used in assessments of chemicals by the OSPAR commission. It involves comparison of the reported environmental concentrations of (210)Po in a given aquatic species against its corresponding Background Assessment Concentration (BAC), which is based upon environmental samples collected from regions assumed to be not enhanced by industrial sources of (210)Po, over the period for which regular monitoring data are available (1990-2010). Unlike RIFE, these BAC values take account of the variability of the natural background level. As an example, for 2010 data, crab, lobster, mussels and winkles passed the modified "green" test (i.e. the null hypothesis is rejected) and as such are deemed not to be enhanced. Since the cessation of phosphoric acid production in 1992, the modified "green" test pass rate for crustaceans is ∼53% and ∼64% for molluscs. Results of dose calculations are made (i) using the RIFE approach and (ii) with the application of the modified "green" test, where samples passing the modified "green" test are assumed to have background levels and hence zero enhancement of (210)Po. Applying the modified "green" test reduces the dose on average by 44% over the period of this study (1990-2010). Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Methamphetamine blood concentrations in human abusers: application to pharmacokinetic modeling.

PubMed

Melega, William P; Cho, Arthur K; Harvey, Dennis; Laćan, Goran

2007-04-01

Characterization of methamphetamine's (METH) dose-dependent effects on brain neurochemistry may represent a critical component for better understanding the range of resultant behavioral pathologies. Most human studies, however, have assessed only the effects of long term, high dose METH abuse (e.g., greater than 1000 mg/day) in individuals meeting DSM-IV criteria for METH dependence. Yet, for the majority of METH abusers, their patterns of METH exposure that consist of lower doses remain less well-characterized. In this study, blood samples were obtained from 105 individuals detained by police for possible criminal activity and testing positive for stimulants by EMIT assay. METH blood concentrations were subsequently quantified by GC-MS and were predominantly in the low micromolar range (0.1-11.1 microM), with median and mean values of 1.3 microM (0.19 mg/l) and 2 microM (0.3 mg/l), respectively. Pharmacokinetic calculations based on these measured values were used to estimate initial METH body burdens, the median value being 52 mg. Modeling a 52 mg dose for a 4 day-METH maintenance exposure pattern of 4 doses/day at 4 h intervals showed that blood concentrations remained between 1 and 4 microM during this period. Collectively, these data present evidence for a METH exposure pattern distinct from high dose-METH abuse and provide the rationale for assessing potential brain pathology associated with such lower dose-METH exposure.

Quantitative Tracking of Salmonella Enteritidis Transmission Routes Using Barcode-Tagged Isogenic Strains in Chickens: Proof-of-Concept Study

PubMed Central

Yang, Yichao; Ricke, Steven C.; Tellez, Guillermo; Kwon, Young Min

2017-01-01

Salmonella is an important foodborne bacterial pathogen, however, a fundamental understanding on Salmonella transmission routes within a poultry flock remains unclear. In this study, a series of barcode-tagged strains were constructed by inserting six random nucleotides into a functionally neutral region on the chromosome of S. Enteritidis as a tool for quantitative tracking of Salmonella transmission in chickens. Six distinct barcode-tagged strains were used for infection or contamination at either low dose (103 CFUs; three strains) or high dose (105 CFUs; three strains) in three independent experiments (Experiment 1 oral gavage; Experiment 2 contaminated feed; Experiment 3 contaminated water). For all chick experiments, cecal and foot-wash samples were collected from a subset of the chickens at days 7 or/and 14, from which genomic DNA was extracted and used to amplify the barcode regions. After the resulting PCR amplicons were pooled and analyzed by MiSeq sequencing, a total of approximately 1.5 million reads containing the barcode sequences were analyzed to determine the relative frequency of every barcode-tagged strain in each sample. In Experiment 1, the high dose of oral infection was correlated with greater dominance of the strains in the ceca of the respective seeder chickens and also in the contact chickens yet at lesser degrees. When chicks were exposed to contaminated feed (Experiment 2) or water (Experiment 3), there were no clear patterns of the barcode-tagged strains in relation to the dosage, except that the strains introduced at low dose required a longer time to colonize the ceca with contaminated feed. Most foot-wash samples contained only one to three strains for the majority of the samples, suggesting potential existence of an unknown mechanism(s) for strain exclusion. These results demonstrated the proof of concept of using barcode tagged to investigate transmission dynamics of Salmonella in chickens in a quantitative manner. PMID:28261587

Therapeutic Human Hyperimmune Polyclonal Antibodies Against Staphylococcal Enterotoxin B

DTIC Science & Technology

2008-05-01

antibodies and to develop the required SOPs. Both goals have been achieved. Body Phase I Objective 1: Assemble a cohort of monkey sera from IBT’s...30 serum samples (2 ml each) from monkeys vaccinated either with adjuvant, or two different doses of STEBVax were collected. The monkey sera...originated from a concurrent GLP-safety study for STEBVax in which monkeys received four injections of STEBVax at 50 and 200 μg. However upon assay, the

Evolution of imidacloprid resistance in Myzus persicae in Greece and susceptibility data for spirotetramat.

PubMed

Voudouris, Costas Ch; Williamson, Martin S; Skouras, Panagiotis J; Kati, Amalia N; Sahinoglou, Anastasia J; Margaritopoulos, John T

2017-09-01

Myzus persicae s.l. is a major crop pest globally and has evolved resistance to a range of insecticide classes making it increasingly difficult to control in some areas. Here we compare bioassay monitoring data for two important compounds, imidacloprid and spirotetramat, on field samples/clones collected in Greece. A total of 122 aphid samples/clones from central and northern Greece were examined in dose-response bioassays with imidacloprid. There was an overall increase in the level of resistance (resistance factor = 15-40) within tobacco-collected samples from 78.7% in 2007 to 86.7% in 2015. The corresponding frequencies for peach samples were 13.3% and 6.7%. These results were confounded however by the first identification of the R81T target mutation in Greece during 2015 (4.3% as heterozygotes in peach) and 2016 (21.3% as heterozygotes in peach). No resistance to spirotetramat was found at the 60 clones collected in 2015. Resistance to imidacloprid is continuing to increase within Greek M. persicae s.l. populations and the situation is likely to deteriorate further with the recent identification of the R81T resistance mutation. Resistance to spirotetramat has not been found and is therefore a good alternative to neonicotinoids for resistance management. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Analysis of variability of concentrations of valproic acid (VPA) and its selected metabolites in the blood serum of patients treated with VPA and patients hospitalized because of VPA poisoning.

PubMed

Wilimowska, J; Kłys, M; Jawień, W

2014-01-01

To compare the metabolic profile of valproic acid (VPA) in the studied groups of cases through an analysis of variability of concentrations of VPA with its selected metabolites (2-ene-VPA, 4-ene-VPA, 3-keto-VPA). Blood serum samples collected from 27 patients treated with VPA drugs in the Psychiatry Unit and in the Neurology and Cerebral Strokes Unit at the Ludwik Rydygier Provincial Specialist Hospital in Krakow, and blood serum samples collected from 26 patients hospitalized because of suspected acute VPA poisoning at the Toxicology Department, Chair of Toxicology and Environmental Diseases, Jagiellonian University Medical College in Krakow. The analysis of concentrations of VPA and its selected metabolites has shown that the metabolic profile of VPA determined in cases of acute poisoning is different from cases of VPA therapy. One of VPA's metabolic pathways - the process of desaturation - is unchanged in acute poisoning and prevails over the process of β-oxidation. The ingestion of toxic VPA doses results in an increased formation of 4-ene-VPA, proportional to an increase in VPA concentration. Acute VPA poisoning involves the saturation of VPA's metabolic transformations at the stage of β-oxidation. The process of oxidation of 2-ene-VPA to 3-keto-VPA is slowed down after the ingestion of toxic doses.

Specific activity of natural and anthropogenic radionuclides and radiological hazard assessment in surface soil samples collected along the Andaman sea coast in southern region of Thailand

NASA Astrophysics Data System (ADS)

Kessaratikoon, P.; Boonkrongcheep, R.; Benjakul, S.; Udomsomporn, S.

2015-05-01

The specific activities of natural (40K, 226Ra and 232Th) and anthropogenic radionuclides (137Cs) in 314 surface soil samples collected from three provinces (Phuket, Phang-Nga and Krabi) along the Andaman sea coast in southern region of Thailand were studied and evaluated. Experimental results were obtained by using a high-purity germanium (HPGe) detector and gamma spectrometry analysis system. It was found that the mean values of specific activities of 40K, 226Ra, 232Th and 137Cs were 2859.63 ± 209.83, 157.10 ± 8.06, 137.16 ± 7.26 and 4.88 ± 2.34 Bq/kg, respectively. Furthermore, four radiological hazard indices which are absorbed dose rate in air (D), radium equivalent activity (Raeq), external hazard index (Hex) and annual effective dose rate (AEDout) in the area under consideration were also calculated and came out to be 277.11 ± 16.96 nGy/h, 575.16 ± 34.67 Bq/kg, 1.55 ± 0.09 and 0.34 ± 0.02 mSv/y, respectively. The experimental results were also compared and found to be comparable with national and global radioactivity measurements and evaluations. Moreover, the radioactive contour maps of the investigated area were also created and presented in this paper.

Dose-dependent intracellular reactive oxygen and nitrogen species (ROS/RNS) production from particulate matter exposure: comparison to oxidative potential and chemical composition

NASA Astrophysics Data System (ADS)

Tuet, Wing Y.; Fok, Shierly; Verma, Vishal; Tagle Rodriguez, Marlen S.; Grosberg, Anna; Champion, Julie A.; Ng, Nga L.

2016-11-01

Elevated particulate matter (PM) concentrations have been associated with cardiopulmonary risks. In this study, alveolar macrophages and ventricular myocytes were exposed to PM extracts from 104 ambient filters collected in multiple rural and urban sites in the greater Atlanta area. PM-induced reactive oxygen/nitrogen species (ROS/RNS) were measured to investigate the effect of chemical composition and determine whether chemical assays are representative of cellular responses. For summer samples, the area under the ROS/RNS dose-response curve per volume of air (AUCvolume) was significantly correlated with dithiothreitol (DTT) activity, water-soluble organic carbon (WSOC), brown carbon, titanium, and iron, while a relatively flat response was observed for winter samples. EC50 was also correlated with max response for all filters investigated, which suggests that certain PM constituents may be involved in cellular protective pathways. Although few metal correlations were observed, exposure to laboratory-prepared metal solutions induced ROS/RNS production, indicating that a lack of correlation does not necessarily translate to a lack of response. Collectively, these results suggest that complex interactions may occur between PM species. Furthermore, the strong correlation between organic species and ROS/RNS response highlights a need to understand the contribution of organic aerosols, especially photochemically driven secondary organic aerosols (SOA), to PM-induced health effects.

Pertussis toxin-sensitive G-protein mediates the alpha 2-adrenergic receptor inhibition of melatonin release in photoreceptive chick pineal cell cultures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pratt, B.L.; Takahashi, J.S.

The avian pineal gland is a photoreceptive organ that has been shown to contain postjunctional alpha 2-adrenoceptors that inhibit melatonin synthesis and/or release upon receptor activation. Physiological response and (32P)ADP ribosylation experiments were performed to investigate whether pertussis toxin-sensitive guanine nucleotide-binding proteins (G-proteins) were involved in the transduction of the alpha 2-adrenergic signal. For physiological response studies, the effects of pertussis toxin on melatonin release in dissociated cell cultures exposed to norepinephrine were assessed. Pertussis toxin blocked alpha 2-adrenergic receptor-mediated inhibition in a dose-dependent manner. Pertussis toxin-induced blockade appeared to be noncompetitive. One and 10 ng/ml doses of pertussis toxinmore » partially blocked and a 100 ng/ml dose completely blocked norepinephrine-induced inhibition. Pertussis toxin-catalyzed (32P)ADP ribosylation of G-proteins in chick pineal cell membranes was assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Membranes were prepared from cells that had been pretreated with 0, 1, 10, or 100 ng/ml pertussis toxin. In the absence of pertussis toxin pretreatment, two major proteins of 40K and 41K mol wt (Mr) were labeled by (32P)NAD. Pertussis toxin pretreatment of pineal cells abolished (32P) radiolabeling of the 40K Mr G-protein in a dose-dependent manner. The norepinephrine-induced inhibition of both cAMP efflux and melatonin release, as assessed by RIA of medium samples collected before membrane preparation, was also blocked in a dose-dependent manner by pertussis toxin. Collectively, these results suggest that a pertussis toxin-sensitive 40K Mr G-protein labeled by (32P)NAD may be functionally associated with alpha 2-adrenergic signal transduction in chick pineal cells.« less

Risk factors associated with default among retreatment tuberculosis patients on DOTS in Paschim Medinipur district (West Bengal).

PubMed

Sarangi, S S; Dutt, D

2014-07-01

In India in 2010, 14.1% of retreatment of TB patients' treatment outcome was 'default'. Since 2002, in Paschim Midnapur District (West Bengal), it has been around 15-20%. To determine the timing, characteristics and risk factors associated with default among retreatment TB patients on DOTS. It was a case control study, conducted in six TB units (TU) of Paschim Midnapur District, which were selected by simple random sampling. Data was collected from treatment records of TUs/DTC. Data was also collected through interviews of the patients using the same pre-tested semi-structured questionnaire from 87 defaulters and 86 consecutively registered non-defaulters registered in first quarter, 2009 to second quarter, 2010. Median duration of treatment taken before default was 121 days (inter-quartile range of 64-176 days). Median number of doses of treatment taken before default was 36 (inter -quartile range of 26-63 doses). No retrieval action was documented in 57.5% cases. Retrieval was done between 0-7 days of missed doses in 29.9% cases. Multiple logistic regression analysis indicated the following important risk factors for default at 95% confidence interval: male-sex limit: [aOR 3.957 (1.162-13.469)], alcoholic inebriation[ aOR6.076 (2.088-17.675)], distance from DOT centre [aOR 4.066 (1.675-9.872)], number of missed doses during treatment [aOR 1.849 (1.282-2.669)] and no initial home visit [aOR 10.607 (2.286 -49.221)]. In Paschim Midnapur district, default of retreatment TB occurs mostly after a few doses in continuation phase. Initial home visit, patient provider meeting, retrieval action, community-based treatment as per RNTCP guidelines are required to uplift the programme.

Pharmacokinetics of intravenous pan-class I phosphatidylinositol 3-kinase (PI3K) inhibitor [14C]copanlisib (BAY 80-6946) in a mass balance study in healthy male volunteers.

PubMed

Gerisch, Michael; Schwarz, Thomas; Lang, Dieter; Rohde, Gabriele; Reif, Stefanie; Genvresse, Isabelle; Reschke, Susanne; van der Mey, Dorina; Granvil, Camille

2017-09-01

To determine the pharmacokinetics of radiolabeled copanlisib (BAY 80-6946) in healthy male volunteers and to investigate the disposition and biotransformation of copanlisib. A single dose of 12 mg copanlisib containing 2.76 MBq [ 14 C]copanlisib was administered as a 1-h intravenous infusion to 6 volunteers with subsequent sampling up to 34 days. Blood, plasma, urine and feces were collected to monitor total radioactivity, parent compound and metabolites. Copanlisib treatment was well tolerated. Copanlisib was rapidly distributed throughout the body with a volume distribution of 1870 L and an elimination half-life of 52.1-h (range 40.4-67.5-h). Copanlisib was the predominant component in human plasma (84% of total radioactivity AUC) and the morpholinone metabolite M1 was the only circulating metabolite (about 5%). Excretion of drug-derived radioactivity based on all 6 subjects was 86% of the dose within a collection interval of 20-34 days with 64% excreted into feces as major route of elimination and 22% into urine. Unchanged copanlisib was the main component excreted into urine (15% of dose) and feces (30% of dose). Excreted metabolites (41% of dose) of copanlisib resulted from oxidative biotransformation. Copanlisib was eliminated predominantly in the feces compared to urine as well as by hepatic biotransformation, suggesting that the clearance of copanlisib would more likely be affected by hepatic impairment than by renal dysfunction. The dual mode of elimination via unchanged excretion of copanlisib and oxidative metabolism decreases the risk of clinically relevant PK-related drug-drug interactions.

Measuring Aerosols Generated Inside Armoured Vehicles Perforated by Depleted Uranium Ammunition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parkhurst, MaryAnn

2003-01-01

In response to questions raised after the Gulf War about the health significance of exposure to depleted uranium (DU), the U.S. Department of Defense initiated a study designed to provide an improved scientific basis for assessment of possible health effects of soldiers in vehicles struck by these munitions. As part of this study, a series of DU penetrators were fired at an Abrams tank and a Bradley fighting vehicle, and the aerosols generated by vehicle perforation were collected and characterized. A robust sampling system was designed to collect aerosols in this difficult environment and to monitor continuously the sampler flowmore » rates. Interior aerosols collected were analyzed for uranium concentration and particle size distribution as a function of time. They were also analyzed for uranium oxide phases, particle morphology, and dissolution in vitro. These data will provide input for future prospective and retrospective dose and health risk assessments of inhaled or ingested DU aerosols. This paper briefly discusses the target vehicles, firing trajectories, aerosol samplers and instrumentation control systems, and the types of analyses conducted on the samples.« less

A biological survey on the Ottoman Archive papers and determination of the D10 value

NASA Astrophysics Data System (ADS)

Kantoğlu, Ömer; Ergun, Ece; Ozmen, Dilan; Halkman, Hilal B. D.

2018-03-01

The Ottoman Archives have one of the richest archive collections in the world. However, not all the archived documents are well preserved and some undergo biodeterioration. Therefore, a rapid and promising treatment method is necessary to preserve the collection for following generations as heritage. Radiation presents as an alternative for the treatment of archival materials for this purpose. In this study, we conducted a survey to determine the contamination species and the D10 values of the samples obtained from the shelves of the Ottoman Archives. The samples also included several insect pests collected at using a pheromone trap placed in the archive storage room. With the exception of few localized problems, no active pest presence was observed. The D10 values of mold contamination and reference mold (A. niger) were found to be 1.0 and 0.68 kGy, respectively. Based on these results, it can be concluded that an absorbed dose of 6 kGy is required to remove the contamination from the materials stored in the Ottoman Archives.

Collective dose estimates by the marine food pathway from liquid radioactive wastes dumped in the Sea of Japan.

PubMed

Togawa, O; Povinec, P P; Pettersson, H B

1999-09-30

IAEA-MEL has been engaged in an assessment programme related to radioactive waste dumping by the former USSR and other countries in the western North Pacific Ocean and its marginal seas. This paper focuses on the Sea of Japan and on estimation of collective doses from liquid radioactive wastes. The results from the Japanese-Korean-Russian joint expeditions are summarized, and collective doses for the Japanese population by the marine food pathway are estimated from liquid radioactive wastes dumped in the Sea of Japan and compared with those from global fallout and natural radionuclides. The collective effective dose equivalents by the annual intake of marine products caught in each year show a maximum a few years after the disposals. The total dose from all radionuclides reaches a maximum of 0.8 man Sv in 1990. Approximately 90% of the dose derives from 137Cs, most of which is due to consumption of fish. The total dose from liquid radioactive wastes is approximately 5% of that from global fallout, the contribution of which is below 0.1% of that of natural 210Po.

Dosimetric property of mineral extracted from calamari and exposed to gamma rays

NASA Astrophysics Data System (ADS)

Cruz-Zaragoza, E.; Roman-Lopez, J.; Cruz, L. Pérez; Furetta, C.; Chiaravalle, E.; Mangiacotti, M.; Marchesani, G.

2013-07-01

Dosimetric property of polymineral fraction, quartz mainly, obtained from calamari was investigated. The commercial calamari samples from China and Sud Africa were collected in the markets of Italy. All polymineral debris were extracted and isolated from the whole body of calamari. The surface of the polymineral samples was analyzed by using the Scanning Electron Microscopy (SEM) and their chemical composition was determined using Energy Dispersive Spectroscopy (EDS). The polymineral was exposed to gamma rays (60Co) at different doses (0.5-80 Gy) to determine dosimetric property. Thermoluminescent (TL) glow curves showed two peaks centered at around 98-100 °C and 128-138 °C temperature range. The glow curves have been analyzed by using a deconvolution program. A linear dose response between 0.5 to 20 Gy was observed. The TL response of the samples as a function of the time storage, fading, presented a reduction of about 36-40 % at the end of 24 h. The reproducibility of the TL response after ten cycles of irradiation-readout showed an acceptable standard deviation in dosimetry. The polimineral fraction obtained from calamari shows an interesting dosimetric property and it may be useful for dosimetry in gamma radiation field.

Comparison of a bioassay and a liquid chromatography-fluorescence-mass spectrometry(n) method for the detection of incurred enrofloxacin residues in chicken tissues.

PubMed

Schneider, M J; Donoghue, D J

2004-05-01

Regulatory monitoring for most antibiotic residues in edible poultry tissues is often accomplished with accurate, although expensive and technically demanding, chemical analytical techniques. The purpose of this study is to determine if a simple, inexpensive bioassay could detect fluoroquinolone (FQ) residues in chicken muscle above the FDA established tolerance (300 ppb) comparable to a liquid chromatography-fluorescencemass spectrometry(n) method. To produce incurred enrofloxacin (ENRO) tissues (where ENRO is incorporated into complex tissue matrices) for the method comparison, 40-d-old broilers (mixed sex) were orally dosed through drinking water for 3 d at the FDA-approved dose of ENRO (50 ppm). At the end of each day of the 3-d dosing period and for 3 d postdosing, birds were sacrificed and breast and thigh muscle collected and analyzed. Both methods were able to detect ENRO at and below the tolerance level in the muscle, with limits of detection of 26 ppb (bioassay), 0.1 ppb for ENRO, and 0.5 ppb for the ENRO metabolite, ciprofloxacin (liquid chromatography-fluorescence-mass spectrometry(n)). All samples that had violative levels of antibiotic were detected by the bioassay. These results support the use of this bioassay as a screening method for examining large numbers of samples for regulatory monitoring. Positive samples should then be examined by a more extensive method, such as liquid chromatography-fluorescence-mass spectrometry(n), to provide confirmation of the analyte.

Biological Monitoring of Human Exposure to Neonicotinoids Using Urine Samples, and Neonicotinoid Excretion Kinetics

PubMed Central

Harada, Kouji H.; Tanaka, Keiko; Sakamoto, Hiroko; Imanaka, Mie; Niisoe, Tamon; Hitomi, Toshiaki; Kobayashi, Hatasu; Okuda, Hiroko; Inoue, Sumiko; Kusakawa, Koichi; Oshima, Masayo; Watanabe, Kiyohiko; Yasojima, Makoto; Takasuga, Takumi; Koizumi, Akio

2016-01-01

Background Neonicotinoids, which are novel pesticides, have entered into usage around the world because they are selectively toxic to arthropods and relatively non-toxic to vertebrates. It has been suggested that several neonicotinoids cause neurodevelopmental toxicity in mammals. The aim was to establish the relationship between oral intake and urinary excretion of neonicotinoids by humans to facilitate biological monitoring, and to estimate dietary neonicotinoid intakes by Japanese adults. Methodology/Principal Findings Deuterium-labeled neonicotinoid (acetamiprid, clothianidin, dinotefuran, and imidacloprid) microdoses were orally ingested by nine healthy adults, and 24 h pooled urine samples were collected for 4 consecutive days after dosing. The excretion kinetics were modeled using one- and two-compartment models, then validated in a non-deuterium-labeled neonicotinoid microdose study involving 12 healthy adults. Increased urinary concentrations of labeled neonicotinoids were observed after dosing. Clothianidin was recovered unchanged within 3 days, and most dinotefuran was recovered unchanged within 1 day. Around 10% of the imidacloprid dose was excreted unchanged. Most of the acetamiprid was metabolized to desmethyl-acetamiprid. Spot urine samples from 373 Japanese adults were analyzed for neonicotinoids, and daily intakes were estimated. The estimated average daily intake of these neonicotinoids was 0.53–3.66 μg/day. The highest intake of any of the neonicotinoids in the study population was 64.5 μg/day for dinotefuran, and this was <1% of the acceptable daily intake. PMID:26731104

Prevalence of intestinal protozoa infection among school-aged children on Pemba Island, Tanzania, and effect of single-dose albendazole, nitazoxanide and albendazole-nitazoxanide.

PubMed

Speich, Benjamin; Marti, Hanspeter; Ame, Shaali M; Ali, Said M; Bogoch, Isaac I; Utzinger, Jürg; Albonico, Marco; Keiser, Jennifer

2013-01-04

Pathogenic intestinal protozoa infections are common in school-aged children in the developing world and they are frequently associated with malabsorption syndromes and gastrointestinal morbidity. Since diagnosis of these parasites is difficult, prevalence data on intestinal protozoa is scarce. We collected two stool samples from school-aged children on Pemba Island, Tanzania, as part of a randomized controlled trial before and 3 weeks after treatment with (i) single-dose albendazole (400 mg); (ii) single-dose nitazoxanide (1,000 mg); (iii) nitazoxanide-albendazole combination (1,000 mg-400 mg), with each drug given separately on two consecutive days; and (iv) placebo. Formalin-fixed stool samples were examined for the presence of intestinal protozoa using an ether-concentration method to determine the prevalence and estimate cure rates (CRs). Almost half (48.7%) of the children were diagnosed with at least one of the (potentially) pathogenic protozoa Giardia intestinalis, Entamoeba histolytica/E. dispar and Blastocystis hominis. Observed CRs were high for all treatment arms, including placebo. Nitazoxanide showed a significant effect compared to placebo against the non-pathogenic protozoon Entamoeba coli. Intestinal protozoa infections might be of substantial health relevance even in settings where they are not considered as a health problem. Examination of a single stool sample with the ether-concentration method lacks sensitivity for the diagnosis of intestinal protozoa, and hence, care is indicated when interpreting prevalence estimates and treatment effects.

Prevalence of intestinal protozoa infection among school-aged children on Pemba Island, Tanzania, and effect of single-dose albendazole, nitazoxanide and albendazole-nitazoxanide

PubMed Central

2013-01-01

Background Pathogenic intestinal protozoa infections are common in school-aged children in the developing world and they are frequently associated with malabsorption syndromes and gastrointestinal morbidity. Since diagnosis of these parasites is difficult, prevalence data on intestinal protozoa is scarce. Methods We collected two stool samples from school-aged children on Pemba Island, Tanzania, as part of a randomized controlled trial before and 3 weeks after treatment with (i) single-dose albendazole (400 mg); (ii) single-dose nitazoxanide (1,000 mg); (iii) nitazoxanide-albendazole combination (1,000 mg–400 mg), with each drug given separately on two consecutive days; and (iv) placebo. Formalin-fixed stool samples were examined for the presence of intestinal protozoa using an ether-concentration method to determine the prevalence and estimate cure rates (CRs). Results Almost half (48.7%) of the children were diagnosed with at least one of the (potentially) pathogenic protozoa Giardia intestinalis, Entamoeba histolytica/E. dispar and Blastocystis hominis. Observed CRs were high for all treatment arms, including placebo. Nitazoxanide showed a significant effect compared to placebo against the non-pathogenic protozoon Entamoeba coli. Conclusions Intestinal protozoa infections might be of substantial health relevance even in settings where they are not considered as a health problem. Examination of a single stool sample with the ether-concentration method lacks sensitivity for the diagnosis of intestinal protozoa, and hence, care is indicated when interpreting prevalence estimates and treatment effects. PMID:23289920

Pharmacokinetics, dose proportionality and permeability of S002-333 and its enantiomers, a potent antithrombotic agent, in rabbits.

PubMed

Saxena, Amrita; Valicherla, Guru R; Joshi, Pankaj; Saxena, Rohit; Cheruvu, Srikanth H; Bhunia, Shome S; Jain, Girish K; Siddiqui, Hefazat H; Saxena, Anil K; Gayen, Jiaur R

2015-01-01

1. S002-333 [(2-(4'-methoxy-benzenesulfonyl)-2,3,4,9-tetrahydro-1H-pyrido (3,4-b) indole-3-carboxylic acid amide)] is a novel and potent antithrombotic active agent. The present work investigates the pharmacokinetics, bioavailability, dose proportionality and permeability of the racemate, S002-333 in male New Zealand White (NZW) rabbits. 2. Rabbits were administered single intravenous (i.v.) (2 mg/kg) and three oral doses of 10, 20 and 40 mg/kg of S002-333, respectively, at different occasions to evaluate dose proportionality. Serial blood samples were collected and analyzed by a liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Since S002-333 is a racemate consisting of S004-1032 (R) and S007-1558 (S), same samples were analyzed using a chiralcel column so as to evaluate the respective enantiomers. 3. The peak plasma concentration, after oral administration, occurred at ∼10 h post-dose. The clearance (CL) and volume of distribution (Vd) after i.v. dose were found to be 3.05 ± 0.09 l/h/kg and 6.73 ± 1.16 l/kg, respectively. The absolute oral bioavailability of S002-333 was 16.32%, whereas it was 6.62 and 5.90% for R- and S-enantiomers, respectively. The absolute bioavailability of 10, 20 and 40 mg/kg doses were found to be 27.91, 14.39 and 16.91%, respectively. The PAMPA (parallel artificial membrane permeability assay) assay shows that S002-333 has a low-passive permeability at gastric and intestinal environment. 4. In conclusion, S002-333 has low-passive permeability, low CL and large Vd. The R-enantiomer has a "slightly" greater bioavailability than the S-enantiomer.

Initial Dosing and Taper Complexity of Methadone and Morphine for Treatment of Neonatal Abstinence Syndrome

PubMed Central

Ibach, Bethany W.; Johnson, Peter N.; Ernst, Kimberly D.; Harrison, Donald; Miller, Jamie L.

2016-01-01

Background: Methadone and morphine are commonly used to treat neonatal abstinence syndrome (NAS). Limited data exist to describe the most appropriate initial doses and taper regimens of these agents. Objectives: Describe the median initial dose and frequency of methadone and morphine for NAS. Compare dose adjustments, time to symptom relief, and taper complexity between groups. Methods: Retrospective study of neonates receiving enteral methadone or morphine for NAS over a 4-year period. Data collection included medication regimen, abstinence scores based on the Modified Finnegan Neonatal Abstinence Scoring Tool, and adverse events. Planned home taper complexity was assessed using the Medication Taper Complexity Score–Revised (MTCS-R). The primary outcome was initial opioid dose. Secondary outcomes included number of dose adjustments, time to symptom relief, and MTCS-R score. Results: Fifty neonates were initially treated for NAS with methadone (n = 36) or morphine (n = 14). The median initial dose was 0.09 mg/kg (range = 0.03-0.2) for methadone and 0.04 mg/kg (range = 0.03-0.4) for morphine. The most common initial dosing interval was q8h for methadone versus q3h for morphine. Number of dose adjustments and time to symptom relief were similar between groups. Median MTCS-R scores were similar between groups. There was no difference in adverse events between groups. Limitations included small sample size, preference toward methadone use, and variability of initial opioid dosing and titration. Conclusions: There was significant variability in initial doses of both agents. Neonates receiving methadone required less frequent dosing than morphine, which may result in easier administration and may allow for safer outpatient administration.

Management of Venetoclax-Posaconazole Interaction in Acute Myeloid Leukemia Patients: Evaluation of Dose Adjustments.

PubMed

Agarwal, Suresh K; DiNardo, Courtney D; Potluri, Jalaja; Dunbar, Martin; Kantarjian, Hagop M; Humerickhouse, Rod A; Wong, Shekman L; Menon, Rajeev M; Konopleva, Marina Y; Salem, Ahmed Hamed

2017-02-01

The effect of posaconazole, a strong cytochrome P450 3A (CYP3A) inhibitor and commonly used antifungal agent, on the pharmacokinetic properties of venetoclax, a CYP3A substrate, was evaluated in patients with acute myeloid leukemia to determine the dose adjustments needed to manage this potential interaction. Twelve patients received 20- to 200-mg ramp-up treatment with oral venetoclax and 20 mg/m 2 of intravenous decitabine on days 1 through 5, followed by 400 mg of venetoclax alone on days 6 through 20. On days 21 through 28, patients received 300 mg of posaconazole plus reduced doses of venetoclax (50 or 100 mg) to account for expected increases in venetoclax plasma concentrations. Blood samples were collected before dosing and up to 24 hours after the venetoclax dose on days 20 and 28. Compared with a venetoclax dose of 400 mg when administered alone (day 20), coadministration of venetoclax at a 50-mg dose with multiple doses of posaconazole increased mean venetoclax C max and AUC 0-24 by 53% and 76%, respectively, whereas coadministration of venetoclax at a 100-mg dose with posaconazole increased mean venetoclax C max and AUC 0-24 by 93% and 155%, respectively. When adjusted for different doses and nonlinearity, posaconazole was estimated to increase venetoclax C max and AUC 0-24 by 7.1- and 8.8-fold, respectively. Both the 50- and 100-mg venetoclax doses administered with posaconazole were well tolerated. The results are consistent with inhibition of CYP3A-mediated metabolism of venetoclax. Posaconazole can be used for antifungal prophylaxis in patients with acute myeloid leukemia receiving venetoclax after reducing the venetoclax dose by at least 75%. ClinicalTrials.gov identifier: NCT02203773. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Temporal changes in physiology and haematology in response to high- and micro-doses of recombinant human erythropoietin.

PubMed

Clark, Brad; Woolford, Sarah M; Eastwood, Annette; Sharpe, Ken; Barnes, Peter G; Gore, Christopher J

2017-10-01

There is evidence to suggest athletes have adopted recombinant human erythropoietin (rHuEPO) dosing regimens that diminish the likelihood of being caught by direct detection techniques. However, the temporal response in physiology, performance, and Athlete Biological Passport (ABP) parameters to such regimens is not clearly understood. Participants were assigned to a high-dose only group (HIGH, n = 8, six rHuEPO doses of 250 IU/kg over two weeks), a combined high micro-dose group (COMB, n = 8, high-dose plus nine rHuEPO micro-doses over a further three weeks), or one of two placebo control groups who received saline in the same pattern as the HIGH (HIGH-PLACEBO, n = 4) or COMB (COMB-PLACEBO, n = 4) groups. Temporal changes in physiology and performance were tracked by graded exercise test (GXT) and haemoglobin mass assessment at baseline, after high dose, after micro-dose (COMB and COMB-PLACEBO only) and after a four-week washout. Venous blood samples were collected throughout the baseline, rHuEPO administration, and washout periods to determine the haematological and ABP response to each dosing regimen. Physiological adaptations induced by a two-week rHuEPO high-dose were maintained by rHuEPO micro-dosing for at least three weeks. However, all participants administered rHuEPO registered at least one suspicious ABP value during the administration or washout periods. These results indicate there is sufficient sensitivity in the ABP to detect use of high rHuEPO doping regimens in athletic populations and they provide important empirical examples for use by anti-doping experts. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Pharmacokinetic Profile and Tolerability of Liposomal Bupivacaine Following a Repeated Dose via Local Subcutaneous Infiltration in Healthy Volunteers.

PubMed

Rice, David; Heil, Justin W; Biernat, Lukasz

2017-03-01

Liposomal bupivacaine is indicated for administration into the surgical site to produce post-surgical analgesia. The objectives of this study were to characterize the pharmacokinetic and safety profiles of liposomal bupivacaine following a repeated dose in healthy volunteers. Healthy adults were assigned to receive liposomal bupivacaine via subcutaneous infiltration in a single 266 mg dose (cohort 1) or in two 266 mg doses, with the second dose given immediately, 24, 48, or 72 h after the first dose (cohorts 2-5). Pharmacokinetic parameters were estimated from blood samples collected up to day 14. Subjects were monitored for adverse events and assessed for neurologic function, cardiac function, and infiltration area abnormalities. Twelve subjects were assigned to each cohort. The mean ± standard deviation maximum observed plasma concentration (C max ) of bupivacaine after a single dose was 129 ± 47 ng/mL. The mean C max after the second dose was higher, but always less than double the C max for cohort 1. The highest individual C max (589 ng/mL) was observed in a subject who received the second dose 24 h after the first dose (cohort 4), but was well below the reported thresholds for neurotoxicity and cardiac toxicity (2000 and 4000 ng/mL, respectively). A single and repeated dose were well-tolerated, and there were no clinically meaningful findings regarding neurologic examinations and electrocardiography. The mean C max following a repeated dose of liposomal bupivacaine remained well below accepted values for central nervous system and cardiac toxicity. Liposomal bupivacaine was well-tolerated and revealed no clinically important safety signals. CLINICALTRIALS. NCT02210247.

Pharmacokinetics of Imipenem/Cilastatin Burn Intensive Care Unit Patients Undergoing High-Dose Continuous Venovenous Hemofiltration.

PubMed

Boucher, Bradley A; Hudson, Joanna Q; Hill, David M; Swanson, Joseph M; Wood, G Christopher; Laizure, S Casey; Arnold-Ross, Angela; Hu, Zhe-Yi; Hickerson, William L

2016-12-01

High-dose continuous venovenous hemofiltration (CVVH) is a continuous renal replacement therapy (CRRT) used frequently in patients with burns. However, antibiotic dosing is based on inference from studies assessing substantially different methods of CRRT. To address this knowledge gap for imipenem/cilastatin (I/C), we evaluated the systemic and extracorporeal clearances (CLs) of I/C in patients with burns undergoing high-dose CVVH. Prospective clinical pharmacokinetic study. Ten adult patients with burns receiving I/C for a documented infection and requiring high-dose CVVH were studied. Blood and effluent samples for analysis of I/C concentrations were collected for up to 6 hours after the I/C infusion for calculation of I/C total CL (CL T otal ), CL by CVVH (CL HF ), half-life during CVVH, volume of distribution at steady state (Vd ss ), and the percentage of drug eliminated by CVVH. In this patient sample, the mean age was 50 ± 17 years, total body surface area burns was 23 ± 27%, and 80% were male. Nine patients were treated with high-dose CVVH for acute kidney injury and one patient for sepsis. The mean delivered CVVH dose was 52 ± 14 ml/kg/hour (range 32-74 ml/kg/hr). The imipenem CL HF was 3.27 ± 0.48 L/hour, which accounted for 23 ± 4% of the CL T otal (14.74 ± 4.75 L/hr). Cilastatin CL HF was 1.98 ± 0.56 L/hour, which accounted for 45 ± 19% of the CL T otal (5.16 + 2.44 L/hr). The imipenem and cilastatin half-lives were 1.77 ± 0.38 hours and 4.21 ± 2.31 hours, respectively. Imipenem and cilastatin Vd ss were 35.1 ± 10.3 and 32.8 ± 13.8 L, respectively. Efficient removal of I/C by high-dose CVVH, a high overall clearance, and a high volume of distribution in burn intensive care unit patients undergoing this CRRT method warrant aggressive dosing to treat serious infections effectively depending on the infection site and/or pathogen. © 2016 Pharmacotherapy Publications, Inc.

Comparison of the Sensitivity of Laboratory Diagnostic Methods from a Well-Characterized Outbreak of Mumps in New York City in 2009

PubMed Central

Rosen, Jennifer B.; Doll, Margaret K.; McNall, Rebecca J.; McGrew, Marcia; Williams, Nobia; Lopareva, Elena N.; Barskey, Albert E.; Punsalang, Amado; Rota, Paul A.; Oleszko, William R.; Hickman, Carole J.; Zimmerman, Christopher M.; Bellini, William J.

2013-01-01

A mumps outbreak in upstate New York in 2009 at a summer camp for Orthodox Jewish boys spread into Orthodox Jewish communities in the Northeast, including New York City. The availability of epidemiologic information, including vaccination records and parotitis onset dates, allowed an enhanced analysis of laboratory methods for mumps testing. Serum and buccal swab samples were collected from 296 confirmed cases with onsets from September through December 2009. All samples were tested using the Centers for Disease Control and Prevention (CDC) capture IgM enzyme immunoassay (EIA) and a real-time reverse transcription-PCR (rRT-PCR) that targets the short hydrophobic gene. A subset of the samples (n = 205) was used to evaluate 3 commercial mumps IgM assays and to assess the sensitivity of using an alternative target gene (nucleoprotein) in the rRT-PCR protocol. Among 115 cases of mumps with 2 documented doses of measles, mumps, and rubella (MMR) vaccine, the CDC capture IgM EIA detected IgM in 51% of serum samples compared to 9% to 24% using three commercial IgM assays. The rRT-PCR that targeted the nucleoprotein gene increased RNA detection by 14% compared to that obtained with the original protocol. The ability to detect IgM improved when serum was collected 3 days or more after symptom onset, whereas sensitivity of RNA detection by rRT-PCR declined when buccal swabs were collected later than 2 days after onset. Selection of testing methods and timing of sample collection are important factors in the ability to confirm infection among vaccinated persons. These results reinforce the need to use virus detection assays in addition to serologic tests. PMID:23324519

²²⁶Ra, ²³²Th and ⁴⁰K radionuclides enhancement rate and dose assessment for residues of lignite-fired thermal power plants in Turkey.

PubMed

Parmaksiz, A; Arikan, P; Vural, M; Yeltepe, E; Tükenmez, I

2011-11-01

A total of 77 coal, slag and fly ash samples collected from six thermal power plants were measured by gamma-ray spectrometry. The average (226)Ra activity concentrations in coal, slag and fly ash were measured as 199.8±16.7, 380.3±21.8 and 431.5±29.0 Bq kg(-1), respectively. The average (232)Th activity concentrations in coal, slag and fly ash were measured as 32.0±2.4, 74.0±9.0 and 87.3±9.8 Bq kg(-1), respectively. The average (40)K activity concentrations in coal, slag and fly ash were found to be 152.8±12.1, 401.3±25.0 and 439.0±30.2 Bq kg(-1), respectively. The radium equivalent activities of samples varied from 147.6±8.5 to 1077.4±53.3 Bq kg(-1). The gamma and alpha index of one thermal power plant's fly ash were calculated to be 3.5 and 5 times higher than that of the reference values. The gamma absorbed dose rates were found to be higher than that of the average Earth's crust. The annual effective dose of residues measured in four thermal power plants were calculated higher than that of the permitted dose rate for public, i.e. 1 mSv y(-1).

Caffeine Stimulation of Cortisol Secretion Across the Waking Hours in Relation to Caffeine Intake Levels

PubMed Central

Lovallo, William R.; Whitsett, Thomas L.; al'Absi, Mustafa; Sung, Bong Hee; Vincent, Andrea S.; Wilson, Michael F.

2008-01-01

Objective Caffeine increases cortisol secretion in people at rest or undergoing mental stress. It is not known whether tolerance develops in this response with daily intake of caffeine in the diet. We therefore tested the cortisol response to caffeine challenge after controlled levels of caffeine intake. Methods Men (N = 48) and women (N = 48) completed a double-blind, crossover trial conducted over 4 weeks. On each week, subjects abstained for 5 days from dietary caffeine and instead took capsules totaling 0 mg, 300 mg, and 600 mg/day in 3 divided doses. On day 6, they took capsules with either 0 mg or 250 mg at 9:00 AM, 1:00 PM, and 6:00 PM, and cortisol was sampled from saliva collected at 8 times from 7:30 AM to 7:00 PM. Results After 5 days of caffeine abstinence, caffeine challenge doses caused a robust increase in cortisol across the test day (p < .0001). In contrast, 5 days of caffeine intake at 300 mg/day and 600 mg/day abolished the cortisol response to the initial 9:00 AM caffeine dose, although cortisol levels were again elevated between 1:00 PM and 7:00 PM (p = .02 to .002) after the second caffeine dose taken at 1:00 PM. Cortisol levels declined to control levels during the evening sampling period. Conclusion Cortisol responses to caffeine are reduced, but not eliminated, in healthy young men and women who consume caffeine on a daily basis. PMID:16204431

The effect of sibutramine, a serotonin-norepinephrine reuptake inhibitor, on platelets and fibrin networks of male Sprague-Dawley rats: a descriptive study.

PubMed

van der Schoor, Ciska; Oberholzer, Hester Magdalena; Bester, Megan Jean; van Rooy, Mia-Jeanne

2014-12-01

Sibutramine is used in the treatment of obesity due to its ability to influence feelings of hunger and satiety by inhibiting the re-uptake of serotonin and noradrenalin in the central nervous system (CNS). Sibutramine use has been associated with numerous adverse events in particular cardiovascular complications possibly due to the formation of thrombi. This ultrastructural descriptive study investigated the effect of sibutramine on blood coagulation, specifically the effect on morphology of platelets and fibrin networks using scanning electron microscopy. Male Sprague-Dawley rats treated with either a recommended therapeutic dose [low dosage 1.32 mg/kg] or a toxicological higher dose [high dosage 13.2 mg/kg] of sibutramine for 28 days were used and compared to control animals. Blood samples were collected and plasma smears were prepared for platelet evaluation. Following the addition of thrombin to the plasma samples, the morphology of the fibrin clots was evaluated. Platelet evaluation by scanning electron microscopy revealed morphology typical of a prothrombotic state with a characteristic excessive platelet activation in both low-dose (LD) and high-dose (HD) rats. The fibrin clots of sibutramine-treated rats, LD and HD revealed fused thick fibers with thin fibers forming a net-like structure over the thick fibers which differ considerably from the organized structure of the control animals. It can be concluded that sibutramine alters the ultrastructure of platelets and fibrin networks creating a prothrombotic state.

[Effect of depsides salts from Salvia miltiorrhiza on human hepatoma cell line SMMC-7721 subcutaneous xenografts in nude mice].

PubMed

Li, Xiangping; Song, Zhouye; Zhong, Haiying; Gong, Zhicheng; Yin, Tao; Zhang, Zanling; Zhou, Boting

2015-02-01

To exlpore the eff ect of depsides salts from Salvia miltiorrhiza on human hepatoma cell line SMMC-7721 xenograft tumors and the possible mechanisms. A total of 36 nude mice were divided into 6 groups: A model group, a negative control group, a positive control group, and 3 treatment groups at low, middle or high dose (n=6). The tumor model of nude mice was given depsides salts at a dose of 10, 20 or 50 mg/kg every 3 day for 16 days. Then samples of subcutaneous tumors in nude mice were collected. The morphological changes of tumor samples were observed by HE staining and the expression of vascular endothelial growth factor (VEGF) and the tumor antigen Ki67 was detected by immunohistochemical method. The tumor growth was inhibited by all doses of depsides salts. The morphology of tumors was shrinkage, broken and irregularly arranged compared with the tumors in the model group and the negative control group. Morphological changes were more obvious in tumors with treatment at high dose. Expression of VEGF and Ki67 in treatment groups and the positive control group were lower than that in the model group and the negative control group, with a significant difference (P<0.05). Depsides salts from Salvia miltiorrhiza can inhibit the growth of human hepatoma cell line SMMC-7721 tumor in nude mice, which is related to the inhibition of Ki67 and VEGF.

Safety of orally administered, USP-compliant levothyroxine sodium tablets in dogs.

PubMed

Hare, J E; Morrow, C M K; Caldwell, J; Lloyd, W E

2018-04-01

The safety of synthetic levothyroxine sodium tablets (Thyro-Tabs® Canine; LLOYD, Inc.) in dogs was evaluated in a randomized, sham-dose controlled, parallel-group study. Young, healthy, euthyroid Beagle dogs were randomized into four groups (four females and four males per group) and received single daily doses of 0×, 2× (0.044 mg/kg), 6× (0.132 mg/kg), or 10× (0.22 mg/kg) the labeled starting dose of 0.022 mg kg -1  day -1 for 182 days. Every 2 weeks, physical examinations, electrocardiology examinations, and sample collections for thyroid panel, hematology, serum biochemistry, coagulation panel, and urinalysis were performed. At the end of the study, the dogs were euthanized and full necropsies performed. The most overt finding was the expected dose-dependent increase in serum concentrations of total and free thyroxine with dose-dependent suppression of the hypothalamic-pituitary-thyroid axis as evidenced by decreased serum thyroid-stimulating hormone concentrations, decreased thyroid+parathyroid/body weight ratios, and a trend for decreased pituitary weight/brain weight ratios. Clinical signs of thyrotoxicosis (excitation, tachypnea, tachycardia) in the treated dogs were sporadic with no dose-response relationship. Other findings statistically associated with levothyroxine treatment were generally mild and not clinically important. In summary, doses of levothyroxine sodium up to 10× the labeled starting dose were well tolerated in healthy dogs. © 2017 The Authors. Journal of Veterinary Pharmacology and Therapeutics Published by John Wiley & Sons Ltd.

Metabolism of americium-241 in dairy animals. [Cows and goats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sutton, W.W.; Patzer, R.G.; Mullen, A.A.

1978-10-01

Groups of lactating cows and goats were used to examine americium-241 metabolism in dairy animals. Following either single oral or intravenous nuclide doses, samples of milk, urine, blood, and feces were taken over a 168-hr collection period and the americium concentrations were determined by gamma counting. Gastrointestinal uptake of americium by both cows and goats was estimated to be 0.014% of the respective oral doses. The cumulative percentage of oral dose transported to milk and urine was 4.4 x 10/sup -4/ and 1.1 x 10/sup -3/ respectively for cows and 4.4 x 10/sup -3/ and 1.2 x 10/sup -3/ respectivelymore » for goats. The relatively high americium concentrations noted in caprine milk following the oral doses are discussed. Plasma concentrations of americium decreased rapidly following all intravenous injections. The average percentage of injected americium transferred to milk, urine, and feces was 3, 6, and 2% respectively for cows and 2, 4, and 2% respectively for goats. In both intravenously dosed groups, approximately 30% of all americium released from the body was found in the urine during the first 24 hrs after injection. All animals were sacrificed 8 to 9 days after dosing. Bovine bone retained the greatest fraction of the administered dose followed by the liver. However, liver retained the greatest amount of americium in the goats following both oral and intravenous doses. Comparisons are presented between americium-241 and plutonium-238 transport in dairy cows.« less

Investigation of magnetic nanoparticles for the rapid extraction and assay of alpha-emitting radionuclides from urine: Demonstration of a novel radiobioassay method

DOE Office of Scientific and Technical Information (OSTI.GOV)

O'Hara, Matthew J.; Carter, Jennifer C.; Maclellan, Jay A.

2011-08-01

In the event of an accidental or intentional release of radionuclides into a populated area, three things must occur in a timely manner: food and drinking water supplies must be determined to be safe to eat / drink, civilians and/or military personnel must be surveyed to ensure that they do not have external contamination, and they must be screened to ensure that significant ingestion or inhalation of radionuclides has not occurred (this paper is concerned with the latter). In the event of such a disaster, the volume of radiobioassays to be performed would be tremendous. If the event released significantmore » levels of β- or α-emitting radionuclides, in vivo assays would be ineffective. Therefore, highly efficient and rapid analytical methods for radionuclide detection from submitted spot urine samples (≤ 50 mL) would be required. At present, the quantitative determination of α-emitting radionuclides from urine samples is highly labor intensive, and requires significant sample preparation and analysis time. Sorbent materials that provide effective collection and enable rapid assay could significantly streamline the radioanalytical process. We have demonstrated the use of paramagnetic nanoparticles as a novel class of extracting media for four α-emitting radionuclides of concern (Po, Ra, Am, and U) from chemically unmodified and pH 2 human urine. Herein the initial experimental sorption results are presented along with a novel method that utilizes paramagnetic nanoparticles for the extraction of radionuclides from unmodified human urine followed by the magnetic field-induced collection of the particles for subsequent α-counting-source preparation. Additionally, we construct a versatile human dose model that determines the detector count times required to estimate internal human dose at specific protective action thresholds. The model provides a means to assess a method’s detection capabilities and use fundamental health physics parameters and actual experimental data as core variables. The modeling shows that with effective sorbent materials, rapid screening for internalized α-emitters is possible from a 50 mL spot urine sample volume collected within one week of exposure/intake.« less

Fast Track Characterization of Highly Radioactive Waste Pits Combining Off-the-Shelf Robotics with Innovative Investigation Protocols

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chabeuf, Jean-Michel; Boya, Didier

The investigation and characterization of radioactive waste pits and effluent storage tanks represents a substantial and challenging step in the overall decommissioning programme launched by AREVA NC in 1998 on the site of Marcoule on behalf of the French Atomic Energy commission. Physical ,radiological and regulatory constraints, combined with a tight schedule, have lead our teams to use proven conventional instrumentation and robotics in innovative configurations . One such investigation, conducted on a particularly challenging radioactive effluent storage pit, is described below. The 'H' pit is a stainless steel clad concrete cavity, located in the second basement of the de-claddingmore » building of Marcoule site. It was used for forty years as buffer storage for high activity effluents and has a length of 5 meters, a width of 3 meters , a height of 2.5 meters, and is topped by lead plates over 5 cm thick and The bottom of the cavity is covered with a layer of mud containing mainly graphite, diatoms and resins. The mud level ranges from about 20 centimeters to over 50 centimeters. The overall mud volume is around 2.4 cubic meters. Ambient dose rates above the lead plates exceed 10 mSv/h. The main purpose of our investigation was to characterize the muds for future recovery and conditioning prior to decontaminating the pit. The history of the pit together with the varying mud altimetry lead us to believe that sedimentation had probably occurred throughout the years. We thus decided to combine dose rate measurements using IF104 probes, gamma spectroscopy with CdTe probes and sample collections at different depths to ensure the representativeness and full characterization of the muds. Poor access, ambient dose rates have lead us to conceive a robotic arm, mounted on an shaft which can be modified to fit a wide range of pits and tanks. Custom built robotic tools with maximum manoeuvrability generally involve costs and delays far exceeding our purposes. SIT, a French manufacturer of high precision handling equipment for the nuclear industry, supplied us with a user customized 'Python' Robotic arm and the associated computerized command and control equipment within 6 months of the order. The arm allowed the necessary free movement for a precise characterization of the entire pit while being flexible enough to carry varying measuring and sample collection tools. Investigations included video imaging, precise dimensional checks, collection of effluent samples, gamma spectroscopy and collimated dose rate measurements. Specific tooling and arm extensions were created by SIT for each measurement type. The investigations were conducted successfully, providing a detailed view of the pit condition, a complete mapping of collimated dose rates, a grid of gamma spectroscopy, as well as 8 samples of radioactive mud which were subsequently analyzed in our laboratory . A simple yet innovative technology allowed us to fully characterize this pit and its content within a time frame of less than Eight months We subsequently developed a mud recovery scenario, a process for the conditioning of radioactive muds by cementation, and a complete scenario for the pit decontamination and dismantling. The robotic arm is now being used for the characterization and decontamination of other similar environments on the site of Marcoule.« less

Formation of halogenated organics during waste-water disinfection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singer, P.C.; Brown, R.A.; Wiseman, J.F.

The research examined the formation of trihalomethanes (THMs) and total organic halides (TOX) during wastewater chlorination at three wastewater treatment plants in the central Piedmont of North Carolina. Secondary effluent samples were collected before and after the addition of chlorine at each of the three treatment facilities; chlorinated samples were taken from various locations within the chlorine contact chambers and at the plant discharge. Water samples were also collected upstream and downstream from two of the plant outfalls to determine the increase and persistence of THMs and TOX below each plant. TOX and THM formation was evaluated in terms ofmore » effluent wastewater quality (e.g., residual chemical oxygen demand, total organic carbon and ammonia concentration), chlorine dose, chlorine contacting system, methods of chlorine addition, and chlorine-to-ammonia ratio. The results showed that TOX was present in the unchlorinated wastewater and that additional TOX was formed immediately after chlorine addition. Small to insignificant amounts of THMS were detected. TOX formation did not increase with increasing contact time, due to the rapid depletion of free chlorine and the formation of combined chlorine in the chlorine contact chamber.« less

Sparse imaging for fast electron microscopy

NASA Astrophysics Data System (ADS)

Anderson, Hyrum S.; Ilic-Helms, Jovana; Rohrer, Brandon; Wheeler, Jason; Larson, Kurt

2013-02-01

Scanning electron microscopes (SEMs) are used in neuroscience and materials science to image centimeters of sample area at nanometer scales. Since imaging rates are in large part SNR-limited, large collections can lead to weeks of around-the-clock imaging time. To increase data collection speed, we propose and demonstrate on an operational SEM a fast method to sparsely sample and reconstruct smooth images. To accurately localize the electron probe position at fast scan rates, we model the dynamics of the scan coils, and use the model to rapidly and accurately visit a randomly selected subset of pixel locations. Images are reconstructed from the undersampled data by compressed sensing inversion using image smoothness as a prior. We report image fidelity as a function of acquisition speed by comparing traditional raster to sparse imaging modes. Our approach is equally applicable to other domains of nanometer microscopy in which the time to position a probe is a limiting factor (e.g., atomic force microscopy), or in which excessive electron doses might otherwise alter the sample being observed (e.g., scanning transmission electron microscopy).

Dose estimation and dating of pottery from Turkey

NASA Astrophysics Data System (ADS)

Altay Atlıhan, M.; Şahiner, Eren; Soykal Alanyalı, Feriştah

2012-06-01

The luminescence method is a widely used technique for environmental dosimetry and dating archaeological, geological materials. In this study, equivalent dose (ED) and annual dose rate (AD) of an archaeological sample were measured. The age of the material was calculated by means of equivalent dose divided by the annual dose rate. The archaeological sample was taken from Antalya, Turkey. Samples were prepared by the fine grain technique and equivalent dose was found using multiple-aliquot-additive-dose (MAAD) and single aliquot regeneration (SAR) techniques. Also the short shine normalization-MAAD and long shine normalization-MAAD were applied and the results of the methods were compared with each other. The optimal preheat temperature was found to be 200 °C for 10 min. The annual doses of concentrations of the major radioactive isotopes were determined using a high-purity germanium detector and a low-level alpha counter. The age of the sample was found to be 510±40 years.

Measurement of natural radioactivity and radon exhalation rate from rock samples of Jaduguda uranium mines and its radiological implications

NASA Astrophysics Data System (ADS)

Mahur, A. K.; Kumar, Rajesh; Sonkawade, R. G.; Sengupta, D.; Prasad, Rajendra

2008-04-01

The Singhbhum shear zone is a 200 km long arcuate belt in Jharkhand state situated in eastern India. The central part between Jaduguda-Bhatin-Nimdih, Narwapahr-Garadih-Turamdih is rich in uranium. Presence of uranium in the host rocks and the prevalence of a confined atmosphere within mines could result in enhanced concentration of radon (222Rn) gas and its progeny. Inhalation of radon daughter products is a major contributor to the radiation dose to exposed subjects. By using high resolution γ-ray spectroscopic system various radionuclides in the rock samples, collected from different places of Jaduguda uranium mines have been identified quantitatively based on the characteristic spectral peaks. The activity concentrations of the natural radionuclides, uranium (238U), thorium (232Th) and potassium (40K) were measured in the rock samples and radiological parameters were calculated. Uranium concentration was found to vary from 123 ± 7 Bq kg-1 to 40,858 ± 174 Bq kg-1. Activity of thorium was not significant in the samples, whereas, few samples have shown potassium activity from 162 ± 11 Bq kg-1 to 9024 ± 189 Bq kg-1. Radon exhalation rates from these samples were also measured using "Sealed Can technique" and found to vary from 4.2 ± 0.05 to 13.7 ± 0.08 Bq m-2 h-1. A positive correlation was found between the radon exhalation rate and the uranium activity. The absorbed dose rates vary from 63.6 to 18876.4 nGy h-1, with an average value of 7054.2 nGy h-1. The annual external effective dose rates vary from 0.7 to 23.2 mSv y-1. Radium equivalent activities (Raeq) varied from 134.3 to 40858.0 Bq kg-1. Value of external hazard index (Hex) varied from 0.4 to 110.4 with an average value of 41.2.

Partitioning of fluoranthene between free and bound forms in stormwater runoff and other urban discharges using passive dosing.

PubMed

Birch, Heidi; Mayer, Philipp; Lützhøft, Hans-Christian Holten; Mikkelsen, Peter Steen

2012-11-15

Partitioning of fluoranthene in stormwater runoff and other urban discharges was measured by a new analytical method based on passive dosing. Samples were collected at the inlet (n = 11) and outlet (n = 8) from a stormwater retention pond in Albertslund (Denmark), and for comparison samples were also obtained at a municipal wastewater treatment plant, a power plant, a contaminated site and a waste deposit in Copenhagen (n = 1 at each site). The freely dissolved concentration of (14)C-fluoranthene in the samples was controlled by equilibrium partitioning from a pre-loaded polymer and the total sample concentration measured. The measurements yielded free fractions of fluoranthene in stormwater in the range 0.04-0.15 in the inlet during the first part of the runoff events increasing to 0.3-0.5 at the end of the events and in the outlet from the retention pond. The enhanced capacity of the different stormwater samples for carrying fluoranthene was 2-23 relative to pure water and decreasing during rain events. The enhanced capacity of stormwater showed a different relationship with suspended solid concentrations than the other types of urban discharges. Partitioning of fluoranthene to dissolved organic carbon was lower than partitioning to particulate organic carbon. Partitioning of fluoranthene to particulate organic matter in the 19 stormwater samples yielded a log K(POM) of 5.18. The presented results can be used in stormwater quality modeling and assessment of efficiency of stormwater treatment systems. This work also shows the potential of the passive dosing method to obtain conversion factors between total concentrations, which are needed for comparison with water quality criteria, and freely dissolved concentrations, which are more related to toxicity and obtained by the use of most passive samplers. Copyright © 2012 Elsevier Ltd. All rights reserved.

The effect of pre-dose on thermally and optically stimulated luminescence from α-Al2O3:C,Mg and α-Al2O3:C.

PubMed

Kalita, J M; Chithambo, M L

2018-06-15

We report the effect of pre-dose on the thermoluminescence (TL) and optically stimulated luminescence (OSL) dose response of α-Al 2 O 3 :C,Mg and α-Al 2 O 3 :C. Before any luminescence measurement, the samples were irradiated with different doses, namely 100, 500 and 1000 Gy to populate the deep electron traps. This is the pre-dose. The results from TL and OSL studies are compared with results from samples used without any pre-measurement dose. The TL glow curves and OSL decay curves of α-Al 2 O 3 :C,Mg recorded after pre-doses of 100, 500 and 1000 Gy are identical to those from a sample used without any pre-dose. Further, the TL and OSL dose response of all α-Al 2 O 3 :C,Mg samples are similar regardless of pre-dose. In comparison, the TL glow curves and OSL decay curves of α-Al 2 O 3 :C are influenced by pre-dose. We conclude that the differences in the TL and OSL dose response of various pre-dosed samples of α-Al 2 O 3 :C are due to the concentration of charge in the deep traps. On the other hand, owing to the lower concentration of such deep traps in α-Al 2 O 3 :C,Mg, the TL or OSL dose responses are not affected by pre-dose in this material. Copyright © 2018 Elsevier Ltd. All rights reserved.

Safety, efficacy and pharmacokinetics of neratinib (HKI-272) in Japanese patients with advanced solid tumors: a Phase 1 dose-escalation study.

PubMed

Ito, Yoshinori; Suenaga, Mitsukuni; Hatake, Kiyohiko; Takahashi, Shunji; Yokoyama, Masahiro; Onozawa, Yusuke; Yamazaki, Kentaro; Hironaka, Shuichi; Hashigami, Kiyoshi; Hasegawa, Hirotaka; Takenaka, Nobuko; Boku, Narikazu

2012-04-01

Neratinib (HKI-272), a potent, irreversible, small-molecule, orally administered, pan-ErbB inhibitor that blocks signal transduction via inhibition of three epidermal growth factor receptors [ErbB1, ErbB2 (Her2) and ErbB4], is being developed for the treatment of solid tumors, including breast cancer. This Phase 1 dose-escalation study assessed the safety, tolerability, maximum-tolerated dose, antitumor activity and pharmacokinetics of neratinib in Japanese patients with advanced solid tumors. Patients received neratinib 80, 160, 240 or 320 mg orally; each patient enrolled in only one dose cohort. Patients received a single dose in week 1, followed by daily continuous doses. Blood samples collected were on days 1 and 21 for pharmacokinetic analyses. Twenty-one patients were enrolled (3 breast cancer; 17 colorectal cancer; 1 gastric cancer). Neratinib-related adverse events (all grades) included diarrhea (20 patients), fatigue (14 patients), nausea and abdominal pain (9 patients each) and anorexia (8 patients). Grade ≥3 neratinib-related adverse events in two or more patients were diarrhea and anorexia (two patients each). Dose-limiting toxicities were diarrhea and anorexia (two patients, 320 mg dose). The maximum-tolerated dose and recommended dose was neratinib 240 mg once daily. Of 21 evaluable patients, 2 with breast cancer had partial response, 3 had stable disease ≥24 weeks, 7 had stable disease ≥16 weeks and 9 had progressive disease. Pharmacokinetic analyses indicated that neratinib exposures increased with dose. The safety, efficacy and pharmacokinetic profiles of neratinib are consistent with those reported for non-Japanese patients and warrant further investigation of neratinib in Japanese patients with solid tumors.

Urinary nickel as bioindicator of workers' Ni exposure in a galvanizing plant in Brazil.

PubMed

Oliveira, J P; de Siqueira, M E; da Silva, C S

2000-01-01

We measured urinary nickel (U-Ni) in ten workers (97 samples) from a galvanizing plant that uses nickel sulfate, and in ten control subjects (55 samples) to examine the association between occupational exposure to airborne Ni and Ni absorption. Samples from the exposed group were taken before and after the work shift on 5 successive workdays. At the same time airborne Ni (A-Ni) was measured using personal samplers. Ni levels in biological material and in the airborne were determined by a graphite furnace atomic absorption spectrometry validated method. In the control group the urine samples were collected twice a day, in the before and after the work shift, on 3 successive days. Ni exposure low to moderate was detected in all the examined places in the plant, the airborne levels varying between 2.8 and 116.7 micrograms/m3 and the urine levels, from samples taken postshift, between 4.5 and 43.2 micrograms/g creatinine (mean 14.7 micrograms/g creatinine). Significant differences in U-Ni creatinine were seen between the exposed and control groups (Student's t test, P < or = 0.01). A significant correlation between U-Ni and A-Ni (r = 0.96; P < or = 0.001) was detected. No statistical difference was observed in U-Ni collected from exposed workers in the 5 successive days, but significant difference was observed between pre- and postshift samples. Urinary nickel may be used as a reliable internal dose bioindicator in biological monitoring of workers exposed to Ni sulfate in galvanizing plants regardless of the day of the workweek on which the samples are collected.

Deployment of the DosiKit System Under Operational Conditions: Experience From a French Defense National Nuclear Exercise.

PubMed

Entine, F; Bensimon Etzol, J; Bettencourt, C; Dondey, M; Michel, X; Gagna, G; Gellie, G; Corre, Y; Ugolin, N; Chevillard, S; Amabile, J-C

2018-07-01

Estimation of the dose received by accidentally irradiated victims is based on a tripod: clinical, biological, and physical dosimetry. The DosiKit system is an operational and mobile biodosimetry device allowing the measurement of external irradiation directly on the site of a radiological accident. This tool is based on capillary blood sample and hair follicle collection. The aim is to obtain a whole-body and local-surface dose assessment. This paper is about the technical evaluation of the DosiKit; the analytical process and scientific validation are briefly described. The Toulon exercise scenario was based on a major accident involving the reactor of a nuclear attack submarine. The design of the scenario made it impossible for several players (firefighters, medical team) to leave the area for a long time, and they were potentially exposed to high dose rates. The DosiKit system was fully integrated into a deployable radiological emergency laboratory, and the response to operational needs was very satisfactory.

Naturally occurring radioactive materials (NORM) in ashes from a fuel-oil power plant in Cienfuegos, Cuba, and the associated radiation hazards.

PubMed

Alonso-Hernández, C M; Bernal-Castillo, J; Morera-Gómez, Y; Guillen-Arruebarrena, A; Cartas-Aguila, H A; Acosta-Milián, R

2014-03-01

The radioactivity of NORM was measured in ashes collected from a fuel-oil power plant in Cienfuegos, Cuba, using an HPGe gamma-ray spectrometer. The (226)Ra, (210)Pb, (40)K, (232)Th and (238)U activity concentrations reached 240, 77, 59, 70 and 15 Bq kg(-1), respectively. The potential radiological hazard of these residuals was assessed. The radium equivalent activities of the samples varied from 54 to 345 Bq kg(-1). The gamma index was calculated to be lower than that of the reference values, and the gamma absorbed dose rate was higher than the average reported for the earth's crust; however, the assessed annual effective dose was slightly lower than the annual effective dose limit for public, i.e. 1 mSv. Therefore, these bottom ashes were not dramatically enriched with radionuclides and may be used as an additive for building materials without restrictions from a radiological protection point of view.

[The effect of aluminum adjuvant and immunization schedule on immunogenicity of Sabin inactivated poliovirus vaccine].

PubMed

Wang, Fang; Zhang, Ming; Xie, Bing-Feng; Cao, Han; Tong, Shao-Yong; Wang, Jun-Rong; Yu, Xiao-Ping; Tang, Yang; Yang, Jing-Ran; Sun, Ming-Bo

2013-04-01

To study the effect of aluminume adjuvant and immunization schedule on immunogenicity of Sabin inactivated poliovirus vaccine. Four batches of Sabin IPV were produced by different concentrations of type 1, 2, and 3 poliovirus and administrated on three-dose schedule at 0, 1, 2 months and 0, 2, 4 months on rats. Serum samples were collected one month after each dose and neutralizing antibody titers against three types poliovirus were determined by micro-neutralization assay. The GMTs of neutralizing antibodies against three types poliovirus increased significantly and the seropositivity rates were 100% in all groups after 3 doses. There was no significant difference between two immunization schedules, and the 0, 2, 4 month schedule could induce higher level neutralizing antibody compared to the 0, 1, 2 month schedule. The groups with aluminum adjuvant could induce higher level neutralizing antibody compared to the groups without adjuvant. Aluminum djuvant and immunization schedule could improve the immunogenicity of Sabin IPV.

Comparative pharmacokinetics of chlorogenic acid after oral administration in rats

PubMed Central

Qi, Wei; Zhao, Ting; Yang, Wen-Wen; Wang, Guang-Hou; Yu, Hua; Zhao, Hai-Xiao; Yang, Chen; Sun, Li-Xin

2011-01-01

The present study was aimed at the comparison of the pharmacokinetics of pure chlorogenic acid and extract of Solanum lyratum Thunb. The animals were allocated to two groups, and were administered chlorogenic acid or extract of S. lyratum Thunb. at a dose of 50.0 mg/kg orally. Blood samples were collected up to 8 h post-dosing. Plasma chlorogenic acid analyses were performed using an HPLC method with UV detector. The pharmacokinetic parameters were evaluated using non-compartmental assessment. Significant differences existed in the two groups for AUC0−t, AUC0−∞ and CLz/F. The reliable HPLC method was successfully applied to the determination of chlorogenic acid in rat plasma at dosage of 50.0 mg/kg. PMID:29403709

Dissipation and distribution behavior of azoxystrobin, carbendazim, and difenoconazole in pomegranate fruits.

PubMed

Utture, Sagar C; Banerjee, Kaushik; Dasgupta, Soma; Patil, Sangram H; Jadhav, Manjusha R; Wagh, Sameer S; Kolekar, Sanjay S; Anuse, Mansing A; Adsule, Pandurang G

2011-07-27

The dissipation behavior and degradation kinetics of azoxystrobin, carbendazim, and difenoconazole in pomegranate are reported. Twenty fruits/hectare (5 kg) were collected at random, ensuring sample-to-sample relative standard deviation (RSD) within 20-25%. Each fruit was cut into eight equal portions, and two diagonal pieces per fruit were drawn and combined to constitute the laboratory sample, resulting in RSDs <6% (n = 6). Crushed sample (15 g) was extracted with 10 mL of ethyl acetate (+ 10 g Na(2)SO(4)), cleaned by dispersive solid phase extraction on primary secondary amine (25 mg) and C(18) (25 mg), and measured by liquid chromatography tandem mass spectrometry. The limit of quantification was ≤0.0025 μg g(-1) for all the three fungicides, with calibration linearity in the concentration range of 0.001-0.025 μg mL(-1) (r(2) ≥ 0.999). The recoveries of each chemical were 75-110% at 0.0025, 0.005, and 0.010 μg g(-1) with intralaboratory Horwitz ratio <0.32 at 0.0025 μg g(-1). Variable matrix effects were recorded in different fruit parts viz rind, albedo, membrane, and arils, which could be correlated to their biochemical constituents as evidenced from accurate mass measurements on a Q-ToF LC-MS. The residues of carbendazim and difenoconazole were confined within the outer rind of pomegranate; however, azoxystrobin penetrated into the inner fruit parts. The dissipation of azoxystrobin, carbendazim, and difenoconazole followed first + first order kinetics at both standard and double doses, with preharvest intervals being 9, 60, and 26 days at standard dose. At double dose, the preharvest intervals extended to 20.5, 100, and 60 days, respectively.

Long-term treatment with green tea polyphenols modifies the gut microbiome of female sprague-dawley rats.

PubMed

Wang, Jincheng; Tang, Lili; Zhou, Hongyuan; Zhou, Jun; Glenn, Travis C; Shen, Chwan-Li; Wang, Jia-Sheng

2018-06-01

Green tea polyphenols (GTP) have been shown to exert a spectrum of health benefits to animals and humans. It is plausible that the beneficial effects of GTP are a result of its interaction with the gut microbiota. This study evaluated the effect of long-term treatment with GTP on the gut microbiota of experimental rats and the potential linkage between changes of the gut microbiota with the beneficial effects of GTP. Six-month-old Sprague-Dawley rats were randomly allocated into three dosing regimens (0, 0.5%, and 1.5% of GTP) and followed for 6 months. At the end of month 3 or month 6, half of the animals from each group were sacrificed and their colon contents were collected for microbiome analysis using 16S ribosomal RNA and shotgun metagenomic community sequencing. GTP treatment significantly decreased the biodiversity and modified the microbial community in a dose-dependent manner; similar patterns were observed at both sampling times. Multiple operational taxonomic units and phylotypes were modified: the phylotypes Bacteroidetes and Oscillospira, previously linked to the lean phenotype in human and animal studies, were enriched; and Peptostreptococcaceae previously linked to colorectal cancer phenotype was depleted in GTP treated groups in a dose-dependent manner. Several microbial gene orthologs were modified, among which genes related to energy production and conversion were consistently enriched in samples from month 6 in a dose-dependent manner. This study showed that long-term treatment with GTP induced a dose-dependent modification of the gut microbiome in experimental rats, which might be linked to beneficial effects of GTP. Copyright © 2018 Elsevier Inc. All rights reserved.

Seasonal measurement and dose assessment of natural radionuclides in sediments of Darbandikhan Lake in Kurdistan-Iraq

NASA Astrophysics Data System (ADS)

Omer Jafir, Adeeb; Ahmed, Ali Hassan; Saridan, Wan Muhammad

2017-11-01

A total of 100 sediment samples were collected from Darbandikhan Lake and its different resources (spring, stream, and lake) during the four seasons. Spectrometry analysis of HPGe detector was used for measuring the specific activity. The seasonally measured mean activity concentration of 238U, 232Th and40K for sediment samples were 11.9±1.0, 7.8±1.0 and 213.4±3.4 Bq/kg in spring; 9.2±1.1, 7.9±1.0 and 205.8±3.0 Bq/kg in summer; 12.7±1.5, 8.2±1.0 and 188.1±3.1 Bq/kg in autumn; 11.9±1.6, 9.1±1.0 and 218.7±3.0 Bq/kg in winter, respectively. The obtained activity concentrations of 238U, 232Th and 40K are all below the recommended values suggested by UNSCEAR (2000) for sediment 35, 30 and 400 Bq/kg, respectively. The ordinary kriging method was used to draw the contour maps using the surfer digital program. RESRAD-BUILD simulation code was used to determine the indoor dose, annual dose rate and cancer risks received and exposed to individuals in the dwellings, which show an increase over a period of 50 years. Two scenario descriptions of changing wall thickness and room dimension were, studied and they shows that the indoor dose and cancer risks increase with wall thicknesses until 50 cm and over a period of 50 years, as well as the increase of room size increases the internal dose and cancer risks inside the buildings. From the analyzed results it was concluded that the sediments in the Darbandikhan Lake has no risks when used in building construction.

Task related doses in Spanish pressurized water reactors over the period 1988-1992

DOE Office of Scientific and Technical Information (OSTI.GOV)

O`Donnell, P.; Labarta, T.; Amor, I.

1995-03-01

In order to evaluate in depth the collective dose trend and its correlation with the effectiveness of the practical application of the ALARA principle in Spanish nuclear facilities, and base the different policy lines to promote this criteria, the CSN has fullfilled an analysis of the task related doses data over the period 1988-1992. Previously, the CSN had required to the utilities the compilation of their refuelling outage collective dose from 1988 according with a predeterminate number of tasks, in order to have available a representative and retrospective set of data in an homogeneous way and coherent with the internationalmore » data banks on occupational exposure in NPP, as the CEC and the NEA ones. The scope of this analysis was the following: first, the collective dose summaries for outage tasks and departments for PWR and for BWR, including the minimum, maximum and average dose (and statistics data) for 18 different refuelling outage tasks and 12 personal departments for each generation of each type of rector, the task and department related collective dose trends in each plant and in each generation, and second, the dose reduction techniques having been used during that period in each plant and the relative level of adoption. In this presentation the main results and conclusions of the first part of the study are reviewed for PWR.« less

Urinary Phenylacetylglutamine as Dosing Biomarker for Patients with Urea Cycle Disorders

PubMed Central

Mokhtarani, M; Diaz, GA; Rhead, W; Lichter-Konecki, U; Bartley, J; Feigenbaum, A; Longo, N; Berquist, W; Berry, SA; Gallagher, R; Bartholomew, D; Harding, CO; Korson, MS; McCandless, SE; Smith, W; Vockley, J; Bart, S; Kronn, D; Zori, R; Cederbaum, S; Dorrani, N; Merritt, JL; Sreenath-Nagamani, Sandesh; Summar, M; LeMons, C; Dickinson, K; Coakley, DF; Moors, TL; Lee, B; Scharschmidt, BF

2013-01-01

We have analyzed pharmacokinetic data for glycerol phenylbutyrate (also GT4P or HPN-100) and sodium phenylbutyrate with respect to possible dosing biomarkers in patients with urea cycle disorders (UCD). Study Design These analyses are based on over 3000 urine and plasma data points from 54 adult and 11 pediatric UCD patients (ages 6–17) who participated in three clinical studies comparing ammonia control and pharmacokinetics during steady state treatment with glycerol phenylbutyrate or sodium phenylbutyrate. All patients received phenylbutyric acid equivalent doses of glycerol phenylbutyrate or sodium phenylbutyrate in a cross over fashion and underwent 24-hour blood samples and urine sampling for phenylbutyric acid, phenylacetic acid and phenylacetylglutamine. Results Patients received phenylbutyric acid equivalent doses of glycerol phenylbutyrate ranging from 1.5–31.8 g/day and of sodium phenylbutyrate ranging from 1.3–31.7 g/day. Plasma metabolite levels varied widely, with average fluctuation indices ranging from 1979% –5690% for phenylbutyric acid, 843% to 3931% for phenylacetic acid, and 881% -to 1434% for phenylacetylglutamine. Mean percent recovery of phenylbutyric acid as urinary phenylacetylglutamine was 66.4 and 69.0 for pediatric patients and 68.7 and 71.4 for adult patients on glycerol phenylbutyrate and sodium phenylbutyrate, respectively. The correlation with dose was strongest for urinary phenylacetylglutamine excretion, either as morning spot urine (r=0.730, p<0.001) or as total 24-hour excretion (r=0.791 p<0.001), followed by plasma phenylacetylglutamine AUC24-hour, plasma phenylacetic acid AUC24-hour and phenylbutyric acid AUC24-hour. Plasma phenylacetic acid levels in adult and pediatric patients did not show a consistent relationship with either urinary phenylacetylglutamine or ammonia control. Conclusion The findings are collectively consistent with substantial yet variable pre-systemic (1st pass) conversion of phenylbutyric acid to phenylacetic acid and/or phenylacetylglutamine. The variability of blood metabolite levels during the day, their weaker correlation with dose, the need for multiple blood samples to capture trough and peak, and the inconsistency between phenylacetic acid and urinary phenylacetylglutamine as a marker of waste nitrogen scavenging limit the utility of plasma levels for therapeutic monitoring. By contrast, 24-hour urinary phenylacetylglutamine and morning spot urine phenylacetylglutamine correlate strongly with dose and appear to be clinically useful non-invasive biomarkers for compliance and therapeutic monitoring. PMID:22958974

Urinary phenylacetylglutamine as dosing biomarker for patients with urea cycle disorders.

PubMed

Mokhtarani, M; Diaz, G A; Rhead, W; Lichter-Konecki, U; Bartley, J; Feigenbaum, A; Longo, N; Berquist, W; Berry, S A; Gallagher, R; Bartholomew, D; Harding, C O; Korson, M S; McCandless, S E; Smith, W; Vockley, J; Bart, S; Kronn, D; Zori, R; Cederbaum, S; Dorrani, N; Merritt, J L; Sreenath-Nagamani, Sandesh; Summar, M; Lemons, C; Dickinson, K; Coakley, D F; Moors, T L; Lee, B; Scharschmidt, B F

2012-11-01

We have analyzed pharmacokinetic data for glycerol phenylbutyrate (also GT4P or HPN-100) and sodium phenylbutyrate with respect to possible dosing biomarkers in patients with urea cycle disorders (UCD). These analyses are based on over 3000 urine and plasma data points from 54 adult and 11 pediatric UCD patients (ages 6-17) who participated in three clinical studies comparing ammonia control and pharmacokinetics during steady state treatment with glycerol phenylbutyrate or sodium phenylbutyrate. All patients received phenylbutyric acid equivalent doses of glycerol phenylbutyrate or sodium phenylbutyrate in a cross over fashion and underwent 24-hour blood samples and urine sampling for phenylbutyric acid, phenylacetic acid and phenylacetylglutamine. Patients received phenylbutyric acid equivalent doses of glycerol phenylbutyrate ranging from 1.5 to 31.8 g/day and of sodium phenylbutyrate ranging from 1.3 to 31.7 g/day. Plasma metabolite levels varied widely, with average fluctuation indices ranging from 1979% to 5690% for phenylbutyric acid, 843% to 3931% for phenylacetic acid, and 881% to 1434% for phenylacetylglutamine. Mean percent recovery of phenylbutyric acid as urinary phenylacetylglutamine was 66.4 and 69.0 for pediatric patients and 68.7 and 71.4 for adult patients on glycerol phenylbutyrate and sodium phenylbutyrate, respectively. The correlation with dose was strongest for urinary phenylacetylglutamine excretion, either as morning spot urine (r = 0.730, p < 0.001) or as total 24-hour excretion (r = 0.791 p<0.001), followed by plasma phenylacetylglutamine AUC(24-hour), plasma phenylacetic acid AUC(24-hour) and phenylbutyric acid AUC(24-hour). Plasma phenylacetic acid levels in adult and pediatric patients did not show a consistent relationship with either urinary phenylacetylglutamine or ammonia control. The findings are collectively consistent with substantial yet variable pre-systemic (1st pass) conversion of phenylbutyric acid to phenylacetic acid and/or phenylacetylglutamine. The variability of blood metabolite levels during the day, their weaker correlation with dose, the need for multiple blood samples to capture trough and peak, and the inconsistency between phenylacetic acid and urinary phenylacetylglutamine as a marker of waste nitrogen scavenging limit the utility of plasma levels for therapeutic monitoring. By contrast, 24-hour urinary phenylacetylglutamine and morning spot urine phenylacetylglutamine correlate strongly with dose and appear to be clinically useful non-invasive biomarkers for compliance and therapeutic monitoring. Copyright © 2012 Elsevier Inc. All rights reserved.

Volatile compounds released by disturbed and calm adults of the tarnished plant bug, Lygus lineolaris.

PubMed

Wardle, A R; Borden, J H; Pierce, H D; Gries, R

2003-04-01

Volatile compounds released by disturbed and calm female and male Lygus lineolaris were collected and analyzed. Six major compounds were present in samples from disturbed bugs and from calm females: (E)-2-hexenal, 1-hexanol, (E)-2-hexenol, hexyl butyrate, (E)-2-hexenyl butyrate, and (E)-2,4-oxohexenal. (E)-2-hexenal was lacking in volatiles collected from calm males. Hexyl butyrate accounted for approximately 68% and 66% of volatiles released by agitated and calm females, and 87% and 88% of volatiles released by agitated and calm males, respectively. Blends released by disturbed insects differed quantitatively from blends released by calm insects, with amounts of compounds increasing 75-350 times in samples from disturbed insects. In static air bioassays, both females and males were repelled by natural volatiles collected from females and by five-component [(E)-2,4-oxohexenal excluded] and six-component synthetic blends at doses of 1 and 10 bug-hours, indicating that these volatiles may serve an alarm or epideictic function, as well as a possible role as defensive allomones. Adults also avoided hexyl butyrate, (E)-2-hexenyl butyrate, (E)-2-hexenol, and (E)-2,4-oxohexenal, but not 1-hexanol and (E)-2-hexenal when compounds were assayed individually in static air bioassays at doses equal to 1 bug-hour. When tested over 1 day in two-choice cage trials, adults did not prefer untreated bean plants over bean plants surrounded by vials releasing up to 8.1 mg/hr (= 234 bug-hours) of the five-component synthetic blend. Therefore, the volatiles produced by disturbed adults would not be useful as a repellent for L. lineolaris.

Perspectives on using a multiplex human kidney safety biomarker panel to detect cisplatin-induced tubular toxicity in male and female Cynomolgus monkeys.

PubMed

Chen, Yafei; Dale Thurman, J; Kinter, Lewis B; Bialecki, Russell; Eric McDuffie, J

2017-12-01

Multiplex biomarker panel assays would enable early de-risking of discovery compound related kidney safety liabilities. The objective of this study was to evaluate the usefulness of the Myriad RBM Human KidneyMAP (Multi-Analyte Profile)® v.1.0 panel to detect experimental nephrotoxicity in Cynomolgus monkeys following a single intravenous administration of cisplatin (2.5mg/kg). Urine samples were collected at baseline on day -2; at approximately 4hr post-dose on day 1; and on days 4, 9, 15 and/or 20. Blood samples were collected at predose on day -2; at 4hr post-dose on day 1; and on days 2, 5, 10 and/or 21. Changes in toxicokinetic and biochemistry parameters in plasma, qualitative/quantitative urinalysis parameters, and urinary kidney safety biomarkers were assessed. Kidney tissues were collected on days 2, 5, 10 and 21 for routine microscopy. Cisplatin-induced tubular alterations were characterized by acute and progressive cortical tubular degeneration/necrosis, regeneration, tubular dilation and proteinaceous cast in the absence of statistically significant changes in traditional plasma biochemistry and urinalysis parameters. When normalized to urinary creatinine, cisplatin-induced significant increases in urinary levels of kidney injury molecule 1 (females on day 4), increases in calbindin D28k (males and females on day 4), decreases in Tamm-Horsfall glycoprotein (males on days 1, 4 and 9), and increases in clusterin (females and males on days 15 and 20, respectively), when compared to concurrent controls. This study revealed the usefulness of the Human KidneyMAP® multiplex panel when measuring changes in urine-based biomarkers to reliably detect cisplatin-induced acute/progressive cortical tubular injury in male and female Cynomolgus monkeys. Copyright © 2017 Elsevier Inc. All rights reserved.

Current Knowledge on Cannabinoids in Oral Fluid

PubMed Central

Lee, Dayong; Huestis, Marilyn A.

2015-01-01

Oral fluid (OF) is a new biological matrix for clinical and forensic drug testing, offering non-invasive and directly observable sample collection reducing adulteration potential, ease of multiple sample collections, lower biohazard risk during collection, recent exposure identification, and stronger correlation with blood than urine concentrations. Because cannabinoids are usually the most prevalent analytes in illicit drug testing, application of OF drug testing requires sufficient scientific data to support sensitive and specific OF cannabinoid detection. This review presents current knowledge on OF cannabinoids, evaluating pharmacokinetic properties, detection windows, and correlation with other biological matrices and impairment from field applications and controlled drug administration studies. In addition, on-site screening technologies, confirmatory analytical methods, drug stability, and effects of sample collection procedure, adulterants, and passive environmental exposure are reviewed. Delta-9-tetrahydrocannabinol OF concentrations could be > 1000 μg/L shortly after smoking, whereas minor cannabinoids are detected at 10-fold and metabolites at 1000-fold lower concentrations. OF research over the past decade demonstrated that appropriate interpretation of test results requires a comprehensive understanding of distinct elimination profiles and detection windows for different cannabinoids, which are influenced by administration route, dose, and drug use history. Thus, each drug testing program should establish cutoff criteria, collection/analysis procedures, and storage conditions tailored to its purposes. Building a scientific basis for OF testing is on-going, with continuing OF cannabinoids research on passive environmental exposure, drug use history, donor physiological conditions, and oral cavity metabolism needed to better understand mechanisms of cannabinoid OF disposition and expand OF drug testing applicability. PMID:23983217

On-line data collection platform for national dose surveys in diagnostic and interventional radiology.

PubMed

Vassileva, J; Simeonov, F; Avramova-Cholakova, S

2015-07-01

According to the Bulgarian regulation for radiation protection at medical exposure, the National Centre of Radiobiology and Radiation Protection (NCRRP) is responsible for performing national dose surveys in diagnostic and interventional radiology and nuclear medicine and for establishing of national diagnostic reference levels (DRLs). The next national dose survey is under preparation to be performed in the period of 2015-16, with the aim to cover conventional radiography, mammography, conventional fluoroscopy, interventional and fluoroscopy guided procedures and CT. It will be performed electronically using centralised on-line data collection platform established by the NCRRP. The aim is to increase the response rate and to improve the accuracy by reducing human errors. The concept of the on-line dose data collection platform is presented. Radiological facilities are provided with a tool to determine local typical patient doses, and the NCRRP to establish national DRLs. Future work will include automatic retrieval of dose data from hospital picture archival and communicating system. The on-line data collection platform is expected to facilitate the process of dose audit and optimisation of radiological procedures in Bulgarian hospitals. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Plasma vemurafenib concentrations in advanced BRAFV600mut melanoma patients: impact on tumour response and tolerance.

PubMed

Funck-Brentano, E; Alvarez, J C; Longvert, C; Abe, E; Beauchet, A; Funck-Brentano, C; Saiag, P

2015-07-01

Vemurafenib improves survival in advanced BRAFV600(mut) melanoma patients, but tolerance is often poor and resistance frequently occurs, without predictive factor. Our aim was to investigate for the first time a relationship between plasma vemurafenib concentration (PVC) and efficacy or tolerance. Plasma samples from unresectable metastatic BRAFV600(mut) melanoma patients treated with vemurafenib monotherapy were prospectively collected at each tumour response evaluation (RECIST 1.1) or when adverse event occurred (CTCAE 4.0). PVC was measured with liquid chromatography-tandem mass spectrometry. Herein, we report on PVC at steady state (≥14 days after vemurafenib introduction or dose modification). Samples collected after first melanoma progression were excluded from the response analysis. All samples were analysed in the tolerance analysis. We kept the closest collected sample from the onset of each adverse effect or the one with the highest PVC in the absence of this adverse effect. Comparisons of means (Student's t-tests and Wilcoxon rank sum tests) and of frequencies (χ(2) tests) were carried out. A logistic regression analysis identified predictors of progression. We included 105 plasma samples in 23 patients (10M/13F). Initial vemurafenib dose was 960 mg b.i.d., reduced by 25% (8 patients) or 50% (2 patients) for intolerance in 10 patients (44%). PVC displayed high inter-individual variability (13.0-109.8 µg/ml, median 54.0). Mean PVC was lower at time of first progression (38.8 ± 19.7 µg/ml) than mean PVC found when tumour was stable or in partial or complete response (56.4 ± 21.0 µg/ml, P = 0.013, 21 patients). Logistic regression revealed that having a low PVC (P = 0.01) or brain metastasis (P = 0.01) were both significantly and independently associated with tumour progression. High PVC was not statistically significantly associated with the occurrence of adverse effects. PVC at steady state is highly variable and low PVC was associated with tumour progression, suggesting a new path to melanoma resistance to vemurafenib. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Podonsky, Glenn S.

The U.S. Department of Energy (DOE) Office of Analysis within the Office of Health, Safety and Security (HSS) publishes the annual DOE Occupational Radiation Exposure Report to provide an overview of the status of radiation protection practices at DOE (including the National Nuclear Security Administration [NNSA]). The DOE 2012 Occupational Radiation Exposure Report provides an evaluation of DOE-wide performance regarding compliance with Title 10, Code of Federal Regulations (C.F.R.), Part 835, Occupational Radiation Protection dose limits and as low as reasonably achievable (ALARA) process requirements. In addition, the report provides data to DOE organizations responsible for developing policies for protectionmore » of individuals from the adverse health effects of radiation. The report provides a summary and an analysis of occupational radiation exposure information from the monitoring of individuals involved in DOE activities. Over the past 5-year period, the occupational radiation exposure information is analyzed in terms of aggregate data, dose to individuals, and dose by site. As an indicator of the overall amount of radiation dose received during the conduct of operations at DOE, the report includes information on collective total effective dose (TED). The TED is comprised of the effective dose (ED) from external sources, which includes neutron and photon radiation, and the internal committed effective dose (CED), which results from the intake of radioactive material into the body. The collective ED from photon exposure decreased by 23% between 2011 and 2012, while the neutron dose increased by 5%. The internal dose components of the collective TED decreased by 7%. Over the past 5-year period, 99.99% of the individuals receiving measurable TED have received doses below the 2 roentgen equivalent in man (rems) (20 millisievert [mSv]) TED administrative control level (ACL), which is well below the DOE regulatory limit of 5 rems (50 mSv) TED annually. The occupational radiation exposure records show that in 2012, DOE facilities continued to comply with DOE dose limits and ACLs and worked to minimize exposure to individuals. The DOE collective TED decreased 17.1% from 2011 to 2012. The collective TED decreased at three of the five sites with the largest collective TED. u Idaho Site – Collective dose reductions were achieved as a result of continuing improvements at the Advanced Mixed Waste Treatment Project (AMWTP) through the planning of drum movements that reduced the number of times a container is handled; placement of waste containers that created highradiation areas in a centralized location; and increased worker awareness of high-dose rate areas. In addition, Idaho had the largest decrease in the total number of workers with measurable TED (1,143 fewer workers). u Hanford Site (Hanford) – An overall reduction of decontamination and decommissioning (D&D) activities at the Plutonium Finishing Plant (PFP) and Transuranic (TRU) retrieval activities resulted in collective dose reductions. u Savannah River Site (SRS) – Reductions were achieved through ALARA initiatives employed site wide. The Solid Waste Management Facility used extended specialty tools, cameras and lead shield walls to facilitate removal of drums. These tools and techniques reduce exposure time through improved efficiency, increase distance from the source of radiation by remote monitoring, shield the workers to lower the dose rate, and reduce the potential for contamination and release of material through repacking of waste. Overall, from 2011 to 2012, there was a 19% decrease in the number of workers with measurable dose. Furthermore, due to a slight decrease in both the DOE workforce (7%) and monitored workers (10%), the ratio of workers with measurable doses to monitored workers decreased to 13%. Another primary indicator of the level of radiation exposure covered in this report is the average measurable dose, which normalizes the collective dose over the population of workers who actually received a measurable dose. The average measurable TED increased by 3% from 2011 to 2012. Additional analyses show that the dose distribution in 2012 was similar to the distribution in 2011. In 2012, 13% of the monitored workers received a measurable TED and the average measurable TED, 0.069 rem, was less than 2% of the DOE limit. From 2011 to 2012, the collective TED and the number of individuals with measurable TED decreased 17.1% and 19%, respectively. These decreases were mainly due to an overall reduction of D&D activities at the PFP and TRU retrieval activities at Hanford; a 78% decrease in the number of targeted waste drums that were processed at the Idaho Site’s Accelerated Retrieval Project (ARP) from 5,566 drums in 2011 to a total of 1,211 drums processed in 2012; and ALARA initiatives employed site wide at SRS. In addition, the decreases were the result of decreased American Recovery and Reinvestment Act (ARRA) activities and continuing D&D, particularly at the DOE sites that comprise the majority of DOE collective dose. Over the past 5 years, the size of the monitored workforce has remained at a fairly stable level (within 12%), while the collective dose has varied up to 37%. No reported doses exceeded the DOE occupational limit of 5 rems TED in 2012 and no reported doses exceeded the DOE ACL of 2 rems TED.« less

Dose reduction and cost-benefit analysis at Japan`s Tokai No. 2 Plant

DOE Office of Scientific and Technical Information (OSTI.GOV)

Humamoto, Hisao; Suzuki, Seishiro; Taniguchi, Kazufumi

1995-03-01

In the Tokai No. 2 power plant of the Japan Atomic Power Company, about 80% of the annual dose equivalent is received during periodic maintenance outages. A project group for dose reduction was organized at the company`s headquarters in 1986; in 1988, they proposed a five-year program to reduce by half the collective dose of 4 person-Sv per normal outage work. To achieve the target dose value, some dose-reduction measures were undertaken, namely, permanent radiation shielding, decontamination, automatic, operating machines, and ALARA organization. As the result, the collective dose from normal outage work was 1.6 person-Sv in 1992, which wasmore » less than the initial target value.« less

A phase I and pharmacokinetic study of the quinoxaline antitumour Agent R(+)XK469 in patients with advanced solid tumours

PubMed Central

Undevia, Samir D.; Innocenti, Federico; Ramirez, Jacqueline; House, Larry; Desai, Apurva A.; Skoog, Linda A.; Singh, Deepti A.; Karrison, Theodore; Kindler, Hedy L.; Ratain, Mark J.

2009-01-01

Purpose To investigate the safety and pharmacokinetics of R(+)XK469, a quinoxaline analogue, in patients with advanced refractory solid tumours. Preclinical studies suggested that efficacy was independent of schedule but that toxicity was decreased by dividing the dose. Methods R(+)XK469 was initially administered as a 30 min intravenous infusion on days 1–5 of a 21-d cycle. Based on the demonstration of a long half-life, the dosing schedule was subsequently amended to infusion on days 1, 3 and 5 of a 21-d cycle. An alternate single-dose schedule of once every 21 d was also explored. Blood samples were collected for pharmaco-kinetic studies. Results Dose-limiting toxicity (DLT) was neutropaenia. There was significant interindividual variability in clearance as evidenced by a coefficient of variation of 46%. A flat-dosing scheme (not based on body surface area) was justified by the absence of correlation between clearance and body surface area. A partial response was observed in a patient with nasopharyngeal carcinoma. Conclusions The recommended phase II doses are 850–1100 mg/d on days 1, 3 and 5 of a 21-d cycle and 2500 mg on day 1 of a 21-d cycle. The observed interpatient pharmacokinetic variability should prompt investigation into the presence of genetic polymorphism in relevant metabolizing enzymes. PMID:18650079

Single dose, CYP2D6 genotype-stratified pharmacokinetic study of atomoxetine in children with ADHD.

PubMed

Brown, J T; Abdel-Rahman, S M; van Haandel, L; Gaedigk, A; Lin, Y S; Leeder, J S

2016-06-01

The effect of CYP2D6 genotype on the dose-exposure relationship for atomoxetine has not been well characterized in children. Children 6-17 years of age diagnosed with attention-deficit hyperactivity disorder (ADHD) were stratified by CYP2D6 genotype into groups with 0 (poor metabolizers [PMs], n = 4), 0.5 (intermediate metabolizers [IMs], n = 3), one (extensive metabolizer [EM]1, n = 8) or two (EM2, n = 8) functional alleles and administered a single 0.5 mg/kg oral dose of atomoxetine (ATX). Plasma and urine samples were collected for 24 (IM, EM1, and EM2) or 72 hours (PMs). Dose-corrected ATX systemic exposure (area under the curve [AUC]0-∞ ) varied 29.6-fold across the study cohort, ranging from 4.4 ± 2.7 μM*h in EM2s to 5.8 ± 1.7 μM*h, 16.3 ± 2.9 μM*h, and 50.2 ± 7.3 μM*h in EM1s, IMs, and PMs, respectively (P < 0.0001). Simulated steady state profiles at the maximum US Food and Drug Administration (FDA)-recommended dose suggest that most patients are unlikely to attain adequate ATX exposures. These data support the need for individualized dosing strategies for more effective use of the medication. © 2015 American Society for Clinical Pharmacology and Therapeutics.

Effects of Different Doses of Levetiracetam on Aquaporin 4 Expression in Rats with Brain Edema Following Fluid Percussion Injury

PubMed Central

Jin, Hongbo; Li, Wenling; Dong, Changzheng; Ma, Li; Wu, Jiang; Zhao, Wenqing

2016-01-01

Background This study was designed to investigate the effects of different doses of levetiracetam on aquaporin 4 (AQP4) expression in rats after fluid percussion injury. Material/Methods Sprague-Dawley rats were randomly divided into 4 groups: sham operation group, traumatic brain injury group, low-dose levetiracetam group, and high-dose levetiracetam group. Brain edema models were established by fluid percussion injury, and intervened by the administration of levetiracetam. Samples from the 4 groups were collected at 2, 6, 12, and 24 h, and at 3 and 7 days after injury. Histological observation was performed using hematoxylin-eosin staining and immunohistochemical staining. AQP4 and AQP4 mRNA expression was detected using Western blot assay and RT-PCR. Brain water content was measured by the dry-wet method. Results Compared with the traumatic brain injury group, brain water content, AQP4 expression, and AQP4 mRNA expression were lower in the levetiracetam groups at each time point and the differences were statistically significant (P<0.05). The intervention effects of high-dose levetiracetam were more apparent. Conclusions Levetiracetam can lessen brain edema from fluid percussion injury by down-regulating AQP4 and AQP4 mRNA expression. There is a dose-effect relationship in the preventive effect of levetiracetam within a certain extent. PMID:26927633

Impact of charcoal waste application on the soil organic matter content and composition of an Haplic Cambisol from South Brazil

NASA Astrophysics Data System (ADS)

dos Anjos Leal, Otávio; Pinheiro Dick, Deborah; Cylene Lombardi, Kátia; Gonçalves Maciel, Vanessa

2014-05-01

In some regions in Brazil, charcoal is usually applied to the soil with the purpose to improve its fertility and its organic carbon (SOC) content. In Brazil, the use of charcoal waste from steel industry with agronomic purposes represents also an alternative and sustainable fate for this material. In this context, the objective of this work was to evaluate the impact of Eucalyptus charcoal waste application on the SOC content and on the soil organic matter (SOM) composition. Increasing doses of charcoal (0, 10, 20 and 40 Mg ha-1) were applied to an Haplic Cambisol, in Irati, South-Brazil. Charcoal was initially applied on the soil surface, and then it was incorporated at 10 cm with a harrow. Soil undisturbed and disturbed samples (four replicates) were collected in September 2011 (1 y and 9 months) after charcoal incorporation. Four soil depths were evaluated (0-5, 5-10, 10-20 and 20-30 cm) and each replicate was composed by three subsamples collected within each plot. The soil samples were air dried, passed through a 9.51 mm sieve and thereafter through a 2.00 mm sieve. The SOC content and total N were quantified by dry combustion. The SOM was concentrated with fluoridric acid 10% and then the SOM composition was evaluated by thermogravimetric analysis along the soil profile. The main impact of charcoal application occurred at the 0-5 cm layer of the area treated with the highest dose: SOC content increased in 15.5 g kg-1 in comparison to the soil without charcoal application. The intermediary doses also increased the SOC content, but the differences were not significant. No differences for N content were found in this soil depth. Further results were observed in the 10-20 cm soil depth, where the highest dose increased the SOC content and N content. Furthermore, this treatment increased the recalcitrance of the SOM, mainly at the 0-5 cm and 10-20 cm soil layers. No differences between doses of charcoal application were found in the 20-30 cm soil depth, suggesting that the charcoal has not migrated so deep in soil even after almost two years of its incorporation.

Measurements of radioactivity and dose assessments in some building materials in Bitlis, Turkey.

PubMed

Kayakökü, Halime; Karatepe, Şule; Doğru, Mahmut

2016-09-01

In this study, samples of perlite, pumice and Ahlat stones (Ignimbrite) extracted from mines in Bitlis and samples of other building materials produced in facilities in Bitlis were collected and analyzed. Activity concentrations of (226)Ra, (232)Th and (40)K in samples of building materials were measured using NaI detector (NaI(Tl)) with an efficiency of 24%. The radon measurements of building material samples were determined using CR-39 nuclear track detectors. (226)Ra, (232)Th and (40)K radioactivity concentrations ranged from (29.6±5.9 to 228.2±38.1Bq/kg), (10.8±5.4 to 95.5±26.1Bq/kg) and (249.3±124.7 to 2580.1±266.9Bq/kg), respectively. Radon concentration, radium equivalent activities, absorbed dose rate, excess lifetime cancer risk and the values of hazard indices were calculated for the measured samples to assess the radiation hazards arising from using those materials in the construction of dwellings. Radon concentration ranged between 89.2±12.0Bq/m(3) and 1141.0±225.0Bq/m(3). It was determined that Raeq values of samples conformed to world standards except for perlite and single samples of brick and Ahlat stone. Calculated values of absorbed dose rate ranged from 81.3±20.5 to 420.6±42.8nGy/h. ELCR values ranged from (1.8±0.3)×10(-3) to (9.0±1.0)×10(-3). All samples had ELCR values higher than the world average. The values of Hin and Hex varied from 0.35±0.11 to 1.78±0.18 and from 0.37±0.09 to 1.17±0.13, respectively. The results were compared with standard radioactivity values determined by international organizations and with similar studies. There would be a radiation risk for people living in buildings made of perlite, Ahlat-1 and Brick-3. Copyright © 2016 Elsevier Ltd. All rights reserved.

Quantification of absorption, retention and elimination of two different oral doses of vitamin A in Zambian boys using accelerator mass spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aklamati, E K; Mulenga, M; Dueker, S R

A recent survey indicated that high-dose vitamin A supplements (HD-VAS) had no apparent effect on vitamin A (VA) status of Zambian children <5 y of age. To explore possible reasons for the lack of response to HD-VAS among Zambian children, we quantified the absorption, retention, and urinary elimination of either a single HDVAS (60 mg) or a smaller dose of stable isotope (SI)-labeled VA (5 mg), which was used to estimate VA pool size, in 3-4 y old Zambian boys (n = 4 for each VA dose). A 25 nCi tracer dose of [{sup 14}C{sub 2}]-labeled VA was co-administered withmore » the HD-VAS or SI-labeled VA, and 24-hr stool and urine samples were collected for 3 and 7 consecutive days, respectively, and 24-hr urine samples at 4 later time points. Accelerator Mass Spectrometry (AMS) was used to measure the cumulative excretion of {sup 14}C in stool and urine 3d after dosing to estimate, respectively, absorption and retention of the VAS and SI-labeled VA. The urinary elimination rate (UER) was estimated by plotting {sup 14}C in urine vs. time, and fitting an exponential equation to the data. Estimates of mean absorption, retention and the UER were 83.8 {+-} 7.1%, 76.3 {+-} 6.7%, and 1.9 {+-} 0.6%/d, respectively, for the HD-VAS and 76.5 {+-} 9.5%, 71.1 {+-} 9.4%, and 1.8 {+-} 1.2%/d, respectively for the smaller dose of SI-labeled VA. Estimates of absorption, retention and the UER did not differ by size of the VA dose administered (P=0.26, 0.40, 0.88, respectively). Estimated absorption and retention were negatively associated with reported fever (P=0.011) and malaria (P =0.010). HD-VAS and SI-labeled VA were adequately absorbed, retained and utilized in apparently healthy Zambian preschool-age boys, although absorption and retention may be affected by recent infections.« less

Choleretic activity of Gentiana lutea ssp. symphyandra in rats.

PubMed

Oztürk, N; Herekman-Demir, T; Oztürk, Y; Bozan, B; Başer, K H

1998-08-01

Effects of an ethanolic extract prepared from G. lutea ssp. symphyandra roots on the bile production and liver in rats were investigated. Bile flows of rats which were treated by a single i.p. dose of CCl(4) 24 h prior to experiments were measured after the cannulation of bile duct under urethane anaesthesia. After an equilibration period of 1 h, the lyophilized extract were administered intraduodenally (500 mg/kg i.p.), while control animals received physiological saline only. To monitor the effect of multiple dose therapy, rats received the same dose of G. lutea ssp. symphyandra extract for 3 days (2 days prior to CCl(4) administration) and their bile flows were measured after the cannulation. In all groups, bile samples were collected for 3 h with 15 min intervals. After the completion of bile flow experiment, rat livers were removed and put in neutral formaldehyde solution (10%) for the histological examination. According to results obtained, multiple dose treatment of rats with the plant extract normalized the decreased bile flow due CCl(4), whereas single dose therapy was ineffective on the impaired bile flow. These data indicate that the extract prepared from Gentiana lutea ssp. symphyandra roots has a hepatoprotective activity. Copyright © 1998 Gustav Fischer Verlag. Published by Elsevier GmbH.. All rights reserved.

Pharmacokinetics of terbinafine after oral administration of a single dose to Hispaniolan Amazon parrots (Amazona ventralis).

PubMed

Evans, Erika E; Emery, Lee C; Cox, Sherry K; Souza, Marcy J

2013-06-01

To determine pharmacokinetics after oral administration of a single dose of terbinafine hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). 6 healthy adult Hispaniolan Amazon parrots. A single dose of terbinafine hydrochloride (60 mg/kg) was administered orally to each bird, which was followed immediately by administration of a commercially available gavage feeding formula. Blood samples were collected at the time of drug administration (time 0) and 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours after drug administration. Plasma concentrations of terbinafine were determined via high-performance liquid chromatography. Data from 1 bird were discarded because of a possible error in the dose of drug administered. After oral administration of terbinafine, the maximum concentration for the remaining 5 fed birds ranged from 109 to 671 ng/mL, half-life ranged from 6 to 13.5 hours, and time to the maximum concentration ranged from 2 to 8 hours. No adverse effects were observed. Analysis of the results indicated that oral administration of terbinafine at a dose of 60 mg/kg to Amazon parrots did not result in adverse effects and may be potentially of use in the treatment of aspergillosis. Additional studies are needed to determine treatment efficacy and safety.

Localized accumulation of lead within and among bones from lead-dosed goats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cretacci, Yan; Department of Environmental Health Sciences, School of Public Health, The University at Albany, P.O. Box 509, Albany, NY 12201-0509; Parsons, Patrick J., E-mail: pparsons@wadsworth.org

2010-01-15

The principal aim of this study was to gain a better understanding of where lead (Pb) accumulates and how it is distributed, within the bones of dosed goats. Adult goats were periodically dosed with Pb over a number of years for the primary purpose of producing blood pools containing endogenously bound Pb, for the New York State Blood Lead Proficiency Testing Program. Bone samples (e.g., primarily tibia, femur, humerus, and radius) were collected post-mortem from 11 animals and were analyzed for Pb content by acid digestion and electrothermal atomic absorption spectrometry (ETAAS or GFAAS). Average tibia Pb levels were foundmore » to correlate strongly with the cumulative Pb dose (r{sup 2}=0.81). However, the concentration of Pb in different bones and even within a small area of the same bone varied tremendously. Blood-rich trabecular (spongy) bone, such as the patella and calcaneus, were much more enriched in Pb than was cortical (compact) bone. In some dosed animals, the Pb concentration in the tibia was markedly higher at the proximal and distal ends of the bone compared to the mid-shaft. The implications of these findings with regard to the noninvasive measurement of lead in bone by XRF methods are discussed.« less

Chamomile and oregano extracts synergistically exhibit antihyperglycemic, antihyperlipidemic, and renal protective effects in alloxan-induced diabetic rats.

PubMed

Prasanna, Rajagopalan; Ashraf, Elbessoumy A; Essam, Mahmoud A

2017-01-01

The bio-activities of separate Matricaria chamomilla (chamomile) and Origanum vulgare (oregano) are well studied; however, the combined effects of both natural products in animal diabetic models are not well characterized. In this study, alloxan-induced male albino rats were treated with single dose aqueous suspension of chamomile or oregano at dose level of either 150 or 300 mg/kg body mass or as equal parts as combination by stomach tube for 6 weeks. After treatment, blood samples were assessed for diabetic, renal, and lipid profiles. Insulin, amylase activity, and diabetic renal apoptosis were further evaluated. Treatment with higher dose of the extracts (300 mg/kg) as individual or as mixture of low doses (150 mg/kg of both the extracts) had significant mass gain, hypoglycemic effect (p ≤ 0.05) with decreased amylase activity and increased serum insulin levels. Restoration of renal profile, lipid profile with increase in HDL-c (p ≤ 0.05) along with reversal of pro-apoptotic Bax and anti-apoptotic Bcl-2 were well observed with 300 mg/kg mixture, showing synergistic activity of the extracts compared with individual low dose of 150 mg/kg. Collectively, our results indicate that combination of chamomile and oregano extracts will form a new class of drugs to treat diabetic complications.

Effective Dose of Radon 222 Bottled Water in Different Age Groups Humans: Bandar Abbas City, Iran.

PubMed

Fakhri, Yadolah; Mahvi, Amir Hossein; Langarizadeh, Ghazaleh; Zandsalimi, Yahya; Amirhajeloo, Leila Rasouli; Kargosha, Morteza; Moradi, Mahboobeh; Moradi, Bigard; Mirzaei, Maryam

2015-06-04

Radon 222 is a natural radioactive element with a half-life of 3.8 days. It is odorless and colorless as well as water-soluble. Consuming waters which contain high concentration of 222Rn would increase the effective dose received by different age groups. It would also be followed by an increased prevalence of cancer. In this research, 72 samples of the most commonly used bottled water in Bandar Abbas were collected in 3 consecutive months, May, June and July of 2013. Concentration 222Rn of was measured by radon-meter model RTM166-2. The effective dose received by the 4 age groups, male and female adults as well as children and infants was estimated using the equation proposed by UNSCEAR. The results revealed that the mean and range concentration of 222Rn in bottled waters were 641±9 Bq/m3 and 0-901 Bq/m3, respectively. The mean concentration of 222Rn in the well-known Marks followed this Zam Zam>Bishe>Koohrng>Dassani>Christal>Polour>Damavand>Sivan. Infants were observed to receive a higher effective dose than children. The highest and lowest effective dose received was found to belong to male adults and children, respectively.

Combining benefits of an adrenergic and a muscarinic blocker in a single formulation - a pharmacokinetic evaluation.

PubMed

Nazarudheen, Shabana; Dey, Surajit; Kandhwal, Kirti; Arora, Rachna; Reyar, Simrit; Khuroo, Arshad H; Monif, Tausif; Madan, Sumit; Arora, Vinod

2013-11-01

A pharmacokinetic bioequivalence study was conducted in Asian subjects, to compare a fixed dose combination capsule single oral dose of alpha adrenoceptor blocker-Alfuzosin hydrochloride 10mg extended release and muscarinic antagonists-Solifenacin succinate 5mg against individually administered Xatral XL 10mg tablets (Alfuzosin) of Sanofi Synthelabo Limited, United Kingdom (UK) and Vesicare 5mg tablets (Solifenacin) of Astellas Pharma Limited, UK under fed conditions. Blood samples were collected pre-dose up to 72 h post dose for determination of plasma Alfuzosin and Solifenacin concentrations and calculation of the pharmacokinetic parameters. ANOVA was performed on the log (natural)-transformed pharmacokinetic parameters. A 90% confidence interval for the ratios of the test and reference product averages (least square means) were calculated for alfuzosin and solifenacin. The 90% confidence intervals obtained for alfuzosin for Cmax, AUC0-t and AUC0-∞ were 102.74-122.75%, 95.84-116.96% and 95.82-116.76%, respectively. The 90% confidence intervals obtained for Solifenacin for Cmax, and AUC0-72 were 89.55-97.91% and 90.47-99.38%, respectively. Based on the results, the fixed dose combination was concluded to be bioequivalent to individually administered products. Copyright © 2013 Elsevier Inc. All rights reserved.

17DD yellow fever vaccine: a double blind, randomized clinical trial of immunogenicity and safety on a dose-response study.

PubMed

Martins, Reinaldo M; Maia, Maria de Lourdes S; Farias, Roberto Henrique G; Camacho, Luiz Antonio B; Freire, Marcos S; Galler, Ricardo; Yamamura, Anna Maya Yoshida; Almeida, Luiz Fernando C; Lima, Sheila Maria B; Nogueira, Rita Maria R; Sá, Gloria Regina S; Hokama, Darcy A; de Carvalho, Ricardo; Freire, Ricardo Aguiar V; Pereira Filho, Edson; Leal, Maria da Luz Fernandes; Homma, Akira

2013-04-01

To verify if the Bio-Manguinhos 17DD yellow fever vaccine (17DD-YFV) used in lower doses is as immunogenic and safe as the current formulation. Doses from 27,476 IU to 587 IU induced similar seroconversion rates and neutralizing antibodies geometric mean titers (GMTs). Immunity of those who seroconverted to YF was maintained for 10 mo. Reactogenicity was low for all groups. Young and healthy adult males (n = 900) were recruited and randomized into 6 groups, to receive de-escalating doses of 17DD-YFV, from 27,476 IU to 31 IU. Blood samples were collected before vaccination (for neutralization tests to yellow fever, serology for dengue and clinical chemistry), 3 to 7 d after vaccination (for viremia and clinical chemistry) and 30 d after vaccination (for new yellow fever serology and clinical chemistry). Adverse events diaries were filled out by volunteers during 10 d after vaccination. Volunteers were retested for yellow fever and dengue antibodies 10 mo later. Seropositivity for dengue was found in 87.6% of volunteers before vaccination, but this had no significant influence on conclusions. In young healthy adults Bio-Manguinhos/Fiocruz yellow fever vaccine can be used in much lower doses than usual. INTERNATIONAL REGISTER: ISRCTN 38082350.

Effective Dose of Radon 222 Bottled Water in Different Age Groups Humans: Bandar Abbas City, Iran

PubMed Central

Fakhri, Yadolah; Mahvi, Amir Hossein; Langarizadeh, Ghazaleh; Zandsalimi, Yahya; Amirhajeloo, Leila Rasouli; Kargosha, Morteza; Moradi, Mahboobeh; Moradi, Bigard; Mirzaei, Maryam

2016-01-01

Radon 222 is a natural radioactive element with a half-life of 3.8 days. It is odorless and colorless as well as water-soluble. Consuming waters which contain high concentration of 222Rn would increase the effective dose received by different age groups. It would also be followed by an increased prevalence of cancer. In this research, 72 samples of the most commonly used bottled water in Bandar Abbas were collected in 3 consecutive months, May, June and July of 2013. Concentration 222Rn of was measured by radon-meter model RTM166-2. The effective dose received by the 4 age groups, male and female adults as well as children and infants was estimated using the equation proposed by UNSCEAR. The results revealed that the mean and range concentration of 222Rn in bottled waters were 641±9 Bq/m3 and 0-901 Bq/m3, respectively. The mean concentration of 222Rn in the well-known Marks followed this Zam Zam>Bishe>Koohrng>Dassani>Christal>Polour>Damavand>Sivan. Infants were observed to receive a higher effective dose than children. The highest and lowest effective dose received was found to belong to male adults and children, respectively. PMID:26383192

Alternative sample sizes for verification dose experiments and dose audits

NASA Astrophysics Data System (ADS)

Taylor, W. A.; Hansen, J. M.

1999-01-01

ISO 11137 (1995), "Sterilization of Health Care Products—Requirements for Validation and Routine Control—Radiation Sterilization", provides sampling plans for performing initial verification dose experiments and quarterly dose audits. Alternative sampling plans are presented which provide equivalent protection. These sampling plans can significantly reduce the cost of testing. These alternative sampling plans have been included in a draft ISO Technical Report (type 2). This paper examines the rational behind the proposed alternative sampling plans. The protection provided by the current verification and audit sampling plans is first examined. Then methods for identifying equivalent plans are highlighted. Finally, methods for comparing the cost associated with the different plans are provided. This paper includes additional guidance for selecting between the original and alternative sampling plans not included in the technical report.

A phase I study with neratinib (HKI-272), an irreversible pan ErbB receptor tyrosine kinase inhibitor, in patients with solid tumors.

PubMed

Wong, Kwok-K; Fracasso, Paula M; Bukowski, Ronald M; Lynch, Thomas J; Munster, Pamela N; Shapiro, Geoffrey I; Jänne, Pasi A; Eder, Joseph P; Naughton, Michael J; Ellis, Matthew J; Jones, Suzanne F; Mekhail, Tarek; Zacharchuk, Charles; Vermette, Jennifer; Abbas, Richat; Quinn, Susan; Powell, Christine; Burris, Howard A

2009-04-01

The dose-limiting toxicities, maximum tolerated dose, pharmacokinetic profile, and preliminary antitumor activity of neratinib (HKI-272), an irreversible pan ErbB inhibitor, were determined in patients with advanced solid tumors. Neratinib was administered orally as a single dose, followed by a 1-week observation period, and then once daily continuously. Planned dose escalation was 40, 80, 120, 180, 240, 320, 400, and 500 mg. For pharmacokinetic analysis, timed blood samples were collected after administration of the single dose and after the first 14 days of continuous daily administration. Dose-limiting toxicity was grade 3 diarrhea, which occurred in one patient treated with 180 mg and in four patients treated with 400 mg neratinib; hence, the maximum tolerated dose was determined to be 320 mg. Other common neratinib-related toxicities included nausea, vomiting, fatigue, and anorexia. Exposure to neratinib was dose dependent, and the pharmacokinetic profile of neratinib supports a once-a-day dosing regimen. Partial response was observed for 8 (32%) of the 25 evaluable patients with breast cancer. Stable disease >or=24 weeks was observed in one evaluable breast cancer patient and 6 (43%) of the 14 evaluable non-small cell lung cancer patients. The maximum tolerated dose of once-daily oral neratinib is 320 mg. The most common neratinib-related toxicity was diarrhea. Antitumor activity was observed in patients with breast cancer who had previous treatment with trastuzumab, anthracyclines, and taxanes, and tumors with a baseline ErbB-2 immunohistochemical staining intensity of 2+ or 3+. The antitumor activity, tolerable toxicity profile, and pharmacokinetic properties of neratinib warrant its further evaluation.

Single- and multiple-dose pharmacokinetics, pharmacodynamics, and safety of apixaban in healthy Chinese subjects

PubMed Central

Cui, Yimin; Song, Yan; Wang, Jessie; Yu, Zhigang; Schuster, Alan; Barrett, Yu Chen; Frost, Charles

2013-01-01

Background The pharmacokinetics (PK), pharmacodynamics (PD), and safety of apixaban were assessed in healthy Chinese subjects in this randomized, placebo-controlled, double-blind, single-sequence, single- and multiple-dose study. Subjects and methods Eighteen subjects 18–45 years of age were randomly assigned (2:1 ratio) to receive apixaban or matched placebo. Subjects received a single 10 mg dose of apixaban or placebo on day 1, followed by 10 mg apixaban or placebo twice daily for 6 days (days 4–9). The PK and PD of apixaban were assessed by collecting plasma samples for 72 hours following the dose on day 1 and the morning dose on day 9, and measuring apixaban concentration and anti-Xa activity. Safety was assessed via physical examinations, vital sign measurements, electrocardiograms, and clinical laboratory evaluations. Results PK analysis showed similar characteristics of apixaban after single and multiple doses, including a median time to maximum concentration of ~3 hours, mean elimination half-life of ~11 hours, and renal clearance of ~1.2 L/hour. The accumulation index was 1.7, consistent with twice-daily dosing and the observed elimination half-life. Single-dose data predict multiple-dose PK, therefore apixaban PK are time-independent. The relationship between anti-Xa activity and plasma apixaban concentrations appears to be linear. Apixaban was safe and well tolerated, with no bleeding-related adverse events reported. Conclusion Apixaban was safe and well tolerated in healthy Chinese subjects. Apixaban PK and PD were predictable and consistent with findings from previous studies in Asian and non-Asian subjects. The administration of apixaban does not require any dose modification based on race. PMID:24353445

Pharmacokinetics of opicapone, a third-generation COMT inhibitor, after single and multiple oral administration: A comparative study in the rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gonçalves, Daniela

Opicapone is a novel potent, reversible and purely peripheral catechol-O-methyltransferase inhibitor that has been developed to be used as an adjunct to levodopa/aromatic L-amino acid decarboxylase inhibitor therapy for Parkinson's disease. Thus, this study aimed to compare the plasma pharmacokinetics of opicapone and its active metabolite (BIA 9-1079) after the administration of single and multiple oral doses to rats. Wistar rats (n = 8 per group) were orally treated with single (30, 60 or 90 mg/kg) or multiple (30 mg/kg once-daily for seven consecutive days) oral doses of opicapone. Blood samples were collected up to 24 h post-dosing through amore » cannula introduced in the tail vein of rats. After quantifying opicapone and BIA 9-1079 in plasma, a non-compartmental pharmacokinetic analysis was performed. Opicapone was quickly absorbed (time to reach the maximum plasma concentration ≤ 2 h) in both dosage regimens and the extent of systemic exposure to opicapone increased approximately in a dose-proportional manner after single-dosing within the studied dose range (30–90 mg/kg). Opicapone and BIA 9-1079 showed a relatively short plasma elimination half-life (1.58–4.50 h) and a small systemic accumulation after multiple-dosing. Hence, no pharmacokinetic concerns are expected when opicapone is administered with a once-daily dosing regimen. - Highlights: • Opicapone is relatively rapid absorbed after oral administration to rats. • Systemic exposure to opicapone increases approximately in a dose-proportional manner. • Opicapone and BIA 9-1079 show a small systemic accumulation after multiple-dosing.« less

Single oral doses of netazepide (YF476), a gastrin receptor antagonist, cause dose-dependent, sustained increases in gastric pH compared with placebo and ranitidine in healthy subjects.

PubMed

Boyce, M; David, O; Darwin, K; Mitchell, T; Johnston, A; Warrington, S

2012-07-01

Nonclinical studies have shown netazepide (YF476) to be a potent, selective, competitive and orally active gastrin receptor antagonist. To administer to humans for the first time single oral doses of netazepide, to assess their tolerability, safety, pharmacokinetics and effect on 24-h gastric pH. We did two randomised double-blind single-dose studies in healthy subjects. The first (n = 12) was a six-way incomplete crossover pilot study of rising doses of netazepide (range 0.5-100 mg) and placebo. The second (n = 20) was a five-way complete crossover study of netazepide 5, 25 and 100 mg, ranitidine 150 mg and placebo. In both trials we collected frequent blood samples, measured plasma netazepide and calculated pharmacokinetic parameters. In the comparative trial we measured gastric pH continuously for 24 h and compared treatments by percentage time gastric pH ≥4. Netazepide was well tolerated. Median t (max) and t (½) for the 100 mg dose were about 1 and 7 h, respectively, and the pharmacokinetics were dose-proportional. Netazepide and ranitidine each increased gastric pH. Onset of activity was similarly rapid for both. All netazepide doses were more effective than placebo (P ≤ 0.023). Compared with ranitidine, netazepide 5 mg was as effective, and netazepide 25 and 100 mg were much more effective (P ≤ 0.010), over the 24 h after dosing. Activity of ranitidine lasted about 12 h, whereas that of netazepide exceeded 24 h. In human: netazepide is an orally active gastrin antagonist, and gastrin has a major role in controlling gastric acidity. Repeated-dose studies are justified. NCT01538784 and NCT01538797. © 2012 Blackwell Publishing Ltd.

A measles outbreak in Sindh, Pakistan caused by a genotype B3 virus.

PubMed

Zaidi, Syed Sohail Zahoor; Hameed, Abdul; Ali, Naeem; Umair, Massab; Alam, Muhammad Masroor; Rana, Muhammad Suleman; Sharif, Salmaan; Aamir, Uzma Bashir; Shaukat, Shahzad; Angez, Mehar; Khurshid, Adnan; Akhtar, Ribqa; Mehmood, Nayab; Badar, Nazish

2017-12-01

Measles continues to be a major public health issue causing substantial outbreaks worldwide, mostly affecting young children. Molecular analysis of measles viruses provides important information on outbreak linkages and transmission pathways that can be helpful towards implementation of appropriate control programs. In Pakistan, the control of measles is still tenuous, and progress towards elimination has been irregular and challenging. In the 2013 measles outbreak we received 4,682 sera collected from suspected patients in 23 districts across Sindh. A total of 3,283 samples were confirmed measles positive using IgM ELISA with the highest infection rate in children aged 1-12 months. Males were more affected than females and a visible peak was observed from January to April. Among the 3,283 cases, 59.1% were unvaccinated, 29.6% had received 1 dose and 10.3% had received 2 doses of measles vaccine while 0.85% had an unknown vaccination status. For genotype detection and phylogenetic analysis, 60 throat swab samples were collected from suspected patients below 15 years of age in eight districts of Sindh province. Forty four (73%; 44/60) throat swab samples were successfully genotyped using RT-PCR. Phylogenetic analyses based on partial sequences of the nucleocapsid protein gene revealed that all Pakistani measles virus strains belonged to genotype B3 and were closely related to those isolated from neighboring countries such as Iran, Afghanistan (99.1-100%) and India with 98.6 - 99.6% nucleotide homology. This is the first report on the phylogenetic analysis of measles B3 genotype strains from Pakistan and highlights the need for strengthening the surveillance systems and improving immunization coverage across the country.

Dermal exposure and urinary 1-hydroxypyrene among asphalt roofing workers

DOE Office of Scientific and Technical Information (OSTI.GOV)

McClean, M.D.; Rinehart, R.D.; Sapkota, A.

2007-07-01

The primary objective of this study was to identify significant determinants of dermal exposure to polycyclic aromatic compounds (PACs) among asphalt roofing workers and use urinary 1-hydroxyprene (1-OHP) measurements to evaluate the effect of dermal exposure on total absorbed dose. The study population included 26 asphalt roofing workers who performed three primary tasks: tearing off old roofs, putting down new roofs, and operating the kettle at ground level. During multiple consecutive work shifts, dermal patch samples were collected from the underside of each worker's wrists and were analyzed for PACs, pyrene, and benzo(a)pyrene (BAP). During the same work week, urinemore » samples were collected at pre-shift, post-shift, and bedtime each day and were analyzed for 1-OHP (205 urine samples). Linear mixed effects models were used to evaluate the dermal measurements for the purpose of identifying important determinants of exposure, and to evaluate urinary 1-OHP measurements for the purpose of identifying important determinants of total absorbed dose. Dermal exposures to PAC, pyrene, and BAP were found to vary significantly by roofing task and by the presence of an old coal tar pitch roof. For each of the three analytes, the adjusted mean dermal exposures associated with tear-off were approximately four times higher than exposures associated with operating the kettle. Exposure to coal tar pitch was associated with a 6-fold increase in PAC exposure, an 8-fold increase in pyrene exposure and a 35-fold increase in BAP exposure. The presence of coal tar pitch was the primary determinant of dermal exposure, particularly for exposure to BAP. However, the task-based differences that were observed while controlling for pitch suggest that exposure to asphalt also contributes to dermal exposures.« less

Evaluation of ambient dose equivalent rates influenced by vertical and horizontal distribution of radioactive cesium in soil in Fukushima Prefecture.

PubMed

Malins, Alex; Kurikami, Hiroshi; Nakama, Shigeo; Saito, Tatsuo; Okumura, Masahiko; Machida, Masahiko; Kitamura, Akihiro

2016-01-01

The air dose rate in an environment contaminated with (134)Cs and (137)Cs depends on the amount, depth profile and horizontal distribution of these contaminants within the ground. This paper introduces and verifies a tool that models these variables and calculates ambient dose equivalent rates at 1 m above the ground. Good correlation is found between predicted dose rates and dose rates measured with survey meters in Fukushima Prefecture in areas contaminated with radiocesium from the Fukushima Dai-ichi Nuclear Power Plant accident. This finding is insensitive to the choice for modeling the activity depth distribution in the ground using activity measurements of collected soil layers, or by using exponential and hyperbolic secant fits to the measurement data. Better predictions are obtained by modeling the horizontal distribution of radioactive cesium across an area if multiple soil samples are available, as opposed to assuming a spatially homogeneous contamination distribution. Reductions seen in air dose rates above flat, undisturbed fields in Fukushima Prefecture are consistent with decrement by radioactive decay and downward migration of cesium into soil. Analysis of remediation strategies for farmland soils confirmed that topsoil removal and interchanging a topsoil layer with a subsoil layer result in similar reductions in the air dose rate. These two strategies are more effective than reverse tillage to invert and mix the topsoil. Copyright © 2015 Elsevier Ltd. All rights reserved.

Collective doses to man from dumping of radioactive waste in the Arctic Seas.

PubMed

Nielsen, S P; Iosjpe, M; Strand, P

1997-08-25

A box model for the dispersion of radionuclides in the marine environment covering the Arctic Ocean and the North Atlantic Ocean has been constructed. Collective doses from ingestion pathways have been calculated from unit releases of the radionuclides 3H, 60Co, 63Ni, 90Sr, 129I, 137Cs, 239Pu and 241Am into a fjord on the east coast of NovayaZemlya. The results show that doses for the shorter-lived radionuclides (e.g. 137Cs) are derived mainly from seafood production in the Barents Sea. Doses from the longer-lived radionuclides (e.g. 239Pu) are delivered through marine produce further away from the Arctic Ocean. Collective doses were calculated for two release scenarios, both of which are based on information of the dumping of radioactive waste in the Barents and Kara Seas by the former Soviet Union and on preliminary information from the International Arctic Sea Assessment Programme. A worst-case scenario was assumed according to which all radionuclides in liquid and solid radioactive waste were available for dispersion in the marine environment at the time of dumping. Release of radionuclides from spent nuclear fuel was assumed to take place by direct corrosion of the fuel ignoring the barriers that prevent direct contact between the fuel and the seawater. The second scenario selected assumed that releases of radionuclides from spent nuclear fuel do not occur until after failure of the protective barriers. All other liquid and solid radioactive waste was assumed to be available for dispersion at the time of discharge in both scenarios. The estimated collective dose for the worst-case scenario was about 9 manSv and that for the second scenario was about 3 manSv. In both cases, 137Cs is the radionuclide predicted to dominate the collective doses as well as the peak collective dose rates.

Pharmacokinetics of experimental pentavalent antimony after intramuscular administration in adult volunteers.

PubMed

Vásquez, Laura; Scorza Dagert, José V; Scorza, José V; Vicuña-Fernández, Nelson; de Peña, Yaneira Petit; López, Sabrina; Bendezú, Herminia; Rojas, Elina; Vásquez, Libia; Pérez, Belén

2006-05-01

Pentavalent antimony (SbV) has demonstrated therapeuticeffectiveness against clinical manifestations of leishmaniasis, an infection caused by Leishmania, a genus of flagellate protozoa comprising parasites of worldwide distribution. Approximately 1.8 million new cases are reported annually. The aim of this study was to assess the pharmacokinetics of the investigational generic SbV, Ulamina (pentachloride of antimony + N-methylglucamine), in healthy adult volunteers. In this study, SbV was administered IM as a single 5-mg/kg dose.Blood samples were collected at 0.25, 0.75, 1, 2, 4, 8, 12, and 24 hours after administration; urine samples were collected at 6-hour intervals during the 24-hour postadministration period. Determination of trivalent antimony, SbV, and total antimony concentrations in blood and urine samples was carried out using atomic absorption spectrometry. Clinical history was reviewed and the subjects were monitored before and after administration of SbV using physical examination, weight, and hepatic- and renal-function studies. The pharmacokinetic parameters calculated were Cmax, Tmax, absorption constant (Ka), elimination constant (Kel), AUC2-24h, AUC0-∞, elimination phase (t½β), volume of distribution (Vd), and urinary excretion rate. Five subjects (3 men, 2 women; mean age, 28 years [range, 18-34 years]) were included in the study. One hour after drug administration the following values were obtained: Cmax, 1.1 μg/mL; Tmax, 1.3 hours; Ka, 1.87 hours; Kel, 0.043 hours; AUC0-24h, 12.26 μg/mL · h; AUC0-∞, 19.84 μg/mL · h; t½β, 17.45 hours; Vd, 6.6 L/kg; and urinary excretion rate, 2.8 μg/h; these were mean values for the entire study group. The single dose was well tolerated by all subjects. The investigational generic SbV, Ulamina, was associated with linearelimination after IM administration of a single 5-mg/kg dose. A 2-compartment pharmacokinetic model was observed in these volunteers; the mean t½β, was 17.45 hours and the mean Vd was 6.6 L/kg.

Emergency EPR and OSL dosimetry with table vitamins and minerals.

PubMed

Sholom, S; McKeever, S W S

2016-12-01

Several table vitamins, minerals and L-lysine amino acid have been preliminarily tested as potential emergency dosemeters using electron paramagnetic resonance (EPR) and optically stimulated luminescence (OSL) techniques. Radiation-induced EPR signals were detected in samples of vitamin B2 and L-lysine while samples of multivitamins of different brands as well as mineral Mg demonstrated prominent OSL signals after exposure to ionizing radiation doses. Basic dosimetric properties of the radiation-sensitive substances were studied, namely dose response, fading of the EPR or OSL signals and values of minimum measurable doses (MMDs). For EPR-sensitive samples, the EPR signal is converted into units of dose using a linear dose response and correcting for fading using the measured fading dependence. For OSL-sensitive materials, a multi-aliquot, enhanced-temperature protocol was developed to avoid the problem of sample sensitization and to minimize the influence of signal fading. The sample dose in this case is also evaluated using the dose response and fading curves. MMDs of the EPR-sensitive samples were below 2 Gy while those of the OSL-sensitive materials were below 500 mGy as long as the samples are analyzed within 1 week after exposure. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The Fukushima nuclear accident and the pale grass blue butterfly: evaluating biological effects of long-term low-dose exposures.

PubMed

Hiyama, Atsuki; Nohara, Chiyo; Taira, Wataru; Kinjo, Seira; Iwata, Masaki; Otaki, Joji M

2013-08-12

On August 9th 2012, we published an original research article in Scientific Reports, concluding that artificial radionuclides released from the Fukushima Dai-ichi Nuclear Power Plant exerted genetically and physiologically adverse effects on the pale grass blue butterfly Zizeeria maha in the Fukushima area. Immediately following publication, many questions and comments were generated from all over the world. Here, we have clarified points made in the original paper and answered questions posed by the readers. The following points were clarified. (1) There are many advantages to using the pale grass blue butterfly as an indicator species. (2) The forewings of the individuals collected in Fukushima were significantly smaller than in the northern and southern localities. (3) We observed growth retardation in the butterflies from the Fukushima area. (4) The aberrant colour patterns in the butterflies obtained in the Fukushima area were different from the colour patterns induced by temperature and sibling crosses but similar to those induced by external and internal exposures to the artificial radionuclides and by a chemical mutagen, suggesting that genetic mutations caused the aberrations. (5) This species of butterfly has been plentiful in Fukushima area for at least half a century. We here present specimens collected from Fukushima Prefecture before the accident. (6) Mutation accumulation was detected by the increase in the abnormality rates from May 2011 to September 2011. (7) The abnormal traits were heritable. (8) Our sampling localities were not affected by the tsunami. (9) We used a high enough number of samples to obtain statistically significant results. (10) The standard rearing method was followed, producing normal adults in the control groups. (11) The exposure experiments successfully reproduced the results of the field work. This species of butterfly is vulnerable to long-term low-dose internal and external exposures; however, insect cells are known to be resistant to short-term high-dose irradiation. This discrepancy is reconcilable based on the differences in the experimental conditions. We are just beginning to understand the biological effects of long-term low-dose exposures in animals. Further research is necessary to accurately assess the possible biological effects of the accident.

Evaluation of coral pathogen growth rates after exposure to atmospheric African dust samples

USGS Publications Warehouse

Lisle, John T.; Garrison, Virginia H.; Gray, Michael A.

2014-01-01

Laboratory experiments were conducted to assess if exposure to atmospheric African dust stimulates or inhibits the growth of four putative bacterial coral pathogens. Atmospheric dust was collected from a dust-source region (Mali, West Africa) and from Saharan Air Layer masses over downwind sites in the Caribbean [Trinidad and Tobago and St. Croix, U.S. Virgin Islands (USVI)]. Extracts of dust samples were used to dose laboratory-grown cultures of four putative coral pathogens: Aurantimonas coralicida (white plague type II), Serratia marcescens (white pox), Vibrio coralliilyticus, and V. shiloi (bacteria-induced bleaching). Growth of A. coralicida and V. shiloi was slightly stimulated by dust extracts from Mali and USVI, respectively, but unaffected by extracts from the other dust sources. Lag time to the start of log-growth phase was significantly shortened for A. coralicida when dosed with dust extracts from Mali and USVI. Growth of S. marcescens and V. coralliilyticus was neither stimulated nor inhibited by any of the dust extracts. This study demonstrates that constituents from atmospheric dust can alter growth of recognized coral disease pathogens under laboratory conditions.

Natural radioelement concentrations in the soil of the Mila region of Algeria

NASA Astrophysics Data System (ADS)

Bramki, Amina; Ramdhane, Mourad; Benrachi, Fatima

2017-09-01

In this study, the levels of the natural and artificial radioactivity in soil samples collected at various depths from Algerian agricultural region El-Athmania Mila was measured. Activity concentrations of the concerned radionuclides were determined by gamma-ray spectrometry using a high-purity germanium detector. The activity concentrations of 226Ra, 232Th and 40K were found unchanged as a function of depth and ranged from 23.72±2.37to 65.47±5.06 Bq.kg-1 for 226Ra, from 26.45±0.78 to 27.10±0.80 Bq.kg-1 for 232Th and from 220.80±10.01 to 260.70±8.24 Bq.kg-1 for 40K respectively. To evaluate the radiological hazard of radioactivity in samples, the radium equivalent activity (Raeq), the absorbed dose rate (D), the annual effective dose and the external (Hex) and internal hazard indices (Hin) were calculated. The mean of the excess lifetime cancer risk observed in this study are under the world's mean values.

Evaluation of Flinders Technology Associates cards for storage and molecular detection of avian metapneumoviruses.

PubMed

Awad, Faez; Baylis, Matthew; Jones, Richard C; Ganapathy, Kannan

2014-01-01

The feasibility of using Flinders Technology Associates (FTA) cards for the molecular detection of avian metapneumovirus (aMPV) by reverse transcriptase-polymerase chain reaction (RT-PCR) was investigated. Findings showed that no virus isolation was possible from aMPV-inoculated FTA cards, confirming viral inactivation upon contact with the cards. The detection limits of aMPV from the FTA card and tracheal organ culture medium were 10(1.5) median ciliostatic doses/ml and 10(0.75) median ciliostatic doses/ml respectively. It was possible to perform molecular characterization of both subtypes A and B aMPV using inoculated FTA cards stored for up to 60 days at 4 to 6°C. Tissues of the turbinate, trachea and lung of aMPV-infected chicks sampled either by direct impression smears or by inoculation of the tissue homogenate supernatants onto the FTA cards were positive by RT-PCR. However, the latter yielded more detections. FTA cards are suitable for collecting and transporting aMPV-positive samples, providing a reliable and hazard-free source of RNA for molecular characterization.

Radiological assessment of Abu-Tartur phosphate, Western Desert Egypt.

PubMed

Uosif, M A M; El-Taher, A

2008-01-01

The contents of natural radionuclides ((226)Ra, (232)Th and (40)K) were measured in sedimentary phosphate rock samples (Abu-Tartur phosphate, Western Desert Egypt) by using gamma spectrometry (NaI (Tl) 3"x 3"). Phosphate and environmental samples were collected from Abu-Tartur phosphate mine and the surrounding region. The results are discussed and compared with the levels in phosphate rocks from different countries. The activities of (226)Ra, (232)Th series and (40)K are between (14.9 +/- 0.8 and 302.4 +/- 15.2), (2.6 +/- 1.0 and 154.9 +/- 7.8) and (10.0 +/- 0.5 and 368.4 +/- 18.4) Bq kg(-1), respectively. The Abu-Tartur phosphate deposit was found to have lower activity than many others exploited phosphate sedimentary deposits, with its average total annual dose being only 114.6 microSv y(-1). This value is about 11.46% of the 1.0 mSv y(-1) recommended by the International Commission on Radiological Protection (ICRP-60, 1990) as the maximum annual dose to members of the public.

An Intervention to Reduce Residential Insecticide Exposure during Pregnancy among an Inner-City Cohort

PubMed Central

Williams, Megan K.; Barr, Dana B.; Camann, David E.; Cruz, Linda A.; Carlton, Elizabeth J.; Borjas, Mejico; Reyes, Andria; Evans, Dave; Kinney, Patrick L.; Whitehead, Ralph D.; Perera, Frederica P.; Matsoanne, Stephen; Whyatt, Robin M.

2006-01-01

Background We previously reported widespread insecticide exposure during pregnancy among inner-city women from New York City. Here we report on a pilot intervention using integrated pest management (IPM) to reduce pest infestations and residential insecticide exposures among pregnant New York City African-American and Latina women (25 intervention and 27 control homes). Methods The IPM consisted of professional cleaning, sealing of pest entry points, application of low-toxicity pesticides, and education. Cockroach infestation levels and 2-week integrated indoor air samples were collected at baseline and one month postintervention. The insecticides detected in the indoor air samples were also measured in maternal and umbilical cord blood collected at delivery. Results Cockroach infestations decreased significantly (p = 0.016) after the intervention among intervention cases but not control households. Among the intervention group, levels of piperonyl butoxide (a pyrethroid synergist) were significantly lower in indoor air samples after the intervention (p = 0.016). Insecticides were detected in maternal blood samples collected at delivery from controls but not from the intervention group. The difference was significant for trans-permethrin (p = 0.008) and of borderline significance (p = 0.1) for cis-permethrin and 2-isopropoxyphenol (a propoxur metabolite). Conclusion To our knowledge, this is the first study to use biologic dosimeters of prenatal pesticide exposure for assessing effectiveness of IPM. These pilot data suggest that IPM is an effective strategy for reducing pest infestation levels and the internal dose of insecticides during pregnancy. PMID:17107853

Detection of significant variation in acoustic output of an electromagnetic lithotriptor.

PubMed

Pishchalnikov, Yuri A; McAteer, James A; Vonderhaar, R Jason; Pishchalnikova, Irina V; Williams, James C; Evan, Andrew P

2006-11-01

We describe the observation of significant instability in the output of an electromagnetic lithotriptor. This instability had a form that was not detected by routine assessment, but rather was observed only by collecting many consecutive shock waves in nonstop regimen. A Dornier DoLi-50 lithotriptor used exclusively for basic research was tested and approved by the regional technician. This assessment included hydrophone measures at select power levels with the collection of about 25 shock waves per setting. Subsequent laboratory characterization used a fiberoptic hydrophone and storage oscilloscope for data acquisition. Waveforms were collected nonstop for hundreds of pulses. Output was typically stable for greater than 1,000 shock waves but substantial fluctuations in acoustic pressures were also observed. For example, output at power level 3 (mean peak positive acoustic pressure +/- SD normally 44 +/- 2 MPa) increased dramatically to greater than 50 MPa or decreased significantly to approximately 30 MPa for hundreds of shock waves. The cause of instability was eventually traced to a faulty lithotriptor power supply. Instability in lithotriptor acoustic output can occur and it may not be detected by routine assessment. Collecting waveforms in a nonstop regimen dramatically increases sampling size, improving the detection of instability. Had the instability that we observed occurred during patient treatment, the energy delivered may well have exceeded the planned dose. Since the potential for adverse effects in lithotripsy increases as the dose is increased, it would be valuable to develop ways to better monitor the acoustic output of lithotriptors.

OSL technique for studies of jasper samples

NASA Astrophysics Data System (ADS)

Teixeira, Maria Inês; Caldas, Linda V. E.

2014-02-01

Jasper samples (green, red, brown, ocean and striped) were studied in relation to their optically stimulated luminescence (OSL) dosimetric properties, in this work. Since 2000, the radiation metrology group of IPEN has studied different stones as new materials for application in high-dose dosimetry. The jasper samples were exposed to different radiation doses, using the Gamma-cell 220 system (60Co) of IPEN. Calibration curves were obtained for the jasper samples between 50 Gy and 300 kGy. The reproducibility of the OSL response and the lower detection doses were determined. All five types of jasper samples showed their usefulness as irradiation indicators and as high-dose dosimeters, using the OSL technique.

Natural radionuclide content and radiological hazard associated with usage of quartzite sand samples from Ovacik-Silifke-Mersin open pit as building material in Turkey.

PubMed

Turhan, S; Aykamis, A S; Kiliç, A M

2009-09-01

Activity concentrations of (238)U, (232)Th, (226)Ra and (40)K in quartzite sand samples collected from the Ovacik-Silifke-Mersin open pit located in the East Mediterranean region of Turkey were determined by using a gamma-ray spectrometry technique. The mean activity concentrations of the (238)U, (232)Th, (226)Ra and (40)K in quartzite sand samples were found as 81.7 +/- 22.9 Bq kg(-1), 6.3 +/- 2.8 Bq kg(-1), 77.5 +/- 24.3 Bq kg(-1)and 140.0 +/- 124.1 Bq kg(-1), respectively. The gamma index (I(gamma)), the internal exposure index (I(alpha)), the indoor absorbed dose rate (D(in)) and the corresponding annual effective dose (H(in)) were evaluated for the public exposure to radiological hazard arising due to the use of quartzite sand samples as building material. The values of I(gamma), I(alpha), D(in) and H(in) ranged from 0.20 to 0.75, with a mean of 0.34 +/- 0.11, 0.23 to 0.77 with a mean of 0.39 +/- 0.12, 58.27 to 201.51 nGy h(-1) with a mean of 93.33 +/- 27.63 nGy h(-1) and 0.29 to 0.99 mSv with a mean of 0.46 +/- 0.14 mSv, respectively.

Fast and low-dose computed laminography using compressive sensing based technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abbas, Sajid, E-mail: scho@kaist.ac.kr; Park, Miran, E-mail: scho@kaist.ac.kr; Cho, Seungryong, E-mail: scho@kaist.ac.kr

2015-03-31

Computed laminography (CL) is well known for inspecting microstructures in the materials, weldments and soldering defects in high density packed components or multilayer printed circuit boards. The overload problem on x-ray tube and gross failure of the radio-sensitive electronics devices during a scan are among important issues in CL which needs to be addressed. The sparse-view CL can be one of the viable option to overcome such issues. In this work a numerical aluminum welding phantom was simulated to collect sparsely sampled projection data at only 40 views using a conventional CL scanning scheme i.e. oblique scan. A compressive-sensing inspiredmore » total-variation (TV) minimization algorithm was utilized to reconstruct the images. It is found that the images reconstructed using sparse view data are visually comparable with the images reconstructed using full scan data set i.e. at 360 views on regular interval. We have quantitatively confirmed that tiny structures such as copper and tungsten slags, and copper flakes in the reconstructed images from sparsely sampled data are comparable with the corresponding structure present in the fully sampled data case. A blurring effect can be seen near the edges of few pores at the bottom of the reconstructed images from sparsely sampled data, despite the overall image quality is reasonable for fast and low-dose NDT.« less

Radon estimation in water resources of Mandi - Dharamshala region of Himachal Pradesh, India for health risk assessments

NASA Astrophysics Data System (ADS)

Kumar, Gulshan; Kumari, Punam; Kumar, Mukesh; Kumar, Arvind; Prasher, Sangeeta; Dhar, Sunil

2017-07-01

The present study deals with the radon estimation in 40 water samples collected from different natural resources and radium content in the soils of Mandi-Dharamshala Region. Radon concentration is determined by using RAD-7 detector and radium contents of the soil in vicinity of water resources is as well measured by using LR-115 type - II detector, which is further correlated with radon concentration in water samples. The potential health risks related with 222Rn have also been estimated. The results show that the radon concentrations within the range of 1.51 to 22.7Bq/l with an average value of 5.93 Bq/l for all type of water samples taken from study area. The radon concentration in water samples is found lower than 100Bq/l, the exposure limit of radon in water recommended by the World Health Organization. The calculated average effective dose of radon received by the people of study area is 0.022 mSv/y with maximum of 0.083 mSv/y and minimum 0.0056 mSv/y. The total effective dose in all sites of the studied area is found to be within the safe limit (0.1 mSv/year) recommended by World Health Organization. The average value of radium content in the soil of study area is 6.326 Bq/kg.

Improvements in dose calculation accuracy for small off-axis targets in high dose per fraction tomotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hardcastle, Nicholas; Bayliss, Adam; Wong, Jeannie Hsiu Ding

2012-08-15

Purpose: A recent field safety notice from TomoTherapy detailed the underdosing of small, off-axis targets when receiving high doses per fraction. This is due to angular undersampling in the dose calculation gantry angles. This study evaluates a correction method to reduce the underdosing, to be implemented in the current version (v4.1) of the TomoTherapy treatment planning software. Methods: The correction method, termed 'Super Sampling' involved the tripling of the number of gantry angles from which the dose is calculated during optimization and dose calculation. Radiochromic film was used to measure the dose to small targets at various off-axis distances receivingmore » a minimum of 21 Gy in one fraction. Measurements were also performed for single small targets at the center of the Lucy phantom, using radiochromic film and the dose magnifying glass (DMG). Results: Without super sampling, the peak dose deficit increased from 0% to 18% for a 10 mm target and 0% to 30% for a 5 mm target as off-axis target distances increased from 0 to 16.5 cm. When super sampling was turned on, the dose deficit trend was removed and all peak doses were within 5% of the planned dose. For measurements in the Lucy phantom at 9.7 cm off-axis, the positional and dose magnitude accuracy using super sampling was verified using radiochromic film and the DMG. Conclusions: A correction method implemented in the TomoTherapy treatment planning system which triples the angular sampling of the gantry angles used during optimization and dose calculation removes the underdosing for targets as small as 5 mm diameter, up to 16.5 cm off-axis receiving up to 21 Gy.« less

Pharmacokinetics of Intravenous Finafloxacin in Healthy Volunteers

PubMed Central

Chiesa, Joseph; Lückermann, Mark; Fischer, Carsten; Dalhoff, Axel; Fuhr, Uwe

2017-01-01

ABSTRACT Finafloxacin is a novel fluoroquinolone exhibiting enhanced activity under acidic conditions and a broad-spectrum antibacterial profile. The present study assessed the pharmacokinetic properties and the safety and tolerability of finafloxacin following intravenous infusions. In this mixed-parallel-group, crossover study, healthy male and female volunteers received single ascending doses (18 volunteers, 200 to 1,000 mg) or multiple ascending doses (40 volunteers, 600 to 1,000 mg) of finafloxacin or placebo. Plasma and urine samples were collected by a dense sampling scheme to determine the pharmacokinetics of finafloxacin using a noncompartmental approach. Standard safety and tolerability data were documented. Finafloxacin had a volume of distribution of 90 to 127 liters (range) at steady state and 446 to 550 liters at pseudoequilibrium, indicating the elimination of a large fraction before pseudoequilibrium was reached. Areas under the concentration-time curves and maximum plasma concentrations (geometric means) increased slightly more than proportionally (6.73 to 45.9 μg · h/ml and 2.56 to 20.2 μg/ml, respectively), the terminal elimination half-life increased (10.6 to 17.1 h), and the urinary recovery decreased (44.2% to 31.7%) with increasing finafloxacin doses (single doses of 200 to 1,000 mg). The pharmacokinetic profiles suggested multiphasic elimination by both glomerular filtration and saturable tubular secretion. The values of the parameters were similar for single and multiple administrations. The coefficient of variation for the between-subject variability of exposure ranged from 10% (≤600 mg) to 38% (>600 mg). Adverse events were mild and nonspecific, with no dependence of adverse events on dose or treatment (including placebo) being detected. Despite a relatively high interindividual variability at higher doses, the level of exposure following intravenous administration of finafloxacin appears to be predictable. Individual elimination processes should be evaluated in more detail. Finafloxacin exhibited a favorable safety and tolerability profile. (This study has been registered at ClinicalTrials.gov under registration no. NCT01910883.) PMID:28784673

Low dose naltrexone administration in morphine dependent rats attenuates withdrawal-induced norepinephrine efflux in forebrain.

PubMed

Van Bockstaele, Elisabeth J; Qian, Yaping; Sterling, Robert C; Page, Michelle E

2008-05-15

The administration of low dose opioid antagonists has been explored as a potential means of detoxification in opiate dependence. Previous results from our laboratory have shown that concurrent administration of low dose naltrexone in the drinking water of rats implanted with subcutaneous morphine pellets attenuates behavioral and biochemical signs of withdrawal in brainstem noradrenergic nuclei. Noradrenergic projections originating from the nucleus tractus solitarius (NTS) and the locus coeruleus (LC) have previously been shown to be important neural substrates involved in the somatic expression of opiate withdrawal. The hypothesis that low dose naltrexone treatment attenuates noradrenergic hyperactivity typically associated with opiate withdrawal was examined in the present study by assessing norepinephrine tissue content and norepinephrine efflux using in vivo microdialysis coupled to high performance liquid chromatography (HPLC) with electrochemical detection (ED). The frontal cortex (FC), amygdala, bed nucleus of the stria terminalis (BNST) and cerebellum were analyzed for tissue content of norepinephrine following withdrawal in morphine dependent rats. Naltrexone-precipitated withdrawal elicited a significant decrease in tissue content of norepinephrine in the BNST and amygdala. This decrease was significantly attenuated in the BNST of rats that received low dose naltrexone pre-treatment compared to controls. No significant difference was observed in the other brain regions examined. In a separate group of rats, norepinephrine efflux was assessed with in vivo microdialysis in the BNST or the FC of morphine dependent rats or placebo treated rats subjected to naltrexone-precipitated withdrawal that received either naltrexone in their drinking water (5 mg/L) or unadulterated water. Following baseline dialysate collection, withdrawal was precipitated by injection of naltrexone and sample collection continued for an additional 4 h. At the end of the experiment, animals were transcardially perfused and the brains were removed for verification of probe placement. Low dose naltrexone pre-treatment significantly attenuated withdrawal-induced increases of extracellular norepinephrine in the BNST, with a smaller effect in the FC. These findings suggest that alterations in norepinephrine release associated with withdrawal may be attenuated in forebrain targets of noradrenergic brainstem neurons that may underlie reduced behavioral signs of withdrawal following low dose naltrexone administration.

9 CFR 113.3 - Sampling of biological products.

Code of Federal Regulations, 2013 CFR

2013-01-01

... bacterial vaccines; (iii) Two samples of Coccidiosis Vaccine; (iv) Eighteen samples of Rabies Vaccine...) Twenty-two single-dose or 14 multiple-dose samples of Rabies Vaccine, Killed Virus; (viii) Sixteen single...

9 CFR 113.3 - Sampling of biological products.

Code of Federal Regulations, 2014 CFR

2014-01-01

... bacterial vaccines; (iii) Two samples of Coccidiosis Vaccine; (iv) Eighteen samples of Rabies Vaccine...) Twenty-two single-dose or 14 multiple-dose samples of Rabies Vaccine, Killed Virus; (viii) Sixteen single...

9 CFR 113.3 - Sampling of biological products.

Code of Federal Regulations, 2012 CFR

2012-01-01

... bacterial vaccines; (iii) Two samples of Coccidiosis Vaccine; (iv) Eighteen samples of Rabies Vaccine...) Twenty-two single-dose or 14 multiple-dose samples of Rabies Vaccine, Killed Virus; (viii) Sixteen single...

Pharmacokinetics and Safety of Bortezomib in Patients with Advanced Malignancies and Varying Degrees of Liver Dysfunction: Phase 1 NCI Organ Dysfunction Working Group Study NCI-6432

PubMed Central

LoRusso, Patricia M; Venkatakrishnan, Karthik; Ramanathan, Ramesh K; Sarantopoulos, John; Mulkerin, Daniel; Shibata, Stephen I; Hamilton, Anne; Dowlati, Afshin; Mani, Sridhar; Rudek, Michelle A; Takimoto, Chris H; Neuwirth, Rachel; Esseltine, Dixie-Lee; Ivy, Percy

2013-01-01

Purpose The proteasome inhibitor bortezomib undergoes oxidative hepatic metabolism. This study (NCI-6432; NCT00091117) was conducted to evaluate bortezomib pharmacokinetics and safety in patients with varying degrees of hepatic impairment, to inform dosing recommendations in these special populations. Methods Patients received bortezomib on days 1, 4, 8, and 11 of 21-day cycles. Patients were assigned to four hepatic function groups based on the National Cancer Institute Organ Dysfunction Working Group classification. Those with normal function received bortezomib at the 1.3 mg/m2 standard dose. Patients with severe, moderate, and mild impairment received escalating doses from 0.5, 0.7, and 1.0 mg/m2, respectively, up to a 1.3 mg/m2 maximum. Serial blood samples were collected for 24 hours post-dose on days 1 and 8, cycle 1, for bortezomib plasma concentration measurements. Results Sixty-one patients were treated, including 14 with normal hepatic function and 17, 12, and 18 with mild, moderate, and severe impairment, respectively. Mild hepatic impairment did not alter dose-normalized bortezomib exposure (AUC0-tlast) or Cmax compared with patients with normal function. Mean dose-normalized AUC0-tlast was increased by approximately 60% on day 8 in patients with moderate or severe impairment. Conclusions Patients with mild hepatic impairment do not require a starting dose adjustment of bortezomib. Patients with moderate or severe hepatic impairment should be started at a reduced dose of 0.7 mg/m2. PMID:22394984

Effect of route of administration and biliary excretion on the pharmacokinetics of isotretinoin in the dog.

PubMed

Cotler, S; Chen, S; Macasieb, T; Colburn, W A

1984-01-01

Oral, intraportal, iv doses of isotretinoin were administered to dogs before and after bile duct cannulation to determine the effect of route of administration and biliary excretion on the pharmacokinetics of this compound. Blood and bile samples were collected and analyzed for isotretinoin using a gradient elution high performance liquid chromatographic method. Blood concentrations were decreased after bile duct cannulation. Decreases in the area under the blood concentration-time curves were greatest following oral dosing, intermediate following intraportal dosing, and least following iv dosing. These results indicate that biliary excretion impacts on the blood profile of isotretinoin as a function of route of administration and that the differences are the result of differences in first pass clearance. In addition, the apparent bioavailability of isotretinoin was 14% in bile cannulated dogs and 54% in the intact (uncannulated) animals, suggesting that enterohepatic recycling of isotretinoin may contribute to its oral bioavailability. Isotretinoin was excreted in the bile; predominantly as a conjugate. The largest percentage (approximately 27%) of the dose was excreted in the bile following intraportal infusion, an intermediate percentage (approximately 8.5%) after iv dosing, and the smallest percentage (approximately 3.3%) after oral dosing. When the amount of drug excreted in bile as intact drug and conjugate is divided by the area under the systemic blood concentration--time curve, the resulting apparent biliary clearances following oral and intraportal administration were almost identical whereas the apparent biliary clearance after iv dosing was substantially less.(ABSTRACT TRUNCATED AT 250 WORDS)