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Sample records for repeated dose inhalation

  1. Comparison in the calculation of committed effective dose using the ICRP 30 and ICRP 60 models for a repeated incorporation by inhalation of I-125

    International Nuclear Information System (INIS)

    Carreno P, A.L.; Cortes C, A.; Alonso V, G.; Serrano P, F.

    2005-01-01

    Presently work, a comparison in the calculation of committed effective dose using the models of the ICRP 30 and those of the ICRP 60 for the analysis of internal dose due to repeated incorporation of I-125 is shown. The estimations of incorporated activity are obtained starting from the proportionate data for an exercise of inter comparison, with which it should be determined the internal dose later on. For to estimate the initial activity incorporated by repeated dose was assumed that this it was given through of multiple individual incorporations which happened in the middle points of the monitoring periods. The results using the models of the ICRP 30 and of the ICRP 60 are compared and the causes of the differences are analyzed. (Author)

  2. [Study of personal best value of peak expiratory flow in patients with asthma--comparison of the highest value of daily PEF under good control and the highest value of daily PEF obtained after using repeated inhaled beta2-agonist during high-dose inhaled steroid treatment].

    Science.gov (United States)

    Watanabe, Naoto; Makino, Sohei; Kihara, Norio; Fukuda, Takeshi

    2008-12-01

    In the guideline for asthma management, it is important to find the personal best value of peak expiratory flow (best PEF). Recently, we have substituted the highest value of PEF in daily life under good control (daily highest PEF) for the best PEF. In the present study, we considered whether the daily highest PEF could be used as the best PEF or not. Subjects were 30 asthmatics who were well controlled but whose baseline PEF values were less than 80 percent of predicted values. We compared the daily highest PEF and the highest of PEF obtained after repeated inhaled beta2-agonist (salbutamol MDI every 20 minutes three times). All subjects then received 1600 microg/day of beclomethasone dipropionate (BDP) for 4 to 8 weeks. We studied the effect of high-dose inhaled steroid treatment on each PEF value and compared the daily highest PEF and the highest PEF obtained after using repeated salbutamol MDI during high dose inhaled steroid therapy on the examination day again. The baseline PEF, daily highest PEF and the highest PEF obtained after salbutamol MDI were significantly less than the each values obtained after high-dose BDP. The best PEF value of them was the value obtained after repeated salbutamol MDI during high dose BDP. We suggest that the daily highest PEF under good control is not a substitute for best PEF because it changes according to the degree of improvement of airway inflammation. We recommend that a course of high dose inhaled steroid is effective in finding the best value of PEF for each individual with moderate asthma.

  3. Inhalation dose assessment for Maralinga and Emu

    International Nuclear Information System (INIS)

    Johnston, P.N.; Lokan, K.H.; Williams, G.A.

    1990-01-01

    Dose assessments for the inhalation of artificial radionuclides are presented for all types of contaminated areas at Maralinga and Emu. These enable Committed Effective Dose Equivalent (CEDE), to be estimated by scaling at any area of interest where activity concentrations are known. In the case of Aborigines, these dose are estimated assuming respirable dust loadings of 1 mg/m 3 for adults and 1.5 mg/m 3 for children and infants. Details of the calculations are presented in the appendix. The model of the respiratory system used in this assessment is that described in Interantional Commission on Radiological Protection (ICRP) Publication 30 (ICRP, 1979a). With the exception of Kuli, which is contaminated with uranium, at all other sites it is only the inhalation of plutonium and americium that contributes significantly to the dose, and of these 239 Pu is the largest contributor. Therefore, considering the long half lives of the radionuclides concerned, it appears that the inhalation problems highlighted by this dose assessment will not diminish significantly within any reasonable period of time and hence management strategies must be developed to deal with such problems. 32 refs., 5 tabs., 1 fig

  4. Tumorigenic responses from single or repeated inhalation exposures to relatively insoluble aerosols of Ce-144

    International Nuclear Information System (INIS)

    Boecker, B.B.; Hahn, F.F.; Mauderly, J.L.; McClellan, R.O.

    1980-01-01

    Human occupational or environmental inhalation exposures may involve repeated or chronic exposures, but most laboratory studies of inhaled radionuclides have involved single exposures. This study was designed to compare the biological effects of repeated inhalation exposures of dogs to a relatively insoluble form of 144 Ce with existing data for singly-exposed dogs that had the same cumulative dose to the lungs two years after exposure. To date, the biological effects observed in these repeatedly-exposed dogs have been substantially different from those seen in singly-exposed dogs, particularly during the first 5 years after the initial exposure. Although pulmonary hemangiosarcoma was the prominent biological effect seen in singly-exposed dogs between 2 and 4 years after exposure, no lung tumors were seen during the 5 years after the first of the repeated exposures. This response plus other clinical observations are discussed in relation to the patterns of dose rate and cumulative dose for the different exposure conditions. (H.K.)

  5. Repeated inhalation exposure of Beagle dogs to aerosols of 239PuO2. XII

    International Nuclear Information System (INIS)

    Diel, J.H.; Hahn, F.F.; Muggenburg, B.A.

    1988-01-01

    Beagle dogs were exposed once or semi-annually for 10 yr by inhalation to aerosols of 239 PuO 2 to study the relative doses and effects of these two types of exposures. All exposures have been completed. Dogs exposed at high levels died predominantly of radiation pneumonitis and pulmonary fibrosis. Dogs exposed at lower levels, either once or repeatedly, are dying of a variety of causes including lung cancer. Dogs have survived up to 11 yr after their first exposure. Preliminary results suggest that single and repeated exposures cause similar health effects for equal accumulated radiation doses. (author)

  6. Committed effective dose from thoron daughters inhalation

    International Nuclear Information System (INIS)

    Campos, M.P.; Pecequilo, B.R.S.

    2000-01-01

    Mankind's interest in natural radiation exposure levels has increased over the past fifty years and it is now recognized that the most significant contributors to human irradiation by natural sources are the short-lived decay products of radon ( 222 Rn) and thoron ( 220 Rn). Despite the thoron short half-life of 55 s, effective dose from inhalation of thoron an its progeny ( 212 Pb and 212 Bi) must be considered, owing to the high thorium background in countries like Brazil, China and India, for example. The indoor committed effective dose was assessed by air sampling at the thorium purification plant and the nuclear materials storage site of the Instituto de Pesquisas Energeticas e Nucleares; Sao Paulo, Brazil. A total of 21 glass fiber filter samples was analyzed by high resolution gamma ray spectrometry in order to obtain the 212 Pb and 212 Bi activities. The equilibrium equivalent concentration (EEC) varied from 0.3 Bq/m 3 to 6.8 Bq/m 3 for the storage site air samples and from 9.9 Bq/m 3 to 249.8 Bq/m 3 for the thorium purification plant air samples. As retention studies indicate a biological half-life of a few hours inhaled thoron progeny in the human lungs, the main fraction of the potential alpha energy (PAEC) deposited is absorbed in the lungs, meaning negligible to the effective dose the contribution of the dose in other times. The committed effective dose due thoron progeny was performed by compartimental analysis following the ICRP 66 lung compartimental model and ICRP 67 lead compartimental model. The values obtained varied from 0.03 mSv/a to 0.67 mSv/a for the storage site air samples and from 0.12 mSv/a to 6.00 mSv/a for the thorium purification plant air samples. (author)

  7. Uncertainties on lung doses from inhaled plutonium.

    Science.gov (United States)

    Puncher, Matthew; Birchall, Alan; Bull, Richard K

    2011-10-01

    In a recent epidemiological study, Bayesian uncertainties on lung doses have been calculated to determine lung cancer risk from occupational exposures to plutonium. These calculations used a revised version of the Human Respiratory Tract Model (HRTM) published by the ICRP. In addition to the Bayesian analyses, which give probability distributions of doses, point estimates of doses (single estimates without uncertainty) were also provided for that study using the existing HRTM as it is described in ICRP Publication 66; these are to be used in a preliminary analysis of risk. To infer the differences between the point estimates and Bayesian uncertainty analyses, this paper applies the methodology to former workers of the United Kingdom Atomic Energy Authority (UKAEA), who constituted a subset of the study cohort. The resulting probability distributions of lung doses are compared with the point estimates obtained for each worker. It is shown that mean posterior lung doses are around two- to fourfold higher than point estimates and that uncertainties on doses vary over a wide range, greater than two orders of magnitude for some lung tissues. In addition, we demonstrate that uncertainties on the parameter values, rather than the model structure, are largely responsible for these effects. Of these it appears to be the parameters describing absorption from the lungs to blood that have the greatest impact on estimates of lung doses from urine bioassay. Therefore, accurate determination of the chemical form of inhaled plutonium and the absorption parameter values for these materials is important for obtaining reliable estimates of lung doses and hence risk from occupational exposures to plutonium.

  8. Understanding pressurized metered dose inhaler performance.

    Science.gov (United States)

    Ivey, James W; Vehring, Reinhard; Finlay, Warren H

    2015-06-01

    Deepening the current understanding of the factors governing the performance of the pressurized metered dose inhaler (pMDI) has the potential to benefit patients by providing improved drugs for current indications as well as by enabling new areas of therapy. Although a great deal of work has been conducted to this end, our knowledge of the physical mechanisms that drive pMDI performance remains incomplete. This review focuses on research into the influence of device and formulation variables on pMDI performance metrics. Literature in the areas of dose metering, atomization and aerosol evolution and deposition is covered, with an emphasis on studies of a more fundamental nature. Simple models which may be of use to those developing pMDI products are summarized. Although researchers have had good success utilizing an empirically developed knowledge base to predict pMDI performance, such knowledge may not be applicable when pursuing innovations in device or formulation technology. Developing a better understanding of the underlying mechanisms is a worthwhile investment for those working to enable the next generation of pMDI products.

  9. Particle exposure and inhaled dose during commuting in Singapore

    Science.gov (United States)

    Tan, Sok Huang; Roth, Matthias; Velasco, Erik

    2017-12-01

    Exposure concentration and inhaled dose of particles during door-to-door trips walking and using motorized transport modes (subway, bus, taxi) are evaluated along a selected route in a commercial district of Singapore. Concentrations of particles smaller than 2.5 μm in size (PM2.5), black carbon, particle-bound polycyclic aromatic hydrocarbons, number of particles, active surface area and carbon monoxide have been measured in-situ using portable instruments. Simultaneous measurements were conducted at a nearby park to capture the background concentrations. The heart rate of the participants was monitored during the measurements as a proxy of the inhalation rate used to calculate the inhaled dose of particles. All measured metrics were highest and well above background levels during walking. No significant difference was observed in the exposure concentration of PM2.5 for the three motorized transport modes, unlike for the metrics associated with ultrafine particles (UFP). The concentration of these freshly emitted particles was significantly lower on subway trips. The absence of combustion sources, use of air conditioning and screen doors at station platforms are effective measures to protect passengers' health. For other transport modes, sections of trips close to accelerating and idling vehicles, such as bus stops, traffic junctions and taxi stands, represent hotspots of particles. Reducing the waiting time at such locations will lower pollutants exposure and inhaled dose during a commute. After taking into account the effect of inhalation and travel duration when calculating dose, the health benefit of commuting by subway for this particular district of Singapore became even more evident. For example, pedestrians breathe in 2.6 and 3.2 times more PM2.5 and UFP, respectively than subway commuters. Public buses were the second best alternative. Walking emerged as the worst commuting mode in terms of particle exposure and inhaled dose.

  10. Accidental Cutaneous Burns Secondary to Salbutamol Metered Dose Inhaler

    Directory of Open Access Journals (Sweden)

    Ashutosh Kale

    2010-01-01

    Full Text Available We report a case of accidental cutaneous burns caused by salbutamol metered dose inhaler. A 9-year-old boy underwent dental extraction at a children's hospital and was incidentally noted to have burn injuries on dorsum of both hands. On questioning, the boy revealed that a few days ago his 14-year-old brother, who is an asthmatic, playfully sprayed his salbutamol metered dose inhaler on the back of both his hands with the inhaler's mouth piece being in direct contact with the patient's skin. On examination, there was a rectangular area of erythema with superficial peeling on the dorsum of both hands, the dimensions of which exactly matched those of the inhaler's mouthpiece. It is possible that the injury could have been a chemical burn from the pharmaceutical/preservative/propellant aerosol or due to the physical effect of severe cooling of the skin or mechanical abrasive effect of the aerosol blasts or a combination of some or all the above mechanisms. This case highlights the importance of informing children and parents of the potentially hazardous consequences of misusing a metered dose inhaler.

  11. Acute and repeated inhalation lung injury by 3-methoxybutyl chloroformate in rats: CT-pathologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Yeon Soo [Department of Radiology, Holy Family Hospital, College of Medicine, Catholic University of Korea, 2, Sosa-dong, Wonmi-gu, Pucheon, Kyung gi-do 420-717 (Korea, Republic of); Chung, Myung Hee [Department of Radiology, Holy Family Hospital, College of Medicine, Catholic University of Korea, 2, Sosa-dong, Wonmi-gu, Pucheon, Kyung gi-do 420-717 (Korea, Republic of)]. E-mail: mhchung@catholic.ac.kr; Park, Seog Hee [Department of Radiology, Kangnam St. Mary Hospital, Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-040 (Korea, Republic of); Kim, Hyeon-Yeong [Industrial Chemicals Research Center, Industrial Safety and Health Research Institute KISCO, 104-8, Moonji-dong, Yusong-gu, Taejon-si 305-380 (Korea, Republic of); Choi, Byung Gil [Department of Radiology, Kangnam St. Mary Hospital, Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-040 (Korea, Republic of); Lim, Hyun Wook [Department of Radiology, Holy Family Hospital, College of Medicine, Catholic University of Korea, 2, Sosa-dong, Wonmi-gu, Pucheon, Kyung gi-do 420-717 (Korea, Republic of); Kim, Jin Ah [Department of Pathology, Holy Family Hospital, Catholic University of Korea, 2, Sosa-dong, Wonmi-gu, Pucheon-si, Kyung gi-do 420-717 (Korea, Republic of); Yoo, Won Jong [Department of Radiology, Holy Family Hospital, College of Medicine, Catholic University of Korea, 2, Sosa-dong, Wonmi-gu, Pucheon, Kyung gi-do 420-717 (Korea, Republic of)

    2007-05-15

    Objectives: To investigate the acute and repeated pulmonary damage in Sprague-Dawley rats caused by the inhalation of 3-methoxybutyl chloroformate (3-MBCF) using computed tomography (CT), and to correlate these results with those obtained from a pathological study. Methods: Sixty, 7-week-old rats were exposed to 3-MBCF vapor via inhalation (6 h/day) for 1 day (N = 20), 3 days (N = 20), and 28 days (5 days/week) (N = 20) using whole body exposure chambers at a concentration of 0 (control), 3, 6 and 12 ppm. CT examinations including densitometry and histopathologic studies were carried out. For the follow-up study, the rats exposed for 3 days were scanned using CT and their pathology was examined at 7, 14, and 28 days. Results: There was a significant decrease in the parenchymal density in the groups exposed to the 3-MBCF vapors for 1 day at 3 ppm (p = 0.022) or 6 ppm (p = 0.010), compared with the control. The parenchymal density of the rats exposed to12 ppm was significantly higher. The pathological findings in this period, the grades of vascular congestion, tracheobronchial exfoliation, and alveolar rupture were significant. In the groups exposed for 3 days, there was a large decrease in the parenchymal density with increasing dose (control: -675.48 {+-} 32.82 HU, 3 ppm: -720.65 {+-} 34.21 HU, 6 ppm: -756.41 {+-} 41.68 HU, 12 ppm: -812.56 {+-} 53.48 HU) (p = 0.000). There were significant density differences between each dose in the groups exposed for 28 days (p = 0.000). The CT findings include an irregular lung surface, areas of multifocal, wedge-shaped increased density, a heterogeneous lung density, bronchial dilatation, and axial peribronchovascular bundle thickening. The histopathology examination revealed the development of alveolar interstitial thickening and vasculitis, and an aggravation of the mainstem bronchial exudates and bronchial inflammation. The alveolar wall ruptures and bronchial dilatation became severe during this period. On the follow

  12. Acute and repeated inhalation lung injury by 3-methoxybutyl chloroformate in rats: CT-pathologic correlation

    International Nuclear Information System (INIS)

    Lim, Yeon Soo; Chung, Myung Hee; Park, Seog Hee; Kim, Hyeon-Yeong; Choi, Byung Gil; Lim, Hyun Wook; Kim, Jin Ah; Yoo, Won Jong

    2007-01-01

    Objectives: To investigate the acute and repeated pulmonary damage in Sprague-Dawley rats caused by the inhalation of 3-methoxybutyl chloroformate (3-MBCF) using computed tomography (CT), and to correlate these results with those obtained from a pathological study. Methods: Sixty, 7-week-old rats were exposed to 3-MBCF vapor via inhalation (6 h/day) for 1 day (N = 20), 3 days (N = 20), and 28 days (5 days/week) (N = 20) using whole body exposure chambers at a concentration of 0 (control), 3, 6 and 12 ppm. CT examinations including densitometry and histopathologic studies were carried out. For the follow-up study, the rats exposed for 3 days were scanned using CT and their pathology was examined at 7, 14, and 28 days. Results: There was a significant decrease in the parenchymal density in the groups exposed to the 3-MBCF vapors for 1 day at 3 ppm (p = 0.022) or 6 ppm (p = 0.010), compared with the control. The parenchymal density of the rats exposed to12 ppm was significantly higher. The pathological findings in this period, the grades of vascular congestion, tracheobronchial exfoliation, and alveolar rupture were significant. In the groups exposed for 3 days, there was a large decrease in the parenchymal density with increasing dose (control: -675.48 ± 32.82 HU, 3 ppm: -720.65 ± 34.21 HU, 6 ppm: -756.41 ± 41.68 HU, 12 ppm: -812.56 ± 53.48 HU) (p = 0.000). There were significant density differences between each dose in the groups exposed for 28 days (p = 0.000). The CT findings include an irregular lung surface, areas of multifocal, wedge-shaped increased density, a heterogeneous lung density, bronchial dilatation, and axial peribronchovascular bundle thickening. The histopathology examination revealed the development of alveolar interstitial thickening and vasculitis, and an aggravation of the mainstem bronchial exudates and bronchial inflammation. The alveolar wall ruptures and bronchial dilatation became severe during this period. On the follow-up study, the

  13. Contribution of inhalation by food animals to man's ingestion dose

    International Nuclear Information System (INIS)

    Zach, R.

    1985-01-01

    Animals' inhalation (AI) pathway was evaluated for 57 radionuclides using infant dose predictions from the food-chain model LIMCAL. With ingestion transfer coefficients fMi to define transfer from the respiratory tract to milk, the AI pathway appeared to be insignificant compared to animals' plant ingestion, as implicitly assumed in most environmental assessment models for nuclear installations. Using ICRP Publication 30 respiratory clearance models for man to adjust ingestion transfer coefficients, animals' inhalation appeared to be important, particularly for some actinide radionuclides. The AI pathway also appeared to be significant relative to man's inhalation, especially for infants. The importance of the AI pathway varied greatly between radionuclides, and results strongly suggest that it cannot be ignored in environmental assessments. Until better data become available to implement this pathway fully, adjusted ingestion transfer coefficient values can be used for transfer from animals' respiratory tract to milk and other food products

  14. Organ dose from inhaled radionuclides taking lull period into account

    International Nuclear Information System (INIS)

    Datta, S.

    1982-01-01

    The dosimetry of inhaled radionuclides is generally carried out in accordance with the lung model recommended by the ICRP Task Group on Lung Dynamics. The relevant expressions are integrated over a given period, assuming continuous inhalation in an atmosphere of constant aerosol concentration. Though for the same amount of intake the dose commitment is found to be independent of variations in the rate of intake, the dose determined over specific intervals of time, is influenced by it or by lull intervals therein. Formulae are developed to arrive at doses to different organs when the subject's intake is constant and continuous for 8 hours, followed by a lull period of 16 hours each day. Results are given for a number of radionuclides and are compared with values characteristic of continuous inhalation. It is observed that when exposure is assumed to be continuous the dose for the same intake of activity is underestimated as compared to the dose when lull period is taken into account. For working periods of 6 days and 30 days the underestimate ranges from 5%-20% and 0.6% to 4.5% respectively. (author)

  15. RSAC, Gamma Doses, Inhalation and Ingestion Doses, Fission Products Inventory after Fission Products Release

    International Nuclear Information System (INIS)

    Richardson, L.C.

    1967-01-01

    1 - Description of problem or function: RSAC generates a fission product inventory from a given set of reactor operating conditions and then computes the external gamma dose, the deposition gamma dose, and the inhalation-ingestion dose to critical body organs as a result of exposure to these fission products. Program output includes reactor operating history, fission product inventory, dosages, and ingestion parameters. 2 - Method of solution: The fission product inventory generated by the reactor operating conditions and the inventory remaining at various times after release are computed using the equations of W. Rubinson in Journal of Chemical Physics, Vol. 17, pages 542-547, June 1949. The external gamma dose and the deposition gamma dose are calculated by determining disintegration rates as a function of space and time, then integrating using Hermite's numerical techniques for the spatial dependence. The inhalation-ingestion dose is determined by the type and quantity of activity inhaled and the biological rate of decay following inhalation. These quantities are integrated with respect to time to obtain the dosage. The ingestion dose is related to the inhalation dose by an input constant

  16. The effect of inhaling concentrated oxygen on performance during repeated anaerobic exercise

    Directory of Open Access Journals (Sweden)

    J Heller

    2010-09-01

    Full Text Available The objective of the pilot study was to test the effect of inhaling 99.5% oxygen on recovery. The source of concentrated oxygen was O-PUR (Oxyfit. Research subjects completed two thirty-second Wingate tests at an interval of ten minutes, and in the interval between the tests the subjects inhaled either oxygen or a placebo in random order. This procedure was then repeated. The pilot study revealed a significantly (p<0.03 smaller performance drop in the second Wingate test following the inhalation of 99.5% oxygen when compared with the placebo. The results of the study indicate that inhaling concentrated oxygen may have a positive effect on short-term recovery processes.

  17. Dose-effect studies with inhaled plutonium in beagles

    International Nuclear Information System (INIS)

    Anon.

    1982-01-01

    Data are presented for all dogs employed in current life-span dose effect studies with inhaled 239 PuO 2 , and 239 Pu nitrate. Information is presented on the estimated initial alveolar deposition, based on external thorax counts and on estimated lung weights at time of exposure. Information is also provided on the current interpretation of the most prominent clinical-pathological features associated with the death of animals

  18. Evaluation of Inhaled Versus Deposited Dose Using the Exponential Dose-Response Model for Inhalational Anthrax in Nonhuman Primate, Rabbit, and Guinea Pig.

    Science.gov (United States)

    Gutting, Bradford W; Rukhin, Andrey; Mackie, Ryan S; Marchette, David; Thran, Brandolyn

    2015-05-01

    The application of the exponential model is extended by the inclusion of new nonhuman primate (NHP), rabbit, and guinea pig dose-lethality data for inhalation anthrax. Because deposition is a critical step in the initiation of inhalation anthrax, inhaled doses may not provide the most accurate cross-species comparison. For this reason, species-specific deposition factors were derived to translate inhaled dose to deposited dose. Four NHP, three rabbit, and two guinea pig data sets were utilized. Results from species-specific pooling analysis suggested all four NHP data sets could be pooled into a single NHP data set, which was also true for the rabbit and guinea pig data sets. The three species-specific pooled data sets could not be combined into a single generic mammalian data set. For inhaled dose, NHPs were the most sensitive (relative lowest LD50) species and rabbits the least. Improved inhaled LD50 s proposed for use in risk assessment are 50,600, 102,600, and 70,800 inhaled spores for NHP, rabbit, and guinea pig, respectively. Lung deposition factors were estimated for each species using published deposition data from Bacillus spore exposures, particle deposition studies, and computer modeling. Deposition was estimated at 22%, 9%, and 30% of the inhaled dose for NHP, rabbit, and guinea pig, respectively. When the inhaled dose was adjusted to reflect deposited dose, the rabbit animal model appears the most sensitive with the guinea pig the least sensitive species. © 2014 Society for Risk Analysis.

  19. Quantity and Quality of Inhaled Dose Predicts Immunopathology in Tuberculosis

    Directory of Open Access Journals (Sweden)

    Kevin Patrick Fennelly

    2015-06-01

    Full Text Available Experimental animal models of tuberculosis (TB have convincingly demonstrated that inhaled dose predicts immunopathology and survival. In contrast, the importance of inhaled dose has generally not been appreciated in TB epidemiology, clinical science, or the practice of TB control. Infectiousness of TB patients has traditionally been assessed using microscopy for acid-fast bacilli in the sputum, which should be considered only a risk factor. We have recently demonstrated that cough aerosol cultures from index cases with pulmonary TB are the best predictors of new infection among household contacts. We suggest that cough aerosols of M. tuberculosis are the best surrogates of inhaled dose, and we hypothesize that the quantity of cough aerosols is associated with TB infection versus disease. Although several factors affect the quality of infectious aerosols, we propose that the particle size distribution of cough aerosols is an important predictor of primary upper airway disease and cervical lymphadenitis and of immune responses in exposed hosts. We hypothesize that large droplet aerosols (> 5 microns containing M. tuberculosis deposit in the upper airway and can induce immune responses without establishing infection. We suggest that this may partially explain the large proportion of humans who never develop TB disease in spite of having immunological evidence of M. tuberculosis infection (e.g. positive TST or IGRA. If these hypotheses are proven true, they would alter the current paradigm of latent TB infection and reactivation, further demonstrating the need for better biomarkers or methods of assessing TB infection and the risk of developing disease.

  20. Effect of repeated benzene inhalation exposures on benzene metabolism, binding to hemoglobin, and induction of micronuclei

    International Nuclear Information System (INIS)

    Sabourin, P.J.; Sun, J.D.; MacGregor, J.T.; Wehr, C.M.; Birnbaum, L.S.; Lucier, G.; Henderson, R.F.

    1990-01-01

    Metabolism of benzene is thought to be necessary to produce the toxic effects, including carcinogenicity, associated with benzene exposure. To extrapolate from the results of rodent studies to potential health risks in man, one must know how benzene metabolism is affected by species, dose, dose rate, and repeated versus single exposures. The purpose of our studies was to determine the effect of repeated inhalation exposures on the metabolism of [14C]benzene by rodents. Benzene metabolism was assessed by characterizing and quantitating urinary metabolites, and by quantitating 14C bound to hemoglobin and micronuclei induction. F344/N rats and B6C3F1 mice were exposed, nose-only, to 600 ppm benzene or to air (control) for 6 hr/day, 5 days/week for 3 weeks. On the last day, both benzene-pretreated and control animals were exposed to 600 ppm, 14C-labeled benzene for 6 hr. Individual benzene metabolites in urine collected for 24 hr after the exposure were analyzed. There was a significant decrease in the respiratory rate of mice (but not rats) pretreated with benzene which resulted in lower levels of urinary [14C]benzene metabolites. The analyses indicated that the only effects of benzene pretreatment on the metabolite profile in rat or mouse urine were a slight shift from glucuronidation to sulfation in mice and a shift from sulfation to glucuronidation in rats. Benzene pretreatment also had no effect, in either species, on formation of [14C]benzene-derived hemoglobin adducts. Mice and rats had similar levels of hemoglobin adduct binding, despite the higher metabolism of benzene by mice. This indicates that hemoglobin adduct formation occurs with higher efficiency in rats. After 1 week of exposure to 600 ppm benzene, the frequency of micronucleated, polychromatic erythrocytes (PCEs) in mice was significantly increased

  1. Quadrupling Inhaled Glucocorticoid Dose to Abort Asthma Exacerbations.

    Science.gov (United States)

    McKeever, Tricia; Mortimer, Kevin; Wilson, Andrew; Walker, Samantha; Brightling, Christopher; Skeggs, Andrew; Pavord, Ian; Price, David; Duley, Lelia; Thomas, Mike; Bradshaw, Lucy; Higgins, Bernard; Haydock, Rebecca; Mitchell, Eleanor; Devereux, Graham; Harrison, Timothy

    2018-03-08

    Asthma exacerbations are frightening for patients and are occasionally fatal. We tested the concept that a plan for patients to manage their asthma (self-management plan), which included a temporary quadrupling of the dose of inhaled glucocorticoids when asthma control started to deteriorate, would reduce the incidence of severe asthma exacerbations among adults and adolescents with asthma. We conducted a pragmatic, unblinded, randomized trial involving adults and adolescents with asthma who were receiving inhaled glucocorticoids, with or without add-on therapy, and who had had at least one exacerbation in the previous 12 months. We compared a self-management plan that included an increase in the dose of inhaled glucocorticoids by a factor of 4 (quadrupling group) with the same plan without such an increase (non-quadrupling group), over a period of 12 months. The primary outcome was the time to a first severe asthma exacerbation, defined as treatment with systemic glucocorticoids or an unscheduled health care consultation for asthma. A total of 1922 participants underwent randomization, of whom 1871 were included in the primary analysis. The number of participants who had a severe asthma exacerbation in the year after randomization was 420 (45%) in the quadrupling group as compared with 484 (52%) in the non-quadrupling group, with an adjusted hazard ratio for the time to a first severe exacerbation of 0.81 (95% confidence interval, 0.71 to 0.92; P=0.002). The rate of adverse effects, which were related primarily to local effects of inhaled glucocorticoids, was higher in the quadrupling group than in the non-quadrupling group. In this trial involving adults and adolescents with asthma, a personalized self-management plan that included a temporary quadrupling of the dose of inhaled glucocorticoids when asthma control started to deteriorate resulted in fewer severe asthma exacerbations than a plan in which the dose was not increased. (Funded by the Health Technology

  2. Experiment of aerosol-release time for a novel automatic metered dose inhaler

    OpenAIRE

    Mingrong Zhang; Songhao Wang; Yu-Ching Yang

    2016-01-01

    The objective of this study was to evaluate the aerosol-release time in the development of a new automatic adapter for metered dose inhaler. With this device, regular manually operated metered dose inhalers become automatic. During the study, an inhalation simulator was designed and tested with the newly developed mechatronic system. By adjusting the volume and the pressure of the vacuum tank, most human inhalation waveforms were able to simulate. As an example, regular quick-deep and slow-de...

  3. Estimation of inhalation doses from airborne releases using gross monitors

    International Nuclear Information System (INIS)

    Goldstein, N.P.

    1978-01-01

    Monitoring programs at most nuclear facilities involve continuous gross measurements supplemented by periodic isotopic analyses of release samples. The isotopic measurements are required to accurately assess the potential dose from the various effluent streams, but in between these measurements, one depends on the gross monitors to provide approximate indications of the dose. The effluent streams release a variety of nuclides, each with its own dose factor. This means that the relationship between the counting rate in a gross monitor and the potential dose of the effluent being monitored will depend on the isotopic composition of this release. If this composition changes, then the dose indicated by the gross monitor (calibrated for the original group of isotopes) may be significantly in error. The problem of indicating inhalation doses from gross monitoring of airborne releases is considered. In order for this type of monitor to accurately indicate dose, regardless of the isotopic makeup of a release, the analysis shows that its response to each isotope should be proportional to the dose factor of that isotope. These ideas are applied to the monitoring of air particulates using gross beta and gross gamma monitors. The study shows that the former more closely satisfies this condition and as a result, satisfactorily indicates the actual dose from reactor effluents, as determined from detailed isotopic data published in the literature. On the other hand, the gross gamma monitor, with its poorer fit to the condition, provided less than satisfactory accuracy in its dose estimates. In addition, a variety of other mathematical response functions were considered but their dose estimation capabilities were not much better than the straight beta response. The study shows that reasonably accurate dose estimates can be made using properly selected gross monitors, but that significant errors can result with improper ones. (author)

  4. Starting with a higher dose of inhaled corticosteroids in primary care asthma treatment

    NARCIS (Netherlands)

    van der Molen, T; Meyboom-de Jong, B; Mulder, HH; Postma, DS

    New British guidelines on the treatment of asthma (9) advocate starting with a higher dose of inhaled corticosteroids in newly detected asthma patients. We investigated whether initiating inhaled steroid treatment with a higher dose is clinically more effective than a lower dose in steroid naive

  5. Cumulative high doses of inhaled formoterol have less systemic effects in asthmatic children 6-11 years-old than cumulative high doses of inhaled terbutaline

    DEFF Research Database (Denmark)

    Kaae, Rikke; Agertoft, Lone; Pedersen, Sören

    2004-01-01

    OBJECTIVES: To evaluate high dose tolerability and relative systemic dose potency between inhaled clinically equipotent dose increments of formoterol and terbutaline in children. METHODS: Twenty boys and girls (6-11 years-old) with asthma and normal ECGs were studied. Ten doses of formoterol (Oxi...

  6. Increasing Doses of Inhaled Corticosteroids Compared to Adding Long-Acting Inhaled beta(2)-Agonists in Achieving Asthma Control

    NARCIS (Netherlands)

    O'Byrne, Paul M.; Naya, Ian P.; Kallen, Anders; Postma, Dirkje S.; Barnes, Peter J.

    2008-01-01

    Background: Combination therapy with inhaled corticosteroids (ICSs) and long-acting beta(2)-agonists (LABAs), or treatment with high doses of ICSs alone improves asthma control when therapy with low-dose ICSs is not sufficient. However, it is not known which of these treatment options is more

  7. Dose-effect studies with inhaled plutonium nitrate in dogs

    International Nuclear Information System (INIS)

    Dagle, G.E.; Cannon, W.C.; Case, A.C.; Madison, R.M.; McShane, J.F.; Stevens, D.L.; Rowe, S.E.; Ragan, H.A.; Schirmer, R.E.

    1980-01-01

    Beagle dogs given a single inhalation exposure to 239 Pu(NO 3 ) 4 , and observed for life-span dose-effect relationship, died from radiation pneumonitis (four of five at the highest dosage level, in 14 to 25 mo postexposure; 1 of 20 at the medium-high dosage level, at 34 mo postexposure). There were also indications in these dogs of radiation osteosis, characterized by peritrabecular fibrosis. One dog, at 39 mo postexposure, has radiographic evidence of an osteosarcoma. Leukopenia, lymphopenia, neutropenia and decreased numbers of circulating monocytes and eosinophils occurred at the two highest dosage levels, as previously reported (Annual Report, 1978). Twelve dogs given a single inhalation exposure to 238 Pu(NO 3 ) 4 showed a more rapid translocation of 238 Pu(NO 3 ) 4 to bone and liver than was observed for 239 Pu(NO 3 ) 4 , but at 1 yr postexposure the percentage of the final body burden in bone and liver were similar for the two isotopes

  8. Influence of variations in dose and dose rates on biological effects of inhaled beta-emitting radionuclides

    International Nuclear Information System (INIS)

    McClellan, R.O.; Benjamin, S.A.; Boecker, B.B.; Hahn, F.F.; Hobbs, C.H.; Jones, R.K.; Lundgren, D.L.

    1976-01-01

    The biological effects of inhaled β-emitting radionuclides, 90 Y, 91 Y, 144 Ce and 90 Sr, are being investigated in beagle dogs that received single acute exposures at 12 to 14 months of age. The aerosols studied have included 91 YC1 3 , 144 CeC1 3 , 90 SrC1 2 , and 90 Y, 91 Y, 144 Ce or 90 Sr in aluminosilicate particles. Thus, 91 YCl 3 , 144 CeCl 3 and the aluminosilicate containing radionuclide particles all resulted in significant exposures to lung; 91 YC1 3 , 144 CeC1 3 an 90 SrC1 2 resulted in significant exposures to bone; 91 YC1 3 and 144 CeC1 3 resulted in significant exposures to liver. The higher initial doserate exposures have been more effective than low dose-rate exposures on a per-rad basis in producing early effects. To date ( 144 CeO 2 , it was observed that, on a μCi initial lung burden per kilogram body weight basis, mice did not develop pulmonary tumours whereas beagle dogs did. To fid out the reason for this observation mice have been repeatedly exposed by inhalation to 144 CeO 2 to maintain lung burdens of 144 Ce that resulted in radiation dose rates similar to that observed in beagle dogs. Several of the repeatedly exposed mice developed malignant pulmonary tumours. Thus, with similar dose rates and cumulative doses to the lung, mice and dogs responded in a similar manner to chronic β radiation

  9. Dose-effect studies with inhaled plutonium oxide in beagles

    International Nuclear Information System (INIS)

    Park, J.F.; Buschbom, R.L.; Case, A.C.

    1976-01-01

    Beagle dogs given single exposure to 239 PuO 2 or 238 PuO 2 aerosols are being observed for life-span dose-effect relationships. The 239 Pu body burden of the nine dogs dying due to pulmonary fibrosis-induced insufficiency during the first 3 years after exposure was 1 to 12 μCi. One of these dogs had a pulmonary tumor. Three additional dogs with body burdens of 0.7 to 1.8 μCi died due to pulmonary neoplasia 4-1/2 years after exposure. None of the dogs exposed to 238 Pu have died during the first two postexposure years. After inhalation of 239 PuO 2 or 238 PuO 2 lymphocytopenia was the earliest observed effect, occuring 0.5 to 2 years after deposition of greater than or equal to 80 nCi plutonium in the lungs

  10. Dose-effect studies with inhaled plutonium oxide in beagles

    International Nuclear Information System (INIS)

    Park, J.F.; Buschbom, R.L.; Case, A.C.

    1977-01-01

    Beagle dogs given a single exposure to 239 PuO 2 or 238 PuO 2 aerosols are being observed for life-span dose-effect relationships. The 239 Pu body burden of the nine dogs that died of pulmonary fibrosis-induced respiratory insufficiency during the first 3 yr after exposure was 1 to 12 μCi. One of these dogs had a pulmonary tumor. Five additional dogs with body burdens of 0.7 to 1.8 μCi died due to pulmonary neoplasia 3 to 5 yr after exposure. None of the dogs exposed to 238 Pu have died during the first 3 postexposure yr. Lymphocytopenia was the earliest observed effect after inhalation of 239 PuO 2 or 238 PuO 2 , occurring 0.5 to 2 yr after deposition of greater than or equal to 80 nCi plutonium in the lungs

  11. Experiment of aerosol-release time for a novel automatic metered dose inhaler

    Directory of Open Access Journals (Sweden)

    Mingrong Zhang

    2016-05-01

    Full Text Available The objective of this study was to evaluate the aerosol-release time in the development of a new automatic adapter for metered dose inhaler. With this device, regular manually operated metered dose inhalers become automatic. During the study, an inhalation simulator was designed and tested with the newly developed mechatronic system. By adjusting the volume and the pressure of the vacuum tank, most human inhalation waveforms were able to simulate. As an example, regular quick-deep and slow-deep waveforms were matched within reasonable accuracy. Finally, with the help of dynamic image processing, the aerosol-release time (Tr was carefully measured and fully discussed, including the switch-on time (Ts, the mechatronics-hysteresis (Tm and the intentional-delay (Ti. Under slow-deep inhalation condition which is suitable for metered dose inhaler medicine delivery, the switch-on flow-rate could reach as low as 10 L/min, and the corresponding switch-on time was approximately 0.20 s. While the mechatronics-hysteresis depended on the brand of metered dose inhaler, assuming there was no intentional-delay, the aerosol-release time could be as low as 0.40 and 0.60 s, respectively, for two commercially available metered dose inhalers studied in this article. Therefore, this newly developed mechatronic adapter system could ensure aerosol-release time (Tr within satisfactory range for metered dose inhalers.

  12. Saharan dust levels in Greece and received inhalation doses

    Directory of Open Access Journals (Sweden)

    C. Mitsakou

    2008-12-01

    Full Text Available The desert of Sahara is one of the major sources of mineral dust on Earth, producing around 2×108 tons/yr. Under certain weather conditions, dust particles from Saharan desert get transported over the Mediterranean Sea and most of Europe. The limiting values set by the directive EC/30/1999 of European Union can easily be exceeded by the transport of desert dust particles in the south European Region and especially in urban areas, where there is also significant contribution from anthropogenic sources. In this study, the effects of dust transport on air quality in several Greek urban areas are quantified. PM10 concentration values from stationary monitoring stations are compared to dust concentrations for the 4-year period 2003–2006. The dust concentration values in the Greek areas were estimated by the SKIRON modelling system coupled with embedded algorithms describing the dust cycle. The mean annual dust contribution to daily-averaged PM10 concentration values was found to be around or even greater than 10% in the urban areas throughout the years examined. Natural dust transport may contribute by more than 20% to the annual number of exceedances – PM10 values greater than EU limits – depending on the specific monitoring location. In a second stage of the study, the inhaled lung dose received by the residents in various Greek locations is calculated. The particle deposition efficiency of mineral dust at the different parts of the human respiratory tract is determined by applying a lung dosimetry numerical model, which incorporates inhalation dynamics and aerosol physical processes. The inhalation dose from mineral dust particles was greater in the upper respiratory system (extrathoracic region and less significant in the lungs, especially in the sensitive alveolar region. However, in cases of dust episodes, the amounts of mineral dust deposited along the human lung are comparable to those

  13. Radiation doses of inhaled ash from the lignite power plants

    International Nuclear Information System (INIS)

    Boshevski, Tome; Pop-Jordanov, Jordan; Chaushevski, Anton

    1997-01-01

    The coal-fired thermal power plants in Macedonia use lignite obtained by surface mining. The lignite contains traces of thorium-232, uranium-238 and uranium-235, which are long-lived natural radioactive isotopes. After lignite combustion, the concentration of these isotopes in the ash is increased. Due to the long life of fossil materials, the decay products are basically grouped in three radioactive chains that are in a semi-steady state, resulting in equal activity of all isotopes from the chain. Among the members of each chain there are α and β emitters followed by γ quanta emitters. The energies of the α and β particles are important for determining the effective dose. The γ quanta provide information about the chain activity and isotope types. Gamma-spectroscopy studies of the ash samples from the power plants in the City of Bitola in Macedonia have confirmed the presence of several radioactive decay products from the uranium and thorium radioactive chains. Using measurements of the radioactivity of the ash in the Bitola region, the total dose from ash inhalation for the population in the Bitola region was calculated and presented in this paper. Also, analysis of the procedure for determining the maximum allowable dose from radioactive contamination of the environment, is described in this paper. (Original)

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  15. Comparative in vitro evaluation of four corticosteroid metered dose inhalers : Consistency of delivered dose and particle size distribution

    NARCIS (Netherlands)

    de Vries, Tjalling W; Rottier, Bart L; Gjaltema, Doetie; Hagedoorn, Paul; Frijlink, Henderik W; de Boer, Anne H

    2009-01-01

    Introduction: Recent developments concerning pressurized metered dose inhalers (pMDIs) with inhaled corticosteroids (ICS) are the introduction of ciclesonide and the replacement of propellants. As the results of in vivo studies depend on pMDI performance, it is necessary to evaluate pMDIs in vitro

  16. Assessment of inhalation dose sensitivity by physicochemical properties of airborne particulates containing naturally occurring radioactive materials

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Si Young; Choi, Cheol Kyu; Kim, Yong Geon; Choi, Won Chul; Kim, Kwang Pyo [Kyung Hee University, Seoul (Korea, Republic of)

    2015-12-15

    Facilities processing raw materials containing naturally occurring radioactive materials (NORM) may give rise to enhanced radiation dose to workers due to chronic inhalation of airborne particulates. Internal radiation dose due to particulate inhalation varies depending on particulate properties, including size, shape, density, and absorption type. The objective of the present study was to assess inhalation dose sensitivity to physicochemical properties of airborne particulates. Committed effective doses to workers resulting from inhalation of airborne particulates were calculated based on International Commission on Radiological Protection 66 human respiratory tract model. Inhalation dose generally increased with decreasing particulate size. Committed effective doses due to inhalation of 0.01μm sized particulates were higher than doses due to 100μm sized particulates by factors of about 100 and 50 for {sup 238}U and {sup 230}Th, respectively. Inhalation dose increased with decreasing shape factor. Shape factors of 1 and 2 resulted in dose difference by about 18 %. Inhalation dose increased with particulate mass density. Particulate mass densities of 11 g·cm{sup -3} and 0.7 g·cm{sup -3} resulted in dose difference by about 60 %. For {sup 238}U, inhalation doses were higher for absorption type of S, M, and F in that sequence. Committed effective dose for absorption type S of {sup 238}U was about 9 times higher than dose for absorption F. For {sup 230}Th, inhalation doses were higher for absorption type of F, M, and S in that sequence. Committed effective dose for absorption type F of {sup 230}Th was about 16 times higher than dose for absorption S. Consequently, use of default values for particulate properties without consideration of site specific physiochemical properties may potentially skew radiation dose estimates to unrealistic values up to 1-2 orders of magnitude. For this reason, it is highly recommended to consider site specific working materials and

  17. Dose-effect studies with inhaled plutonium oxide in beagles

    International Nuclear Information System (INIS)

    Park, J.F.; Case, A.C.; Catt, D.L.

    1978-01-01

    Beagle dogs given a single exposure to 239 PuO 2 and 238 PuO 2 aerosols are being observed for life-span dose-effect relationships. The 239 Pu body burden of the nine dogs that died of pulmonary fibrosis-induced respiratory insufficiency during the first 3 yr after exposure was 1 to 12 μCi. One of these dogs had a pulmonary tumor; nine additional dogs with body burdens of 0.6 to 1.8 μCi died due to pulmonary neoplasia 3 to 6 yr after exposure. Two of the dogs exposed to 238 Pu have died during the first 4 yr postexposure, due to bone and lung tumors, with body burdens at death of 10 μCi. Lymphocytopenia was the earliest observed effect after inhalation of 239 PuO 2 or 238 PuO 2 , occurring 0.5 to 2 yr after deposition of equal to or greater than 80 nCi plutonium in the lungs

  18. Dose-effect studies with inhaled plutonium oxide in beagles

    International Nuclear Information System (INIS)

    Park, J.F.; Case, A.C.; Catt, D.L.

    1980-01-01

    Beagle dogs given a single exposure to 239 PuO 2 and 238 PuO 2 aerosols are being observed for life-span dose-effect relationships. The 239 Pu body burden of the nine dogs that died of pulmonary-fibrosis-induced respiratory insufficiency during the first 3 yr after exposure was 1 to 12 μCi; one of these dogs had a pulmonary tumor. Seventeen additional dogs, with body burdens of 0.2 to 1.8 μCi, died due to pulmonary neoplasia 3 to 8 yr after exposure. Ten of the dogs exposed to 238 Pu have died during the first 5 1/2 yr postexposure due to bone and/or lung tumors; the body burden at death ranged from 1.5 to 10 μCi. Lymphopenia was the earliest observed effect after inhalation of 239 PuO 2 or 238 PuO 2 , occurring 0.5 to 2 yr after deposition of >80 nCi plutonium in the lungs

  19. Dose-effect studies with inhaled plutonium oxide in beagles

    International Nuclear Information System (INIS)

    Park, J.F.; Busch, R.H.; Case, A.C.

    1979-01-01

    Beagle dogs given a single exposure to 239 PuO 2 and 238 PuO 2 aerosols are being observed for life-span dose-effect relationships. The 239 Pu body burden of the nine dogs that dies of pulmonary fibrosis-induced respiratory insufficiency during the first 3 yr after exposure was 1 to 12 μCi; one of these dogs had a pulmonary tumor. Eleven additional dogs with body burdens of 0.6 to 1.8 μCi died due to pulmonary neoplasia 3 to 7 yr after exposure. Four of the dogs exposed to 238 Pu have died during the first 4 1/2 yr postexposure due to bone and/or lung tumors; the body burden at death ranged from 6 to 10 μCi. Lymphopenia was the earliest observed effect after inhalation of 239 PuO 2 or 238 PuO 2 , occurring 0.5 to 2 yr after deposition of greater than or equal to 80 nCi plutonium in the lungs

  20. Inhalants

    Science.gov (United States)

    ... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

  1. RSAC-6, Gamma doses, inhalation and ingestion doses, fission products inventory after fission products release

    International Nuclear Information System (INIS)

    Wenzel, Douglas R.; Schrader, Brad J.

    2007-01-01

    1 - Description of program or function: RSAC-6 is the latest version of the program RSAC (Radiological Safety Analysis Computer Program). It calculates the consequences of a release of radionuclides to the atmosphere. Using a personal computer, a user can generate a fission product inventory; decay and in-grow the inventory during transport through processes, facilities, and the environment; model the downwind dispersion of the activity; and calculate doses to downwind individuals. Internal dose from the inhalation and ingestion pathways is calculated. External dose from ground surface and plume gamma pathways is calculated. New and exciting updates to the program include the ability to evaluate a release to an enclosed room, resuspension of deposited activity and evaluation of a release up to 1 meter from the release point. Enhanced tools are included for dry deposition, building wake, occupancy factors, respirable fraction, AMAD adjustment, updated and enhanced radionuclide inventory and inclusion of the dose-conversion factors from FOR 11 and 12. 2 - Methods: RSAC6 calculates meteorological dispersion in the atmosphere using Gaussian plume diffusion for Pasquill-Gifford, Hilmeier-Gifford and Markee models. A unique capability is the ability to model Class F fumigation conditions, the meteorological condition that causes the highest ground level concentrations from an elevated release. Doses may be calculated for various pathways including inhalation, ingestion, ground surface, air immersion, water immersion pathways. Dose calculations may be made for either acute or chronic releases. Internal doses (inhalation and ingestion) are calculated using the ICRP-30 model with dose conversion factors from FOR 11. External factors are calculated using FOR 12. 3 - Unusual Features: RSAC6 calculates complete progeny in-growth and decay during all accident phases. The calculation of fission product inventories in particularly useful in the analysis of accidents where the

  2. ANALYSIS OF RESPIRATORY DEPOSITION OF INHALED AMBIENT AEROSOLS FOR DIFFERENT DOSE METRICS

    Science.gov (United States)

    ANALYSIS OF RESPIRATORY DEPOSITION OF INHALED AMBIENT AEROSOLS FOR DIFFERENT DOSE METRICS.Chong S. Kim, SC. Hu**, PA Jaques*, US EPA, National Health and Environmental Effects Research Laboratory, Research Triangle Park, NC 27711; **IIT Research Institute, Chicago, IL; *South...

  3. ANALYSIS OF RESPIRATORY DESPOSITION DOSE OF INHALED AMBIENT AEROSOLS FOR DIFFERENT SIZE FRACTIONS

    Science.gov (United States)

    ANALYSIS OF RESPIRATORY DEPOSITION DOSE OF INHALED AMBIENT AEROSOLS FOR DIFFERENT SIZE FRACTIONS. Chong S. Kim, SC. Hu**, PA Jaques*, US EPA, National Health and Environmental Effects Research Laboratory, Research Triangle Park, NC 27711; **IIT Research Institute, Chicago, IL; *S...

  4. Comparison in the calculation of committed effective dose using the ICRP 30 and ICRP 60 models for a repeated incorporation by inhalation of I-125; Comparacion en el calculo de la dosis efectiva comprometida usando los modelos del ICRP 30 y del ICRP 60 para una incorporacion repetida por inhalacion de I-125

    Energy Technology Data Exchange (ETDEWEB)

    Carreno P, A.L.; Cortes C, A. [CNSNS, Dr. Barragan 779, Col. Narvarte, Mexico D.F. (Mexico); Alonso V, G.; Serrano P, F. [IPN, Edificio de Fisica Avanzada Zacatenco, 07300 Mexico D.F. (Mexico)

    2005-07-01

    Presently work, a comparison in the calculation of committed effective dose using the models of the ICRP 30 and those of the ICRP 60 for the analysis of internal dose due to repeated incorporation of I-125 is shown. The estimations of incorporated activity are obtained starting from the proportionate data for an exercise of inter comparison, with which it should be determined the internal dose later on. For to estimate the initial activity incorporated by repeated dose was assumed that this it was given through of multiple individual incorporations which happened in the middle points of the monitoring periods. The results using the models of the ICRP 30 and of the ICRP 60 are compared and the causes of the differences are analyzed. (Author)

  5. Radiation dose to the lungs due to inhalation of alpha emitters

    International Nuclear Information System (INIS)

    Haque, A.K.M.M.; Al-Affan, I.A.M.

    1987-01-01

    The radiation dose to the lungs due to inhalation of radon daughters has been computed with improved data on lung models, aerosol parameters, deposition and clearance mechanisms. The dose corresponds to mean radon concentration of 23 Bq/m 3 indoors (recent NRPB Survey) for different living conditions. The dose rate to basal cells in gen. 5 is 12 mGy/WLM. (author)

  6. Inhaled corticosteroid metered-dose inhalers: how do variations in technique for solutions versus suspensions affect drug distribution?

    Science.gov (United States)

    Robinson, Christie A; Tsourounis, Candy

    2013-03-01

    To assess the literature that evaluates how variations in metered-dose inhaler (MDI) technique affect lung distribution for inhaled corticosteroids (ICSs) formulated as MDI suspensions and solutions. PubMed (up to November 2012) and Cochrane Library (up to November 2012) were searched using the terms metered-dose inhalers, HFA 134a, Asthma/*drug therapy, and inhaled corticosteroids. In addition, reference citations from publications identified were reviewed. All articles in English from the data sources that assessed MDI technique comparing total lung distribution (TLD) of MDI solutions or suspensions formulated with ICSs were included in the review. Five relevant studies were identified. Five controlled studies compared how variations in MDI technique affect TLD for ICS MDI solutions with suspensions. MDI solutions resulted in greater TLD compared with larger particle MDI suspensions. Delayed or early inspiration upon device actuation of MDI solutions resulted in less TLD than coordinated actuation, but with a 3- to 4-times greater TLD than MDI suspensions inhaled using a standard technique. A sixth study evaluated inspiratory flow rates (IFR) for small, medium, and large particles. Rapid and slow IFRs resulted in similar TLD for small particles, while far fewer particles reached the airways with medium and large particles at rapid, rather than slow, IFRs. Based on the literature evaluated, standard MDI technique should be used for ICS suspensions. ICS MDI solutions can provide a higher average TLD than larger-particle ICS suspensions using standard technique, discoordinated inspiration and medication actuation timing, or rapid and slow IFRs. ICS MDI solutions allow for a more forgiving technique, which makes them uniquely suitable options for patients with asthma who have difficultly with MDI technique.

  7. Spiromax, a New Dry Powder Inhaler: Dose Consistency under Simulated Real-World Conditions.

    Science.gov (United States)

    Canonica, Giorgio Walter; Arp, Jan; Keegstra, Johan René; Chrystyn, Henry

    2015-10-01

    Spiromax(®) is a novel dry powder inhaler for patients with asthma or chronic obstructive pulmonary disease (COPD). The studies presented here provide further data on attributes (in vitro dosing consistency with budesonide-formoterol (DuoResp) Spiromax; flow rates through empty versions of the Spiromax and Turbuhaler inhaler) of importance to patients with asthma or COPD. Dose-delivery studies were performed using low-, middle-, and high-strength DuoResp Spiromax. Dose consistency was assessed over inhaler life. Total emitted doses (TEDs) were measured at various flow rates, after exposure to high and low temperature or humidity, at different inhaler orientations, and after dropping the inhaler. The criterion for evaluating dose uniformity was whether mean TEDs were within the product specification limits. In separate studies, flow rates were measured after training, using the patient information leaflets, and again after enhanced training as part of a randomized, open-label, cross-over study. Mean values for both budesonide and formoterol were within 85%-115% of the label claim for each strength of DuoResp Spiromax for initial dose uniformity and for the other investigated conditions (temperature, humidity, orientation, dropping, knocking), with the exception of approximately an 80% increase in first dose after dropping the inhaler (subsequent doses not affected). In the flow rate patient study, two patients' inhalations with Spiromax and six with Turbuhaler were 60 L/min. DuoResp Spiromax consistently meets dose uniformity criteria, under controlled laboratory conditions and with variations intended to mimic real-world use. Following enhanced training, all patients in the flow study were able to achieve the minimal inspiratory flow rate of >30 L/min, which is required for effective treatment.

  8. Inhalants

    Science.gov (United States)

    ... uses inhalants may be unable to learn new things or may have a hard time carrying on simple conversations. If the cerebral ... get drugs on the street, it is really hard to know what you get, Sometimes, ... put in, all sorts of things could happen. And other times, one might get ...

  9. Cumulative high doses of inhaled formoterol have less systemic effects in asthmatic children 6-11 years-old than cumulative high doses of inhaled terbutaline.

    Science.gov (United States)

    Kaae, Rikke; Agertoft, Lone; Pedersen, Sören; Nordvall, S Lennart; Pedroletti, Christophe; Bengtsson, Thomas; Johannes-Hellberg, Ingegerd; Rosenborg, Johan

    2004-10-01

    To evaluate high dose tolerability and relative systemic dose potency between inhaled clinically equipotent dose increments of formoterol and terbutaline in children. Twenty boys and girls (6-11 years-old) with asthma and normal ECGs were studied. Ten doses of formoterol (Oxis) 4.5 microg (F4.5) or terbutaline (Bricanyl) 500 microg (T500) were inhaled cumulatively via a dry powder inhaler (Turbuhaler) over 1 h (three patients) or 2.5 h (17 patients) and compared to a day of no treatment, in a randomised, double-blind (active treatments only), crossover trial. Blood pressure (BP), ECG, plasma potassium, glucose, lactate, and adverse events were monitored up to 10 h to assess tolerability and relative systemic dose potency. Formoterol and terbutaline had significant beta2-adrenergic effects on most outcomes. Apart from the effect on systolic BP, QRS duration and PR interval, the systemic effects were significantly more pronounced with terbutaline than with formoterol. Thus, mean minimum plasma potassium, was suppressed from 3.56 (95% confidence interval, CI: 3.48-3.65) mmol l(-1) on the day of no treatment to 2.98 (CI: 2.90-3.08) after 10 x F4.5 and 2.70 (CI: 2.61-2.78) mmol l(-1) after 10 x T500, and maximum Q-Tc (heart rate corrected Q-T interval [Bazett's formula]) was prolonged from 429 (CI: 422-435) ms on the day of no treatment, to 455 (CI: 448-462) ms after 10 x F4.5 and 470 (CI: 463-476) ms after 10 x T500. Estimates of relative dose potency indicated that F4.5 microg had the same systemic activity as the clinically less effective dose of 250 microg terbutaline. The duration of systemic effects differed marginally between treatments. Spontaneously reported adverse events (most frequently tremor) were fewer with formoterol (78% of the children) than with terbutaline (95%). A serious adverse event occurred after inhalation of 45 microg formoterol over the 1 h dosing time, that prompted the extension of dosing time to 2.5 h. Multiple inhalations over 2.5 h of

  10. Cumulative high doses of inhaled formoterol have less systemic effects in asthmatic children 6–11 years-old than cumulative high doses of inhaled terbutaline

    Science.gov (United States)

    Kaae, Rikke; Agertoft, Lone; Pedersen, Sören; Nordvall, S Lennart; Pedroletti, Christophe; Bengtsson, Thomas; Johannes-Hellberg, Ingegerd; Rosenborg, Johan

    2004-01-01

    Objectives To evaluate high dose tolerability and relative systemic dose potency between inhaled clinically equipotent dose increments of formoterol and terbutaline in children. Methods Twenty boys and girls (6–11 years-old) with asthma and normal ECGs were studied. Ten doses of formoterol (Oxis®) 4.5 µg (F4.5) or terbutaline (Bricanyl®) 500 µg (T500) were inhaled cumulatively via a dry powder inhaler (Turbuhaler®) over 1 h (three patients) or 2.5 h (17 patients) and compared to a day of no treatment, in a randomised, double-blind (active treatments only), crossover trial. Blood pressure (BP), ECG, plasma potassium, glucose, lactate, and adverse events were monitored up to 10 h to assess tolerability and relative systemic dose potency. Results Formoterol and terbutaline had significant β2-adrenergic effects on most outcomes. Apart from the effect on systolic BP, QRS duration and PR interval, the systemic effects were significantly more pronounced with terbutaline than with formoterol. Thus, mean minimum plasma potassium, was suppressed from 3.56 (95% confidence interval, CI: 3.48–3.65) mmol l−1 on the day of no treatment to 2.98 (CI: 2.90–3.08) after 10 × F4.5 and 2.70 (CI: 2.61–2.78) mmol l−1 after 10 × T500, and maximum Q-Tc (heart rate corrected Q-T interval [Bazett's formula]) was prolonged from 429 (CI: 422–435) ms on the day of no treatment, to 455 (CI: 448–462) ms after 10 × F4.5 and 470 (CI: 463–476) ms after 10 × T500. Estimates of relative dose potency indicated that F4.5 µg had the same systemic activity as the clinically less effective dose of 250 µg terbutaline. The duration of systemic effects differed marginally between treatments. Spontaneously reported adverse events (most frequently tremor) were fewer with formoterol (78% of the children) than with terbutaline (95%). A serious adverse event occurred after inhalation of 45 µg formoterol over the 1 h dosing time, that prompted the extension of dosing time to 2.5 h

  11. Repeated episodes of ozone inhalation amplifies the effects of allergen sensitization and inhalation on airway immune and structural development in Rhesus monkeys.

    Science.gov (United States)

    Schelegle, Edward S; Miller, Lisa A; Gershwin, Laurel J; Fanucchi, Michelle V; Van Winkle, Laura S; Gerriets, Joan E; Walby, William F; Mitchell, Valerie; Tarkington, Brian K; Wong, Viviana J; Baker, Gregory L; Pantle, Lorraine M; Joad, Jesse P; Pinkerton, Kent E; Wu, Reen; Evans, Michael J; Hyde, Dallas M; Plopper, Charles G

    2003-08-15

    Twenty-four infant rhesus monkeys (30 days old) were exposed to 11 episodes of filtered air (FA), house dust mite allergen aerosol (HDMA), ozone (O3), or HDMA + O3 (5 days each followed by 9 days of FA). Ozone was delivered for 8 h/day at 0.5 ppm. Twelve of the monkeys were sensitized to house dust mite allergen (Dermatophagoides farinae) at ages 14 and 28 days by subcutaneous inoculation (SQ) of HDMA in alum and intraperitoneal injection of heat-killed Bordetella pertussis cells. Sensitized monkeys were exposed to HDMA aerosol for 2 h/day on days 3-5 of either FA (n = 6) or O3 (n = 6) exposure. Nonsensitized monkeys were exposed to either FA (n = 6) or O3 (n = 6). During the exposure regimen, parameters of allergy (i.e., serum IgE, histamine, and eosinophilia), airways resistance, reactivity, and structural remodeling were evaluated. Eleven repeated 5-day cycles of inhaling 0.5 ppm ozone over a 6-month period had only mild effects on the airways of nonsensitized infant rhesus monkeys. Similarly, the repeated inhalation of HDMA by HDMA-sensitized infant monkeys resulted in only mild airway effects, with the exception of a marked increase in proximal airway and terminal bronchiole content of eosinophils. In contrast, the combined cyclic inhalation of ozone and HDMA by HDMA sensitized infants monkeys resulted in a marked increase in serum IgE, serum histamine, and airways eosinophilia. Furthermore, combined cyclic inhalation of ozone and HDMA resulted in even greater alterations in airway structure and content that were associated with a significant elevation in baseline airways resistance and reactivity. These results suggest that ozone can amplify the allergic and structural remodeling effects of HDMA sensitization and inhalation.

  12. HADOC: a computer code for calculation of external and inhalation doses from acute radionuclide releases

    International Nuclear Information System (INIS)

    Strenge, D.L.; Peloquin, R.A.

    1981-04-01

    The computer code HADOC (Hanford Acute Dose Calculations) is described and instructions for its use are presented. The code calculates external dose from air submersion and inhalation doses following acute radionuclide releases. Atmospheric dispersion is calculated using the Hanford model with options to determine maximum conditions. Building wake effects and terrain variation may also be considered. Doses are calculated using dose conversion factor supplied in a data library. Doses are reported for one and fifty year dose commitment periods for the maximum individual and the regional population (within 50 miles). The fractional contribution to dose by radionuclide and exposure mode are also printed if requested

  13. Antithrombotic effect of repeated doses of the ethanolic extract of ...

    African Journals Online (AJOL)

    Antithrombotic effect of repeated doses of the ethanolic extract of local olive ( Olea europaea L.) leaves in rabbits. ... The incidence of thromboembolic diseases is increasing, and they are a major cause of mortality and morbidity worldwide. Mediterranean diet is known for its high content of olive products, especially olive oil, ...

  14. Monte Carlo calculation of received dose from ingestion and inhalation of natural uranium

    International Nuclear Information System (INIS)

    Trobok, M.; Zupunski, Lj.; Spasic-Jokic, V.; Gordanic, V.; Sovilj, P.

    2009-01-01

    For the purpose of this study eighty samples are taken from the area Bela Crkva and Vrsac. The activity of radionuclide in the soil is determined by gamma- ray spectrometry. Monte Carlo method is used to calculate effective dose received by population resulting from the inhalation and ingestion of natural uranium. The estimated doses were compared with the legally prescribed levels. (author) [sr

  15. Reversibility of pulmonary function after inhaling salbutamol in different doses and body postures in asthmatic children.

    Science.gov (United States)

    Visser, R; Kelderman, S; de Jongh, F H C; van der Palen, J; Thio, B J

    2015-10-01

    Pulmonary medication is often delivered in the form of medical aerosols designed for inhalation. Recently, breath actuated inhalers (BAI's) gained popularity as they can be used without spacers. A major drawback of BAI's is the impaction in the upper airway. Stretching the upper airway by a forward leaning body posture with the neck extended ("sniffing position") during inhalation may reduce upper airway impaction and improve pulmonary deposition. Aim of this study was to investigate the reversibility of lung function with different doses salbutamol inhaled with a BAI in the forward leaning posture compared to the standard posture in asthmatic children. 22 clinically stable asthmatic children, 5-14 years old, performed four reversibility measurements. Children inhaled 200 μg or 400 μg salbutamol with a BAI in the standard or in the forward leaning posture with the neck extended in a randomized single-blinded cross-over design. Reversibility of lung function after inhaling salbutamol in the forward leaning posture was not significantly different compared to inhalation in the standard posture. Mean FEV1 reversibility was significantly greater after inhaling 400 μg salbutamol compared to 200 μg salbutamol in the standard posture (9.4% ± 9.5% versus 4.5% ± 7.5%, difference 4.9% (95CI 0.9; 9.0%); p = 0.021). In clinically stable asthmatic children, inhalation of salbutamol with a BAI in a forward leaning posture does not increase reversibility of lung function. Inhalation of 400 μg compared to 200 μg salbutamol with a BAI does improve reversibility. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Systemic delivery of atropine sulfate by the MicroDose Dry-Powder Inhaler.

    Science.gov (United States)

    Corcoran, T E; Venkataramanan, R; Hoffman, R M; George, M P; Petrov, A; Richards, T; Zhang, S; Choi, J; Gao, Y Y; Oakum, C D; Cook, R O; Donahoe, M

    2013-02-01

    Inhaled atropine is being developed as a systemic and pulmonary treatment for the extended recovery period after chemical weapons exposure. We performed a pharmacokinetics study comparing inhaled atropine delivery using the MicroDose Therapeutx Dry Powder Inhaler (DPIA) with intramuscular (IM) atropine delivery via auto-injector (AUTO). The MicroDose DPIA utilizes a novel piezoelectric system to aerosolize drug and excipient from a foil dosing blister. Subjects inhaled a 1.95-mg atropine sulfate dose from the dry powder inhaler on one study day [5 doses × 0.4 mg per dose (nominal) delivered over 12 min] and received a 2-mg IM injection via the AtroPen® auto-injector on another. Pharmacokinetics, pharmacodynamic response, and safety were studied for 12 hr. A total of 17 subjects were enrolled. All subjects completed IM dosing. One subject did not perform inhaled delivery due to a skin reaction from the IM dose. Pharmacokinetic results were as follows: area under the curve concentration, DPIA=20.1±5.8, AUTO=23.7±4.9 ng hr/mL (means±SD); maximum concentration reached, DPIA=7.7±3.5, AUTO=11.0±3.8 ng/mL; time to reach maximum concentration, DPIA=0.25±0.47, AUTO=0.19±0.23 hr. Pharmacodynamic results were as follows: maximum increase in heart rate, DPIA=18±12, AUTO=23±13 beats/min; average change in 1-sec forced expiratory volume at 30 min, DPIA=0.16±0.22 L, AUTO=0.11±0.29 L. The relative bioavailability for DPIA was 87% (based on output dose). Two subjects demonstrated allergic responses: one to the first dose (AUTO), which was mild and transient, and one to the second dose (DPIA), which was moderate in severity, required treatment with oral and intravenous (IV) diphenhydramine and IV steroids, and lasted more than 7 days. Dry powder inhalation is a highly bioavailable route for attaining rapid and consistent systemic concentrations of atropine.

  17. Estimation of chloroform inhalation dose by other routes based on the relationship of area under the blood concentration-time curve (AUC)-inhalation dose to chloroform distribution in the blood of rats.

    Science.gov (United States)

    Take, Makoto; Takeuchi, Tetsuya; Haresaku, Mitsuru; Matsumoto, Michiharu; Nagano, Kasuke; Yamamoto, Seigo; Takamura-Enya, Takeji; Fukushima, Shoji

    2014-01-01

    The present study investigated the time-course changes of concentration of chloroform (CHCl3) in the blood during and after exposure of male rats to CHCl3 by inhalation. Increasing the dose of CHCl3 in the inhalation exposed groups caused a commensurate increase in the concentration of CHCl3 in the blood and the area under the blood concentration-time curve (AUC). There was good correlation (r = 0.988) between the inhalation dose and the AUC/kg body weight. Based on the AUC/kg body weight-inhalation dose curve and the AUC/kg body weight after oral administration, inhalation equivalent doses of orally administered CHCl3 were calculated. Calculation of inhalation equivalent doses allows the body burden due to CHCl3 by inhalation exposure and oral exposure to be directly compared. This type of comparison facilitates risk assessment in humans exposed to CHCl3 by different routes. Our results indicate that when calculating inhalation equivalent doses of CHCl3, it is critical to include the AUC from the exposure period in addition to the AUC after the end of the exposure period. Thus, studies which measure the concentration of volatile organic compounds in the blood during the inhalation exposure period are crucial. The data reported here makes an important contribution to the physiologically based pharmacokinetic (PBPK) database of CHCl3 in rodents.

  18. Radiation dose estimates and hazard evaluations for inhaled airborne radionuclides: Final report

    International Nuclear Information System (INIS)

    Mewhinney, J.A.

    1987-09-01

    The project objective was to conduct confirmatory research on physical chemical characteristics of aerosols produced during manufacture of mixed plutonium and uranium oxide nuclear fuel, to determine the radiation dose distribution in tissues of animals after inhalation exposure to representative aerosols of these materials, and to provide estimates of the relationship of radiation dose and biological response in animals after such inhalation exposure. The first chapter summarizes the physical chemical characterization of samples of aerosols collected from gloveboxes at industrial facilities during normal operations. This chapter provides insights into key aerosol characteristics which are of potential importance in determining the biological fate of specific radionuclides contained in the particulates that would be inhaled by humans following accidental release. The second chapter describes the spatial and temporal distribution of radiation dose in tissues of three species of animals exposed to representative aerosols collected from the industrial facilities. These inhalation studies provide a basis for comparison of the influence of physical chemical form of the inhaled particulates and the variability among species of animal in the radiation dose to tissue. The third chapter details to relationship between radiation dose and biological response in rats exposed to two aerosol forms each at three levels of initial pulmonary burden. This study, conducted over the lifespan of the rats and assuming results to be applicable to humans, indicates that the hazard to health due to inhalation of these industrial aerosols is not different than previously determined for laboratory produced aerosol of PuO 2 . Each chapter is processed separately for the data base

  19. Studies on possibility for alleviation of lifestyle diseases by low-dose irradiation or radon inhalation

    International Nuclear Information System (INIS)

    Kataoka, T.; Sakoda, A.; Yoshimoto, M.; Nakagawa, S.; Toyota, T.; Nishiyama, Y.; Yamato, K.; Ishimori, Y.; Kawabe, A.; Hanamoto, K.; Taguchi, T.; Yamaoka, K.

    2011-01-01

    Our previous studies showed the possibility that activation of the anti-oxidative function alleviates various oxidative damages, which are related to lifestyle diseases. Results showed that, low-dose X-ray irradiation activated superoxide dismutase and inhibits oedema following ischaemia-reperfusion. To alleviate ischaemia-reperfusion injury with transplantation, the changes of the anti-oxidative function in liver graft using low-dose X-ray irradiation immediately after exenteration were examined. Results showed that liver grafts activate the anti-oxidative function as a result of irradiation. In addition, radon inhalation enhances the anti-oxidative function in some organs, and alleviates alcohol-induced oxidative damage of mouse liver. Moreover, in order to determine the most effective condition of radon inhalation, mice inhaled radon before or after carbon tetrachloride (CCl 4 ) administration. Results showed that radon inhalation alleviates CCl 4 -induced hepatopathy, especially prior inhalation. It is highly possible that adequate activation of anti-oxidative functions induced by low-dose irradiation can contribute to preventing or reducing oxidative damages, which are related to lifestyle diseases. (authors)

  20. In vitro dose comparison of Respimat® inhaler with dry powder inhalers for COPD maintenance therapy

    Directory of Open Access Journals (Sweden)

    Ciciliani A

    2017-05-01

    Full Text Available Anna-Maria Ciciliani,1,2 Peter Langguth,1 Herbert Wachtel2 1Institute of Pharmacy and Biochemistry, Faculty 09 (Chemistry, Pharmaceutics and Geosciences, Johannes Gutenberg University, Mainz, 2Analytical Development Department, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany Background: Combining in vitro mouth–throat deposition measurements, cascade impactor data and computational fluid dynamics (CFD simulations, four different inhalers were compared which are indicated for chronic obstructive pulmonary disease (COPD treatment.Methods: The Respimat inhaler, the Breezhaler, the Genuair, and the Ellipta were coupled to the idealized Alberta throat model. The modeled dose to the lung (mDTL was collected downstream of the Alberta throat model using either a filter or a next generation impactor (NGI. Idealized breathing patterns from COPD patient groups – moderate and very severe COPD – were applied. Theoretical lung deposition patterns were assessed by an individual path model.Results and conclusion: For the Respimat the mDTL was found to be 59% (SD 5% for the moderate COPD breathing pattern and 67% (SD 5% for very severe COPD breathing pattern. The percentages refer to nominal dose (ND in vitro. This is in the range of 44%–63% in vivo in COPD patients who display large individual variability. Breezhaler showed a mDTL of 43% (SD 2% for moderate disease simulation and 51% (SD 2% for very severe simulation. The corresponding results for Genuair are mDTL of 32% (SD 2% for moderate and 42% (SD 1% for very severe disease. Ellipta vilanterol particles showed a mDTL of 49% (SD 3% for moderate and 55% (SD 2% for very severe disease simulation, and Ellipta fluticasone particles showed a mDTL of 33% (SD 3% and 41% (SD 2%, respectively for the two breathing patterns. Based on the throat output and average flows of the different inhalers, CFD simulations were performed. Laminar and turbulent steady flow calculations indicated that

  1. Impact of multiple-dose versus single-dose inhaler devices on COPD patients’ persistence with long-acting β2-agonists: a dispensing database analysis

    Science.gov (United States)

    van Boven, Job FM; van Raaij, Joost J; van der Galiën, Ruben; Postma, Maarten J; van der Molen, Thys; Dekhuijzen, PN Richard; Vegter, Stefan

    2014-01-01

    Background: With a growing availability of different devices and types of medication, additional evidence is required to assist clinicians in prescribing the optimal medication in relation to chronic obstructive pulmonary disease (COPD) patients’ persistence with long-acting β2-agonists (LABAs). Aims: To assess the impact of the type of inhaler device (multiple-dose versus single-dose inhalers) on 1-year persistence and switching patterns with LABAs. Methods: A retrospective observational cohort study was performed comparing a cohort of patients initiating multiple-dose inhalers and a cohort initiating single-dose inhalers. The study population consisted of long-acting bronchodilator naive COPD patients, initiating inhalation therapy with mono-LABAs (formoterol, indacaterol or salmeterol). Analyses were performed using pharmacy dispensing data from 1994 to 2012, obtained from the IADB.nl database. Study outcomes were 1-year persistence and switching patterns. Results were adjusted for initial prescriber, initial medication, dosing regimen and relevant comorbidities. Results: In all, 575 patients initiating LABAs were included in the final study cohort. Among them, 475 (83%) initiated a multiple-dose inhaler and 100 (17%) a single-dose inhaler. Further, 269 (47%) initiated formoterol, 9 (2%) indacaterol and 297 (52%) salmeterol. There was no significant difference in persistence between users of multiple-dose or single-dose inhalers (hazard ratio: 0.98, 95% confidence interval: 0.76–1.26, P=0.99). Over 80% re-started or switched medication. Conclusions: There seems no impact of inhaler device (multiple-dose versus single-dose inhalers) on COPD patients’ persistence with LABAs. Over 80% of patients who initially seemed to discontinue LABAs, re-started their initial medication or switched inhalers or medication within 1 year. PMID:25274453

  2. Dose and effect of inhaled ozone in resting versus exercising human subjects: comparison with resting rats

    Science.gov (United States)

    Dose and effect of inhaled ozone in resting versus exercising human subjects: comparison with resting rats Authors: Gary E. Hatch, John McKee, James Brown, Bill McDonnell, Elston Seal, Joleen Soukup, Ralph Slade, Kay Crissman and Robert Devlin, National Health and Environmental...

  3. Pharmacology of ayahuasca administered in two repeated doses.

    Science.gov (United States)

    Dos Santos, Rafael G; Grasa, Eva; Valle, Marta; Ballester, Maria Rosa; Bouso, José Carlos; Nomdedéu, Josep F; Homs, Rosa; Barbanoj, Manel J; Riba, Jordi

    2012-02-01

    Ayahuasca is an Amazonian tea containing the natural psychedelic 5-HT(2A/2C/1A) agonist N,N-dimethyltryptamine (DMT). It is used in ceremonial contexts for its visionary properties. The human pharmacology of ayahuasca has been well characterized following its administration in single doses. To evaluate the human pharmacology of ayahuasca in repeated doses and assess the potential occurrence of acute tolerance or sensitization. In a double-blind, crossover, placebo-controlled clinical trial, nine experienced psychedelic drug users received PO the two following treatment combinations at least 1 week apart: (a) a lactose placebo and then, 4 h later, an ayahuasca dose; and (b) two ayahuasca doses 4 h apart. All ayahuasca doses were freeze-dried Amazonian-sourced tea encapsulated to a standardized 0.75 mg DMT/kg bodyweight. Subjective, neurophysiological, cardiovascular, autonomic, neuroendocrine, and cell immunity measures were obtained before and at regular time intervals until 12 h after first dose administration. DMT plasma concentrations, scores in subjective and neurophysiological variables, and serum prolactin and cortisol were significantly higher after two consecutive doses. When effects were standardized by plasma DMT concentrations, no differences were observed for subjective, neurophysiological, autonomic, or immunological effects. However, we observed a trend to reduced systolic blood pressure and heart rate, and a significant decrease for growth hormone (GH) after the second ayahuasca dose. Whereas there was no clear-cut tolerance or sensitization in the psychological sphere or most physiological variables, a trend to lower cardiovascular activation was observed, together with significant tolerance to GH secretion.

  4. Dioxin inhalation doses from wood combustion in indoor cookfires

    Science.gov (United States)

    Northcross, Amanda L.; Katharine Hammond, S.; Canuz, Eduardo; Smith, Kirk R.

    2012-03-01

    Approximately 3 billion people worldwide rely on solid biomass fuels for household cooking and space heating, and approximately 50-60% use wood, often indoors in poorly ventilated situations. Daily exposures to high concentrations of smoke from cookstoves inside kitchens create large smoke exposures for women cooks and their small children. The smoke from burning the wood fuel contains hundred of toxic compounds, including dioxins and furans some of the most toxic compounds known to science. Health effects from exposure to dioxins include reproductive and developmental problems, damage the immune system, interference with hormones and also cause cancer. This study measured concentrations of dioxins and furans in a typical Guatemalan village home during open cookfires. Measured concentrations averaged 0.32 ± 0.07 ng m-3 over 31 fires. A Monte Carlo simulation was conducted using parameter estimates based on 8 years of research experience in the study area. The estimated total daily intake of 17 particle phase dioxin and furans for women, a 5-year-old child and a 6-month-old infant were 1.2 (S.D. = 0.4), 1.7 (S.D. = 0.7) and 2.0 (S.D. = 0.5) respectively. The 46% of babies have and estimated total daily intake (TDI) which exceed the WHO TDI guideline for dioxins and furans, 3% of women and 26% of 5-year-old children based solely inhalation of particle phase dioxins in woodsmoke from an open cooking fire. These values maybe underestimates, as they did not include gas phase concentrations or ingestion of dioxins and furans through food, which is the largest route of exposure in the developed world.

  5. Radioactivity of 210Pb in Japanese cigarettes and radiation dose from smoking inhalation

    International Nuclear Information System (INIS)

    Sakoda, A.; Fukao, K.; Kawabe, A.; Kataoka, T.; Hanamoto, K.; Yamaoka, K.

    2012-01-01

    It is well known that cigarette tobaccos contain naturally occurring radioactive nuclides such as 210 Pb and 210 Po. In many countries, the radioactivity of tobaccos has been measured to estimate the effective dose from smoking inhalation. The present study covered 24 cigarette brands including the top 20 of sales in Japan between April 2008 and March 2009. The activity concentrations of 210 Pb were measured by gamma-ray spectrometry, and then those of its progeny ( 210 Po) were evaluated assuming the radioactive equilibrium between the two nuclides. Their concentrations were in the range of 2-14 mBq cigarette -1 with an arithmetic mean of 8±3 mBq cigarette -1 . The annual committed effective doses were also calculated, based on the scenario that a smoker consumes 20 cigarettes a day. The average doses from 210 Pb and 210 Po inhalations were 22±9 and 68±27 uμSv y -1 , respectively. (authors)

  6. ACRO - a computer program for calculating organ doses from acute or chronic inhalation and ingestion of radionuclides

    International Nuclear Information System (INIS)

    Hirayama, Akio; Kishimoto, Yoichiro; Shinohara, Kunihiko.

    1978-01-01

    The computer program ACRO has been developed to calculate organ doses from acute or chronic inhalation and ingestion of radionuclides. The ICRP Task Group Lung Model (TGLM) was used for inhalation model, and a simple one-compartment model for ingestion. This program is written in FORTRAN IV, and can be executed with storage requirements of about 260 K bytes. (auth.)

  7. Protective effect of budesonide/formoterol compared with formoterol, salbutamol and placebo on repeated provocations with inhaled AMP in patients with asthma: a randomised, double-blind, cross-over study

    Directory of Open Access Journals (Sweden)

    van der Woude Hanneke J

    2010-05-01

    Full Text Available Abstract Background The budesonide/formoterol combination is successfully used for fast relief of asthma symptoms in addition to its use as maintenance therapy. The temporarily increased corticosteroid dose during increasing inhaler use for symptom relief is likely to suppress any temporary increase in airway inflammation and may mitigate or prevent asthma exacerbations. The relative contribution of the budesonide and formoterol components to the improved asthma control is unclear. Methods The acute protective effect of inhaled budesonide was tested in a model of temporarily increased airway inflammation with repeated indirect airway challenges, mimicking an acute asthma exacerbation. A randomised, double-blind, cross-over study design was used. Asthmatic patients (n = 17, mean FEV1 95% of predicted who previously demonstrated a ≥30% fall in forced expiratory volume in 1 second (FEV1 after inhaling adenosine 5'-monophosphate (AMP, were challenged on four consecutive test days, with the same dose of AMP (at 09:00, 12:00 and 16:00 hours. Within 1 minute of the maximal AMP-induced bronchoconstriction at 09:00 hours, the patients inhaled one dose of either budesonide/formoterol (160/4.5 μg, formoterol (4.5 μg, salbutamol (2 × 100 μg or placebo. The protective effects of the randomised treatments were assessed by serial lung function measurements over the test day. Results In the AMP provocations at 3 and 7 hours after inhalation, the budesonide/formoterol combination provided a greater protective effect against AMP-induced bronchoconstriction compared with formoterol alone, salbutamol and placebo. In addition all three active treatments significantly increased FEV1 within 3 minutes of administration, at a time when inhaled AMP had induced the 30% fall in FEV1. Conclusions A single dose of budesonide/formoterol provided a greater protective effect against inhaled AMP-induced bronchoconstriction than formoterol alone, both at 3 and at 7 hours

  8. Biological clearance and committed dose equivalent in pulmonary region from inhaled radioaerosols for lung scanning

    Energy Technology Data Exchange (ETDEWEB)

    Soni, P.S.; Sharma, S.M.; Raghunath, B.; Somasundaram, S.

    1987-01-01

    Biological clearance half-lives (Tsub(b)) of different /sup 99/Tcsup(m)-labelled compounds from each lung have been determined, after administering the radioaerosol to normal subjects using the BARC dry aerosol generation and inhalation system. Based on these experimental clearance half-lives, the committed dose equivalent to the lungs has been computed using both the ICRP lung model and MIRD-11 values.

  9. Biological clearance and committed dose equivalent in pulmonary region from inhaled radioaerosols for lung scanning

    International Nuclear Information System (INIS)

    Soni, P.S.; Sharma, S.M.; Raghunath, B.; Somasundaram, S.

    1987-01-01

    Biological clearance half-lives (Tsub(b)) of different 99 Tcsup(m)-labelled compounds from each lung have been determined, after administering the radioaerosol to normal subjects using the BARC dry aerosol generation and inhalation system. Based on these experimental clearance half-lives, the committed dose equivalent to the lungs has been computed using both the ICRP lung model and MIRD-11 values. (author)

  10. A development of computer code for evaluating internal radiation dose through ingestion and inhalation pathways

    International Nuclear Information System (INIS)

    Lee, Jeong Ho; Lee, Chang Woo; Choi, Yong Ho; Chun, Ki Jung; Kim, Kook Chan; Kim, Sang Bok; Kim, Jin Kyu

    1991-07-01

    The computer codes were developed to evaluate internal radiation dose when radioactive isotopes released from nuclear facilities are taken through ingestion and inhalation pathways. Food chain models and relevant data base representing the agricultural and social environment of Korea are set up. An equilibrium model-KFOOD, which can deal with routine releases from a nuclear facility and a dynamic model-ECOREA, which is suitable for the description of acute radioactivity release following nuclear accident. (Author)

  11. Humidity affects the morphology of particles emitted from beclomethasone dipropionate pressurized metered dose inhalers.

    Science.gov (United States)

    Ivey, James W; Bhambri, Pallavi; Church, Tanya K; Lewis, David A; McDermott, Mark T; Elbayomy, Shereen; Finlay, Warren H; Vehring, Reinhard

    2017-03-30

    The effects of propellant type, cosolvent content, and air humidity on the morphology and solid phase of the particles produced from solution pressurized metered dose inhalers containing the corticosteroid beclomethasone dipropionate were investigated. The active ingredient was dissolved in the HFA propellants 134a and 227ea with varying levels of the cosolvent ethanol and filled into pressurized metered dose inhalers. Inhalers were actuated into an evaporation chamber under controlled temperature and humidity conditions and sampled using a single nozzle, single stage inertial impactor. Particle morphology was assessed qualitatively using field emission scanning electron microscopy and focused ion beam-helium ion microscopy. Drug solid phase was assessed using Raman microscopy. The relative humidity of the air during inhaler actuation was found to have a strong effect on the particle morphology, with solid spheroidal particles produced in dry air and highly porous particles produced at higher humidity levels. Air humidification was found to have no effect on the solid phase of the drug particles, which was predominantly amorphous for all tested formulations. A critical level of air relative humidity was required to generate porous particles for each tested formulation. This critical relative humidity was found to depend on the amount of ethanol used in the inhaler, but not on the type of propellant utilized. The results indicate that under the right circumstances water vapor saturation followed by nucleated water condensation or ice deposition occurs during particle formation from evaporating propellant-cosolvent-BDP droplets. This finding reveals the importance of condensed water or ice as a templating agent for porosity when particle formation occurs at saturated conditions, with possible implications on the pharmacokinetics of solution pMDIs and potential applications in particle engineering for drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Ease-of-use preference for the ELLIPTA® dry powder inhaler over a commonly used single-dose capsule dry powder inhaler by inhalation device-naïve Japanese volunteers aged 40 years or older

    Directory of Open Access Journals (Sweden)

    Komase Y

    2014-12-01

    Full Text Available Yuko Komase,1 Akimoto Asako,2 Akihiro Kobayashi,3 Raj Sharma4 1Department of Respiratory Internal Medicine, St Marianna University School of Medicine, Yokohama City Seibu Hospital, Yokohama, Kanagawa, Japan; 2MA Respiratory Department, Development and Medical Affairs Unit, GlaxoSmithKline KK, Tokyo, Japan; 3Biomedical Data Sciences Department, GlaxoSmithKline KK, Tokyo, Japan; 4Global Respiratory Franchise Medical Department, GSK, Stockley Park, UK Background: In patients receiving inhaled medication, dissatisfaction with and difficulty in using the inhaler can affect treatment adherence. The incidence of handling errors is typically higher in the elderly than in younger people. The aim of the study was to assess inhaler preference for and handling errors with the ELLIPTA® dry powder inhaler (DPI, (GSK, compared with the established BREEZHALER™, a single-dose capsule DPI (Novartis, in inhalation device-naïve Japanese volunteers aged ≥40 years. Methods: In this open-label, nondrug interventional, crossover DPI preference study comparing the ELLIPTA DPI and BREEZHALER, 150 subjects were randomized to handle the ELLIPTA or BREEZHALER DPIs until the point of inhalation, without receiving verbal or demonstrative instruction (first attempt. Subjects then crossed over to the other inhaler. Preference was assessed using a self-completed questionnaire. Inhaler handling was assessed by a trained assessor using a checklist. Subjects did not inhale any medication in the study, so efficacy and safety were not measured. Results: The ELLIPTA DPI was preferred to the BREEZHALER by 89% of subjects (odds ratio [OR] 70.14, 95% confidence interval [CI] 33.69–146.01; P-value not applicable for this inhaler for ease of use, by 63% of subjects (OR 2.98, CI 1.87–4.77; P<0.0001 for ease of determining the number of doses remaining in the inhaler, by 91% for number of steps required, and by 93% for time needed for handling the inhaler. The BREEZHALER was

  13. Microprocessor-controlled inhalation system for repeated exposure of animals to aerosols

    International Nuclear Information System (INIS)

    Carpenter, R.L.; Barr, F.P.; Leydig, R.L.; Rajala, R.E.

    1979-01-01

    A microprocessor-controlled inhalation exposure system (MCIES) has been built to automate aerosol generation and sampling while controlling exposure time for animal toxicity studies. The system has a time resolution of 0.1 s and automatically sequences the exposure events from initiation to temination of the exposure. The operator is required to preset all airflows, read in a paper tape containing the time sequence of events, and initiate the automatic sequence by closing a switch

  14. A review of the uncertainties in internal radiation dose assessment for inhaled thorium

    International Nuclear Information System (INIS)

    Hewson, G.S.

    1989-01-01

    Present assessments of internal radiation dose to designated radiation workers in the mineral sands industry, calculated using ICRP 26/30 methodology and data, indicate that some workers approach and exceed statutory radiation dose limits. Such exposures are indicative of the need for a critical assessment of work and operational procedures and also of metabolic and dosimetric models used to estimate internal dose. This paper reviews past occupational exposure experience with inhaled thorium compounds, examines uncertainties in the underlying radiation protection models, and indicates the effect of alternative assumptions on the calculation of committed effective dose equivalent. The extremely low recommended inhalation limits for thorium in air do not appear to be well supported by studies on the health status of former thorium refinery workers who were exposed to thorium well in excess of presently accepted limits. The effect of cautious model assumptions is shown to result in internal dose assessments that could be up to an order of magnitude too high. It is concluded that the effect of such uncertainty constrains the usefulness of internal dose estimates as a reliable indicator of actual health risk. 26 refs., 5 figs., 3 tabs

  15. Lung dose and lung cancer risk by inhalation of radon daughters

    International Nuclear Information System (INIS)

    Jacobi, W.

    1983-01-01

    The inhalation of short-lived radon daughters constitutes the most important occupational radiation exposure in mines, particularly in uranium mines. Among some groups of miners exposed in the past to relatively high radon levels, an excess lung cancer incidence has been observed. In addition to this occupational hazard, the observed radon levels in domestic houses indicate that the inhalation of short-lived radon daughters seems to be the most important component of the radiation exposure of the population from natural sources. For the quantification and judgment of the radiological impact by inhalation of radon daughters in mines as well as in houses, it is necessary to estimate the relationships between the inhaled activity or potential alpha (α) energy of these radionuclides, the dose to target tissues in the lung, and the possible associated lung cancer (LC) risk. It is the purpose of this paper to give a condensed review of our present knowledge in this field and to indicate the main gaps and uncertainties where future research seems necessary

  16. In vitro performance of three combinations of spacers and pressurized metered dose inhalers for treatment in children

    DEFF Research Database (Denmark)

    Berg, E; Madsen, J; Bisgaard, H

    1998-01-01

    The performance of pressurized metered dose inhalers (pMDIs) and spacers in correct dose recommendations is important, but limited information on dose delivery and fine-particle dose from different combinations of spacers and pMDIs is available. In this study, three combinations of spacers and p...... and spacers, with the NebuChamber giving the highest dose, both as delivered dose and in droplets account for these differences....

  17. Radon-thoron levels and inhalation dose distribution patterns in India dwellings

    International Nuclear Information System (INIS)

    Ramachandran, T.V.; Eappen, K.P.; Nair, R.N.; Mayya, Y.S.; Sadasivan, S.

    2003-09-01

    A countrywide survey on radon and thoron levels has been carried out in Indian dwellings under a Coordinated Research Project sponsored by the Board of Research in Nuclear Sciences (BRNS), Department of Atomic Energy (DAE). Eight universities and a few research institutions from different parts of the country participated in this project. Under this project, radon and thoron levels were measured using Solid State Nuclear Track Detector (SSNTD) -spark counter based passive technique. A plastic twin chamber radon -thoron dosimeter was developed and standardized for the survey. This radon-thoron discriminating dosimeter uses three SSNTDs; two of which are exposed in cup modes and the third one is exposed in bare mode. Calibration factors (CF) are obtained for cup and bare mode SSNTDs through controlled experiments in a calibration facility. Calibration factors obtained from experiments showed very good agreement with the calibration factors derived from theoretical models. Four nodal centres were set up each at Kalpakkam, Jodhpur, Jaduguda and Mumbai for calibration and standardization of the dosimeter system. Inter calibration of the dosimeters were also carried out for comparison purpose. Nearly 4500 measurements in about 1400 dwellings were made during the survey period. An analysis of the data shows that the indoor radon gas concentrations at different locations vary between 4.6 and 147.0 Bq.m -3 with a geometric mean of 23.0 Bq.m -3 (GSD 2.61). Indoor thoron gas concentrations, in general, are found to be less than the radon concentrations and vary from 3.6 to 42.8 Bq.m -3 with a geometric mean of 12.2 Bq.m -3 (GSD 3.22). The mean annual inhalation dose rate due to radon, thoron and their progeny in the dwellings is estimated to be 0.97 mSv.y -1 (GSD 2.49). It is observed that the major contribution to the indoor inhalation dose is due to radon and its progeny. However, the contribution due to thoron and its progeny is not trivial as it is about 20 % of the total

  18. The effects of repeated low-dose sarin exposure

    International Nuclear Information System (INIS)

    Shih, T.-M.; Hulet, S.W.; McDonough, J.H.

    2006-01-01

    This project assessed the effects of repeated low-dose exposure of guinea pigs to the organophosphorus nerve agent sarin. Animals were injected once a day, 5 days per week (Monday-Friday), for 2 weeks with fractions (0.3x, 0.4x, 0.5x, or 0.6x) of the established LD 5 dose of sarin (42 μg/kg, s.c.). The animals were assessed for changes in body weight, red blood cell (RBC) acetylcholinesterase (AChE) levels, neurobehavioral reactions to a functional observational battery (FOB), cortical electroencephalographic (EEG) power spectrum, and intrinsic acetylcholine (ACh) neurotransmitter (NT) regulation over the 2 weeks of sarin exposure and for up to 12 days postinjection. No guinea pig receiving 0.3, 0.4 or 0.5 x LD 5 of sarin showed signs of cortical EEG seizures despite decreases in RBC AChE levels to as low as 10% of baseline, while seizures were evident in animals receiving 0.6 x LD 5 of sarin as early as the second day; subsequent injections led to incapacitation and death. Animals receiving 0.5 x LD 5 sarin showed obvious signs of cholinergic toxicity; overall, 2 of 13 animals receiving 0.5 x LD 5 sarin died before all 10 injections were given, and there was a significant increase in the angle of gait in the animals that lived. By the 10th day of injection, the animals receiving saline were significantly easier to remove from their cages and handle and significantly less responsive to an approaching pencil and touch on the rump in comparison with the first day of testing. In contrast, the animals receiving 0.4 x LD 5 sarin failed to show any significant reductions in their responses to an approaching pencil and a touch on the rump as compared with the first day. The 0.5 x LD 5 sarin animals also failed to show any significant changes to the approach and touch responses and did not adjust to handling or removal from the cage from the first day of injections to the last day of handling. Thus, the guinea pigs receiving the 0.4 and 0.5 x LD 5 doses of sarin failed to

  19. Comparison of the effect of high-dose inhaled budesonide and fluticasone on adrenal function in patients with severe chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Ahmed Fahim

    2012-01-01

    Conclusion: Inhaled budesonide and fluticasone have no significantly different effect on adrenal function in moderate to severe COPD. The adverse event profile of high-dose inhaled steroids should not influence the choice of medication.

  20. Granulometric determinations and inhalation dose assessment for atmospheric aerosol contaminated by 137Cs

    International Nuclear Information System (INIS)

    Castellani, C.M.; Luciani, A.; Oliviero, L.; Donato, R.

    1996-07-01

    During the redevelopment of Brescia freight-yard a measurement campaign of atmospheric aerosol was carried out: in fact a 137 Cs ground contamination, caused by the permanence of wagons carrying iron materials contaminated by this radionuclide, had been found out. During the redevelopment phases of excavation and can filling the workers were exposed to the danger of radioactive aerosol inhalation. The aim of the measurement campaign was to test the aerosol sampling and granulometric analysis methodologies with their sensitivity related to the inhalation dose assessments. The results of both aerosuspended mass and activity, evaluated by means of a portable cascade impactor, are presented. The granulometries have been interpolated with a log normal distribution using an iterative routine minimizing the square deviation between the calculated and experimental data. The results related to the dose assessments are also presented. These evaluations have been carried out using both the granulometric information obtained and the more recent models (ICRP 66) both the total concentration data and the dose coefficients referring to the standard conditions of ICRP 68 and of the Italian law (D.Lgs. 230/95). Furthermore the significance and the reliability of the dose assessments referring to the different methodologies are discussed, also in relation to the possibility of using this sampling methodologies for other radionuclides and different exposure conditions

  1. Measurement of specific parameters for dose calculation after inhalation of aerols containing transuranium elements

    International Nuclear Information System (INIS)

    Ramounet-le Gall, B.; Fritsch, P.; Abram, M.C.; Rateau, G.; Grillon, G.; Guillet, K.; Baude, S.; Berard, P.; Ansoborlo, E.; Delforge, J.

    2002-01-01

    A review on specific parameter measurements to calculate doses per unit of incorporation according to recommendations of the International Commission of Radiological Protection has been performed for inhaled actinide oxides. Alpha activity distribution of the particles can be obtained by autoradiography analysis using aerosol sampling filters at the work places. This allows us to characterize granulometric parameters of 'pure' actinide oxides, but complementary analysis by scanning electron microscopy is needed for complex aerosols. Dissolution parameters with their standard deviation are obtained after rat inhalation exposure, taking into account both mechanical lung clearance and actinide transfer to the blood estimated from bone retention. In vitro experiments suggest that the slow dissolution rate might decrease as a function of time following exposure. Dose calculation software packages have been developed to take into account granulometry and dissolution parameters as well as specific physiological parameters of exposed individuals. In the case of poorly soluble actinide oxides, granulometry and physiology appear as the main parameters controlling dose value, whereas dissolution only alters dose distribution. Validation of these software packages are in progress. (author)

  2. Growth of extrapulmonary tumours after inhalation of small doses of plutonium oxide by rats

    International Nuclear Information System (INIS)

    Nolibe, D.; Masse, R.; L'Hullier, I.; Metivier, H.; Lafuma, J.

    1983-01-01

    After inhalation of plutonium oxide ( 239 PuO 2 ) involving initial lung burdens ranging from 74 to 103 Bq, male rats of the Wistar strain are kept in conditions allowing maximum survival; tumour incidences for the target organ (lung) and for the rest of the organs are calculated separately after the death of the animals. In the outbred Wistar rat the incidence of lung tumours is 18.5% for an initial lung burden of 74 Bq. The mean survival time of animals having such tumours is 973 days after inhalation. For an initial burden of 103 Bq syngenetic Wistar AG rats show a lower frequency of lung tumours (6.1%), but also a much reduced mean survival time, namely 757 days. Compared with the frequencies observed in the corresponding control groups, the frequency of non-pulmonary tumours is twice as high (12%) in consanguineous rats and six times as high (25.9%) in conventional rats. A supralinear dose-effect relationship at very low doses seems improbable in view of the dose delivered ( -3 Gy in the most exposed organs, such as the liver) and, in particular, because there is no correlation between the dose delivered to the organs and the location of the tumours. The exposed animals show, on the one hand, no specificity of organs for the surplus extrapulmonary tumours observed, and on the other, an inhibition by about 45% in the natural cytotoxic activity (natural killers) measured one year after inhalation. These observations suggest the hypothesis that an anti-tumour control mechanism is affected, perhaps as a result of the irradiation experienced during the circulation of blood cells in the lung capillaries. The failure of this system would in that case allow the expression of neoplastic characters as ageing progresses. A non-specific BCG immunotherapy does not restore this anti-tumour control system. (author)

  3. Inhalation dose due to indoor radon and thoron concentrations in the surrounding villages of Hyderabad, Andhra Pradesh, India

    International Nuclear Information System (INIS)

    Sreenath Reddy, M.; Sreenivasa Reddy, B.; Yadagiri Reddy, P.; Gopal Reddy, Ch.; Rama Reddy, K.

    2006-01-01

    Inhalation of radon, thoron and their decay products is the major contribution to the total radioactive dose received by the human population from the natural radiation. The indoor inhalation doses due to radon, thoron and their progenies in the surrounding villages of Hyderabad, India are evaluated. The average inhalation dose due to radon and its progeny is found to be 0.26 ± 0.21 mSv y -1 and due to thoron and its progeny is 0.35 ± 0.38 mSv y -1 . The inhalation dose is also analyzed based on the types of floor, roof and walls of the dwellings and it is found that the dwellings with mud type construction materials have higher inhalation dose. Generally, the contribution of thoron and its progeny to the total dose is neglected but in the present study area the fractional dose of thoron and its progeny is found to be comparable to that of radon and its progeny. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-03-15

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

  5. EVALUATION OF THE METERED-DOSE INHALER TECHNIQUE AMONG HEALTHCARE PROVIDERS

    Directory of Open Access Journals (Sweden)

    E. Nadi F. Zeraati

    2005-07-01

    Full Text Available Poor inhaler technique is a common problem both in asthmatic patients and healthcare providers, which contributes to poor asthma control. This study was performed to evaluate the adequacy of metered-dose inhaler (MDI technique in a sample of physicians and nurses practicing in hospitals of Hamadan University of Medical Sciences. A total of 173 healthcare providers voluntary participated in this study. After the participants answered a questionnaire aimed at identifying their involvement in MDI prescribing and counseling, a trained observer assessed their MDI technique using a checklist of nine steps. Of the 173 participants, 35 (20.2% were physicians and 138 (79.8% were nurses. Only 12 participants (6.93% performed all steps correctly. Physicians performed essential steps significantly better than nurses (85.7% vs. 63.8%, P < 0.05. The majority of healthcare providers responsible for instructing patients on the correct MDI technique were unable to perform this technique correctly, indicating the need for regular formal training programs on inhaler techniques.

  6. Dose conversion factors for inhalation applicable to the mining and milling of radioactive ores

    International Nuclear Information System (INIS)

    Hartley, B.M.

    1992-01-01

    The ICRP recommended revised dose limits for exposure to ionising radiation in November 1990. As well as reducing the annual occupational dose equivalent limit to an average of 20 mSv over 5 years, modified organ weighting factors were recommended, reflecting improved understanding of cancer risk factors for tissues and organs. The adjustment of weighting factors means that derived air concentrations conversion factors and annual limits on intake for exposure to airborne radionuclides are not simply modified by the ratio of the old to the new limits. A recalculation of these factors for radionuclides of interest in the mining and milling of radioactive ores is presented. A computer program for this purpose, based on the ICRP 30 inhalation model, is described. Rapid calculations of dose conversion factors are possible for the naturally occurring radionuclides in the 235 U, 238 U and 232 Th decay chains for which data are given in the supplements to ICRP 30. 7 refs., 12 tabs., 5 figs

  7. Age-specific inhalation radiation dose commitment factors for selected radionuclides

    International Nuclear Information System (INIS)

    Strenge, D.L.; Peloquin, R.A.; Baker, D.A.

    1982-08-01

    Inhalation dose commitment factors are presented for selected radionuclides for exposure of individuals in four age groups: infant, child, teen and adult. Radionuclides considered are 35 S, 36 Cl, 45 Ca, 67 Ga, 75 Se, 85 Sr, 109 Cd, 113 Sn, 125 I, 133 Ba, 170 Tm, 169 Yb, 182 Ta, 192 Ir, 198 Au, 201 Tl, 204 Tl, and 236 Pu. The calculational method is based on the human metabolic model of ICRP as defined in Publication 2 (ICRP 1959) and as used in previous age-specific dose factor calculations by Hoenes and Soldat (1977). Dose commitment factors are presented for the following organs of reference: total body, bone, liver, kidney, thyroid, lung and lower large intestine

  8. From dust to dose: Effects of forest disturbance on increased inhalation exposure

    International Nuclear Information System (INIS)

    Whicker, Jeffrey J.; Pinder, John E.; Breshears, David D.; Eberhart, Craig F.

    2006-01-01

    Ecosystem disturbances that remove vegetation and disturb surface soils are major causes of excessive soil erosion and can result in accelerated transport of soils contaminated with hazardous materials. Accelerated wind erosion in disturbed lands that are contaminated is of particular concern because of potential increased inhalation exposure, yet measurements regarding these relationships are lacking. The importance of this was highlighted when, in May of 2000, the Cerro Grande fire burned over roughly 30% of Los Alamos National Laboratory (LANL), mostly in ponderosa pine (Pinus ponderosa) forest, and through areas with soils containing contaminants, particularly excess depleted and natural uranium. Additionally, post-fire thinning was performed in burned and unburned forests on about 25% of LANL land. The first goal of this study was to assess the potential for increased inhalation dose from uranium contaminated soils via wind-driven resuspension of soil following the Cerro Grande Fire and subsequent forest thinning. This was done through analysis of post-disturbance measurements of uranium air concentrations and their relationships with wind velocity and seasonal vegetation cover. We found a 14% average increase in uranium air concentrations at LANL perimeter locations after the fire, and the greatest air concentrations occurred during the months of April-June when wind velocities are highest, no snow cover, and low vegetation cover. The second goal was to develop a methodology to assess the relative contribution of each disturbance type towards increasing public and worker exposure to these resuspended soils. Measurements of wind-driven dust flux in severely burned, moderately burned, thinned, and unburned/unthinned forest areas were used to assess horizontal dust flux (HDF) in these areas. Using empirically derived relationships between measurements of HDF and respirible dust, coupled with onsite uranium soil concentrations, we estimate relative increases in

  9. Asthma control in patients receiving inhaled corticosteroid and long-acting beta2-agonist fixed combinations. A real-life study comparing dry powder inhalers and a pressurized metered dose inhaler extrafine formulation

    Directory of Open Access Journals (Sweden)

    Nicolini Gabriele

    2011-07-01

    Full Text Available Abstract Background Although patients have more problems using metered dose inhalers, clinical comparisons suggest they provide similar control to dry powder inhalers. Using real-life situations this study was designed to evaluate asthma control in outpatients with moderate to severe persistent asthma and to compare efficacy of fixed combinations of inhaled corticosteroids (ICS and long acting beta-agonists (LABA. Methods This real-life study had a cross-sectional design. Patients using fixed combinations of ICS and LABA had their asthma control and spirometry assessed during regular visits. Results 111 patients were analyzed: 53 (47.7% received maintenance therapy of extrafine beclomethasone-formoterol (BDP/F pressurized metered dose inhaler (pMDI, 25 (22.5% fluticasone-salmeterol (FP/S dry powder inhaler (DPI, and 33 (29.7% budesonide-formoterol (BUD/F DPI. Severity of asthma at time of diagnosis, assessed by the treating physician, was comparable among groups. Asthma control was achieved by 45.9% of patients; 38.7% were partially controlled and 15.3% were uncontrolled. In the extrafine BDF/F group, asthma control total score, daytime symptom score and rescue medication use score were significantly better than those using fixed DPI combinations (5.8 ± 6.2 vs. 8.5 ± 6.8; 1.4 ± 1.8 vs. 2.3 ± 2.1; 1.8 ± 2.2 vs. 2.6 ± 2.2; p = 0.0160; p = 0.012 and p = 0.025, respectively and the mean daily ICS dose were significantly lower. Conclusions pMDI extrafine BDP/F combination demonstrated better asthma control compared to DPIs formulated with larger particles. This could be due to the improved lung deposition of the dose or less reliance on the optimal inhalation technique or both.

  10. Radiation load of the electro-thermal production of phosphorus. Part 1. The inhalation dose for operators

    International Nuclear Information System (INIS)

    Erkens, W.H.H.

    2003-01-01

    The phosphate ore which is processed by Thermphos International in Vlissingen, Netherlands, to produce element phosphorus contains circa 1 Bq per gram uranium 238. As a result of this production process radionuclides are emitted and slags that contain natural radioisotopes are formed. The slags can be used as a building material for roads and water works. During the production of phosphorus the waste material calcinate is formed as well. Operators, working in the production process of phosphorus and laborers, working in road construction and hydraulic engineering inhale radioisotopes. In two articles attention will be paid to the inhalation doses, how the doses are measured, measures that were taken to reduce and control the doses, and the ALARA-principles. This article is focused on the inhalation doses for operators in the phosphorus production industry [nl

  11. Radiation load of the electro-thermal production of phosphorus. Part 2. The inhalation dose in road construction

    International Nuclear Information System (INIS)

    Erkens, W.H.H.; Hermans, P.M.J.A.; Timmermans, C.W.M.

    2003-01-01

    The phosphate ore which is processed by Thermphos International in Vlissingen, Netherlands, to produce element phosphorus contains circa 1 Bq per gram uranium 238. As a result of this production process radionuclides are emitted and slags that contain natural radioisotopes are formed. The slags can be used as a building material for roads and water works. During the production of phosphorus the waste material calcinate is formed as well. Operators, working in the production process of phosphorus and laborers, working in road construction and hydraulic engineering inhale radioisotopes. In two articles attention will be paid to the inhalation doses, how the doses are measured, measures that were taken to reduce and control the doses, and the ALARA-principles. This article is focused on the inhalation doses for road construction workers [nl

  12. Comparative electrophysiological evaluation of hippocampal function following repeated inhalation exposures to JP-8, Jet A, JP-5, and the synthetic Fischer Tropsch fuel.

    Science.gov (United States)

    Rohan, Joyce G; McInturf, Shawn M; Miklasevich, Molly K; Gut, Chester P; Grimm, Michael D; Reboulet, James E; Howard, William R; Mumy, Karen L

    2018-01-01

    Exposure to fuels continues to be a concern in both military and general populations. The aim of this study was to examine effects of in vivo rat repeated exposures to different types of jet fuel utilizing microelectrode arrays for comparative electrophysiological (EP) measurements in hippocampal slices. Animals were exposed to increasing concentrations of four jet fuels, Jet Propellant (JP)-8, Jet A, JP-5, or synthetic Fischer Tropsch (FT) fuel via whole-body inhalation for 20 d (6 hr/d, 5 d/week for 28 d) and synaptic transmission as well as behavioral performance were assessed. Our behavioral studies indicated no significant changes in behavioral performance in animals exposed to JP-8, Jet A, or JP-5. A significant deviation in learning pattern during the Morris water maze task was observed in rats exposed to the highest concentration of FT (2000 mg/m 3 ). There were also significant differences in the EP profile of hippocampal neurons from animals exposed to JP-8, Jet A, JP-5, or FT compared to control air. However, these differences were not consistent across fuels or dose dependent. As expected, patterns of EP alterations in brain slices from JP-8 and Jet A exposures were more similar compared to those from JP-5 and FT. Further longitudinal investigations are needed to determine if these EP effects are transient or persistent. Such studies may dictate if and how one may use EP measurements to indicate potential susceptibility to neurological impairments, particularly those that result from inhalation exposure to chemicals or mixtures.

  13. Computational fluid dynamics (CFD) assisted performance evaluation of the Twincer (TM) disposable high-dose dry powder inhaler

    NARCIS (Netherlands)

    de Boer, Anne H.; Hagedoorn, Paul; Woolhouse, Robert; Wynn, Ed

    Objectives To use computational fluid dynamics (CFD) for evaluating and understanding the performance of the high-dose disposable Twincer (TM) dry powder inhaler, as well as to learn the effect of design modifications on dose entrainment, powder dispersion and retention behaviour. Methods Comparison

  14. Formulation and Development of Metered Dose Inhalations of Salbutamol in Solution Form

    Science.gov (United States)

    Khale, Anubha; Bajaj, Amrita

    2011-01-01

    In the present study attempts were made to prepare metered dose inhalation of salbutamol in solution form and compared it with the marketed metered dose inhalation in suspension form. Solution form of the drug was found better than marketed suspension formulation with respect to homogeneity and content uniformity. Propellant blend P-11 and P-12 in the proportion 30:70 was selected as it gave optimum vapour pressure. Surfactant oleic acid in concentration 10 mg per can was selected as it gave best results with clarity, spray pattern, vapour pressure, content per spray and rate of evaporation. Ethyl alcohol 2 ml per can was used as a cosolvent to give a clear solution, optimum vapour pressure, maximum content per spray and fair rate of evaporation. The selected formulation was subjected to the physico-chemical evaluation tests as per the standard pharmacopoeial procedures and the characteristics of the formulations were further compared with a conventional marketed formulation. In vitro study reveled the net respirable fraction was better than marketed preparation. PMID:22923867

  15. Dose assessment for inhalation intakes in complex, energetic environments: experience from the US Capstone study

    International Nuclear Information System (INIS)

    Guilmette, Raymond A.; Parkhurst, Mary Ann

    2007-01-01

    Because of the lack of existing information needed to evaluate the risks from inhalation exposures to depleted uranium (DU) aerosols of US soldiers during the 1991 Persian Gulf War, the US Department of Defense funded an experimental study to measure the characteristics of DU aerosols created when Abrams tanks and Bradley fighting vehicles are struck with large-caliber DU penetrators, and a dose and risk assessment for individuals present in such vehicles. This paper describes some of the difficulties experienced in dose assessment modelling of the very complex DU aerosols created in the Capstone studies, e.g. high concentrations, heterogeneous aerosol properties, non-lognormal particle size distributions, triphasic in vitro dissolution and rapid time-varying functions of both DU air concentration and particle size. The approaches used to solve these problems along with example results are presented. (authors)

  16. An In Vitro Aerosolization Efficiency Comparison of Generic and Branded Salbutamol Metered Dose Inhalers

    Directory of Open Access Journals (Sweden)

    Sara Rahimkhani, Saeed Ghanbarzadeh, Ali Nokhodchi, Hamed Hamishehkar

    2017-03-01

    Full Text Available Background: Due to the high rate of pulmonary diseases, respiratory drug delivery systems have been attracted excessive attention for the past decades. Because of limitations and growing drug bill, physicians are encouraged to prescribe generically whenever possible. The purpose of this study was to evaluate whether there was any significant difference in aerosolization performance between a reference brand Salbutamol (A Metered Dose Inhalers (MDIs and two generic products (B and C. Methods: The aerosolization performance of MDIs was evaluated by calculating aerosolization indexes including fine particle fraction (FPF, fine particle dose (FPD, geometric standard deviation (GSD and mass median aerodynamic diameters (MMAD by using the next generation impactor. Results: Although aerosolization indexes of MDI A were superior than the Iranian brands, but the differences were not statistically significant. Conclusion: These results verified that generic MDIs deliver similar quantities of Salbutamol to the reference brand and aerosolization performance parameters of generic Salbutamol MDIs did not differ significantly from the reference brand.

  17. Lifestyle and age as determinates of intake and dose from inhaled radionuclides

    International Nuclear Information System (INIS)

    Fields, D.E.; Yalcintas, M.G.

    1989-01-01

    The whole-body dose from inhaled radionuclides is a complex function of factors describing exposure and physiology. Exposure-related factors may be estimated by considering likely emission rates combined with measured time-varying meteorological (transport) parameters and estimated exercise patterns. Physiological factors, strongly influencing radionuclide intake and consequent radiation dose, have been catalogued as functions of age and activity level. Both exercise patterns and physiological factors are related to age of the exposed individual. Combining these factors permits estimates to be made of the span of exposures that may be expected in a typical population. The ratio of highest to lowest radionuclide intake is predicted to be of the order of 40, suggesting that specification of an 'average' value may be misleading if this value approaches regulatory limits. Individuals exposed to maximal risk may be identified, and are likely to be active children. Activity pattern (lifestyle) is a primary determinant of risk. (author)

  18. Uncertainty of the thyroid dose conversion factor for inhalation intakes of 131I and its parametric uncertainty

    International Nuclear Information System (INIS)

    Harvey, R. P.; Hamby, D. M.; Palmer, T. S.

    2006-01-01

    Inhalation exposures of 131 I may occur in the physical form of a gas as well as a particulate. The physical characteristics pertaining to these different types of releases influence the intake and subsequent dose to an exposed individual. The thyroid dose received is influenced by the route through which 131 I enters the body and its subsequent clearance, absorption and movement throughout the body. The radioactive iodine taken up in the gas-exchange tissues is cleared to other tissues or absorbed into the bloodstream of the individual and transferred to other organs. Iodine in the circulatory system is then taken up by the thyroid gland with resulting dose to that tissue. The magnitude of and uncertainty in the thyroid dose is important to the assessment of individuals exposed to airborne releases of radioiodine. Age- and gender-specific modelling parameters have resulted in significant differences between gas uptake, particulate deposition and inhalation dose conversion factors for each age and gender group. Inhalation dose conversion factors and their inherent uncertainty are markedly affected by the type of iodine intake. These differences are expected due to the modelling of particulate deposition versus uptake of gas in the respiratory tract. Inhalation dose estimates via iodine gases are very similar and separate classifications may not be necessarily based on this assessment. (authors)

  19. ANALYSIS OF RESPIRATORY DEPOSITION OF INHALED PARTICLES FOR DIFFERENT DOSE METRICS: COMPARISON OF NUMBER, SURFACE AREA AND MASS DOSE OF TYPICAL AMBIENT BI-MODAL AEROSOLS

    Science.gov (United States)

    ANALYSIS OF RESPIRATORY DEPOSITION OF INHALED PARTICLES FOR DIFFERENT DOSE METRICS: COMPARISON OF NUMBER, SURFACE AREA AND MASS DOSE OF TYPICAL AMBIENT BI-MODAL AEROSOLS.Chong S. Kim, SC. Hu*, PA Jaques*, US EPA, National Health and Environmental Effects Research Laboratory, ...

  20. [Deliberate interruptions and changes of dose of inhaled corticosteroids by asthma patients: "a community pharmacy study"].

    Science.gov (United States)

    Laforest, L; Van Ganse, É; Devouassoux, G; Chatté, G; Tamberou, C; Belhassen, M; Chamba, G

    2015-01-01

    Adherence to inhaled corticosteroids (ICS) remains a major issue for asthma management, even among patients receiving a regular prescription from their doctor. The frequency of deliberate interruption of ICS, and of spontaneous changes of dose, were studied in a population of asthma patients recruited in community pharmacies. Asthma patients (aged 18-50) recruited in community pharmacies reported in self-administered questionnaires their spontaneous interruptions and changes of doses of ICS during the past 3 months. The characteristics of patients who interrupted their therapy or who modified the dose were compared with other patients. The studied population included 252 patients (mean age 35 year-old, females: 59%), of whom 62% had inadequately controlled asthma. Among these patients, 25% had interrupted ICS therapy during the past 3 months, while 21% spontaneously changed the dose. The most reported reason for interrupting ICS was the cessation of symptoms (50%). In multivariate analysis, interrupting ICS was mainly associated with inadequate asthma control (OR=3.1, 95% CI 1.5-6.4), while the strongest association with changing ICS doses was the patients' perception of asthma as a concern in their lives (OR=3.2, 95% CI 1.2-8.4). These results underline a poor understanding of the purpose of ICS therapy by patients. They also highlight the need of therapeutic education to improve the management of the disease. Copyright © 2014 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  1. Doses from potential inhalation by people living near plutonium contaminated areas

    International Nuclear Information System (INIS)

    Iranzo Gonzales, E.; Salvador Ruiz, S.

    1983-09-01

    An aviation accident above the town of Palomares, Spain resulted in four thermonuclear bombs carried by one of the planes falling. The nuclear fuel in two of them ignited and formed an aerosol which contaminated a 226-hectare area of underbrush, farmland and an urban center. The magnitude of risk to people living in the area who may have inhaled the plutonium aerosol or dusts during the fifteen-year period since the time the accident is addressed in this report. In addition the internal radiation doses that people may have received during this period and during a fifty-year period commencing with the accident is estimated. In brief summary, the lungs received the greatest dose equivalent (1966 to 1980). Over the fifty year period (to 2015) the bones are projected to receive the greatest dose. For the remaining organs - liver-intestines-kidneys, - the relationships or between the doses that will be accumulated up to the year 2015 and the corresponding annual dose equivalent limits are less than those for the bones and lungs

  2. From dust to dose: Effects of forest disturbance on increased inhalation exposure.

    Science.gov (United States)

    Whicker, Jeffrey J; Pinder, John E; Breshears, David D; Eberhart, Craig F

    2006-09-15

    Ecosystem disturbances that remove vegetation and disturb surface soils are major causes of excessive soil erosion and can result in accelerated transport of soils contaminated with hazardous materials. Accelerated wind erosion in disturbed lands that are contaminated is of particular concern because of potential increased inhalation exposure, yet measurements regarding these relationships are lacking. The importance of this was highlighted when, in May of 2000, the Cerro Grande fire burned over roughly 30% of Los Alamos National Laboratory (LANL), mostly in ponderosa pine (Pinus ponderosa) forest, and through areas with soils containing contaminants, particularly excess depleted and natural uranium. Additionally, post-fire thinning was performed in burned and unburned forests on about 25% of LANL land. The first goal of this study was to assess the potential for increased inhalation dose from uranium contaminated soils via wind-driven resuspension of soil following the Cerro Grande Fire and subsequent forest thinning. This was done through analysis of post-disturbance measurements of uranium air concentrations and their relationships with wind velocity and seasonal vegetation cover. We found a 14% average increase in uranium air concentrations at LANL perimeter locations after the fire, and the greatest air concentrations occurred during the months of April-June when wind velocities are highest, no snow cover, and low vegetation cover. The second goal was to develop a methodology to assess the relative contribution of each disturbance type towards increasing public and worker exposure to these resuspended soils. Measurements of wind-driven dust flux in severely burned, moderately burned, thinned, and unburned/unthinned forest areas were used to assess horizontal dust flux (HDF) in these areas. Using empirically derived relationships between measurements of HDF and respirible dust, coupled with onsite uranium soil concentrations, we estimate relative increases in

  3. Computational fluid dynamics (CFD) assisted performance evaluation of the Twincer™ disposable high-dose dry powder inhaler.

    Science.gov (United States)

    de Boer, Anne H; Hagedoorn, Paul; Woolhouse, Robert; Wynn, Ed

    2012-09-01

    To use computational fluid dynamics (CFD) for evaluating and understanding the performance of the high-dose disposable Twincer™ dry powder inhaler, as well as to learn the effect of design modifications on dose entrainment, powder dispersion and retention behaviour. Comparison of predicted flow and particle behaviour from CFD computations with experimental data obtained with cascade impactor and laser diffraction analysis. Inhaler resistance, flow split, particle trajectories and particle residence times can well be predicted with CFD for a multiple classifier based inhaler like the Twincer™. CFD computations showed that the flow split of the Twincer™ is independent of the pressure drop across the inhaler and that the total flow rate can be decreased without affecting the dispersion efficacy or retention behaviour. They also showed that classifier symmetry can be improved by reducing the resistance of one of the classifier bypass channels, which for the current concept does not contribute to the swirl in the classifier chamber. CFD is a highly valuable tool for development and optimisation of dry powder inhalers. CFD can assist adapting the inhaler design to specific physico-chemical properties of the drug formulation with respect to dispersion and retention behaviour. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

  4. Evaluation of Pulmonary and Systemic Toxicity of Oil Dispersant (COREXIT EC9500A(®)) Following Acute Repeated Inhalation Exposure.

    Science.gov (United States)

    Roberts, Jenny R; Anderson, Stacey E; Kan, Hong; Krajnak, Kristine; Thompson, Janet A; Kenyon, Allison; Goldsmith, William T; McKinney, Walter; Frazer, David G; Jackson, Mark; Fedan, Jeffrey S

    2014-01-01

    Oil spill cleanup workers come into contact with numerous potentially hazardous chemicals derived from the oil spills, as well as chemicals applied for mitigation of the spill, including oil dispersants. In response to the Deepwater Horizon Macondo well oil spill in the Gulf of Mexico in 2010, a record volume of the oil dispersant, COREXIT EC9500A, was delivered via aerial applications, raising concern regarding potential health effects that may result from pulmonary exposure to the dispersant. The current study examined the effects on pulmonary functions, cardiovascular functions, and systemic immune responses in rats to acute repeated inhalation exposure of COREXIT EC9500A at 25 mg/m(3), five hours per day, over nine work days, or filtered air (control). At one and seven days following the last exposure, a battery of parameters was measured to evaluate lung function, injury, and inflammation; cardiovascular function; peripheral vascular responses; and systemic immune responses. No significant alterations in airway reactivity were observed at one or seven days after exposure either in baseline values or following methacholine (MCh) inhalation challenge. Although there was a trend for an increase in lung neutrophils and phagocyte oxidant production at one-day post exposure, there were no significant differences in parameters of lung inflammation. In addition, increased blood monocytes and neutrophils, and decreased lymphocyte numbers at one-day post exposure also did not differ significantly from air controls, and no alterations in splenocyte populations, or serum or spleen immunoglobulin M (IgM) to antigen were observed. There were no significant differences in peripheral vascular responsiveness to vasoconstrictor and vasodilator agonists or in blood pressure (BP) responses to these agents; however, the baseline heart rate (HR) and HR responses to isoproterenol (ISO) were significantly elevated at one-day post exposure, with resolution by day 7. In summary, acute

  5. Evaluation of Pulmonary and Systemic Toxicity of Oil Dispersant (COREXIT EC9500A following Acute Repeated Inhalation Exposure

    Directory of Open Access Journals (Sweden)

    Jenny R. Roberts

    2014-01-01

    Full Text Available Introduction Oil spill cleanup workers come into contact with numerous potentially hazardous chemicals derived from the oil spills, as well as chemicals applied for mitigation of the spill, including oil dispersants. In response to the Deepwater Horizon Macondo well oil spill in the Gulf of Mexico in 2010, a record volume of the oil dispersant, COREXIT EC9500A, was delivered via aerial applications, raising concern regarding potential health effects that may result from pulmonary exposure to the dispersant. Methods The current study examined the effects on pulmonary functions, cardiovascular functions, and systemic immune responses in rats to acute repeated inhalation exposure of COREXIT EC9500A at 25 mg/m 3 , five hours per day, over nine work days, or filtered air (control. At one and seven days following the last exposure, a battery of parameters was measured to evaluate lung function, injury, and inflammation; cardiovascular function; peripheral vascular responses; and systemic immune responses. Results No significant alterations in airway reactivity were observed at one or seven days after exposure either in baseline values or following metha-choline (MCh inhalation challenge. Although there was a trend for an increase in lung neutrophils and phagocyte oxidant production at one-day post exposure, there were no significant differences in parameters of lung inflammation. In addition, increased blood monocytes and neutrophils, and decreased lymphocyte numbers at one-day post exposure also did not differ significantly from air controls, and no alterations in splenocyte populations, or serum or spleen immunoglobulin M (IgM to antigen were observed. There were no significant differences in peripheral vascular responsiveness to vasoconstrictor and vasodilator agonists or in blood pressure (BP responses to these agents; however, the baseline heart rate (HR and HR responses to isoproterenol (ISO were significantly elevated at one-day post exposure

  6. Biological effects of repeated inhalation exposure of beagle dogs to relatively insoluble aerosols of 144Ce

    International Nuclear Information System (INIS)

    Boecker, B.B.; Hahn, F.F.; Muggenburg, B.A.; McClellan, R.O.; Mauderly, J.L.; Pickrell, J.A.

    1980-01-01

    Beagle dogs were exposed repeatedly to a relatively insoluble form of 144 Ce (in fused aluminosilicate particles) to study the deposition, retention, and long-term biological effects for comparison with data from dogs that were exposed only once to a similar aerosol. Four groups of nine dogs each were exposed once every 8 weeks for 2 years (13 exposures) to achieve specified exposure goals. These goals were: to increase the lung burden by 2.5 μCi 144 Ce/kg body weight with each exposure; to reestablish lung burdens of 9 or 4.5 μCi 144 Ce/kg body weight and to expose controls to fused aluminosilicate particles containing nonradioactive cerium. To date, 19 exposed dogs and 2 control dogs have died or were euthanized. The most prevalent findings to date have been pulmonary carcinomas (7 dogs) and hemangiosarcomas in the tracheobronchial lymph nodes (3 dogs). Observations are continuing on the surviving 8 144 Ce-exposed and 7 control dogs who are now at approximately 2500 days (6.8 years) after the first exposure

  7. Dose patterns for 106RuO4 inhaled by Fischer-344 rats and Beagle dogs

    International Nuclear Information System (INIS)

    Runkle, G.E.; Snipes, M.B.

    1978-01-01

    Ruthenium-106 is an abundant fission product radionuclide in the nuclear fuel cycle which has potential for release as ruthenium tetroxide. Ruthenium tetroxide is a vapor, diffuses rapidly through air and porous materials, is chemically reactive and is rapidly reduced by any organic material to the dioxide form. Current ICRP recommendations consider the lung and gastrointestinal tract as critical organs for inhaled particles of radioactive ruthenium. This study was designed to provide additional data needed to adequately assess the risk for humans potentially exposed to 106 Ru encountered in this vapor form. Fischer-344 rats and Beagle dogs were given a nose-only exposure to 106 RuO 4 vapor to determine its distribution and retention patterns. The largest percentage of the initial body burden was found in the nasopharyngeal region of the respiratory tract. Less than 1% of the initial body burden was deposited in the pulmonary region. Most of the 106 Ru was cleared via the feces. A biomathematical simulation model was developed to fit the tissue and excreta data from the rat. This model was used to assess the short-term and long-term risks after inhalation of 106 RuO 4 . The observed deposition, retention and dose patterns for ruthenium tetroxide indicate the nasopharyngeal region should be considered as a critical region when considering the consequences of human exposure to this vapor

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

    Directory of Open Access Journals (Sweden)

    Eric J Griez

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

  9. Nonparametric statistical techniques used in dose estimation for beagles exposed to inhaled plutonium nitrate

    International Nuclear Information System (INIS)

    Stevens, D.L.; Dagle, G.E.

    1986-01-01

    Retention and translocation of inhaled radionuclides are often estimated from the sacrifice of multiple animals at different time points. The data for each time point can be averaged and a smooth curve fitted to the mean values, or a smooth curve may be fitted to the entire data set. However, an analysis based on means may not be the most appropriate if there is substantial variation in the initial amount of the radionuclide inhaled or if the data are subject to outliers. A method has been developed that takes account of these problems. The body burden is viewed as a compartmental system, with the compartments identified with body organs. A median polish is applied to the multiple logistic transform of the compartmental fractions (compartment burden/total burden) at each time point. A smooth function is fitted to the results of the median polish. This technique was applied to data from beagles exposed to an aerosol of 239 Pu(NO 3 ) 4 . Models of retention and translocation for lungs, skeleton, liver, kidneys, and tracheobronchial lymph nodes were developed and used to estimate dose. 4 refs., 3 figs., 4 tabs

  10. Variability in dose-equivalent assessments for inhaled U3O8 concentrations

    International Nuclear Information System (INIS)

    Hewson, G.; Blyth, D.I.

    1985-01-01

    A potentially significant radiological hazard exists in the packaging area of uranium mills through the inhalation of airborne uranium octoxide (U 3 O 8 ). The Radiation Protection (Mining and Milling Code (1980) requires the measurement and assessment of quarterly, annual and cumulative dose equivalents for employees working in these areas. Arising through differences which exist between the abovementioned Code and ICRP 30, and assumptions of particle size and dust concentration distributions, confusion exists within Australia regarding the methods which can be used to make the required assessments. Exposure data were collected during routine monitoring at an operating mill facility and were interpreted using different methods and a range of assumptions. Results indicated the dust at this facility is characterised by an AMAD greater than 10 μ, and dust concentrations were distributed lognormally. Assumptions of a normal distribution may result in an overestimate of the dose equivalent. The importance of particle size in dose assessments using ICRP 30 techniques was highlighted. Information was masked when employee data was grouped to provide work category dose assessments. The use of ICRP 30 methods were recommended to provide uniformity throughout Australia

  11. Competence in metered dose inhaler technique among community pharmacy professionals in Gondar town, Northwest Ethiopia: Knowledge and skill gap analysis.

    Science.gov (United States)

    Belachew, Sewunet Admasu; Tilahun, Fasil; Ketsela, Tirsit; Achaw Ayele, Asnakew; Kassie Netere, Adeladlew; Getnet Mersha, Amanual; Befekadu Abebe, Tamrat; Melaku Gebresillassie, Begashaw; Getachew Tegegn, Henok; Asfaw Erku, Daniel

    2017-01-01

    When compared to systemic administration, if used correctly inhalers deliver a smaller enough percent of the drug right to the site of action in the lungs, with a faster onset of effect and with reduced systemic availability that minimizes adverse effects. However, the health professionals' and patients' use of metered dose inhaler is poor. This study was aimed to explore community pharmacy professionals' (pharmacists' and druggists') competency on metered dose inhaler (MDI) technique. A cross sectional study was employed on pharmacy professionals working in community drug retail outlets in Gondar town, northwest Ethiopia from March to May 2017. Evaluation tool was originally taken and adapted from the National Asthma Education and Prevention Programmes of America (NAEPP) step criteria for the demonstration of a metered dose inhaler to score the knowledge/proficiency of using the inhaler. Among 70 community pharmacy professionals approached, 62 (32 pharmacists and 30 druggists/Pharmacy technicians) completed the survey with a response rate of 85.6%. Only three (4.8%) respondents were competent by demonstrating the vital steps correctly. Overall, only 13 participants got score seven or above, but most of them had missed the essential steps which included steps 1, 2, 5, 6, 7 or 8. There was a significant difference (P = 0.015) in competency of demonstrating adequate inhalational technique among respondents who took training on basic inhalational techniques and who did not. This study shown that, community pharmacy professionals' competency of MDI technique was very poor. So as to better incorporate community pharmacies into future asthma illness management and optimize the contribution of pharmacists, interventions would emphasis to improve the total competence of community pharmacy professionals through establishing and providing regular educational programs.

  12. Economics of "essential use exemptions" for metered-dose inhalers under the Montreal Protocol.

    Science.gov (United States)

    DeCanio, Stephen J; Norman, Catherine S

    2007-10-01

    The Montreal Protocol on Substances that Deplete the Ozone Layer has led to rapid reductions in the use of ozone-depleting substances worldwide. However, the Protocol provides for "essential use exemptions" (EUEs) if there are no "technically and economically feasible" alternatives. An application that might qualify as an "essential use" is CFC-powered medical metered-dose inhalers (MDIs) for the treatment of asthma and chronic obstructive pulmonary disease (COPD), and the US and other nations have applied for exemptions in this case. One concern is that exemptions are necessary to ensure access to medications for low-income uninsureds. We examine the consequences of granting or withholding such exemptions, and conclude that government policies and private-sector programs are available that make it economically feasible to phase out chlorofluorocarbons (CFCs) in this application, thereby furthering the global public health objectives of the Montreal Protocol without compromising the treatment of patients who currently receive medication by means of MDIs.

  13. The effects of exercise on dose and dose distribution of inhaled automotive pollutants.

    Science.gov (United States)

    Kleinman, M T; Mautz, W J

    1991-10-01

    The purpose of this study was to determine how changes in ventilation rate and in the entry route of air pollutants into the respiratory tract (nose versus mouth breathing) affected the respiratory tract uptake and penetration of inhaled gaseous and particulate pollutants associated with automobile emissions. Experiments were performed with female beagle dogs exposed while standing at rest or while exercising on a treadmill at 5 km/hour and a 7.5 percent grade. Dogs were exposed to nitrogen dioxide at concentrations of 1 and 5 parts per million (ppm), to formaldehyde at 2 and 10 ppm, and to an aerosol of ammonium nitrate particles (0.3 micron mass median aerodynamic diameter) at 1 mg/m3. Total respiratory system uptake and effects on breath time, expired tidal volume, fractional expiration time, minute ventilation, respiratory gas exchange, ventilation equivalents for oxygen and carbon dioxide, and dynamic pulmonary resistance and compliance were measured in exercising and resting dogs exposed for two hours to 5 ppm nitrogen dioxide and 10 ppm formaldehyde in combination with 1 mg/m3 of ammonium nitrate particles. Regional penetration of pollutants through oral and nasal airways and pollutant uptake in the lung were measured in a separate group of six tracheostomized dogs standing at rest while being exposed to nitrogen dioxide, formaldehyde, and ammonium nitrate particles. Hypercapnic stimulation was used to modify ventilation rates in the tracheostomized dogs while pollutant penetration and uptake were measured. Dogs exposed to 5 ppm of nitrogen dioxide at rest tended to breathe more rapidly (p less than 0.05) and more shallowly (a nonsignificant trend) than dogs exposed to purified air. The changes observed were similar in direction, but of smaller magnitude, to changes observed when the same dogs were exposed during exercise to ozone at 0.6 ppm in a separate study. Rapid-shallow breathing was not observed when the dogs were exposed during exercise to 5 ppm

  14. Repeated dose titration versus age-based method in electroconvulsive therapy: a pilot study

    NARCIS (Netherlands)

    Aten, J.J.; Oudega, M.L.; van Exel, E.; Stek, M.L.; van Waarde, J.A.

    2015-01-01

    In electroconvulsive therapy (ECT), a dose titration method (DTM) was suggested to be more individualized and therefore more accurate than formula-based dosing methods. A repeated DTM (every sixth session and dose adjustment accordingly) was compared to an age-based method (ABM) regarding treatment

  15. Performance of Dry Powder Inhalers with Single Dosed Capsules in Preschool Children and Adults Using Improved Upper Airway Models

    Directory of Open Access Journals (Sweden)

    Sandra Lindert

    2014-02-01

    Full Text Available The pulmonary administration of pharmaceutical aerosols to patients is affected by age-dependent variations in the anatomy of the upper airways and the inhalation pattern. Considering this aspect, different upper airway models, representing the geometries of adults and preschool children, and a conventional induction port according to the European Pharmacopeia were used for in vitro testing of dry powder inhalers with single dosed capsules (Cyclohaler®, Handihaler® and Spinhaler®. Deposition measurements were performed using steady flow rates of 30 and 60 L/min for the Handihaler®/Spinhaler® and 30, 60 and 75 L/min for the Cyclohaler®. The inhalation volume was set at 1 L. For the Cyclohaler®, the in vitro testing was supplemented by a pediatric inhalation profile. Slight differences of pulmonary deposition between the idealized adult (11%–15% and pediatric (9%–11% upper airway model were observed for the Cyclohaler®. The applied pediatric inhalation profile resulted in a reduction of pulmonary deposition by 5% compared to steady conditions and indicated the influence of the inhalation pattern on the amount of pulmonary deposited particles. The comparison of two pediatric upper airway models showed no differences. The performance of the Handihaler® was similar to the Cyclohaler®. The Spinhaler® showed an insufficient performance and limited reproducibility in our investigations.

  16. A user's guide to the inhalation and external radiation collective dose module NECTAR-POPDOS

    International Nuclear Information System (INIS)

    Merlin, J.H.

    1982-02-01

    NECTAR-POPDOS is a module of the computer program NECTAR, which has been written in modular form to evaluate radioactive releases from nuclear fuel, their dispersion in the environment and the consequent individual and collective doses to man. The NECTAR-POPDOS module may be used to evaluate external and inhalation collective doses to any specified area of Great Britain, either to the total population or to any one of six age groups, using population data from the 1971 UK census. If a dose-risk function is defined, the module may be used to assess population health effects or for optimisation studies. The module is based on the stand-alone program POPDOS2, and is written in Fortran IV. The input data to the module is described and the module's limitations and sources of inaccuracy are discussed. Appendices to the report contain the necessary Job Control Language for running NECTAR, a list of NECTAR-POPDOS subroutines, and the input and output of two sample NECTAR-POPDOS cases. (author)

  17. Enantioselective disposition of (R)-salmeterol and (S)-salmeterol in urine following inhaled dosing and application to doping control

    DEFF Research Database (Denmark)

    Jacobson, Glenn A; Hostrup, Morten; Narkowicz, Christian K

    2017-01-01

    Salmeterol (USAN, INN, BAN) is a long-acting beta2-adrenoceptor agonist (LABA) widely used in the treatment of airways disease. Although salmeterol is permitted via inhalation by athletes and supratherapeutic dosing may enhance performance, no urine threshold has been established by the World Anti...

  18. Influence of radiation-dose pattern from inhaled beta--gamma-emitting radionuclides on canine peripheral lymphocytes

    International Nuclear Information System (INIS)

    Jones, R.K.; Boecker, B.B.; Pickrell, J.A.; Hobbs, C.H.; McClellan, R.O.

    1976-01-01

    As part of studies assess the biological hazards associated with inhaled radionuclides, periodic hematologic evaluations were performed on beagle dogs given a single nose-only exposure to aerosols of beta--gamma-emitting isotopes. The physical form and specific radionuclides selected produced radiation-dose patterns representative of those which might be encountered in the event of human accidental exposures. Dogs received graded lung burdens of either 90 Y, 91 Y, 144 Ce, or 90 Sr, each in fused clay. Differences in the effective half-lives of these radionuclides resulted in a spectrum of cumulative radiation doses to lung delivered at a variety of dose rates. Since the form in which the radionuclides were inhaled was relatively insoluble, the lung and intrathoracic tissues represented the primary recipient of the dose. Regardless of the effective half-life of radionuclide retention, a dose-related depression of peripheral lymphocytes was observed at various times after inhalation exposure. The time at which maximum depression and subsequent recovery occurred, however, was most directly related to the effective half-life of the radionuclide. Of special interest was the persistence of lymphopenia through 2 1 / 2 years after exposure to 144 Ce and 90 Sr in fused clay where, other than tracheobronchial lymph nodes, the lymphoid tissue received very little radiation dose. The possible mechanisms responsible for lymphocyte depression from these various radiation-dose patterns are discussed

  19. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... KB] Using a metered dose inhaler (inhaler in mouth) Your browser does not support iframes Using a metered dose inhaler (inhaler in mouth) [PDF – 370 KB] Your browser does not support ...

  20. Indoor radon levels and inhalation doses in dwellings near the some sites of Himachal Pradesh, India

    International Nuclear Information System (INIS)

    Bajwa, B.S.; Singh, S.; Virk, H.S.

    2005-01-01

    In view of the fact that radon and its daughters are a major source of natural radiation exposure, the measurement of radon concentration levels in dwellings has assumed ever-increasing importance. Keeping this in view, the indoor radon level measurements were carried out in the dwellings of different villages known to be located in the vicinity of uranium-mineralized pockets of Hamirpur district, Himachal Pradesh. Track-etch technique, a passive method using the Solid State Nuclear Track Detectors (SSNTDs), LR-115 type II, was utilized for these measurements. An attempt has been made to assess the levels of the indoor radon in the dwellings and inhalation dose rates of the population living in these villages. The radon concentrations were found to be varying with seasonal changes, building materials and mode of construction of houses. The radon concentrations were found to be higher in houses made from local sandstone and with mud floor in comparison to the houses having cemented brick floors. The annual indoor radon concentration and thus annual effective dose in most of the dwellings of these villages is certainly quite higher and even in some of the dwellings it even exceeds the upper limit of the proposed action level of ICRP, 1993. The inhalation dose rates in dwellings of these villages located in the vicinity of uranium mineralized pockets of Hamirpur district, Himachal Pradesh have been found to be quite higher than dose rate in the dwellings in the Amritsar city, Punjab, which is located in a completely uranium free zone. The radon survey in the dwellings of these villages has also been carried out using the Alpha-Guard technique, which is based on the pulse ionization chamber. The indoor radon concentration levels measured using the active technique of Alpha Guard have been found to be quite different from those measured in these dwellings by the passive technique of SSNTDs; indicating the importance of the SSNTDs in the long-term integrated measurement

  1. Effect of Pressurized Metered Dose Inhaler Spray Characteristics and Particle Size Distribution on Drug Delivery Efficiency.

    Science.gov (United States)

    Yousefi, Morteza; Inthavong, Kiao; Tu, Jiyuan

    2017-10-01

    A key issue in pulmonary drug delivery is improvement of the delivery device for effective and targeted treatment. Pressurized metered dose inhalers (pMDIs) are the most popular aerosol therapy device for treating lung diseases. This article studies the effect of spray characteristics: injection velocity, spray cone angle, particle size distribution (PSD), and its mass median aerodynamic diameter (MMAD) on drug delivery. An idealized oral airway geometry, extending from mouth to the main bronchus, was connected to a pMDI device. Inhalation flow rates of 15, 30, and 60 L/min were used and drug particle tracking was a one-way coupled Lagrangian model. The results showed that most particles deposited in the pharynx, where the airway has a reduced cross-sectional area. Particle deposition generally decreased with initial spray velocity and with increased spray cone angle for 30 and 60 L/min flow rates. However, for 15 L/min flow rate, the deposition increased slightly with an increase in the spray velocity and cone angle. The effect of spray cone angle was more significant than the initial spray velocity on particle deposition. When the MMAD of a PSD was reduced, the deposition efficiency also reduces, suggesting greater rates of particle entry into the lung. The deposition rate showed negligible change when the MMAD was more than 8 μm. Spray injection angle and velocity change the drug delivery efficacy; however, the efficiency shows more sensitivity to the injection angle. The 30 L/min airflow rate delivers spray particles to the lung more efficiently than 15 and 60 L/min airflow rate, and reducing MMAD can help increase drug delivery to the lung.

  2. Characterization of the spray velocities from a pressurized metered-dose inhaler.

    Science.gov (United States)

    Crosland, Brian Michael; Johnson, Matthew Ronald; Matida, Edgar Akio

    2009-06-01

    Pressurized metered dose inhalers (pMDIs) are widely used to deliver aerosolized medications to the lungs, most often to relieve the symptoms of asthma. Over the past decade, pMDIs have been modified in several ways to eliminate the use of chlorofluorocarbons in their manufacture while increasing efficacy. Numerical simulations are being used more frequently to predict the flow and deposition of particles at various locations, both inside the respiratory tract as well as in pMDIs and add-on devices. These simulations require detailed information about the spray generated by a pMDI to ensure the validity of their results. This paper presents detailed, spatially resolved velocity measurements of the spray emitted from salbutamol sulfate pMDIs obtained using optically triggered particle image velocimetry (PIV). Instantaneous planar velocity measurements were taken and ensemble-averaged at nine different times during the spray event ranging from 1.3 to 100 msec after a pneumatically controlled actuation. The mean spray velocities were shown to be bimodal in time, with two velocity peaks and velocity magnitudes found to be much lower than published data from instantaneous single point measurements. Planar velocity data at each time step were analyzed to produce prescriptive velocity profiles suitable for use in numerical simulations. Spray geometry data are also reported. Statistical comparisons from several thousand individual spray events indicate that there is no significant difference in measured velocity among (1) two brands of pMDI canisters, (2) two pMDIs of the same brand but having different lot numbers, and (3) a full pMDI versus an almost empty pMDI. The addition of a secondary air flow of 30 SLPM (to represent simultaneous inhalation and spray actuation) deflected the spray downward but did not have a significant effect on flow velocity. Further experiments with an added cylindrical spacer revealed that within the spacer, the spray direction and cone angle

  3. Long-term dose-response studies of inhaled or injected radionuclides

    International Nuclear Information System (INIS)

    Boecker, B.B.; Muggenburg, B.A.; Miller, S.C.; Bradley, P.L.

    1994-01-01

    This report describes the scientific progress in, and current status of, life-span studies of the long-term health risks in Beagle dogs of chronic irradiation from internally deposited radionuclides or from an external source. The reporting period for this document is the 2-year period from October 1, 1991 through September 30, 1993. Studies that were initiated at three different laboratories (Inhalation Toxicology Research Institute, ITRI, University of Utah, and Argonne National Laboratory, ANL) are presented here because they are being completed at ITRI. All living dogs in the Utah-initiated studies were transferred to the ITRI facility for the remainder of their life-span observations and measurements in September 1987. This report is the fourth in a series of reports dealing with the current status and progress of both the Utah and ITRI studies. Other life-span studies involving dogs exposed to gamma radiation from an external source were initiated and conducted for many years at ANL. In 1991, the decision was made to discontinue the chronic irradiation of the remaining living dogs and to transfer all remaining dogs to ITRI for care, clinical observations, and pathological observations at death or euthanasia. This report provides the current status of these dogs. Status reports on the Utah and ITRI studies comprise most of this report. The ITRI-related section presents brief statements of project objectives, the general procedures used in these studies, and some study-specific features for each of the 19 studies being conducted with either beta- or alpha-emitting radionuclides. Dose- and effect-modifying factors being addressed in these studies include total dose, dose rate, LET, solubility, nonuniformity of dose, species, age, sex, health status, and mode of exposure. Recent additions to experimental protocols for studies in which dogs are still alive involve the collection and analysis of tumor tissues using currently available molecular biology techniques

  4. Inhalation dose assessment inside various storage godowns of a phosphatic fertiliser plant

    International Nuclear Information System (INIS)

    Shukla, V.K.; Eapen, C.D.; Mishra, U.C.

    1995-01-01

    The paper presents the assessment of inhalation dose from 222 Rn daughters received by the persons working inside various godowns, meant for storing rock phosphate and different types of phosphatic fertilisers produced by a plant at Bombay. The dose assessment was made by measuring the respirable airborne concentrations of 222 Rn daughters inside the godowns. Rock phosphate is the base material for the production of phosphatic fertilisers and it contains significant quantities of 226 Ra. 226 Ra activity in rock phosphate from different places is ranging between 5 (Udaipur, India) to 1480 Bq/kg (Florida, USA) and its range in NP: 20-20-0 and NPK: 15-15-15 type fertilisers is 254 to 272 Bq/kg and 127 to 208 Bq/kg respectively. 226 Ra is the source of emanation of 222 Rn inside the godowns. It was observed that though the specific activity of 218 Po, 214 Pb and 214 Bi in the total airborne particulate matter was higher inside the rock phosphate godown but the specific activity of the aforementioned radionuclides in the respirable fractions inside the phosphatic fertilisers' godown were more. The reasons for these observations are discussed in the paper. (author). 7 refs., 2 tabs

  5. Impact of droplet evaporation rate on resulting in vitro performance parameters of pressurized metered dose inhalers.

    Science.gov (United States)

    Sheth, Poonam; Grimes, Matthew R; Stein, Stephen W; Myrdal, Paul B

    2017-08-07

    Pressurized metered dose inhalers (pMDIs) are widely used for the treatment of pulmonary diseases. The overall efficiency of pMDI drug delivery may be defined by in vitro parameters such as the amount of drug that deposits on the model throat and the proportion of the emitted dose that has particles that are sufficiently small to deposit in the lung (i.e., fine particle fraction, FPF). The study presented examines product performance of ten solution pMDI formulations containing a variety of cosolvents with diverse chemical characteristics by cascade impaction with three inlets (USP induction port, Alberta Idealized Throat, and a large volume chamber). Through the data generated in support of this study, it was demonstrated that throat deposition, cascade impactor deposition, FPF, and mass median aerodynamic diameter of solution pMDIs depend on the concentration and vapor pressure of the cosolvent, and the selection of model throat. Theoretical droplet lifetimes were calculated for each formulation using a discrete two-stage evaporation process model and it was determined that the droplet lifetime is highly correlated to throat deposition and FPF indicating that evaporation kinetics significantly influences pMDI drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    International Nuclear Information System (INIS)

    1996-01-01

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

  7. Which inhaled corticosteroid and long-acting β-agonist combination is better in patients with moderate-to-severe asthma, a dry powder inhaler or a pressurized metered-dose inhaler?

    Science.gov (United States)

    Muraki, Masato; Gose, Kyuya; Hanada, Soichiro; Sawaguchi, Hirochiyo; Tohda, Yuji

    2017-11-01

    Two main types of devices are used to facilitate the administration of inhaled corticosteroid (ICS) and long-acting β-agonist (LABA) in combination, dry powder inhalers (DPIs) and pressurized metered-dose inhalers (pMDIs). There are few reports comparing the effects of the two devices, and it is unknown which should be recommended for asthma patients with given sets of characteristics. In the current study, the beneficial effects and side effects associated with DPIs and pMDIs were compared, and the question of which device should be recommended for asthma patients was investigated. A prospective, randomized, crossover, comparative study in adult outpatients with asthma was conducted using salmeterol/fluticasone propionate combination (SFC) 50 μg/250 μg, one inhalation of Adoair ® 250 Diskus ® twice daily or two inhalations of Adoair ® 125 Aerosol twice daily, for 8 weeks. Questionnaires, exhaled nitric oxide (FeNO) tests and pulmonary function tests were administered after the use of each device for 8 weeks, and the results derived from each device were compared. Sixty-eight subjects were included in the final analysis. There were no significant differences between quality-of-life scores, FeNO, spirometry test results and forced oscillation results. With regard to patient preferences, 57.4% preferred the Adoair ® Aerosol and 35.3% preferred the Adoair ® Diskus ® , as determined via the comparative evaluation questionnaire. Although DPI prescription accounts for the predominant market share of combined ICS/LABA in Japan, patients preferred a pMDI device to a DPI device. Compared to DPIs, pMDIs may be the preferential choice for patients with asthma.

  8. Puffing and inhalation behaviour in cigarette smoking: Implications for particle diameter and dose

    Energy Technology Data Exchange (ETDEWEB)

    Dickens, Colin; McGrath, Conor; Warren, Nigel; Biggs, Philip; McAughey, John, E-mail: colin_dickens@bat.co [British American Tobacco, Group R and D Centre, Southampton, SO15 8TL (United Kingdom)

    2009-02-01

    Inhalation of tobacco smoke aerosol is a two-step process involving puffing followed by inhalation. Measured smoke deposition efficiencies in the lung (20-70%) are greater than expected for smoke particles of diameter 150 - 250 nm CMD. Various mechanisms have been put forward to explain this enhanced deposition pattern, including coagulation, hygroscopic growth, condensation and evaporation, changes in composition, or changes in inhalation behaviour. This paper represents one of a series of studies seeking to better quantify smoke chemistry, inhalation behaviour and cumulative particle growth. The studies have been conducted to better understand smoke dosimetry and links to disease as part of a wider programme defining risk and potential harm reduction. In this study, it was noted that particle deposition increased with increasing inhalation depth, and that smoke inhalation volumes were generally greater than normal tidal breathing volumes. A weak association was observed between particle diameter and puff flow, but no strong association between particle diameter and retention efficiency.

  9. Puffing and inhalation behaviour in cigarette smoking: Implications for particle diameter and dose

    International Nuclear Information System (INIS)

    Dickens, Colin; McGrath, Conor; Warren, Nigel; Biggs, Philip; McAughey, John

    2009-01-01

    Inhalation of tobacco smoke aerosol is a two-step process involving puffing followed by inhalation. Measured smoke deposition efficiencies in the lung (20-70%) are greater than expected for smoke particles of diameter 150 - 250 nm CMD. Various mechanisms have been put forward to explain this enhanced deposition pattern, including coagulation, hygroscopic growth, condensation and evaporation, changes in composition, or changes in inhalation behaviour. This paper represents one of a series of studies seeking to better quantify smoke chemistry, inhalation behaviour and cumulative particle growth. The studies have been conducted to better understand smoke dosimetry and links to disease as part of a wider programme defining risk and potential harm reduction. In this study, it was noted that particle deposition increased with increasing inhalation depth, and that smoke inhalation volumes were generally greater than normal tidal breathing volumes. A weak association was observed between particle diameter and puff flow, but no strong association between particle diameter and retention efficiency.

  10. Radiation dose exposure in patients affected by lymphoma undergoing repeat CT examinations: how to manage the radiation dose variability.

    Science.gov (United States)

    Paolicchi, Fabio; Bastiani, Luca; Guido, Davide; Dore, Antonio; Aringhieri, Giacomo; Caramella, Davide

    2018-03-01

    To assess the variability of radiation dose exposure in patients affected by lymphoma undergoing repeat CT (computed tomography) examinations and to evaluate the influence of different scan parameters on the overall radiation dose. A series of 34 patients (12 men and 22 women with a median age of 34.4 years) with lymphoma, after the initial staging CT underwent repeat follow-up CT examinations. For each patient and each repeat examination, age, sex, use of AEC system (Automated Exposure Control, i.e. current modulation), scan length, kV value, number of acquired scans (i.e. number of phases), abdominal size diameter and dose length product (DLP) were recorded. The radiation dose of just one venous phase was singled out from the DLP of the entire examination. All scan data were retrieved by our PACS (Picture Archiving and Communication System) by means of a dose monitoring software. Among the variables we considered, no significant difference of radiation dose was observed among patients of different ages nor concerning tube voltage. On the contrary the dose delivered to the patients varied depending on sex, scan length and usage of AEC. No significant difference was observed depending on the behaviour of technologists, while radiologists' choices had indirectly an impact on the radiation dose due to the different number of scans requested by each of them. Our results demonstrate that patients affected by lymphoma who undergo repeat whole body CT scanning may receive unnecessary overexposure. We quantified and analyzed the most relevant variables in order to provide a useful tool to manage properly CT dose variability, estimating the amount of additional radiation dose for every single significant variable. Additional scans, incorrect scan length and incorrect usage of AEC system are the most relevant cause of patient radiation exposure.

  11. A computer program to calculate the committed dose equivalent after the inhalation of radioactivity

    International Nuclear Information System (INIS)

    Van der Woude, S.

    1989-03-01

    A growing number of people are, as part of their occupation, at risk of being exposed to radiation originating from sources inside their bodies. The quantification of this exposure is an important part of health physics. The International Commission on Radiological Protection (ICRP) developed a first-order kinetics compartmental model to determine the transport of radioactive material through the human body. The model and the parameters involved in its use, are discussed. A versatile computer program was developed to do the following after the in vivo measurement of either the organ- or whole-body activity: calculate the original amount of radioactive material which was inhaled (intake) by employing the ICRP compartmental model of the human body; compare this intake to calculated reference levels and state any action to be taken for the case under consideration; calculate the committed dose equivalent resulting from this intake. In the execution of the above-mentioned calculations, the computer program makes provision for different aerosol particle sizes and the effect of previous intakes. Model parameters can easily be changed to take the effects of, for instance, medical intervention into account. The computer program and the organization of the data in the input files are such that the computer program can be applied to any first-order kinetics compartmental model. The computer program can also conveniently be used for research on problems related to the application of the ICRP model. 18 refs., 25 figs., 5 tabs

  12. Oronasal and Tracheostomy Delivery of Soft Mist and Pressurized Metered-Dose Inhalers With Valved Holding Chamber.

    Science.gov (United States)

    Berlinski, Ariel; Cooper, Brandy

    2016-07-01

    Some pediatric tracheostomized patients who receive inhaled drugs undergo decannulation, and it is unknown whether the dose has to be adjusted. Pressurized metered-dose inhalers (pMDIs) and soft mist inhalers (SMIs) used with valved holding chambers (VHCs) made of non-electrostatic material are available. We hypothesized that using an SMI and changing the delivery route from tracheostomy to oronasal would increase lung dose. Four units of a metallic VHC were studied with albuterol hydrofluoroalkane (pMDI) and albuterol/ipratropium bromide with an SMI using an anatomically correct in vitro model of a 5-y-old spontaneously breathing tracheostomized child. The drug was captured in a filter and was termed lung dose. We tested breathing patterns with tidal volumes of 50, 155, and 300 mL. A mask and a special adapter were used as interfaces for oronasal and tracheostomy delivery, respectively. Spectrophotometry (276 nm) was used to determine albuterol concentration. The use of SMI resulted in a higher lung dose than the pMDI for all tested conditions except delivery through tracheostomy with tidal volume of 155 mL (P = .69). Switching from oronasal to tracheostomy delivery increased the lung dose for all tested conditions except for the pMDI with the 300-mL tidal volume (P = .83). The use of SMI resulted in higher deposition in the tracheostomy tube than the pMDI. In general, an SMI delivers a higher lung dose than a pMDI when using a metallic spacer during oronasal and tracheostomy route with the latter providing a higher lung dose. Copyright © 2016 by Daedalus Enterprises.

  13. Real-time measurement of inhaled and exhaled cigarette smoke: Implications for dose

    Energy Technology Data Exchange (ETDEWEB)

    McGrath, Conor; Warren, Nigel; Biggs, Philip; McAughey, John, E-mail: conor_mcgrath@bat.co [British American Tobacco, Group R and D Centre, Southampton, SO15 8TL (United Kingdom)

    2009-02-01

    Inhalation of tobacco smoke aerosol is a two-step process involving puffing followed by inhalation. Measured smoke deposition efficiencies in the lung (20-70%) are greater than expected for smoke particles of 150 -- 250 nm count median diameter (CMD). Various mechanisms have been put forward to explain this enhanced deposition pattern, including coagulation, hygroscopic growth, condensation and evaporation, changes in composition, or changes in inhalation behaviour. This paper represents one of a series of studies seeking to better quantify smoke chemistry, inhalation behaviour and cumulative particle growth. The studies have been conducted to better understand smoke dosimetry and links to disease as part of a wider programme defining risk and potential harm reduction. In this study, the average CMD of inhaled smoke was 160 nm while the average CMD of exhaled smoke was 239 nm with an average growth factor of 1.5.

  14. Real-time measurement of inhaled and exhaled cigarette smoke: Implications for dose

    International Nuclear Information System (INIS)

    McGrath, Conor; Warren, Nigel; Biggs, Philip; McAughey, John

    2009-01-01

    Inhalation of tobacco smoke aerosol is a two-step process involving puffing followed by inhalation. Measured smoke deposition efficiencies in the lung (20-70%) are greater than expected for smoke particles of 150 -- 250 nm count median diameter (CMD). Various mechanisms have been put forward to explain this enhanced deposition pattern, including coagulation, hygroscopic growth, condensation and evaporation, changes in composition, or changes in inhalation behaviour. This paper represents one of a series of studies seeking to better quantify smoke chemistry, inhalation behaviour and cumulative particle growth. The studies have been conducted to better understand smoke dosimetry and links to disease as part of a wider programme defining risk and potential harm reduction. In this study, the average CMD of inhaled smoke was 160 nm while the average CMD of exhaled smoke was 239 nm with an average growth factor of 1.5.

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

    International Nuclear Information System (INIS)

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

    2016-01-01

    During the production of iodine-131 from neutron irradiated tellurium dioxide by the dry distillation, a considerable amount of "1"3"1I 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 "1"3"1I. This study aims to estimate the inhalation dose for individuals manipulating the "1"3"1I 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 "1"3"1I 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÷6 mSv. 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. - Highlights: • We constructed the time-microenvironment patterns with 1-min resolution by using a smartphone application. • Exposure to "1"3"1I at the dry distillation areas may lead to an acute inhalation dose significantly. • Using smartphone as a motion detector in indoor exposure monitoring is a reliable method.

  16. Radiation dose estimates and hazard evaluations for inhaled airborne radionuclides. Annual progress report, July 1980-June 1981

    International Nuclear Information System (INIS)

    Mewhinney, J.A.

    1982-04-01

    The objective of this project is to conduct confirmatory research on aerosol characteristics and the resulting radiation dose distribution in animals following inhalation and to provide prediction of health consequences in humans due to airborne radioactivity which might be released in normal operations or under accident conditions during production of nuclear fuel composed of mixed oxides of U and Pu. Four research reports summarize the results of specific areas of research being conducted. The first presents final results for several types of physical chemical characterization accomplished on samples of aerosols collected at an industrial facility during normal fabrication of mixed oxide fuel. Many of these characterizations were also done on aerosol samples collected during animal inhalation exposure procedures for biological studies using these aerosol materials. The second paper reports on the methods development process used for establishing a capability for measurement of the specific surface area of aerosols, an important determinant in the rate of dissolution of particulates deposited in lung. The third paper provides updated information on the retention, distribution and excretion of Pu after inhalation by Beagles of aerosols of either 750 0 C treated UO 2 + PuO 2 , 1750 0 C treated (U,Pu)O 2 or 850 0 C treated pure PuO 2 . This paper also reports the results of the formulation of a biomathematical model useful in describing the results of these three inhalation studies. The fourth paper describes the early results from two studies in which Fischer-344 rats received inhalation exposure to aerosols of (U,Pu)O 2 or pure PuO 2 to determine the relationship of radiation dose to biological response

  17. Radiation-dose estimates and hazard evaluations for inhaled airborne radionuclides. Annual progress report, July 1981-June 1982

    International Nuclear Information System (INIS)

    Mewhinney, J.A.

    1983-06-01

    The objective was to conduct confirmatory research on aerosol characteristics and the resulting radiation dose distribution in animals following inhalation and to provide prediction of health consequences in humans due to airborne radioactivity which might be released in normal operations or under accident conditions during production of nuclear fuel composed of mixed oxides of U and Pu. Four research reports summarize the results of specific areas of research. The first paper details development of a method for determination of specific surface area of small samples of mixed oxide or pure PuO 2 particles. The second paper details the extension of the biomathematical model previously used to describe retention, distribution and excretion of Pu from these mixed oxide aerosols to include a description of Am and U components of these aerosols. The third paper summarizes the biological responses observed in radiation dose pattern studies in which dogs, monkeys and rate received inhalation exposures to either 750 0 C heat treated UO 2 + PuO 2 , 1750 0 C heat-treated (U,Pu)O 2 or 850 0 C heat-treated pure PuO 2 . The fourth paper described dose-response studies in which rats were exposed to (U,Pu)O 2 or pure PuO 2 . This paper updates earlier reports and summarizes the status of animals through approximately 650 days after inhalation

  18. Characterization of a New High-Dose Dry Powder Inhaler (DPI) Based on a Fluidized Bed Design.

    Science.gov (United States)

    Farkas, Dale R; Hindle, Michael; Longest, P Worth

    2015-11-01

    The objective of this study was to develop a new high-efficiency dry powder inhaler (DPI) that can effectively aerosolize large masses (25-100 mg) of spray dried powder formulations. The DPI was designed to implement a concept similar to a fluidized bed for aerosolization using small mixing balls made of polytetrafluoroethylene along with a larger, hollow dosing sphere filled with the powder. The performance of the fluidized bed DPI was compared, based on emitted dose (ED) and aerosolization efficiency, to other recently developed capsule-based DPIs that were designed to accommodate smaller powder masses (~2-20 mg). The inhalers were tested with spray dried excipient enhanced growth (EEG) formulations that contained an antibiotic (ciprofloxacin) and hygroscopic excipient (mannitol). The new fluidized bed design produced an ED of 71% along with a mass median aerodynamic diameter of 1.53 μm and fine particle fractions <5 and 1 μm of 93 and 36%, respectively, when used to deliver a 100 mg loaded mass of EEG powder with the advantage of not requiring multiple capsules. Surprisingly, performance of the device was further improved by removing the mixing balls from the inhaler and only retaining the dose containment sphere.

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

    Science.gov (United States)

    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.

  20. The variation of organ doses with the particle size and chemical form of an inhaled radioactive aerosol

    International Nuclear Information System (INIS)

    Hunt, B.W.; Adams, N.; Reissland, J.A.

    1979-04-01

    In this report, radiation doses to organs are calculated as a function of the particle size of the inhaled radioactive material. Aerosols with an Activity Median Aerodynamic Diameter (AMAD) from 0.1 μm to 20 μm are considered and doses accumulated by various organs in periods ranging from 1 day to 70 years are given for 65 radionuclides. A computer program is used which calculates the transformations taking place in each organ per curie of inhaled nuclide from the basic radioactivity and metabolic data. The program also calculates the resulting doses both for the organ in which the transformations occur and from penetrating radiation emitted as a result of transformations in other organs. The effects of particle size and chemical form of the nuclides on the doses received by organs are discussed. Tables of doses accumulated by 10 specific organs and other organs together with effective whole body doses are given for particle sizes 0.1 μm, 1 μm and 10 μm (AMAD). (author)

  1. Lead-210, bismuth-210, polonium-210. Natural activity, internal dosimetry, and dose factors for ingestion and inhalation

    International Nuclear Information System (INIS)

    Jacobi, W.

    1979-02-01

    Starting with a comprehensive review of the normal, natural activity of 210 Pb and 210 Po in the environment and in the tissues of the human body, a model of the activity and dose distributions of this nuclides in the human body is developed. Dose factors for ingestion with food and for inhalation are derived from this model, related to the intake rate unit. This 'natural exposure model' can be used for an estimation of the population exposure due to normal natural radiation as well as to man-made sourcess of these nuclides, e.g. coal-fired power plants. (orig.) [de

  2. Human pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) after repeated doses taken 4 h apart Human pharmacology of MDMA after repeated doses taken 4 h apart.

    Science.gov (United States)

    Farré, Magí; Tomillero, Angels; Pérez-Mañá, Clara; Yubero, Samanta; Papaseit, Esther; Roset, Pere-Nolasc; Pujadas, Mitona; Torrens, Marta; Camí, Jordi; de la Torre, Rafael

    2015-10-01

    3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a popular psychostimulant, frequently associated with multiple administrations over a short period of time. Repeated administration of MDMA in experimental settings induces tolerance and metabolic inhibition. The aim is to determine the acute pharmacological effects and pharmacokinetics resulting from two consecutive 100mg doses of MDMA separated by 4h. Ten male volunteers participated in a randomized, double-blind, crossover, placebo-controlled trial. The four conditions were placebo plus placebo, placebo plus MDMA, MDMA plus placebo, and MDMA plus MDMA. Outcome variables included pharmacological effects and pharmacokinetic parameters. After a second dose of MDMA, most effects were similar to those after a single dose, despite a doubling of MDMA concentrations (except for systolic blood pressure and reaction time). After repeated MDMA administration, a 2-fold increase was observed in MDMA plasma concentrations. For a simple dose accumulation MDMA and MDA concentrations were higher (+23.1% Cmax and +17.1% AUC for MDMA and +14.2% Cmax and +10.3% AUC for MDA) and HMMA and HMA concentrations lower (-43.3% Cmax and -39.9% AUC for HMMA and -33.2% Cmax and -35.1% AUC for HMA) than expected, probably related to MDMA metabolic autoinhibition. Although MDMA concentrations doubled after the second dose, most pharmacological effects were similar or slightly higher in comparison to the single administration, except for systolic blood pressure and reaction time which were greater than predicted. The pharmacokinetic-effects relationship suggests that when MDMA is administered at a 4h interval there exists a phenomenon of acute tolerance to its effects. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  3. A GPU implementation of a track-repeating algorithm for proton radiotherapy dose calculations

    International Nuclear Information System (INIS)

    Yepes, Pablo P; Mirkovic, Dragan; Taddei, Phillip J

    2010-01-01

    An essential component in proton radiotherapy is the algorithm to calculate the radiation dose to be delivered to the patient. The most common dose algorithms are fast but they are approximate analytical approaches. However their level of accuracy is not always satisfactory, especially for heterogeneous anatomical areas, like the thorax. Monte Carlo techniques provide superior accuracy; however, they often require large computation resources, which render them impractical for routine clinical use. Track-repeating algorithms, for example the fast dose calculator, have shown promise for achieving the accuracy of Monte Carlo simulations for proton radiotherapy dose calculations in a fraction of the computation time. We report on the implementation of the fast dose calculator for proton radiotherapy on a card equipped with graphics processor units (GPUs) rather than on a central processing unit architecture. This implementation reproduces the full Monte Carlo and CPU-based track-repeating dose calculations within 2%, while achieving a statistical uncertainty of 2% in less than 1 min utilizing one single GPU card, which should allow real-time accurate dose calculations.

  4. Preclinical assessment of HIV vaccines and microbicides by repeated low-dose virus challenges.

    Directory of Open Access Journals (Sweden)

    Roland R Regoes

    2005-08-01

    Full Text Available Trials in macaque models play an essential role in the evaluation of biomedical interventions that aim to prevent HIV infection, such as vaccines, microbicides, and systemic chemoprophylaxis. These trials are usually conducted with very high virus challenge doses that result in infection with certainty. However, these high challenge doses do not realistically reflect the low probability of HIV transmission in humans, and thus may rule out preventive interventions that could protect against "real life" exposures. The belief that experiments involving realistically low challenge doses require large numbers of animals has so far prevented the development of alternatives to using high challenge doses.Using statistical power analysis, we investigate how many animals would be needed to conduct preclinical trials using low virus challenge doses. We show that experimental designs in which animals are repeatedly challenged with low doses do not require unfeasibly large numbers of animals to assess vaccine or microbicide success.Preclinical trials using repeated low-dose challenges represent a promising alternative approach to identify potential preventive interventions.

  5. An evaluation of children's metered-dose inhaler technique for asthma medications.

    Science.gov (United States)

    Burkhart, Patricia V; Rayens, Mary Kay; Bowman, Roxanne K

    2005-03-01

    Regardless of the medication delivery system, health care providers need to teach accurate medication administration techniques to their patients, educate them about the particular nuances of the prescribed delivery system (eg, proper storage), and reinforce these issues at each health encounter. A single instruction session is not sufficient to maintain appropriate inhaler techniques for patients who require continued use. Providing written steps for the administration technique is helpful so that the patient can refer to them later when using the medication. The National Heart, Lung, and Blood Institute's "Practical Guide for the Diagnosis and Management of Asthma" recommends that practitioners follow these steps for effective inhaler technique training when first prescribing an inhaler: 1. Teach patients the steps and give written instruction handouts. 2. Demonstrate how to use the inhaler step-by-step. 3. Ask patients to demonstrate how to use the inhaler. Let the patient refer to the handout on the first training. Then use the handout asa checklist to assess the patient's future technique. 4. Provide feedback to patients about what they did right and what they need to improve. Have patients demonstrate their technique again, if necessary. The last two steps should be performed (ie, demonstration and providing feedback on what patients did right and what they need to improve) at every subsequent visit. If the patient makes multiple errors, it is advisable to focus on improving one or two key steps at a time. With improvements in drug delivery come challenges, necessitating that practitioners stay current with new medication administration techniques. Teaching and reinforcing accurate technique at each health care encounter are critical to help ensure medication efficacy for patients with asthma. Since one fifth of children in the study performed incorrect medication technique even after education, checklists of steps for the correct use of inhalation devices

  6. Repeated CT scans in trauma transfers: An analysis of indications, radiation dose exposure, and costs

    International Nuclear Information System (INIS)

    Hinzpeter, Ricarda; Sprengel, Kai; Wanner, Guido A.; Mildenberger, Peter; Alkadhi, Hatem

    2017-01-01

    Highlights: • Repetition of CT in trauma patients occurs relatively often. • Repetition of CT is mainly caused by inadequate image data transfer. • Potentially preventable CT examinations add radiation dose to patients. • Repeated CT is associated with excess costs to the health care system. - Abstract: Objectives: To identify the number of CT scans repeated in acute trauma patients receiving imaging before being referred to a trauma center, to define indications, and to assess radiation doses and costs of repeated CT. Methods: This retrospective study included all adult trauma patients transferred from other hospitals to a Level-I trauma center during 2014. Indications for repeated CT scans were categorized into: inadequate CT image data transfer, poor image quality, repetition of head CT after head injury together with completion to whole-body CT (WBCT), and follow-up of injury known from previous CT. Radiation doses from repeated CT were determined; costs were calculated using a nation-wide fee schedule. Results: Within one year, 85/298 (28.5%) trauma patients were transferred from another hospital because of severe head injury (n = 45,53%) and major body trauma (n = 23;27%) not manageable in the referring hospital, repatriation from a foreign country (n = 14;16.5%), and no ICU-capacity (n = 3;3.5%). Of these 85 patients, 74 (87%) had repeated CT in our center because of inadequate CT data transfer (n = 29;39%), repetition of head CT with completion to WBCT (n = 24;32.5%), and follow-up of known injury (n = 21;28.5%). None occurred because of poor image quality. Cumulative dose length product (DLP) and annual costs of potential preventable, repeated CT (inadequate data transfer) was 631mSv (81′304mGy*cm) and 35′233€, respectively. Conclusion: A considerable number of transferred trauma patients undergo potentially preventable, repeated CT, adding radiation dose to patients and costs to the health care system.

  7. Repeated CT scans in trauma transfers: An analysis of indications, radiation dose exposure, and costs

    Energy Technology Data Exchange (ETDEWEB)

    Hinzpeter, Ricarda, E-mail: Ricarda.Hinzpeter@usz.ch [Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, University of Zurich, Raemistr. 100, Zurich CH-8091 (Switzerland); Sprengel, Kai, E-mail: Kai.Sprengel@usz.ch [Division of Trauma Surgery, Department of Surgery, University Hospital Zurich, University of Zurich, Raemistr. 100, CH-8091 Zurich (Switzerland); Wanner, Guido A., E-mail: Guido.Wanner@sbk-vs.de [Division of Trauma Surgery, Department of Surgery, University Hospital Zurich, University of Zurich, Raemistr. 100, CH-8091 Zurich (Switzerland); Department of General Surgery, Schwarzwald-Baar Klinikum, University of Freiburg, Klinikstr. 11, D-78052 Villingen-Schwenningen (Germany); Mildenberger, Peter, E-mail: peter.mildenberger@unimedizin-mainz.de [Department of Diagnostic and Interventional Radiology, University Hospital of Mainz, Langenbeckstr. 1, D-55131 Mainz (Germany); Alkadhi, Hatem, E-mail: hatem.alkadhi@usz.ch [Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, University of Zurich, Raemistr. 100, Zurich CH-8091 (Switzerland)

    2017-03-15

    Highlights: • Repetition of CT in trauma patients occurs relatively often. • Repetition of CT is mainly caused by inadequate image data transfer. • Potentially preventable CT examinations add radiation dose to patients. • Repeated CT is associated with excess costs to the health care system. - Abstract: Objectives: To identify the number of CT scans repeated in acute trauma patients receiving imaging before being referred to a trauma center, to define indications, and to assess radiation doses and costs of repeated CT. Methods: This retrospective study included all adult trauma patients transferred from other hospitals to a Level-I trauma center during 2014. Indications for repeated CT scans were categorized into: inadequate CT image data transfer, poor image quality, repetition of head CT after head injury together with completion to whole-body CT (WBCT), and follow-up of injury known from previous CT. Radiation doses from repeated CT were determined; costs were calculated using a nation-wide fee schedule. Results: Within one year, 85/298 (28.5%) trauma patients were transferred from another hospital because of severe head injury (n = 45,53%) and major body trauma (n = 23;27%) not manageable in the referring hospital, repatriation from a foreign country (n = 14;16.5%), and no ICU-capacity (n = 3;3.5%). Of these 85 patients, 74 (87%) had repeated CT in our center because of inadequate CT data transfer (n = 29;39%), repetition of head CT with completion to WBCT (n = 24;32.5%), and follow-up of known injury (n = 21;28.5%). None occurred because of poor image quality. Cumulative dose length product (DLP) and annual costs of potential preventable, repeated CT (inadequate data transfer) was 631mSv (81′304mGy*cm) and 35′233€, respectively. Conclusion: A considerable number of transferred trauma patients undergo potentially preventable, repeated CT, adding radiation dose to patients and costs to the health care system.

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

    Science.gov (United States)

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

    2018-04-25

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

  9. Evaluation of the Metered-Dose Inhaler Technique among Health Care Providers Practicing in Hamadan University of Medical Sciences

    Directory of Open Access Journals (Sweden)

    E. Nadi

    2004-07-01

    Full Text Available Poor inhaler technique is a common problem both in asthma patients and health care providers , which contributes to poor asthma control. The aim of this study was to evaluate the correctness of metered-dose inhaler (MDI technique in a sample of physicians , pharmacists and nurses practicing in Hamadan University hospitals. A total of 176 healthcare providers (35 internists and general physicians , 138 nurses and 3 pharmacists were participated voluntary in this study. After the participants answered a questionnaire aimed at identifying their involvement in MDI prescribing and counseling , a trained observer assessed their MDI technique using a checklist of ten steps.Of the 176 participants , 35(20% were physician , and 3 subjects (2% were pharmacists , and 138 (78% were nurses. However only 6 participants (3.4% performed all steps correctly. Physicians performed significantly better than non-physicians (8.6% vs. 2.13%.The majority of healthcare providers responsible for instructing patients on the correct MDI technique were unable to perform this technique correctly ‘indicating the need for regular formal training programmes on inhaler techniques.

  10. Estimation of risk for lung cancer induced by inhaled alpha-emitting radionuclides at very low doses

    International Nuclear Information System (INIS)

    Mahaffey, J.A.; Sanders, C.L.

    1979-01-01

    Results of statistical analyses of data from experiments in which rats were exposed to transuranics by inhalation imply that tumor incidence extrapolated to lower doses is not dependent on the chemical form of the transuranic. Using many questionable assumptions and several alternative models, most of the analyses predicted that irradiation at the current occupational exposure limit of 15 rem/year would increase the tumor incidence in rats to about three times the spontaneous incidence--the spontaneous incidence being defined by a single observed tumor

  11. Argon inhalation attenuates retinal apoptosis after ischemia/reperfusion injury in a time- and dose-dependent manner in rats.

    Directory of Open Access Journals (Sweden)

    Felix Ulbrich

    Full Text Available Retinal ischemia and reperfusion injuries (IRI permanently affect neuronal tissue and function by apoptosis and inflammation due to the limited regenerative potential of neurons. Recently, evidence emerged that the noble gas Argon exerts protective properties, while lacking any detrimental or adverse effects. We hypothesized that Argon inhalation after IRI would exert antiapoptotic effects in the retina, thereby protecting retinal ganglion cells (RGC of the rat's eye.IRI was performed on the left eyes of rats (n = 8 with or without inhaled Argon postconditioning (25, 50 and 75 Vol% for 1 hour immediately or delayed after ischemia (i.e. 1.5 and 3 hours. Retinal tissue was harvested after 24 hours to analyze mRNA and protein expression of Bcl-2, Bax and Caspase-3, NF-κB. Densities of fluorogold-prelabeled RGCs were analyzed 7 days after injury in whole-mounts. Histological tissue samples were prepared for immunohistochemistry and blood was analyzed regarding systemic effects of Argon or IRI. Statistics were performed using One-Way ANOVA.IRI induced RGC loss was reduced by Argon 75 Vol% inhalation and was dose-dependently attenuated by lower concentrations, or by delayed Argon inhalation (1504±300 vs. 2761±257; p<0.001. Moreover, Argon inhibited Bax and Bcl-2 mRNA expression significantly (Bax: 1.64±0.30 vs. 0.78±0.29 and Bcl-2: 2.07±0.29 vs. 0.99±0.22; both p<0.01, as well as caspase-3 cleavage (1.91±0.46 vs. 1.05±0.36; p<0.001. Expression of NF-κB was attenuated significantly. Immunohistochemistry revealed an affection of Müller cells and astrocytes. In addition, IRI induced leukocytosis was reduced significantly after Argon inhalation at 75 Vol%.Immediate and delayed Argon postconditioning protects IRI induced apoptotic loss of RGC in a time- and dose-dependent manner, possibly mediated by the inhibition of NF-κB. Further studies need to evaluate Argon's possible role as a therapeutic option.

  12. Inhalation Therapy in Horses.

    Science.gov (United States)

    Cha, Mandy L; Costa, Lais R R

    2017-04-01

    This article discusses the benefits and limitations of inhalation therapy in horses. Inhalation drug therapy delivers the drug directly to the airways, thereby achieving maximal drug concentrations at the target site. Inhalation therapy has the additional advantage of decreasing systemic side effects. Inhalation therapy in horses is delivered by the use of nebulizers or pressured metered dose inhalers. It also requires the use of a muzzle or nasal mask in horses. Drugs most commonly delivered through inhalation drug therapy in horses include bronchodilators, antiinflammatories, and antimicrobials. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Repeated dose titration versus age-based method in electroconvulsive therapy: a pilot study.

    Science.gov (United States)

    Aten, Jan Jaap; Oudega, Mardien; van Exel, Eric; Stek, Max L; van Waarde, Jeroen A

    2015-06-01

    In electroconvulsive therapy (ECT), a dose titration method (DTM) was suggested to be more individualized and therefore more accurate than formula-based dosing methods. A repeated DTM (every sixth session and dose adjustment accordingly) was compared to an age-based method (ABM) regarding treatment characteristics, clinical outcome, and cognitive functioning after ECT. Thirty-nine unipolar depressed patients dosed using repeated DTM and 40 matched patients treated with ABM were compared. Montgomery-Åsberg Depression Rating Scale (MADRS) and Mini-Mental State Examination (MMSE) were assessed at baseline and at the end of the index course, as well as the total number of ECT sessions. Both groups were similar regarding age, sex, psychotic features, mean baseline MADRS, and median baseline MMSE. At the end of the index course, the two methods showed equal outcome (mean end MADRS, 11.6 ± 8.3 in DTM and 9.5 ± 7.6 in ABM (P = 0.26); median end MMSE, 28 (25-29) and 28 (25-29.8), respectively (P = 0.81). However, the median number of all ECT sessions differed 16 (11-22) in DTM versus 12 (10-14.8) in ABM; P = 0.02]. Using regression analysis, dosing method and age were independently associated with the total number of ECT sessions, with less sessions needed in ABM (P = 0.02) and in older patients (P = 0.001). In this comparative cohort study, ABM and DTM showed equal outcome for depression and cognition. However, the median ECT course duration in repeated DTM appeared longer. Additionally, higher age was associated with shorter ECT courses regardless of the dosing method. Further prospective studies are needed to confirm these findings.

  14. Fevipiprant, an oral prostaglandin DP2 receptor (CRTh2) antagonist, in allergic asthma uncontrolled on low-dose inhaled corticosteroids.

    Science.gov (United States)

    Bateman, Eric D; Guerreros, Alfredo G; Brockhaus, Florian; Holzhauer, Björn; Pethe, Abhijit; Kay, Richard A; Townley, Robert G

    2017-08-01

    Dose-related efficacy and safety of fevipiprant (QAW039), an oral DP 2 (CRTh2) receptor antagonist, was assessed in patients with allergic asthma uncontrolled by low-dose inhaled corticosteroids (ICS).Adult patients were randomised to 12 weeks' treatment with once-daily (1, 3, 10, 30, 50, 75, 150, 300 or 450 mg q.d ) or twice-daily (2, 25, 75 or 150 mg b.i.d ) fevipiprant (n=782), montelukast 10 mg q.d (n=139) or placebo (n=137). All patients received inhaled budesonide 200 μg b.i.d Fevipiprant produced a statistically significant improvement in the primary end-point of change in pre-dose forced expiratory volume in 1 s at week 12 (p=0.0035) with a maximum model-averaged difference to placebo of 0.112 L. The most favourable pairwise comparisons to placebo were for the fevipiprant 150 mg q.d and 75 mg b.i.d groups, with no clinically meaningful differences between q.d and b.i.d Montelukast also demonstrated a significant improvement in this end-point. No impact on other efficacy end-points was observed. Adverse events were generally mild/moderate in severity, and were evenly distributed across doses and treatments.Fevipiprant appears to be efficacious and well-tolerated in this patient population, with an optimum total daily dose of 150 mg. Further investigations into the clinical role of fevipiprant in suitably designed phase III clinical trials are warranted. Copyright ©ERS 2017.

  15. High-dose inhaled terbutaline increases muscle strength and enhances maximal sprint performance in trained men

    DEFF Research Database (Denmark)

    Hostrup, Morten; Kalsen, Anders; Bangsbo, Jens

    2014-01-01

    ) participated in a double-blinded randomized crossover study. After administration of inhaled terbutaline (30 × 0.5 mg) or placebo, subjects' maximal voluntary isometric contraction (MVC) of m.quadriceps was measured. After MVC, subjects performed a 30-s Wingate test. Sixty minutes following the Wingate test......, subjects exercised for 10 min at 80 % of [Formula: see text] and completed a 100-kcal time trial. Aerobic contribution was determined during the Wingate test by indirect calorimetry. Furthermore, plasma terbutaline, lactate, glucose, and K(+) were measured. RESULTS: Inhalation of 15 mg terbutaline resulted...... = 0.019) and 3.3 ± 1.0 % (P = 0.009) higher for terbutaline than placebo. Net accumulation of plasma lactate was higher (P = 0.003) for terbutaline than placebo during the Wingate test, whereas [Formula: see text] above baseline was unchanged by terbutaline (P = 0.882). Time-trial performance...

  16. Changes of indoor aerosol characteristics and their associated variation on the dose conversion factor due to radon progeny inhalation

    International Nuclear Information System (INIS)

    Tokonami, Shinji; Ishikawa, Tetsuo; Yonehara, Hidenori; Yamada, Yuji; Matsuzawa, Takao; Iimoto, Takeshi

    2003-01-01

    Since the dose conversion factor (hereafter called DCF) due to radon progeny inhalation is strongly dominated by aerosol characteristics in the environment, it is important to understand the air quality for accurate dose assessment. Thus temporal variations on aerosol concentration, its particle size and its related airborne radioactivities were continuously measured in an actual indoor environment with a relatively high radon concentration. The following human activities were added during the observation period: air-conditioning, removal of aerosol with an air cleaner and ventilation. DCFs based on these activities were evaluated with the latest International Commission of Radiological Protection (ICRP) respiratory tract model and were compared among them. Consequently, the present study has shown that operation of air cleaner enhanced the DCF critically because the unattached fraction increased significantly due to removal of aerosols. (author)

  17. Comparative study of the pharmacokinetics of carbon tetrachloride in the rat following repeated inhalation exposures of 8 and 11.5 hr/day

    International Nuclear Information System (INIS)

    Paustenbach, D.J.; Carlson, G.P.; Christian, J.E.; Born, G.S.

    1986-01-01

    To evaluate whether exposure to inhaled vapors for periods longer than 8 hr/day could affect the rates and routes of elimination, male Sprague-Dawley rats were repeatedly exposed to 100 ppm of radiolabeled carbon tetrachloride ( 14 CCl 4 ) in a closed-loop chamber. One group was exposed for 8 hr/day for 5 days and another group for 11.5 hr/day for 4 days. Two other groups were exposed for either 8 hr/day for 10 of 12 consecutive days or 11.5 hr/day for 7 of 10 days. The elimination of 14 C activity was measured in the expired air, urine, and feces for up to 100 hr following exposure and the pharmacokinetic parameters were determined. Following 2 weeks of exposure to the 8-hr/day schedule, 14 CCl 4 in the breath and 14 C activity in the feces comprised 45 and 48% of the total 14 C excreted, respectively. Following 2 weeks of exposure to the 11.5-hr/day schedule, the values were 32 and 62%, respectively, indicating that repeated exposure to the longer schedule altered the route of elimination of CCl 4 . Regardless of the period of exposure, less than 8% of the inhaled 14 CCl 4 was excreted in the urine and less than 2% was exhaled in the breath as the 14 CO 2 metabolite. Approximately 97-98% of the 14 C activity in the expired air was 14 CCl 4 . The quantities of 14 C noted in the feces and urine suggest that more than 60% of the inhaled CCl 4 was metabolized. Elimination of 14 CCl 4 and 14 CO 2 in the breath followed a two-compartment, first-order pharmacokinetic model (r2 = 0.98). For rats exposed 8 hr/day and 11.5 hr/day for 2 weeks, the average half-lives for elimination of 14 CCl 4 in the breath for the fast (alpha) and slow (beta) phases averaged 96 and 455 min, and 89 and 568 min, respectively. The average alpha and beta half-lives for elimination of 14 CO 2 in the breath

  18. An Automated Inpatient Split-dose Bowel Preparation System Improves Colonoscopy Quality and Reduces Repeat Procedures.

    Science.gov (United States)

    Yadlapati, Rena; Johnston, Elyse R; Gluskin, Adam B; Gregory, Dyanna L; Cyrus, Rachel; Werth, Lindsay; Ciolino, Jody D; Grande, David P; Keswani, Rajesh N

    2017-07-19

    Inpatient colonoscopy preparations are often inadequate, compromising patient safety and procedure quality, while resulting in greater hospital costs. The aims of this study were to: (1) design and implement an electronic inpatient split-dose bowel preparation order set; (2) assess the intervention's impact upon preparation adequacy, repeated colonoscopies, hospital days, and costs. We conducted a single center prospective pragmatic quasiexperimental study of hospitalized adults undergoing colonoscopy. The experimental intervention was designed using DMAIC (define, measure, analyze, improve, and control) methodology. Prospective data collected over 12 months were compared with data from a historical preintervention cohort. The primary outcome was bowel preparation quality and secondary outcomes included number of repeated procedures, hospital days, and costs. On the basis of a Delphi method and DMAIC process, we created an electronic inpatient bowel preparation order set inclusive of a split-dose bowel preparation algorithm, automated orders for rescue medications, and nursing bowel preparation checks. The analysis data set included 969 patients, 445 (46%) in the postintervention group. The adequacy of bowel preparation significantly increased following intervention (86% vs. 43%; P<0.01) and proportion of repeated procedures decreased (2.0% vs. 4.6%; P=0.03). Mean hospital days from bowel preparation initiation to discharge decreased from 8.0 to 6.9 days (P=0.02). The intervention resulted in an estimated 1-year cost-savings of $46,076 based on a reduction in excess hospital days associated with repeated and delayed procedures. Our interdisciplinary initiative targeting inpatient colonoscopy preparations significantly improved quality and reduced repeat procedures, and hospital days. Other institutions should consider utilizing this framework to improve inpatient colonoscopy value.

  19. Effect of repeated oral therapeutic doses of methylphenidate on food intake and growth rate in rats.

    Science.gov (United States)

    Alam, Nausheen; Najam, Rahila

    2015-01-01

    Central nervous system stimulants are known to produce anorexia. Previous data suggest that methylphenidate can have variable effects on caloric intake and growth rate. A dose-response study was performed to monitor caloric intake, liquid intake and growth rate in rats following repeated administration of human oral therapeutic doses 2 mg/kg/day, 5mg/kg/day and 8mg/kg/day of methylphenidate. We found that food intake and water intake, increased in all weeks and at all doses used in the study. Growth rate increased more at higher dose (8mg/kg/day) and at low dose (2mg/kg/day) of methylphenidate in 1(st) and 2(nd) week whereas more decreased by the above doses in 3(rd) week, suggesting that food stimulation leads to initial increase in growth rate but long term administration of methylphenidate attenuate growth rate that is not due to modulation of appetite but may be due to anxiety and increased activity produce by stimulants. A possible role of DA, 5HT receptors in modulation of appetite and anxiety is discussed.

  20. Characterization of Medication Velocity and Size Distribution from Pressurized Metered-Dose Inhalers by Phase Doppler Anemometry.

    Science.gov (United States)

    Alatrash, Abubaker; Matida, Edgar

    2016-12-01

    Particle size and velocity are two of the most significant factors that impact the deposition of pressurized metered-dose inhaler (pMDI) sprays in the mouth cavity. pMDIs are prominently used around the world in the treatment of patients suffering from a variety of lung diseases such as asthma and chronic obstructive pulmonary disease. Since their introduction in the field, and as a result of their effectiveness and simplicity of usage, pMDIs are considered to be the most widely prescribed medical aerosol delivery system. In the current study, particle velocity and size distribution were measured at three different locations along the centerline of a pMDI spray using Phase Doppler Anemometry. pMDIs from four different pharmaceutical companies were tested, each using salbutamol sulfate as the medication. Measurements along at the pMDI centerline (at 0, 75, and 100 mm downstream of the inhaler mouthpiece) showed that the spray velocities were bimodal in time for all four pMDI brands. The first peak occurred as the spray was leaving the mouthpiece, while the second peak (at the same location, 0 mm) occurred at around 60, 95, 95, and 115 milliseconds later, respectively, for the four tested inhalers, with a drop in the velocity between the two peaks. Three probability density functions (PDFs) were tested, and the Rosin-Rammler PDF best fit the empirical data, as determined using a chi-squared test. These results suggest that there is a difference in the mean particle velocities at the centerline for the tested pMDIs and the diameter of released particles varied statistically for each brand.

  1. Neurotoxicity of low-dose repeatedly intranasal instillation of nano- and submicron-sized ferric oxide particles in mice

    Energy Technology Data Exchange (ETDEWEB)

    Wang Bing; Feng Weiyue, E-mail: fengwy@mail.ihep.ac.cn; Zhu Motao; Wang Yun; Wang Meng [Chinese Academy of Sciences, Laboratory for Bio-Environmental Effects of Nanomaterials and Nanosafety and Key Laboratory of Nuclear Analytical Techniques, Institute of High Energy Physics (China); Gu Yiqun [Maternity Hospital of Haidian District (China); Ouyang Hong; Wang Huajian; Li Ming; Zhao Yuliang, E-mail: zhaoyuliang@mail.ihep.ac.cn; Chai Zhifang [Chinese Academy of Sciences, Laboratory for Bio-Environmental Effects of Nanomaterials and Nanosafety and Key Laboratory of Nuclear Analytical Techniques, Institute of High Energy Physics (China); Wang Haifang [Peking University, College of Chemistry and Molecular Engineering (China)

    2009-01-15

    Olfactory tract has been demonstrated to be an important portal for inhaled solid nanoparticle transportation into the central nervous system (CNS). We have previously demonstrated that intranasally instilled Fe{sub 2}O{sub 3} nanoparticles could transport into the CNS via olfactory pathway. In this study, we investigated the neurotoxicity and size effect of repeatedly low-dose (130 {mu}g) intranasal exposure of nano- and submicron-sized Fe{sub 2}O{sub 3} particles (21 nm and 280 nm) to mice. The biomarkers of oxidative stress, activity of nitric oxide synthases and release of monoamine neurotransmitter in the brain were studied. Our results showed that significant oxidative stress was induced by the two sizes of Fe{sub 2}O{sub 3} particles. The activities of GSH-Px, Cu,Zn-SOD, and cNOS significantly elevated and the total GSH and GSH/GSSG ratio significantly decreased in the olfactory bulb and hippocampus after the nano- and submicron-sized Fe{sub 2}O{sub 3} particle treatment (p < 0.05). The nano-sized Fe{sub 2}O{sub 3} generally induced greater alteration and more significant dose-effect response than the submicron-sized particle did. Some slight perturbation of monoamine neurotransmitters were found in the hippocampus after exposure to the two sizes of Fe{sub 2}O{sub 3} particle. The TEM image showed that some ultrastructural alterations in nerve cells, including neurodendron degeneration, membranous structure disruption and lysosome increase in the olfactory bulb, slight dilation in the rough endoplasmic reticulum and lysosome increase in the hippocampus were induced by the nano-sized Fe{sub 2}O{sub 3} treatment. In contrast, in the submicron-sized Fe{sub 2}O{sub 3} treated mice, slightly swollen mitochondria and some vacuoles were observed in the olfactory bulb and hippocampus, respectively. These results indicate that intranasal exposure of Fe{sub 2}O{sub 3} nanoparticles could induce more severe oxidative stress and nerve cell damage in the brain than the

  2. Factors affecting the efficiency of aerosolized salbutamol delivery via a metered dose inhaler and equine spacer device.

    Science.gov (United States)

    Pirie, R S; McGorum, B C; Owen, C; Carr, O; Oakley, H; McLachlan, G

    2017-06-01

    Despite frequent use of metered dose inhalers (MDIs) and spacers in equine practice, limited information exists on the efficiency of aerosol delivery using such devices. We determined the particle size distribution within an MDI-generated salbutamol aerosol delivered via an equine spacer using 'best practice' delivery technique and assessed the effect of variations in MDI use technique (shaking prior to each actuation, rapid repetitive actuations, and MDI angulation) on aerosol delivery efficiency. Under optimal conditions, only 53(±18) μg salbutamol per 100 μg actuation was delivered beyond the spacer. Although this aerosol had a high [89.6% (±2.4)] fine particle (aerodynamic diameter [2.52 (±0.29) μm], and particle size variability [geometric SD - 1.66 (±0.16) μm], within all particle size fractions, there was a high coefficient of variance (31-79%) of the percentage salbutamol delivered between experimental runs, thus impeding any effort to predict drug delivery to the patient during equine inhalation therapy. Despite observable trends and with the exception of minor statistically significant changes in the least abundant particle sizes, none of the deviations from a 'best practice' delivery technique significantly altered the relative salbutamol delivery beyond the spacer, a finding which has potential relevance with regard to maintaining user compliance. © 2016 John Wiley & Sons Ltd.

  3. Comparative study of budesonide as a nebulized suspension vs pressurized metered-dose inhaler in adult asthmatics

    DEFF Research Database (Denmark)

    Bisgaard, H; Nikander, K; Munch, E

    1998-01-01

    The study objective was to compare the effect of budesonide administered as a nebulized suspension as compared to a spray with a spacer in adult asthmatics. In a double-blind, double-dummy crossover study, 26 adult patients with moderately severe unstable asthma were randomized to three 4-week...... treatment periods with budesonide 0.8 mg b.i.d. administered by a pressurized metered-dose inhaler (pMDI) with spacer (Nebuhaler) and budesonide 1 mg and 4 mg b.i.d. administered by a Pari Inhalier Boy jet nebulizer. The nebulizer was activated only during inspiration. The total mass output was similar from...... the two devices but their fraction of small particles differed by a factor of 2 in favour of pMDI. Effect was evaluated from daily home measurements of peak expiratory flow (PEF), need of beta 2-agonist and symptom scores. Plasma cortisol and budesonide levels were measured in a subgroup of 10 patients...

  4. An experimental study on the toxicity of several radionuclides inhaled at different doses

    International Nuclear Information System (INIS)

    Lafuma, J.; Nenot, J.C.; Morin, M.; Masse, R.; Metivier, H.; Nolibe, D.; Skupinski, W.

    1975-01-01

    For over 5 years investigations have been carried out on large lots of rats on the toxicological action of several inhaled radionuclides. Various physico chemical forms of α-emitting actinides and β-emitting lanthanides were used, respectively 239 Pu, 238 Pu, 241 Am, as oxide or nitrate solution at pH1, 244 Cm nitrate, and 144 Ce chloride and 141 Ce chloride and oxide. The activities deposited per gram of lung varied between 10nCi and 10μCi. The first effect observed was life-shortening. A comparison of the survival curves shows a heterogeneity factor whose values for the various radionuclides is given. Lung cancers were also observed. Rarely lung carcinomas were the cause of death, which was unknown and seemed to vary with the different compounds [fr

  5. Repeated-dose effects of mequitazine, cetirizine and dexchlorpheniramine on driving and psychomotor performance.

    Science.gov (United States)

    Theunissen, Eef L; Vermeeren, Annemiek; Ramaekers, Johannes G

    2006-01-01

    Previous studies have demonstrated that the antihistamines mequitazine, cetirizine and dexchlorpheniramine produce mild sedation after single doses. It is unknown, however, whether acute sedation persists after repeated dosing. Therefore, this study assessed the effects of repeated dosing of these antihistamines on driving and psychomotor performance. Sixteen healthy volunteers were treated with mequitazine 10 mg q.a.m., cetirizine 10 mg q.a.m., dexchlorpheniramine Repetab 6 mg b.i.d. and placebo for four separate 8-day periods. Drug effects were assessed on days 1 and 8 using on-the-road driving tests (highway driving and car following), psychomotor tests (tracking and divided attention) and subjective questionnaires. Dexchlorpheniramine and mequitazine significantly impaired driving performance on the highway driving test on the first day; dexchlorpheniramine increased Standard Deviation of Lateral Position by 2 cm [95% confidence interval (CI) 0.5, 3.8] and mequitazine by 2.5 cm (CI 1.0, 4.3). These effects on driving performance disappeared after 8 days of treatment. No effect of treatment was found on car following, tracking and divided attention. Although subjective ratings confirmed that subjects knew their driving had been impaired in the mequitazine and dexchlorpheniramine condition after completion of the highway driving test on day 1, they did not expect their driving to be affected before the start of the test. Cetirizine did not impair performance on any of the tests. Single doses of mequitazine 10 mg and dexchlorpheniramine Repetab 6 mg cause mild driving impairment. However, when taken over several days, the impairing effect wears off, possibly as a result of tolerance.

  6. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... Controlling Tools for Control Triggers Indoors In the Workplace Outdoors Management Asthma Action Plan Flu Shots Inhalers ... inhaler with a spacer Your browser does not support iframes Using a metered dose inhaler with a ...

  7. Efficacy and safety of budesonide/formoterol single inhaler therapy versus a higher dose of budesonide in moderate to severe asthma

    NARCIS (Netherlands)

    Scicchitano, R; Aalbers, R; Ukena, D; Manjra, A; Fouquert, L; Centanni, S; Boulet, LP; Naya, IP; Hultquist, C

    Objectives:This study evaluated the efficacy and safety of a novel asthma management strategy - budesonide/formoterol for both maintenance and symptom relief (Symbicort Single Inhaler Therapy*) - compared with a higher maintenance dose of budesonide in patients with moderate to severe asthma.

  8. Pharmacokinetics and pharmacodynamics of high doses of pharmaceutically prepared heroin, by intravenous or by inhalation route in opioid-dependent patients

    NARCIS (Netherlands)

    Rook, Elisabeth J.; van Ree, Jan M.; van den Brink, Wim; Hillebrand, Michel J. X.; Huitema, Alwin D. R.; Hendriks, Vincent M.; Beijnen, Jos H.

    2006-01-01

    A pharmacokinetic-pharmacodynamic study was performed in opioid-dependent patients in the Netherlands, who were currently treated with high doses of pharmaceutically prepared heroin on medical prescription. Besides intravenous heroin, heroin was prescribed for inhalation by "chasing the dragon"

  9. Toxicity of inhaled alpha-emitting radionuclides - Status report

    International Nuclear Information System (INIS)

    Muggenburg, B.A.; Mewhinney, J.A.; Guilmette, R.A.; Gillett, N.A.; Diel, J.H.; Lundgren, D.L.; Hahn, F.F.; Boecker, B.B.; McClellan, R.O.

    1988-01-01

    The toxicity of inhaled alpha-emitting radionuclides is being investigated in a series of interrelated dose-response studies. Dogs, rodents, and nonhuman primates have been exposed to monodisperse or polydisperse aerosols of the oxides of 239 Pu, 238 Pu, 241 Am, or 244 Cm to measure the relative importance of average organ dose, local dose around particles, specific activity, chemical form, particle size, and number of particles inhaled to the development of biological effects. The influence of animal species, age at exposure, and pre-existing lung disease, as well as the effects of repeated exposure, are also being studied, because they may influence the toxicity of these radionuclides. (author)

  10. An equivalence study comparing nitrous oxide and oxygen with low-dose sevoflurane and oxygen as inhalation sedation agents in dentistry for adults.

    Science.gov (United States)

    Allen, M; Thompson, S

    2014-11-01

    The aim of this study was to examine whether sevoflurane in oxygen was equivalent to near equipotent concentrations of nitrous oxide in oxygen when used as an inhalation sedation agent in terms of patient and user acceptability. Forty anxious dental patients referred to the sedation suite at Cardiff University School of Dentistry received either nitrous oxide to a maximum concentration of 40% or sevoflurane to a maximum concentration of 0.3% for a routine maxillary plastic restoration with articaine infiltration local analgesia. The inhalation sedation agent to be administered was chosen by a random number allocator. Measurements of blood pressure, oxygen saturation, heart rate, respiratory rate and bispectral index were recorded every 5 minutes. At the end of the treatment episode the patient, the operator and an observer who was unaware of the agent used, recorded their impressions about the episode by completing questionnaires. In the doses used in this study, sevoflurane was found to be as effective as an inhalation sedation agent as the standard dose of nitrous oxide used in normal inhalation sedation in the treatment of adult anxious dental patients. Sevoflurane in low concentrations is equivalent in effect to near equipotent concentrations of nitrous oxide. This would suggest that further research, perhaps with slightly higher concentrations of sevoflurane, is needed. If sevoflurane was shown to be acceptable at slightly higher concentrations, there is scope to explore the development of equipment specifically designed to deliver sevoflurane as an inhalation sedation agent in future.

  11. Repeated episodes of ozone inhalation attenuates airway injury/repair and release of substance P, but not adaptation.

    Science.gov (United States)

    Schelegle, Edward S; Walby, William F; Alfaro, Mario F; Wong, Viviana J; Putney, Lei; Stovall, Mary Y; Sterner-Kock, Anja; Hyde, Dallas M; Plopper, Charles G

    2003-02-01

    To determine the impact of repeated episodes of ozone exposure on physiologic adaptation, epithelial injury/repair, and tracheal substance P levels, adult rats were subjected to episodes of ozone (5 days, 1 ppm, 8 h/day) followed by 9 days of filtered air for four cycles. Rats were sampled on days 1 and 5 of each episode and 9 days after day 5 of episodes 1, 2, and 4. One hour before being euthanized each rat was injected with 5-bromo-2'-deoxyuridine to label proliferating cells. Each 5-day episode showed a characteristic pattern of rapid shallow breathing (days 1 and 2), epithelial injury, and interstitial and intraluminal inflammation. In contrast, the neutrophil component of inflammation, tracheal substance P release, and cell proliferation became attenuated with each consecutive episode of exposure. Concurrent with this cyclic and attenuated response there was progressive hypercellularity and hyperplasia in all airways studied and a progressive remodeling present in the terminal bronchioles. Our findings are consistent with the notion that the cumulative distal airway lesion is at least in part the result of a depressed cell proliferative response to injury in these airways. This depressed cell proliferative response may be in part the result of diminished neutrophil inflammation and/or release of mitogenic neuropeptides in response to ozone-induced injury.

  12. Evaluation of metered dose inhaler spray velocities using phase Doppler anemometry (PDA).

    Science.gov (United States)

    Liu, Xiaofei; Doub, William H; Guo, Changning

    2012-02-28

    Droplet velocity is an important parameter which can significantly influence inhalation drug delivery performance. Together with the droplet size, this parameter determines the efficiency of the deposition of MDI products at different sites within the lungs. In this study, phase Doppler anemometry (PDA) was used to investigate the instantaneous droplet velocity emitted from MDIs as well as the corresponding droplet size distribution. The nine commercial MDI products surveyed showed significantly different droplet velocities, indicating that droplet velocity could be used as a discriminating parameter for in vitro testing of MDI products. The droplet velocity for all tested MDI products decreased when the testing distance was increased from 3 cm to 6 cm from the front of mouthpiece, with CFC formulations showing a larger decrease than HFA formulations. The mean droplet diameters of the nine MDIs were also significantly different from one-another. Droplet size measurements made using PDA (a number-based technique) could not be directly compared to results obtained using laser light scattering measurements (a volume-based technique). This work demonstrates that PDA can provide unique information useful for characterizing MDI aerosol plumes and evaluating MDI drug delivery efficiency. PDA could also aid the evaluation of in vitro equivalence in support of formulation or manufacturing changes and in evaluation of abbreviated new drug applications (ANDAs) for MDIs. Published by Elsevier B.V.

  13. Single and repeated dose pharmacokinetics of dexketoprofen trometamol in patients with impaired liver function.

    Science.gov (United States)

    Valles, J; Artigas, R; Bertolotti, M; Crea, A; Muller, F; Paredes, I; Capriati, A

    2006-06-01

    Dexketoprofen trometamol, a high water-soluble salt of the active enantiomer of rac-ketoprofen, is a nonsteroidal antiinflammatory drug (NSAID) used for pain relief. This study compared the pharmacokinetics of dexketoprofen in patients with impaired liver function and normal subjects following single and repeated oral dosing. Subjects with normal liver function (n = 6) and with Child-Pugh A (n = 7) or Child-Pugh B (n = 5) hepatic impairment scores completed this open-label and parallel study. They received 25 mg dexketoprofen (equivalent to 37 mg of its tromethamine salt) as a single (day 1) and a 3-day repeated dose (1 dose every 8 hours for a total of 10 doses). Dexketoprofen concentrations were determined in plasma and urine by reverse-phase high performance liquid chromatography (HPLC). Model-independent pharmacokinetic parameters were obtained. All subjects completed the study. No serious adverse events were recorded. Following the single dose, mean (+/- SEM) Cmax were 3027.7 +/- 429.3 ng/ml (healthy subjects), 2856.3 +/- 340.3 ng/ml (Child-Pugh A) and 1937.2 +/- 328.0 ng/ml (Child-Pugh B). Median tmax were 0.49 h (0.33-0.68) h, 0.50 h (0.33-0.67) h and 0.67 h (0.33-1.50) h. AUC0-x averaged 3778.0 +/- 439.0 ng.h/ml, 4890.4 +/- 539.1 ng.h/ml and 3985.0 +/- 712.0 ng.h/ml. Mean CL/F were 101.1 +/- 11.3 ml/h/kg, 73.3 +/- 9.9 ml/h/kg and 88.8 +/- 15.5 ml/h/kg and V/F averaged 0.192 +/- 0.018 l/kg, 0.162 +/- 0.006 l/kg and 0.214 +/- 0.044 l/kg. Following the repeated administration, similar results were obtained showing no drug accumulation. As related to the administered dose, median excretions of unchanged and conjugated dexketoprofen in urine were 2.1% and 67.1% in healthy subjects, 2.8% and 60.9% in Child-Pugh A subjects and 4.4% and 47.7% in Child-Pugh B volunteers. A trend towards a reduced urinary excretion of conjugated dexketoprofen in hepatic patients, more evident in the Child-Pugh B than in the Child-Pugh A groups, was observed when compared with healthy

  14. Radiation dose to workers due to the inhalation of dust during granite fabrication

    International Nuclear Information System (INIS)

    Zwack, L M; Stewart, J H; McCarthy, J F; Allen, J G; McCarthy, W B

    2014-01-01

    There has been very little research conducted to determine internal radiation doses resulting from worker exposure to ionising radiation in granite fabrication shops. To address this issue, we estimated the effective radiation dose of granite workers in US fabrication shops who were exposed to the maximum respirable dust and silica concentrations allowed under current US regulations, and also to concentrations reported in the literature. Radiation doses were calculated using standard methods developed by the International Commission on Radiological Protection. The calculated internal doses were very low, and below both US occupational standards (50 mSv yr −1 ) and limits applicable to the general public (1 mSv yr −1 ). Workers exposed to respirable granite dust concentrations at the US Occupational Safety and Health Administration (OSHA) respirable dust permissible exposure limit (PEL) of 5 mg m −3 over a full year had an estimated radiation dose of 0.062 mSv yr −1 . Workers exposed to respirable granite dust concentrations at the OSHA silica PEL and at the American Conference of Governmental Industrial Hygienists Threshold Limit Value for a full year had expected radiation doses of 0.007 mSv yr −1 and 0.002 mSv yr −1 , respectively. Using data from studies of respirable granite dust and silica concentrations measured in granite fabrication shops, we calculated median expected radiation doses that ranged from <0.001 to 0.101 mSv yr −1 . (paper)

  15. Indoor inhalation dose estimates due to radon and thoron in some areas of South-Western Punjab (India))

    International Nuclear Information System (INIS)

    Kumar, S.; Singh, S.; Bajwa, B. S.; Singh, B.; Sabharwal, A. D.; Eappen, K. P.

    2008-01-01

    LR-115 (type II)-based radon-thoron discriminating twin-chamber dosemeters have been used for estimating radon 222 Rn) and thoron 220 Rn) concentrations in dwellings of south-western Punjab (India)). The present study region has shown pronounced cases of cancer incidents in the public [Thakur, Rao, Rajwanshi, Parwana and Kumar (Epidemiological study of high cancer among rural agricultural community of Punjab in Northern India. Int J Environ Res Public Health 2008; 5(5):399-407) and Kumar et al. (Risk assessment for natural uranium in subsurface water of Punjab state (India)). Hum Ecol Risk Assess 2011;17:381-93)]. Radon being a carcinogen has been monitored in some dwellings selected randomly in the study area. Results show that the values of radon 222 Rn) varied from 21 to 79 Bq m -3 , with a geometric mean of 45 Bq m -3 [geometric standard deviation (GSD 1.39)], and those of thoron 220 Rn) from minimum detection level to 58 Bq m -3 with a geometric mean of 19 Bq m -3 (GSD 1.88). Bare card data are used for computing the progeny concentration by deriving the equilibrium factor (F) using a root finding method [Mayya, Eappen and Nambi (Methodology for mixed field inhalation dosimetry in monazite areas using a twin-cup dosemeter with three track detectors. Radiat Prot Dosim 1998; 77(3): 177-84)]. Inhalation doses have been calculated and compared using UNSCEAR equilibrium factors and by using the calculated F-values. The results show satisfactory comparison between the values. (authors)

  16. Study of four week repeated dose toxic test of Sweet Bee Venom in Beagle Dogs

    Directory of Open Access Journals (Sweden)

    Jae-Seuk Park

    2010-12-01

    Full Text Available Objectives: This study was performed to analyse four week repeated dose toxicity of Sweet Bee Venom(Sweet BV extracted from the bee venom in Beagle dogs. Methods: All experiments were conducted under the regulations of Good Laboratory Practice (GLP at Biotoxtech Company, a non-clinical study authorized institution. Male and female Beagle dogs of 5-6 months old were chosen for the pilot study of four week repeated dose toxicity of Sweet BV which was administered at the level of 0.56㎎/㎏ body weight which is eighty times higher than the clinical application dosage as the high dosage, followed by 0.28 and 0.14㎎/㎏ as midium and low dosage, respectively. Equal amount of excipient(normal saline to the Sweet BV experiment groups was administered as the control group every day for four weeks. Results: 1. No mortality was witnessed in all of the experiment groups. 2. All experiment groups were appealed pain sense in the treating time compared to the control group, and hyperemia and movement disorder were observed around the area of administration in all experiment groups, and higher occurrence in the higher dosage treatment. 3. For weight measurement, Neither male nor female groups showed significant changes. 4. In the urine analysis, CBC and biochemistry didn't show any significant changes in the experiment groups compared with control group. 5. For weight measurement of organs, experiment groups didn't show any significant changes compared with control group. 6. To verify abnormalities of organs and tissues, thigh muscle which treated with Sweet BV, cerebrum, liver, lung, kidney, and spinal cords were removed and conducted histologocal observation with H-E staining. In the histologocal observation of thigh muscle, cell infiltration, inflammatory, degeneration, necrosis of muscle fiber, and fibrosis were found in both thigh tissue. And the changes were depend on the dose of Sweet BV. But another organs were not detected in any abnormalities. 7

  17. Inhalation dose due to presence of 131I in air above septic tank system of an endocrinology hospital

    International Nuclear Information System (INIS)

    Mietelski, J. W.; Grabowska, S.; Nowak, T.; Bogacz, J.; Gaca, P.; Bartyzel, M.; Budzanowski, M.

    2005-01-01

    We present here measurements of the 131 I concentration for both: Gaseous and aerosol fraction of 131 I in the air above the septic tank containing wastes from medical application of this isotope. Aerosols were collected using air filters, whereas gaseous forms of iodine were trapped in KI impregnated charcoal double layer cartridge. Besides an active method (pumping of the air through system of filters) an attempt for using a passive method (charcoal traps) for monitoring of radio-iodine is described. For better characterisation of a site the external kerma was determined by means of G - M and TLD techniques as well as the activity kept in the septic tank was measured by gamma spectrometry. Results show that the activity of the aerosol fraction can be neglected compared to that of the gaseous fraction. He measured activity of air is low, on the level of 1 Bq m -3 , even during simulated failure of the ventilation system. Estimated inhalation dose for the serviceman of septic tanks is low (∼10%) compared with external dose obtained by such person due to gamma radiation from the tank (on the level ∼500 nSv h -1 ). Therefore, the concept of passive monitoring of the iodine in air was abandoned. Also estimated is the efficiency of 131 I reduction by a charcoal filter of the ventilation system and 131 I input to the environment by the ventilation chimney. (authors)

  18. Inhalation dose due to presence of 131I in air above septic tank system of an endocrinology hospital.

    Science.gov (United States)

    Mietelski, J W; Grabowska, S; Nowak, T; Bogacz, J; Gaca, P; Bartyzel, M; Budzanowski, M

    2005-01-01

    We present here measurements of the 131I concentration for both: gaseous and aerosol fraction of 131I in the air above the septic tank containing wastes from medical application of this isotope. Aerosols were collected using air filters, whereas gaseous forms of iodine were trapped in KI impregnated charcoal double layer cartridge. Besides an active method (pumping of the air through system of filters) an attempt for using a passive method (charcoal traps) for monitoring of radio-iodine is described. For better characterisation of a site the external kerma was determined by means of G-M and TLD techniques as well as the activity kept in the septic tank was measured by gamma spectrometry. Results show that the activity of the aerosol fraction can be neglected compared to that of the gaseous fraction. He measured activity of air is low, on the level of 1 Bq m(-3), even during simulated failure of the ventilation system. Estimated inhalation dose for the serviceman of septic tanks is low ( approximately 10%) compared with external dose obtained by such person due to gamma radiation from the tank (on the level approximately 500 nSv h(-1)). Therefore, the concept of passive monitoring of the iodine in air was abandoned. Also estimated is the efficiency of 131I reduction by a charcoal filter of the ventilation system and 131I input to the environment by the ventilation chimney.

  19. Influence of lung parameter values for the Brazilian population on inhalation dose

    International Nuclear Information System (INIS)

    Reis, Arlene A.; Lopes, Ricardo T.

    2009-01-01

    The Human Respiratory Tract Model (HRTM) proposed by the ICRP Publication 66 accounts for the morphology and physiology of the respiratory tract. The ICRP 66 presents deposition fraction in the respiratory tract regions considering reference values from Caucasian man. However, in order to obtain a more accurate assessment of intake and dose the ICRP recommends the use of specific information when they are available. The main objective of this study is to evaluate the influence in dose calculation to each region of the respiratory tract when physiological parameters from samples of Brazilian population, in different levels of exercise, are applied in the deposition model.The dosimetric model of HRTM was implemented in the software EXCEL for Windows and committed equivalent dose was determined for each respiratory tract region. First it was calculated the total number of nuclear transformations considering the fractional deposition of activity in each source tissue obtained by application of physiological and morphological Brazilian parameters in the deposition model and then it was calculated the total energy absorbed per unit mass in the target tissue.The variation in the fractional deposition in the compartments of the respiratory tract in changing the physiological parameters from Caucasian to Brazilian adult man causes variation in the number of total transformations and also in the equivalent dose in each region of the respiratory tract. The variations are not the same for all regions of the respiratory tract and depend on levels of exercise. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-12-01

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

  1. Uncertainty of inhalation dose coefficients for representative physical and chemical forms of iodine-131

    Science.gov (United States)

    Harvey, Richard Paul, III

    Releases of radioactive material have occurred at various Department of Energy (DOE) weapons facilities and facilities associated with the nuclear fuel cycle in the generation of electricity. Many different radionuclides have been released to the environment with resulting exposure of the population to these various sources of radioactivity. Radioiodine has been released from a number of these facilities and is a potential public health concern due to its physical and biological characteristics. Iodine exists as various isotopes, but our focus is on 131I due to its relatively long half-life, its prevalence in atmospheric releases and its contribution to offsite dose. The assumption of physical and chemical form is speculated to have a profound impact on the deposition of radioactive material within the respiratory tract. In the case of iodine, it has been shown that more than one type of physical and chemical form may be released to, or exist in, the environment; iodine can exist as a particle or as a gas. The gaseous species can be further segregated based on chemical form: elemental, inorganic, and organic iodides. Chemical compounds in each class are assumed to behave similarly with respect to biochemistry. Studies at Oak Ridge National Laboratories have demonstrated that 131I is released as a particulate, as well as in elemental, inorganic and organic chemical form. The internal dose estimate from 131I may be very different depending on the effect that chemical form has on fractional deposition, gas uptake, and clearance in the respiratory tract. There are many sources of uncertainty in the estimation of environmental dose including source term, airborne transport of radionuclides, and internal dosimetry. Knowledge of uncertainty in internal dosimetry is essential for estimating dose to members of the public and for determining total uncertainty in dose estimation. Important calculational steps in any lung model is regional estimation of deposition fractions

  2. Oral repeated-dose systemic and reproductive toxicity of 6:2 fluorotelomer alcohol in mice

    Directory of Open Access Journals (Sweden)

    Pushkor Mukerji

    2015-01-01

    Full Text Available 6:2 fluorotelomer alcohol (6:2 FTOH was evaluated for potential systemic repeated-dose and reproductive toxicity in mice. 6:2 FTOH was administered by oral gavage to CD-1 mice as a suspension in 0.5% aqueous methylcellulose with 0.1% Tween-80 at dosages of 1, 5, 25, or 100 mg/kg/day. The no-observed-adverse-effect level (NOAEL for systemic toxicity was 25 mg/kg/day (males and 5 mg/kg/day (females, based on effects at higher doses on mortality, clinical observations, body weight, nutritional parameters, hematology (red and white blood cell, clinical chemistry (liver-related, liver weights, and histopathology (liver, teeth, reproductive tract, and mammary gland. However, 6:2 FTOH was not a selective reproductive toxicant. The NOAEL for reproductive toxicity was >100 mg/kg/day; no effects on reproductive outcome were observed at any dosage. The NOAEL for viability and growth of the offspring was 25 mg/kg/day, based on clinical signs of delayed maturation in pups, and reductions in pup survival and pup body weight during lactation at 100 mg/kg/day. While the severity of the effects was generally greater in mice than previously reported in CD rats, the overall NOAELs were identical in both species, 5 mg/kg/day for systemic toxicity and 25 mg/kg/day for offspring viability/growth. 6:2 FTOH was not a selective reproductive toxicant in either species; no effects on reproductive outcome occurred at any dose level, and any effects observed in offspring occurred at dose levels that induced mortality and severe toxicity in maternal animals.

  3. A method for comparison of animal and human alveolar dose and toxic effect of inhaled ozone

    International Nuclear Information System (INIS)

    Hatch, G.E.; Koren, H.; Aissa, M.

    1989-01-01

    Present models for predicting the pulmonary toxicity of O 3 in humans from the toxic effects observed in animals rely on dosimetric measurements of O 3 mass balance and species comparisons of mechanisms that protect tissue against O 3 . The goal of the study described was to identify a method to directly compare O 3 dose and effect in animals and humans using bronchoalveolar lavage fluid markers. The feasibility of estimating O 3 dose to alveoli of animals and humans was demonstrated through assay of reaction products of 18 O-labeled O 3 in lung surfactant and macrophage pellets of rabbits. The feasibility of using lung lavage fluid protein measurements to quantify the O 3 toxic response in humans was demonstrated by the finding of significantly increased lung lavage protein in 10 subjects exposed to 0.4 ppm O 3 for 2 h with intermittent periods of heavy exercise. The validity of using the lavage protein marker to quantify the response in animals has already been established. The positive results obtained in both the 18 O 3 and the lavage protein studies reported here suggest that it should be possible to obtain a direct comparison of both alveolar dose and toxic effect of O 3 to alveoli of animals or humans

  4. Evaluation of inhaled and cutaneous doses of imidacloprid during stapling ornamental plants in tunnels or greenhouses.

    Science.gov (United States)

    Aprea, Cristina; Lunghini, Liana; Banchi, Bruno; Peruzzi, Antonio; Centi, Letizia; Coppi, Luana; Bogi, Mirella; Marianelli, Enrico; Fantacci, Mariella; Catalano, Pietro; Benvenuti, Alessandra; Miligi, Lucia; Sciarra, Gianfranco

    2009-09-01

    The aim of this research was to assess dermal and respiratory exposure of workers to imidacloprid during manual operations with ornamental plants previously treated in greenhouses or tunnels. A total of 10 female workers, 5 in greenhouses and 5 in tunnels, were monitored for 3 or 5 consecutive days. Actual skin contamination, excluding hands, was evaluated using nine filter paper pads placed directly on the skin. To evaluate the efficacy of protective clothing in reducing occupational exposure we also placed four pads on top of the outer clothing. Hand contamination was evaluated by washing with 95% ethanol. Respiratory exposure was evaluated by personal air sampling. Respiratory dose was calculated on the basis of a lung ventilation of 15 l/min. Absorbed doses were calculated assuming a skin penetration of 10% and a respiratory retention of 100%. Dislodgeable foliar residues (DFRs) were determined during the days of re-entry in order to determine the dermal transfer factor. From the dependence of dermal exposure of hands from DFRs, a mean transfer factor was estimated to be 36.4 cm(2)/h. Imidacloprid was determined by liquid chromatography with selective mass detection and electrospray interface in all matrices analysed. Respiratory dose was 4.1+/-4.0 (0.1-14.3)% and 3.0+/-2.0 (0.6-6.9)% (mean+/-SD (range)) of the total real dose during work in tunnels and greenhouses, respectively. The estimated absorbed doses, 0.29+/-0.45 microg/kg (0.06-2.25 microg/kg) body weight and 0.32+/-0.18 microg/kg (0.07-0.66 microg/kg) body weight (mean+/-SD (range)) in tunnels and in greenhouses, respectively, were less than the acceptable operator exposure level of 0.15 mg/kg body weight and than the acceptable daily intake of 0.05 mg/kg body weight. The hands and exposed skin of all workers were found to be contaminated, indicating that greater precautions, such as daily changing of gloves and clothing, are necessary to reduce skin exposure.

  5. 210Po in cigarette and the radiation dose inhaled by smoker

    International Nuclear Information System (INIS)

    Wang Xin; Chen Xingan; Pan Yingdong

    2000-01-01

    The contents of Polonium-210 in 16 brands of cigarettes from China and 4 brands of cigarettes from abroad were reported. The method that the authors used for separating Polonium-210 was electrochemical deposition method. The 210 Po contents were analyzed in whole cigarettes from freshly opened packs. The 210 Po contents of the China-made cigarettes ranged from 13.7 to 43.4 mBq/cig, from 18.0 to 67.3 mBq/g respectively, the mean values were 26.5 mBq/cig and 33.7 mBq/g respectively. The content of 210 Po in cigarettes from China is higher than that from abroad. The polonium contents of the ash, butt and main stream smoke were reported. The cigarettes were smoked with the eight-channel smoking machine for determining the concentration of the radionuclides in main stream smoke. ('Main Stream' means smoke taken into the mouth). About 15% of 210 Po contained in a cigarette was transferred into the main stream smoke, 40% of the whole 210 Po content remained in the ash and butt for filter cigarette, 60% for non-filter. The daily intake of the 210 Po from cigarette was 80 mBq, the annual dose equivalent to the lung tissue of human body was 0.46 mSv. In view of present knowledge, it is improbable that this dose is significant for the higher incidence of lung tissue of human body was 0.46 mSv. In view of present knowledge, it is improbable that this dose is significant for the higher incidence of lung cancer in smokers

  6. Repeated low-dose exposures to sarin, soman, or VX affect acoustic startle in guinea pigs.

    Science.gov (United States)

    Smith, C D; Lee, R B; Moran, A V; Sipos, M L

    2016-01-01

    Chemical warfare nerve agents (CWNAs) are known to cause behavioral abnormalities in cases of human exposures and in animal models. The behavioral consequences of single exposures to CWNAs that cause observable toxic signs are particularly well characterized in animals; however, less is known regarding repeated smaller exposures that may or may not cause observable toxic signs. In the current study, guinea pigs were exposed to fractions (0.1, 0.2, or 0.4) of a medial lethal dose (LD50) of sarin, soman, or VX for two weeks. On each exposure day, and for a post-exposure period, acoustic startle response (ASR) was measured in each animal. Although relatively few studies use guinea pigs to measure behavior, this species is ideal for CWNA-related experiments because their levels of carboxylesterases closely mimic those of humans, unlike rats or mice. Results showed that the 0.4 LD50 doses of soman and VX transiently increased peak startle amplitude by the second week of injections, with amplitude returning to baseline by the second week post-exposure. Sarin also increased peak startle amplitude independent of week. Latencies to peak startle and PPI were affected by agent exposure but not consistently among the three agents. Most of the changes in startle responses returned to baseline following the cessation of exposures. These data suggest that doses of CWNAs not known to produce observable toxic signs in guinea pigs can affect behavior in the ASR paradigm. Further, these deficits are transient and usually return to baseline shortly after the end of a two-week exposure period. Published by Elsevier Inc.

  7. A 28-Day Repeated Dose Toxicological Study of an Aqueous Extract of Morus Alba L.

    Science.gov (United States)

    Marx, Tennille K; Glávits, Róbert; Endres, John R; Palmer, Philip A; Clewell, Amy E; Murbach, Timothy S; Hirka, Gábor; Pasics, Ilona

    2016-11-01

    Morus alba L. (white mulberry) leaves are one of the oldest recognized traditional Chinese medicines. More recently, M alba leaves and their constituents, particularly iminosugars (or azasugars), have garnered attention for their ability to maintain normal blood glucose concentrations, an effect identified in both animal studies and human clinical trials. Reducose (Phynova Group Limited) is a commercial water-soluble extract of M alba leaves standardized to 5% 1-deoxynojirimycin (DNJ), an iminosugar with α-glucosidase inhibition properties. Although there is an extensive history of consumption of M alba leaves by humans and animals worldwide, suggesting that the leaves and their extracts have a relatively good safety profile, we are unaware of safety assessments on an extract containing a higher amount of DNJ than that occurs naturally. The current 28-day repeated dose oral toxicity study in rats, conducted according to Organisation for Economic Co-operation and Development guidelines, was carried out to assess the safety of Reducose. Male and female Hsd.Han Wistar rats (4 groups of 10 animals/sex) were administered Reducose via gavage at doses of 0, 1,000, 2,000 and 4,000 mg/kg body weight (bw)/d. No treatment-related mortality or adverse effects (per clinical observations, body weight/weight gain, food consumption, ophthalmoscopy, clinical pathology, gross pathology, organ weights, or histopathology) were observed, and no target organs were identified. The no observed adverse effect level was determined to be 4,000 mg/kg bw/d for both male and female rats, the highest dose tested. © The Author(s) 2016.

  8. The effect of actuator nozzle designs on the electrostatic charge generated in pressurised metered dose inhaler aerosols.

    Science.gov (United States)

    Chen, Yang; Young, Paul M; Fletcher, David F; Chan, Hak Kim; Long, Edward; Lewis, David; Church, Tanya; Traini, Daniela

    2015-04-01

    To investigate the influence of different actuator nozzle designs on aerosol electrostatic charges and aerosol performances for pressurised metered dose inhalers (pMDIs). Four actuator nozzle designs (flat, curved flat, cone and curved cone) were manufactured using insulating thermoplastics (PET and PTFE) and conducting metal (aluminium) materials. Aerosol electrostatic profiles of solution pMDI formulations containing propellant HFA 134a with different ethanol concentration and/or model drug beclomethasone dipropionate (BDP) were studied using a modified electrical low-pressure impactor (ELPI) for all actuator designs and materials. The mass of the deposited drug was analysed using high performance liquid chromatography (HPLC). Both curved nozzle designs for insulating PET and PTFE actuators significantly influenced aerosol electrostatics and aerosol performance compared with conducting aluminium actuator, where reversed charge polarity and higher throat deposition were observed with pMDI formulation containing BDP. Results are likely due to the changes in plume geometry caused by the curved edge nozzle designs and the bipolar charging nature of insulating materials. This study demonstrated that actuator nozzle designs could significantly influence the electrostatic charges profiles and aerosol drug deposition pattern of pMDI aerosols, especially when using insulating thermoplastic materials where bipolar charging is more dominant.

  9. Real-world healthcare utilization in asthma patients using albuterol sulfate inhalation aerosol (ProAir® HFA with and without integrated dose counters

    Directory of Open Access Journals (Sweden)

    Kerwin EM

    2017-05-01

    Full Text Available Edward M Kerwin,1 Thomas J Ferro,2 Rinat Ariely,3 Debra E Irwin,4 Ruchir Parikh3 1Clinical Trials Division, Clinical Research Institute of Southern Oregon, PC, Medford, OR, 2Global Medical Affairs, 3Global Health Economics and Outcome Research, Teva Pharmaceuticals, Frazer, PA, 4Outcomes Research, Truven Health Analytics, Durham, NC, USA Background: Accurate tracking of the administered dose of asthma rescue inhalers is critical for optimal disease management and is related to reductions in rates of unscheduled health care utilization in asthma patients. There are few published data on the real-world impact of rescue inhalers with integrated dose counters (IDCs on health care resource utilization (HRU for asthma patients. This study evaluates HRU among users of ProAir® hydrofluoroalkane (HFA (albuterol sulfate inhalation aerosol, with IDC versus without IDC, in asthma patients.Methods: This was a retrospective administrative claims study of asthma patients receiving a new prescription for albuterol inhalation aerosol without IDC during 2 years (January 2011–December 2012 or with IDC during the first full year after IDC implementation in the USA (July 2013–July 2014. Six months of continuous enrollment with medical and prescription drug benefits were required before and after the first prescription during the study period. Data on respiratory-related hospitalizations and emergency department (ED visits were collected during the follow-up period.Results: A total of 135,305 (32% patients used albuterol inhalation aerosol with IDC, and 287,243 (68% patients received albuterol inhalation aerosol without IDC. After adjusting for baseline confounding factors, the odds ratio (OR for experiencing a respiratory-related hospitalization (OR=0.92; 95% confidence interval [CI] 0.88–0.96 or ED visit (OR=0.92; 95% CI 0.90–0.94 was significantly lower among patients using albuterol inhalation aerosol with IDC versus without IDC.Conclusion: In a real

  10. Inhaled Steroids

    Science.gov (United States)

    ... considerations when your dosage changes. What about side effects and inhaled steroids? The most common side effects with inhaled steroids ... inhaled steroid has much less potential for side effects than steroid pills or syrups. There have been concerns regarding ...

  11. Inhalant Abuse

    Science.gov (United States)

    ... is when you pour the product into a bag, hold it over your mouth and nose, and inhale. How is inhalant abuse diagnosed? If you think your child is abusing inhalants, talk to them. Be honest and open. Tell them ...

  12. Upper respiratory tract nociceptor stimulation and stress response following acute and repeated Cyfluthrin inhalation in normal and pregnant rats: Physiological rat-specific adaptions can easily be misunderstood as adversities.

    Science.gov (United States)

    Pauluhn, Juergen

    2018-01-05

    This paper reviews the results from past regulatory and mechanistic inhalation studies in rats with the type II pyrethroid Cyfluthrin. Apart from many chemical irritants, Cyfluthrin was shown to be a neuroexcitatory agent without any inherent tissue-destructive or irritant property. Thus, any Cyfluthrin-induced neuroexcitatory afferent sensory stimulus from peripheral nociceptors in the upper respiratory tract is likely to be perceived as a transient stimulus triggering annoyance and/or avoidance by both rats and humans. However, while thermolabile rats respond to such stresses reflexively, homeothermic humans appear to respond psychologically. With this focus in mind, past inhalation studies in rats and human volunteers were reevaluated and assessed to identify common denominators to such neuroexcitatory stimuli upon inhalation exposure. This analysis supports the conclusion that the adaptive physiological response occurring in rats secondary to such chemosensory stimuli requires inhalation exposures above the chemosensory threshold. Rats, a species known to undergo adaptively a hibernation-like physiological state upon environmental stresses, experienced reflexively-induced bradypnea, bradycardia, hypothermia, and changes in acid-base status during inhalation exposure. After cessation of the sensory stimulus, rapid recovery occurred. Physiological data of male and female rats from a 4-week repeated inhalation study (exposure 6-h/day, 5-times/week) were used to select concentration for a 10-day developmental inhalation toxicity study in pregnant rats. Maternal hypothermia and hypoventilation were identified as likely cause of fetal and placental growth retardations because of a maternal adaptation-driven reduced feto-placental transfer of oxygen. In summary, maternal reflex-hypothermia, reduced cardiac output and placental perfusion, and disruption of the gestation-related hyperventilation are believed to be the maternally mediated causes for developmental

  13. Chip-based human liver-intestine and liver-skin co-cultures--A first step toward systemic repeated dose substance testing in vitro.

    Science.gov (United States)

    Maschmeyer, Ilka; Hasenberg, Tobias; Jaenicke, Annika; Lindner, Marcus; Lorenz, Alexandra Katharina; Zech, Julie; Garbe, Leif-Alexander; Sonntag, Frank; Hayden, Patrick; Ayehunie, Seyoum; Lauster, Roland; Marx, Uwe; Materne, Eva-Maria

    2015-09-01

    Systemic repeated dose safety assessment and systemic efficacy evaluation of substances are currently carried out on laboratory animals and in humans due to the lack of predictive alternatives. Relevant international regulations, such as OECD and ICH guidelines, demand long-term testing and oral, dermal, inhalation, and systemic exposure routes for such evaluations. So-called "human-on-a-chip" concepts are aiming to replace respective animals and humans in substance evaluation with miniaturized functional human organisms. The major technical hurdle toward success in this field is the life-like combination of human barrier organ models, such as intestine, lung or skin, with parenchymal organ equivalents, such as liver, at the smallest biologically acceptable scale. Here, we report on a reproducible homeostatic long-term co-culture of human liver equivalents with either a reconstructed human intestinal barrier model or a human skin biopsy applying a microphysiological system. We used a multi-organ chip (MOC) platform, which provides pulsatile fluid flow within physiological ranges at low media-to-tissue ratios. The MOC supports submerse cultivation of an intact intestinal barrier model and an air-liquid interface for the skin model during their co-culture with the liver equivalents respectively at (1)/100.000 the scale of their human counterparts in vivo. To increase the degree of organismal emulation, microfluidic channels of the liver-skin co-culture could be successfully covered with human endothelial cells, thus mimicking human vasculature, for the first time. Finally, exposure routes emulating oral and systemic administration in humans have been qualified by applying a repeated dose administration of a model substance - troglitazone - to the chip-based co-cultures. Copyright © 2015. Published by Elsevier B.V.

  14. Use of low-dose oral theophylline as an adjunct to inhaled corticosteroids in preventing exacerbations of chronic obstructive pulmonary disease: study protocol for a randomised controlled trial.

    Science.gov (United States)

    Devereux, Graham; Cotton, Seonaidh; Barnes, Peter; Briggs, Andrew; Burns, Graham; Chaudhuri, Rekha; Chrystyn, Henry; Davies, Lisa; De Soyza, Anthony; Fielding, Shona; Gompertz, Simon; Haughney, John; Lee, Amanda J; McCormack, Kirsty; McPherson, Gladys; Morice, Alyn; Norrie, John; Sullivan, Anita; Wilson, Andrew; Price, David

    2015-06-10

    Chronic obstructive pulmonary disease (COPD) is associated with high morbidity, mortality, and health-care costs. An incomplete response to the anti-inflammatory effects of inhaled corticosteroids is present in COPD. Preclinical work indicates that 'low dose' theophylline improves steroid responsiveness. The Theophylline With Inhaled Corticosteroids (TWICS) trial investigates whether the addition of 'low dose' theophylline to inhaled corticosteroids has clinical and cost-effective benefits in COPD. TWICS is a randomised double-blind placebo-controlled trial conducted in primary and secondary care sites in the UK. The inclusion criteria are the following: an established predominant respiratory diagnosis of COPD (post-bronchodilator forced expiratory volume in first second/forced vital capacity [FEV1/FVC] of less than 0.7), age of at least 40 years, smoking history of at least 10 pack-years, current inhaled corticosteroid use, and history of at least two exacerbations requiring treatment with antibiotics or oral corticosteroids in the previous year. A computerised randomisation system will stratify 1424 participants by region and recruitment setting (primary and secondary) and then randomly assign with equal probability to intervention or control arms. Participants will receive either 'low dose' theophylline (Uniphyllin MR 200 mg tablets) or placebo for 52 weeks. Dosing is based on pharmacokinetic modelling to achieve a steady-state serum theophylline of 1-5 mg/l. A dose of theophylline MR 200 mg once daily (or placebo once daily) will be taken by participants who do not smoke or participants who smoke but have an ideal body weight (IBW) of not more than 60 kg. A dose of theophylline MR 200 mg twice daily (or placebo twice daily) will be taken by participants who smoke and have an IBW of more than 60 kg. Participants will be reviewed at recruitment and after 6 and 12 months. The primary outcome is the total number of participant-reported COPD exacerbations requiring

  15. Estimate of 50-year dose commitment to various organs and tissues of the body from inhalation of 222Rn free of its daughters

    International Nuclear Information System (INIS)

    Bernard, S.R.; Ford, M.R.; Snyder, W.S.

    1976-01-01

    Some topics discussed are as follows: retention of 222 Rn in fat, bone, heart, muscle, skin, testes, and urinary bladder; retention equations for Rn; decay scheme for Rn and 226 Ra; metabolic models for Po, Pb, and Bi; dose estimates to target organs for 222 Rn and its daughters that are not inhaled but produced from decay of 222 Rn; and estimation of MPC for bone marrow, gonads, and total body

  16. Evaluation of the dose-response and fate in the lung and pleura of chrysotile-containing brake dust compared to chrysotile or crocidolite asbestos in a 28-day quantitative inhalation toxicology study.

    Science.gov (United States)

    Bernstein, D M; Toth, B; Rogers, R A; Sepulveda, R; Kunzendorf, P; Phillips, J I; Ernst, H

    2018-04-26

    This study provides an understanding of the biokinetics and potential toxicology in the lung and pleura following inhalation of brake-dust (brakes manufactured with chrysotile). The design included a 28-day repeated multi-dose inhalation exposure (6 h/d, 5 d/wk, 4 wks) followed by 28-days without exposure. Fiber control groups included a similar grade chrysotile as used in the brakes and a commercial crocidolite asbestos. Aerosol fiber distributions of the chrysotile and crocidolite were similar (fiber-length > 20 μm/cm 3 : Chrysotile-low/high 42/62; Crocidolite-low/high 36/55; WHO-fibers/cm 3 : Chrysotile-low/high 192/219; Crocidolite-low/high 211/255). The total number of aerosol particles/cm 3 in the brake-dust was similar to that in the chrysotile (Brake-dust 710-1065; Chrysotile 532-1442). Brake-dust at particle exposure levels equal to or greater than chrysotile or crocidolite caused no indication of microgranulomas, epithelial hyperplasia, or fibrosis (Wagner score brake-dust and chrysotile-HD groups or in thickness of visceral or parietal pleural. The crocidolite exposure resulted in extensive inflammatory response, collagen development and adhesions between the visceral and parietal surfaces with double the surface thickness. These results provide essential information for the design of a subsequent subchronic study. Copyright © 2018. Published by Elsevier Inc.

  17. The importance of determining the air exchange rate in flats and buildings for calculations of the averted indoor inhalation doses arising from contaminated outdoor air

    International Nuclear Information System (INIS)

    Jilek, Karel; Thomas, J.; Bulanek, B.; Lenk, J.; Marikova, S.

    2015-01-01

    The indoor-outdoor air exchange rate is an important parameter when refining estimates of the averted inhaled doses to population in houses and buildings after an emergency event resulting in contamination of outdoor air with a radioactive material. The air exchange rates measured in 70 occupied houses and in 20 unoccupied houses using N 2 O as the tracer gas are presented, and the results of modelling the averted doses in the residential buildings for both gaseous and aerosol outdoor contaminants are demonstrated. (orig.)

  18. Radon in the Underground Workplaces; Assessment of the Annual Effective Dose due to Inhaled Radon for the Seoul Subway Station Staffs

    Energy Technology Data Exchange (ETDEWEB)

    Song, Myeong Han; Chang, Byung Uck; Kim, Yong Jae [University of Science and Technology, Daejeon (Korea, Republic of); Lee, Hwa Yong [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of); Heo, Dong Hey [Korea Research Institute of Standards and Science, Daejeon (Korea, Republic of)

    2010-12-15

    The effective dose of the Seoul subway staffs due to inhaled radon ({sup 222}Rn) in their workplace was investigated depended on radon concentration exposed at each workplace, and working hours and working types of the staffs. Annual average radon concentrations ranged from 16.5 to 93.0 Bq·m{sup -3}. The staffs commonly spend 2,304 hours in the underground spaces a year. With the radon concentrations and the working hours of the staffs, estimated annual effective doses ranged from 0.23 to 0.73 mSv·y{sup -1}.

  19. Radon in the Underground Workplaces; Assessment of the Annual Effective Dose due to Inhaled Radon for the Seoul Subway Station Staffs

    International Nuclear Information System (INIS)

    Song, Myeong Han; Chang, Byung Uck; Kim, Yong Jae; Lee, Hwa Yong; Heo, Dong Hey

    2010-01-01

    The effective dose of the Seoul subway staffs due to inhaled radon ( 222 Rn) in their workplace was investigated depended on radon concentration exposed at each workplace, and working hours and working types of the staffs. Annual average radon concentrations ranged from 16.5 to 93.0 Bq·m -3 . The staffs commonly spend 2,304 hours in the underground spaces a year. With the radon concentrations and the working hours of the staffs, estimated annual effective doses ranged from 0.23 to 0.73 mSv·y -1

  20. Utility of repeated praziquantel dosing in the treatment of schistosomiasis in high-risk communities in Africa: a systematic review.

    Directory of Open Access Journals (Sweden)

    Charles H King

    2011-09-01

    Full Text Available Controversy persists about the optimal approach to drug-based control of schistosomiasis in high-risk communities. In a systematic review of published studies, we examined evidence for incremental benefits from repeated praziquantel dosing, given 2 to 8 weeks after an initial dose, in Schistosoma-endemic areas of Africa.We performed systematic searches of electronic databases PubMed and EMBASE for relevant data using search terms 'schistosomiasis', 'dosing' and 'praziquantel' and hand searches of personal collections and bibliographies of recovered articles. In 10 reports meeting study criteria, improvements in parasitological treatment outcomes after two doses of praziquantel were greater for S. mansoni infection than for S. haematobium infection. Observed cure rates (positive to negative conversion in egg detection assays were, for S. mansoni, 69-91% cure after two doses vs. 42-79% after one dose and, for S. haematobium, 46-99% cure after two doses vs. 37-93% after a single dose. Treatment benefits in terms of reduction in intensity (mean egg count were also different for the two species-for S. mansoni, the 2-dose regimen yielded an weighted average 89% reduction in standardized egg counts compared to a 83% reduction after one dose; for S. haematobium, two doses gave a 93% reduction compared to a 94% reduction with a single dose. Cost-effectiveness analysis was performed based on Markov life path modeling.Although schedules for repeated treatment with praziquantel require greater inputs in terms of direct costs and community participation, there are incremental benefits to this approach at an estimated cost of $153 (S. mansoni-$211 (S. haematobium per additional lifetime QALY gained by double treatment in school-based programs. More rapid reduction of infection-related disease may improve program adherence, and if, as an externality of the program, transmission can be reduced through more effective coverage, significant additional benefits are

  1. Reverse water-in-fluorocarbon emulsions for use in pressurized metered-dose inhalers containing hydrofluoroalkane propellants.

    Science.gov (United States)

    Butz, N; Porté, C; Courrier, H; Krafft, M P; Vandamme, Th F

    2002-05-15

    Pulmonary administration of drugs has demonstrated numerous advantages in the treatment of pulmonary diseases due to direct targeting to the respiratory tract. It enables avoiding the first pass effect, reduces the amount of drugs administered, targets drugs to specific sites and reduces their side effects. Reverse water-in-fluorocarbon (FC) emulsions are potential drug delivery systems for pulmonary administration using pressurized metered-dose inhalers (pMDI). The external phase of these emulsions consists of perfluorooctyl bromide (PFOB, perflubron), whereas their internal phase contains the drugs solubilized or dispersed in water. These emulsions are stabilized by a perfluoroalkylated dimorpholinophosphate (F8H11DMP), i.e. a fluorinated surfactant. This study demonstrates the possibility of delivering a reverse fluorocarbon emulsion via the pulmonary route using a CFC-free pMDI. Two hydrofluoroalkanes (HFAs) (Solkane(R) 134a and Solkane(R) 227) were used as propellants, and various solution (or emulsion)/propellant ratios (1/3, 1/2, 2/3, 1/1, 3/2, 3/1 v/v) were investigated. The insolubility of water (with or without the fluorinated surfactant F8H11DMP) in both HFA 227 and HFA 134a was demonstrated. PFOB and the reverse emulsion were totally soluble or dispersible in all proportions in both propellants. This study demonstrated also that the reverse FC emulsion can be successfully used to deliver caffeine in a homogeneous and reproducible way. The mean diameter of the emulsion water droplets in the pressured canister was investigated immediately after packaging and after 1 week of storage at room temperature. Best results were obtained with emulsion/propellant ratios comprised between 2/3 and 3/2, and with HFA 227 as propellant.

  2. The influence of actuator materials and nozzle designs on electrostatic charge of pressurised metered dose inhaler (pMDI) formulations.

    Science.gov (United States)

    Chen, Yang; Young, Paul M; Fletcher, David F; Chan, Hak Kim; Long, Edward; Lewis, David; Church, Tanya; Traini, Daniela

    2014-05-01

    To investigate the influence of different actuator materials and nozzle designs on the electrostatic charge properties of a series of solution metered dose inhaler (pMDI) aerosols. Actuators were manufactured with flat and cone nozzle designs using five different materials from the triboelectric series (Nylon, Polyethylene terephthalate, Polyethylene-High density, Polypropylene copolymer and Polytetrafluoroethylene). The electrostatic charge profiles of pMDI containing beclomethasone dipropionate (BDP) as model drug in HFA-134a propellant, with different concentrations of ethanol were studied. Electrostatic measurements were taken using a modified electrical low-pressure impactor (ELPI) and the deposited drug mass assayed chemically using HPLC. The charge profiles of HFA 134a alone have shown strong electronegativity with all actuator materials and nozzle designs, at an average of -1531.34 pC ± 377.34. The presence of co-solvent ethanol significantly reduced the negative charge magnitude. BDP reduced the suppressing effect of ethanol on the negative charging of the propellant. For all tested formulations, the flat nozzle design showed no significant differences in net charge between different actuator materials, whereas the charge profiles of cone designs followed the triboelectric series. The electrostatic charging profiles from a solution pMDI containing BDP and ethanol can be significantly influenced by the actuator material, nozzle design and formulation components. Ethanol concentration appears to have the most significant impact. Furthermore, BDP interactions with ethanol and HFA have an influence on the electrostatic charge of aerosols. By choosing different combinations of actuator materials and orifice design, the fine particle fractions of formulations can be altered.

  3. Lung tumors and radon inhalation in over 2000 rats: Approximate linearity across a wide range of doses and potentiation by tobacco smoke

    International Nuclear Information System (INIS)

    Gray, R.G.; Lafuma, J.; Parish, S.E.; Peto, R.; CEA Centre d'Etudes Nucleaires de Fontenay-aux-Roses

    1986-01-01

    More than 2000 rats were exposed to cumulative doses of up to 28,000 WLMs of radon gas. More than 300 pulmonary tumors were induced by this exposure, most being nonfatal lesions detected only at autopsy of animals that had died of unrelated causes. Above 6000 WLMs rats suffered increasingly from life shortening due to radiation-induced nonneoplastic causes and so had less time in which to develop tumors. When adjusted for these competing causes of death, the hazard function for the excess risk of developing pulmonary tumors was approximately linearly related to dose throughout the range of doses studied. This suggests that some previously reported high-dose ''reductions'' in radiogenic tumor-induction rates may chiefly have involved the killing of rats rather than the killing of precursor cells. Rats exposed to radon and then to six months of inhalation of tobacco smoke had a four times greater age-specific prevalence of pulmonary tumors than rats exposed to an identical radon dose either alone or preceded by tobacco smoke inhalation. This suggests that tobacco smoke may accelerate the carcinogenic process by acting as a promoter of radiation-induced somatic damage. These data suggest that, for assessing human risk from exposure to radon, the linear model should be assumed, but that the WLM is not on its own an adequate index of carcinogenic insult. 7 refs., 2 figs., 4 tabs

  4. Repeat Gamma-Knife Radiosurgery for Refractory or Recurrent Trigeminal Neuralgia with Consideration About the Optimal Second Dose.

    Science.gov (United States)

    Park, Seong-Cheol; Kwon, Do Hoon; Lee, Do Hee; Lee, Jung Kyo

    2016-02-01

    To investigate adequate radiation doses for repeat Gamma Knife radiosurgery (GKS) for trigeminal neuralgia in our series and meta-analysis. Fourteen patients treated by ipsilateral repeat GKS for trigeminal neuralgia were included. Median age of patients was 65 years (range, 28-78), the median target dose, 140-180). Patients were followed a median of 10.8 months (range, 1-151) after the second gamma-knife surgery. Brainstem dose analysis and vote-counting meta-analysis of 19 studies were performed. After the second gamma-knife radiosurgeries, pain was relieved effectively in 12 patients (86%; Barrow Neurological Institute Pain Intensity Score I-III). Post-gamma-knife radiosurgery trigeminal nerve deficits were mild in 5 patients. No serious anesthesia dolorosa was occurred. The second GKS radiation dose ≤ 60 Gy was significantly associated with worse pain control outcome (P = 0.018 in our series, permutation analysis of variance, and P = 0.009 in the meta-analysis, 2-tailed Fisher's exact test). Cumulative dose ≤ 140-150 Gy was significantly associated with poor pain control outcome (P = 0.033 in our series and P = 0.013 in the meta-analysis, 2-tailed Fisher's exact test). A cumulative brainstem edge dose >12 Gy tended to be associated with trigeminal nerve deficit (P = 0.077). Our study suggests that the second GKS dose is a potentially important factor. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Single and 2-week repeated intravenous dose toxicity studies of disodium mercaptoundecahydro-closo-dodecaborate in rats

    Energy Technology Data Exchange (ETDEWEB)

    Itoh, Fumio; Yabuuchi, Kazuya; Ohno, Kouji; Muraoka, Yoshihiro [Shionogi and Co. Ltd., Toyonaka, Osaka (Japan). Developmental Research Lab.; Ikeuchi, Isao

    1998-10-01

    Disodium mercaptoundecahydro-closo-dodecaborate (BSH) is a boron compound used in Boron Neutron Capture Therapy for malignant brain tumors. Intravenous single and 2-week repeated dose toxicity studies of BSH were performed in Sprague-Dawley rats. In the single-dose study, BSH was administered at doses of 100, 300 or 600 mg/kg. Death occurred within 10 min (acute type) or from 5 hr to 2 days (delayed type) after dosing in the 600 mg/kg group. No differences in mortality by sex and dosing speed were observed. Major causes of death were considered to be circulatory disorder in acute death and renal injury in delayed death. The renal injury was observed in the 300 and 600 mg/kg groups. In the 2-week repeated dose study, BSH was administered at doses of 30, 100 or 300 mg/kg/day for 14 days. Body weight gain was suppressed in the 100 and 300 mg/kg groups. One male in the 300 mg/kg group died due to renal and pulmonary lesions at day 8. Slight anemia was observed in the 300 mg/kg group. Pathologically, the kidney showed tubular regeneration with increase of weight in the 300 mg/kg. From these results, the NOAEL of BSH is 30 mg/kg/day. (author)

  6. Cost-effectiveness of fluticasone propionate administered via metered-dose inhaler plus babyhaler spacer in the treatment of asthma in preschool-aged children

    DEFF Research Database (Denmark)

    Bisgaard, H; Price, M J; Maden, Christian Nicolai

    2001-01-01

    a metered-dose inhaler and a Babyhaler (Glaxo Wellcome; Middlesex, UK) spacer device. MEASUREMENTS: Effectiveness in terms of asthma exacerbations, control of cough and wheeze symptoms, symptom-free days, overall direct costs of asthma management in Danish kroner at 1999 prices, and mean and incremental......STUDY OBJECTIVES: To evaluate the cost-effectiveness of inhaled fluticasone propionate (FP) in children aged 12 to 47 months with asthma symptoms. DESIGN: A retrospective economic analysis conducted from the perspective of the Danish health-care system, based on clinical data from a 12-week study...... cost-effectiveness ratios. RESULTS: FP, 200 microg/d, was significantly more effective than placebo treatment in terms of the proportion of exacerbation-free patients (73.7% vs 59.8%; p = 0.025) and patients experiencing a > or = 25% improvement in cough symptoms (57.9% vs 39.0%; p = 0.018). The costs...

  7. Single, 14-Day, and 13-Week Repeated Dose Toxicity Studies of Daily Oral Gelidium elegans Extract Administration to Rats.

    Science.gov (United States)

    Choi, Jia; Ryu, Su-Jung; Kim, Kui-Jin; Kim, Hyung-Min; Chung, Hee-Chul; Lee, Boo-Yong

    2018-01-20

    Gelidium elegans extract (GEE) is derived from a red alga from the Asia-Pacific region, which has antioxidant, anti-adipogenic, and anti-hyperglycemic effects. However, detailed studies of the toxicology of GEE have not been performed. We evaluated the single oral dose toxicity of GEE in male and female Sprague-Dawley (CD) rats. GEE did not cause deaths or have toxic effects at dosages of 5000 mg/kg/day, although compound-colored stools and diarrhea were observed in both sexes, which lasted 5000 mg/kg. We next evaluated the repeated oral dose toxicity of GEE in CD rats over 14 days and 13 weeks. GEE did not induce any significant toxicological changes in either sex at 2000 mg/kg/day. Repeated oral dose toxicity studies showed no adverse effects, in terms of clinical signs, mortality, body mass, food consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy, organ masses, or histopathology, at dosages of 500, 1000, or 2000 mg/kg/day. The no observed adverse effect level (NOAEL) for GEE is thus likely to be >2000 mg/kg/day, and no pathology was identified in potential target organs. Therefore, this study indicates that repeated oral dosing with GEE is safe in CD rats.

  8. Single, 14-Day, and 13-Week Repeated Dose Toxicity Studies of Daily Oral Gelidium elegans Extract Administration to Rats

    Directory of Open Access Journals (Sweden)

    Jia Choi

    2018-01-01

    Full Text Available Gelidium elegans extract (GEE is derived from a red alga from the Asia–Pacific region, which has antioxidant, anti-adipogenic, and anti-hyperglycemic effects. However, detailed studies of the toxicology of GEE have not been performed. We evaluated the single oral dose toxicity of GEE in male and female Sprague-Dawley (CD rats. GEE did not cause deaths or have toxic effects at dosages of 5000 mg/kg/day, although compound-colored stools and diarrhea were observed in both sexes, which lasted <2 days. Therefore, the LD50 of GEE is likely to be >5000 mg/kg. We next evaluated the repeated oral dose toxicity of GEE in CD rats over 14 days and 13 weeks. GEE did not induce any significant toxicological changes in either sex at 2000 mg/kg/day. Repeated oral dose toxicity studies showed no adverse effects, in terms of clinical signs, mortality, body mass, food consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy, organ masses, or histopathology, at dosages of 500, 1000, or 2000 mg/kg/day. The no observed adverse effect level (NOAEL for GEE is thus likely to be >2000 mg/kg/day, and no pathology was identified in potential target organs. Therefore, this study indicates that repeated oral dosing with GEE is safe in CD rats.

  9. Evaluating the potential of gold, silver, and silica nanoparticles to saturate mononuclear phagocytic system tissues under repeat dosing conditions.

    Science.gov (United States)

    Weaver, James L; Tobin, Grainne A; Ingle, Taylor; Bancos, Simona; Stevens, David; Rouse, Rodney; Howard, Kristina E; Goodwin, David; Knapton, Alan; Li, Xiaohong; Shea, Katherine; Stewart, Sharron; Xu, Lin; Goering, Peter L; Zhang, Qin; Howard, Paul C; Collins, Jessie; Khan, Saeed; Sung, Kidon; Tyner, Katherine M

    2017-07-17

    As nanoparticles (NPs) become more prevalent in the pharmaceutical industry, questions have arisen from both industry and regulatory stakeholders about the long term effects of these materials. This study was designed to evaluate whether gold (10 nm), silver (50 nm), or silica (10 nm) nanoparticles administered intravenously to mice for up to 8 weeks at doses known to be sub-toxic (non-toxic at single acute or repeat dosing levels) and clinically relevant could produce significant bioaccumulation in liver and spleen macrophages. Repeated dosing with gold, silver, and silica nanoparticles did not saturate bioaccumulation in liver or spleen macrophages. While no toxicity was observed with gold and silver nanoparticles throughout the 8 week experiment, some effects including histopathological and serum chemistry changes were observed with silica nanoparticles starting at week 3. No major changes in the splenocyte population were observed during the study for any of the nanoparticles tested. The clinical impact of these changes is unclear but suggests that the mononuclear phagocytic system is able to handle repeated doses of nanoparticles.

  10. Effect of repeated small-dose γ-ray irradiation on atopic dermatitis in NC/Nga mice

    International Nuclear Information System (INIS)

    Fang, Su-Ping; Muto, Yasuko; Tago, Fumitoshi; Simura, Noriko; Kojima, Shuji

    2006-01-01

    We previously showed that several small-dose 0.5 Gy whole-body γ-ray irradiation inhibits tumor growth in mice via elevation of the interferon (IFN)-γ/interleukin 4 (IL-4) ratio concomitantly with a decrease in the percentage of B cells. Here, we examined whether repeated small-dose (0.5 Gy, 10 times) γ-ray irradiation influences atopic dermatitis in an NC/Nga mouse model. It was found that repeated γ-ray irradiation increased total IgE in comparison with the disease-control group. Levels of IL-4 and IL-5 were increased versus the disease-control group, while IFN-γ was slightly decreased, resulting in a further decrease of the IFN-γ/IL-4 ratio compared with the disease-control group. These results indicate that repeated small-dose γ-ray irradiation may exacerbate atopic dermatitis. This may be because the irradiation induces not helper T lymphocyte 1 (Th1), but Th2 polarization in this atopic mouse model, i.e., the effects of small-dose irradiation may be different in conditions involving immune hypersensitivity and impaired immunity. (author)

  11. High-dose inhaled salbutamol has no acute effects on aerobic capacity or oxygen uptake kinetics in healthy trained men

    DEFF Research Database (Denmark)

    Elers, J; Mørkeberg, Jakob; Jansen, T

    2012-01-01

    enrolled nine healthy well-trained men in a randomized, blinded, placebo-controlled crossover study. Subjects were randomized to inhalation of 40 puffs of 0.2 mg salbutamol or two placebo tablets and performed an incremental test to exhaustion and three submaximal tests at 75% of peak power to determine...... oxygen uptake kinetics. During the incremental test, there were no effects of inhaled salbutamol on VO(2max) in absolute or relative terms, and no effect on peak power and lactate threshold. During the submaximal test, we found no effects on the time constant, time delay, the mean response time or O(2...

  12. Terbutaline: level the playing field for inhaled β2-agonists by introducing a dosing and urine threshold

    DEFF Research Database (Denmark)

    Jacobson, Glenn A; Hostrup, Morten

    2017-01-01

    Terbutaline, a short-acting β2-agonist similar to salbutamol, is widely used in Europe in the treatment of asthma and exercise-induced bronchoconstriction. Unlike salbutamol, terbutaline requires therapeutic use exemption (TUE) for therapeutic inhaled use in competitive sport. There is now compel...

  13. AGE-DEPENDENT INHALATION DOSE DUE TO EXPOSURE OF SHORT LIVED PROGENY OF RADON AND THORON FOR DIFFERENT AGE GROUPS IN JAMMU & KASHMIR, HIMALAYAS.

    Science.gov (United States)

    Sharma, Sumit; Kumar, Ajay; Mehra, Rohit

    2018-05-16

    Dosimetric approach is used in this study for the assessment of doses due to inhalation of short lived radon/thoron progeny to the inhabitants of Udhampur district of Jammu & Kashmir. This paper also presents the activity concentrations and unattached fraction of radon and thoron progeny. The observed annual concentration of attached and unattached 222Rn and 220Rn progeny has been found to vary from 8 to 32 and 0.09 to 14 Bq/m3, 0.75 to 3.16 and 0.01 to 1.13 Bq/m3, respectively. The inhalation doses from radon progeny to different body organs of different age groups have been calculated by using the age dependent biokinetic model. The attachment rate of 222Rn and indoor aerosol concentration of 222Rn and 220Rn have been estimated and their relation between them has also been studied. The dose conversion factor for mouth and nasal breathing to different exposure conditions has been obtained from Porstendorfer model.

  14. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... metered dose inhaler with a spacer [ PDF – 377 KB] Your browser does not support iframes Cómo usar ... inhalador de dosis fija con espaciador [PDF – 343 KB] Using a metered dose inhaler (inhaler in mouth) ...

  15. A method for determining an indicator of effective dose calculation due to inhalation of Radon and its progeny from in vivo measurements

    International Nuclear Information System (INIS)

    Estrada, Julio Jose da Silva

    1994-01-01

    Direct measurement of the absolved dose to lung tissue from inhalation of radon and its progeny is not possible and must be calculated using dosimetric models, taking into consideration the several parameters upon which the dose calculation depends. To asses the dose due to inhalation of radon and its progeny, it is necessary to estimate the cumulative exposure. Historically, this has been done using WLM values estimated with measurements of radon concentration in air. The radon concentration in air varies significantly, however, in space with time, and the exposed individual is also constantly moving around. This makes it almost impossible to obtain a precise estimate of an individual's inhalation exposure. This work describes a pilot study to calculate lung dose from the deposition of radon progeny, via estimates of cumulative exposure derived from in vivo measurements of 210 Pb, in subjects exposed to above-average radon and its progeny concentrations in their home environments. The measurements were performed in a whole body counter. With this technique, the exposed individuals become, in affect, their own samplers and dosimeters and the estimate of cumulative exposure is not affected by the variation of the atmospheric concentration of radon and its progeny in time and space. Forty individuals identified as living in homes with radon levels ranging from about 740 Bq/m 3 to 150.000 Bq/m 3 were measured. Also, additional 34 measurements were made on personnel from NYUMC/NIEM who live in a residential area surrounding the laboratory in which the levels of radon have been shown to be at below average values. To realize these measurements a methodology was developed to determine the subject's background, using a head phantom made with a cubic plastic container containing known amounts of potassium and calcium dissolved in four liters of water. The effective doses calculated from the in vivo measurements are compared to effective doses estimated, for the same

  16. A critical role of acute bronchoconstriction in the mortality associated with high-dose sarin inhalation: Effects of epinephrine and oxygen therapies

    Energy Technology Data Exchange (ETDEWEB)

    Gundavarapu, Sravanthi; Zhuang, Jianguo; Barrett, Edward G.; Xu, Fadi; Russell, Robert G.; Sopori, Mohan L., E-mail: msopori@lrri.org

    2014-01-15

    Sarin is an organophosphate nerve agent that is among the most lethal chemical toxins known to mankind. Because of its vaporization properties and ease and low cost of production, sarin is the nerve agent with a strong potential for use by terrorists and rouge nations. The primary route of sarin exposure is through inhalation and, depending on the dose, sarin leads to acute respiratory failure and death. The mechanism(s) of sarin-induced respiratory failure is poorly understood. Sarin irreversibly inhibits acetylcholine esterase, leading to excessive synaptic levels of acetylcholine and, we have previously shown that sarin causes marked ventilatory changes including weakened response to hypoxia. We now show that LD{sub 50} sarin inhalation causes severe bronchoconstriction in rats, leading to airway resistance, increased hypoxia-induced factor-1α, and severe lung epithelium injury. Transferring animals into 60% oxygen chambers after sarin exposure improved the survival from about 50% to 75% at 24 h; however, many animals died within hours after removal from the oxygen chambers. On the other hand, if LD{sub 50} sarin-exposed animals were administered the bronchodilator epinephrine, > 90% of the animals survived. Moreover, while both epinephrine and oxygen treatments moderated cardiorespiratory parameters, the proinflammatory cytokine surge, and elevated expression of hypoxia-induced factor-1α, only epinephrine consistently reduced the sarin-induced bronchoconstriction. These data suggest that severe bronchoconstriction is a critical factor in the mortality induced by LD{sub 50} sarin inhalation, and epinephrine may limit the ventilatory, inflammatory, and lethal effects of sarin. - Highlights: • Inhalation exposure of rats to LD{sub 50} sarin causes death through respiratory failure. • Severe bronchoconstriction is the major cause of sarin-induced respiratory failure. • Transfer of sarin exposed rats to 60% oxygen improves the mortality temporarily.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Balaji Ramachandran

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

  19. Estimation of breast doses and breast cancer risk associated with repeated fluoroscopic chest examinations of women with tuberculosis

    International Nuclear Information System (INIS)

    Boice, J.D. Jr.; Rosenstein, M.; Trout, E.D.

    1978-01-01

    A methodology is presented to estimate cumulative breast dose and breast cancer risk for women exposed to repeated fluoroscopic chest examinations during air collapse therapy for pulmonary tuberculosis. Medical record abstraction, physician interview, patient contact, machine exposure measurements, and absorbed dose computations were combined to estimate average breast doses for 1047 Massachusetts women who were treated between 1930 and 1954. The methodology presented considers breast size and composition, patient orientation, x-ray field size and location, beam quality, type of examination, machine exposure rate, and exposure time during fluoroscopic examinations. The best estimate for the risk of radiation-induced cancer for the women living longer than 10 years after initial fluoroscopic exposure is 6.2 excess breast cancers per million woman-year-rad with 90% confidence limits of 2.8 and 10.7 cancers/10 6 WY-rad. When breast cancer risk is considered as a function of absorbed dose in the breast, instead of as a function of the number of fluoroscopic examinations, a linear dose--response relationship over the range of estimated doses is consistent with the data. However, because of the uncertainty due to small-sample variability and because of the wide range of assumptions regarding certain fluoroscopy conditions, other dose--response relationships are compatible with the data

  20. Comparison of the bronchodilatation produced by inhalation of ipratropium bromide and salbutamol sequentially and in fixed dose combination in stable bronchial asthma patients

    Directory of Open Access Journals (Sweden)

    Mohan A

    2006-01-01

    Full Text Available Objectives : The combination of a 43-2 agonist and an anticholinergic agent is of-ten used to manage bronchial asthma. However, it is unclear whether these drugs should be given separately in sequence or in a fixed dose combination for maximum effect. Methods : 27 patients with stable bronchial asthma were given the above two drugs in two separate sessions one week apart. In one session they were given the above two drugs as a fixed dose combination and in the other session, they were given se-quentially with salbutamol following ipratropium after 30 minutes. Spirometry was performed at baseline and 15, 30 and 60 minutes after inhaling the second drug. Results : Both groups showed significant improvement in forced vital capacity (FVC, forced expiratory time in one second (FEV 1 , peak expiratory flow rate (PEFR and forced expiratory flow (FEF 25-75 from baseline upto one hour. FVC increased initially and then stabilized; however, the increase was more sustained in the group getting combination treatment. This group also showed a higher rise in FEV 1 (p=0.02. Both FEV 1 and FEF 25-75 decreased after 30 minutes in the group that received sequential therapy. PEFR increased continuously till 60 minutes in both groups and there was no significant difference between them (p=0.98. Interpretation and Conclusion: Both methods of drug dosing produce equivalent bronchodilation. Fixed dose combinations produced a more sustained rise in FVC and higher increase in FEV 1 . Hence fixed dose combinations are more effective short-term bronchodilators and give an added advantage of reducing the number of inhalers required, thus improv-ing compliance.

  1. Late occurring lesions in the skin of rats after repeated doses of X-rays

    International Nuclear Information System (INIS)

    Hopewell, J.W.

    1985-01-01

    Late radiation damage, characterized by atrophy and necrosis in the skin and subcutaneous tissues, has been demonstrated in both the tail and feet of rats. The incidence of necrosis increased with total dose. These total doses, in the range 72-144 Gy, were given as 4-8 treatment of 18 Gy, each dose separated from the next by an interval of 28 days. This treatment protocol minimized acute epithelial skin reactions. The same regime applied to the skin on the back of rats resulted in a very severe acute reaction occurring after the second to fifth dose of 18 Gy. This was surprising since back skin, like tail skin, is less sensitive to large single doses of radiation than that of the foot. The late radiation reaction in the foot and tail of rats are compared and contrasted with other attempts to assess late effects in rodent skin and with late changes seen in pig skin. (author)

  2. Cognitive enhancement and antipsychotic-like activity following repeated dosing with the selective M4 PAM VU0467154.

    Science.gov (United States)

    Gould, Robert W; Grannan, Michael D; Gunter, Barak W; Ball, Jacob; Bubser, Michael; Bridges, Thomas M; Wess, Jurgen; Wood, Michael W; Brandon, Nicholas J; Duggan, Mark E; Niswender, Colleen M; Lindsley, Craig W; Conn, P Jeffrey; Jones, Carrie K

    2018-01-01

    Although selective activation of the M 1 muscarinic acetylcholine receptor (mAChR) subtype has been shown to improve cognitive function in animal models of neuropsychiatric disorders, recent evidence suggests that enhancing M 4 mAChR function can also improve memory performance. Positive allosteric modulators (PAMs) targeting the M 4 mAChR subtype have shown therapeutic potential for the treatment of multiple symptoms observed in schizophrenia, including positive and cognitive symptoms when assessed in acute preclinical dosing paradigms. Since the cholinergic system has been implicated in multiple stages of learning and memory, we evaluated the effects of repeated dosing with the highly selective M 4 PAM VU0467154 on either acquisition and/or consolidation of learning and memory when dosed alone or after pharmacologic challenge with the N-methyl-d-aspartate subtype of glutamate receptors (NMDAR) antagonist MK-801. MK-801 challenge represents a well-documented preclinical model of NMDAR hypofunction that is thought to underlie some of the positive and cognitive symptoms observed in schizophrenia. In wildtype mice, 10-day, once-daily dosing of VU0467154 either prior to, or immediately after daily testing enhanced the rate of learning in a touchscreen visual pairwise discrimination task; these effects were absent in M 4 mAChR knockout mice. Following a similar 10-day, once-daily dosing regimen of VU0467154, we also observed 1) improved acquisition of memory in a cue-mediated conditioned freezing paradigm, 2) attenuation of MK-801-induced disruptions in the acquisition of memory in a context-mediated conditioned freezing paradigm and 3) reversal of MK-801-induced hyperlocomotion. Comparable efficacy and plasma and brain concentrations of VU0467154 were observed after repeated dosing as those previously reported with an acute, single dose administration of this M 4 PAM. Together, these studies are the first to demonstrate that cognitive enhancing and antipsychotic

  3. Pharmacokinetic evaluation of pamidronate after oral administration: a study on dose proportionality, absolute bioavailability, and effect of repeated administration

    DEFF Research Database (Denmark)

    Hyldstrup, Lars; Flesch, G; Hauffe, S A

    1993-01-01

    30 minutes at constant infusion rate. Repeated peroral doses (75 and 150 mg) were administered to 12 females (aged 51-70 years) for 10 consecutive days. Urinary excretion of pamidronate after peroral and i.v. administration was used for estimation of pamidronate absorption. Renal excretion...... of pamidronate ranged from 0.01% to 0.35% of dose, with mean values of 0.11, 0.16, and 0.18% for 75, 150, and 300 mg, respectively. After i.v. infusion, the renal excretion of pamidronate was 26-53% of the dose, lower than for other bisphosphonates. The absolute bioavailability was 0.31% (range 0.08-0.7%) after...

  4. Contribution of time-activity pattern and microenvironment to black carbon (BC) inhalation exposure and potential internal dose among elementary school children

    Science.gov (United States)

    Jeong, Hyeran; Park, Donguk

    2017-09-01

    The aims of this study were to quantify the contributions of activities or microenvironments (MEs) to daily total exposure to and potential dose of black carbon (BC). Daily BC exposures (24-h) were monitored using a micro-aethalometer micoAeth AE51 with forty school-aged children living in an urban area in Korea from August 2015 to January 2016. The children's time-activity patterns and the MEs they visited were investigated by means of a time-activity diary (TAD) and follow-up interviews with the children and their parents. Potential inhaled dose was estimated by multiplying the airborne BC concentrations (μg/m3) we monitored for the time the children spent in a particular ME by the inhalation rate (IR, m3/h) for the time-activity performed. The contribution of activities and MEs to overall daily exposure to and potential dose of BC was quantified. Overall mean daily potential dose was equal to 24.1 ± 10.6 μg/day (range: 6.6-46.3 μg/day). The largest contribution to BC exposure and potential dose (51.9% and 41.7% respectively) occurred in the home thanks to the large amount of time spent there. Transportation was where children received the most intense exposure to (14.8%) and potential dose (20.2%) of BC, while it accounted for 7.6% of daily time. School on weekdays during the semester was responsible for 20.3% of exposure and 22.5% of potential dose. Contribution to BC exposure and potential dose was altered by several time-activity parameters, such as type of day (weekdays vs. weekends; school days vs. holidays), season, and gender. Traveling by motor vehicle and subway showed more elevated exposure or potential dose intensity on weekdays or school days, probably influenced by the increased surrounding traffic volumes on these days compared to on weekends or holidays. This study may be used to prioritize targets for minimizing children's exposure to BC and to indicate outcomes of BC control strategies.

  5. Deposition and transport of linezolid mediated by a synthetic surfactant Synsurf® within a pressurized metered dose inhaler: a Calu-3 model

    Science.gov (United States)

    van Rensburg, Lyné; van Zyl, Johann M; Smith, Johan

    2018-01-01

    Background Previous studies in our laboratory demonstrated that a synthetic peptide containing lung surfactant enhances the permeability of chemical compounds through bronchial epithelium. The purpose of this study was to test two formulations of Synsurf® combined with linezolid as respirable compounds using a pressurized metered dose inhaler (pMDI). Methods Aerosolization efficiency of the surfactant-drug microparticles onto Calu-3 monolayers as an air interface culture was analyzed using a Next Generation Impactor™. Results The delivered particles and drug dose showed a high dependency from the preparation that was aerosolized. Scanning electron microscopy imaging allowed for visualization of the deposited particles, establishing them as liposomal-type structures (diameter 500 nm to 2 μm) with filamentous features. Conclusion The different surfactant drug combinations allow for an evaluation of the significance of the experimental model system, as well as assessment of the formulations providing a possible noninvasive, site-specific, delivery model via pMDI.

  6. The determination of the inhalable fraction of 40K activity in marijuana (Cannabis sativa L. buds by instrumental neutron activation analysis and the effective dose to the body

    Directory of Open Access Journals (Sweden)

    Johann M.R. Antoine

    2017-07-01

    Full Text Available Total potassium in marijuana (Cannabis sativa L. buds was determined using instrumental neutron activation analysis. The mass fraction of 40K and its activity were derived using the natural isotopic ratios of potassium. The total potassium in the marijuana buds ranged from 0.84% to 3.15% with a mean mass fraction of 1.93%. The activity concentrations of 40K in the samples of marijuana ranged from 253 to 946 Bq kg−1 with a mean activity concentration of 581 Bq kg−1. The effective dose to the body from smoking marijuana is lower than that for comparable tobacco smoking. Simulated smoking experiments show that over 90% of 40K is retained in the cigarette ash. Accepted methods of determining effective dose to the body from 40K inhalation are likely overestimations for both marijuana and tobacco cigarette smoke.

  7. 40 CFR 799.9305 - TSCA Repeated dose 28-day oral toxicity study in rodents.

    Science.gov (United States)

    2010-07-01

    ... considered necessary. The limit test applies except when human exposure indicates the need for a higher dose..., stereotypies (e.g., excessive grooming, repetitive circling) or bizarre behaviour (e.g., self-mutilation...

  8. Granulometric determinations and inhalation dose assessment for atmospheric aerosol contaminated by {sup 137}Cs; Determinazioni granulometriche e valutazioni di dose da inalazione per aerosol atmosferico contaminato da {sup 137}CS

    Energy Technology Data Exchange (ETDEWEB)

    Castellani, C.M.; Luciani, A. [ENEA, Centro Ricerche `E. Clementel`, Bologna (Italy). Dip. Ambiente; Oliviero, L.; Donato, R. [ENEA, Centro Ricerche Saluggia, Vercelli (Italy). Dip. Ambiente

    1996-07-01

    During the redevelopment of Brescia freight-yard a measurement campaign of atmospheric aerosol was carried out: in fact a {sup 137}Cs ground contamination, caused by the permanence of wagons carrying iron materials contaminated by this radionuclide, had been found out. During the redevelopment phases of excavation and can filling the workers were exposed to the danger of radioactive aerosol inhalation. The aim of the measurement campaign was to test the aerosol sampling and granulometric analysis methodologies with their sensitivity related to the inhalation dose assessments. The results of both aerosuspended mass and activity, evaluated by means of a portable cascade impactor, are presented. The granulometries have been interpolated with a log normal distribution using an iterative routine minimizing the square deviation between the calculated and experimental data. The results related to the dose assessments are also presented. These evaluations have been carried out using both the granulometric information obtained and the more recent models (ICRP 66) both the total concentration data and the dose coefficients referring to the standard conditions of ICRP 68 and of the Italian law (D.Lgs. 230/95). Furthermore the significance and the reliability of the dose assessments referring to the different methodologies are discussed, also in relation to the possibility of using this sampling methodologies for other radionuclides and different exposure conditions.

  9. Repeated-dose toxicological studies of Tithonia diversifolia (Hemsl.) A. gray and identification of the toxic compounds.

    Science.gov (United States)

    Passoni, Flávia Donaire; Oliveira, Rejane Barbosa; Chagas-Paula, Daniela Aparecida; Gobbo-Neto, Leonardo; Da Costa, Fernando Batista

    2013-05-20

    Tithonia diversifolia (Hemsl.) A. Gray has been commonly used in folk medicine to treat abscesses, microbiological infections, snake bites, malaria and diabetes. Both anti-inflammatory and anti-malarial properties have been identified using appropriate assays, but the effective doses have demonstrated toxic effects for the experimental animals. Most of the pharmacological activities have been attributed to sesquiterpene lactones (STLs) and some chlorogenic acid derivatives (CAs) in the leaves of this species. This work aimed to evaluate the repeated-dose toxicity of an aqueous extract (AE) from Tithonia diversifolia leaves and to compare the results with an extract rich in STLs (LRE) and a polar extract (PE) without STLs but rich in CAs. The purpose of this work was to provide insights into the identity of the compounds responsible for the toxic effects of Tithonia diversifolia. The major classes of compounds were confirmed in each extract by IR spectra and HPLC-UV-DAD profiling using previously isolated or standard compounds. The toxicity of each extract was evaluated in a repeated-dose toxicity study in Wistar rats for 90 days. The AE is composed of both STLs and CAs, the LRE is rich in STLs, and the PE is rich in CAs. The AE caused alterations in haematological parameters but few alterations in biochemical parameters and was relatively safe at doses lower than 100mg/kg. However, the PE and LRE demonstrated several adverse effects by damaging the liver and kidneys, respectively. STLs and CAs can be toxic in prolonged use at higher doses in extracts prepared from Tithonia diversifolia by affecting the kidneys and liver. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  10. Bile Salt Homeostasis in Normal and Bsep Gene Knockout Rats with Single and Repeated Doses of Troglitazone.

    Science.gov (United States)

    Cheng, Yaofeng; Chen, Shenjue; Freeden, Chris; Chen, Weiqi; Zhang, Yueping; Abraham, Pamela; Nelson, David M; Humphreys, W Griffith; Gan, Jinping; Lai, Yurong

    2017-09-01

    The interference of bile acid secretion through bile salt export pump (BSEP) inhibition is one of the mechanisms for troglitazone (TGZ)-induced hepatotoxicity. Here, we investigated the impact of single or repeated oral doses of TGZ (200 mg/kg/day, 7 days) on bile acid homoeostasis in wild-type (WT) and Bsep knockout (KO) rats. Following oral doses, plasma exposures of TGZ were not different between WT and KO rats, and were similar on day 1 and day 7. However, plasma exposures of the major metabolite, troglitazone sulfate (TS), in KO rats were 7.6- and 9.3-fold lower than in WT on day 1 and day 7, respectively, due to increased TS biliary excretion. With Bsep KO, the mRNA levels of multidrug resistance-associated protein 2 (Mrp2), Mrp3, Mrp4, Mdr1, breast cancer resistance protein (Bcrp), sodium taurocholate cotransporting polypeptide, small heterodimer partner, and Sult2A1 were significantly altered in KO rats. Following seven daily TGZ treatments, Cyp7A1 was significantly increased in both WT and KO rats. In the vehicle groups, plasma exposures of individual bile acids demonstrated variable changes in KO rats as compared with WT. WT rats dosed with TGZ showed an increase of many bile acid species in plasma on day 1, suggesting the inhibition of Bsep. Conversely, these changes returned to base levels on day 7. In KO rats, alterations of most bile acids were observed after seven doses of TGZ. Collectively, bile acid homeostasis in rats was regulated through bile acid synthesis and transport in response to Bsep deficiency and TGZ inhibition. Additionally, our study is the first to demonstrate that repeated TGZ doses can upregulate Cyp7A1 in rats. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  11. Acute toxicity and the 28-day repeated dose study of a Siddha medicine Nuna Kadugu in rats

    Directory of Open Access Journals (Sweden)

    Ramaswamy Ramaswamy

    2012-10-01

    Full Text Available Abstract Background Nuna Kadugu (NK, a Siddha medicine prepared from leaves and fruits of Morinda Pubescens, used for the treatment of various skin diseases. Though NK has been widely used for several decades, no scientific report was available on its safety. Present study was undertaken to demonstrate the oral toxicity of NK in Sprague Dawley rats. Methods Acute and 28-day repeated oral toxicity studies were performed following OECD test guidelines 423 and 407, respectively, with minor modifications. In acute oral toxicity study, NK was administered at 2000mg/kg b.wt., p.o and animals were observed for toxic signs at 0, 0.5, 1, 4, 24 h and for next 14 days. Gross pathology was performed at the end of the study. In repeated dose, the 28- day oral toxicity study, NK was administered at 300, 600 and 900 mg/kg b.wt./p.o/day. Two satellite groups (control and high dose were also maintained to determine the delayed onset toxicity of NK. Animals were observed for mortality, morbidity, body weight changes, feed and water intake. Haematology, clinical biochemistry, electrolytes, gross pathology, relative organ weight and histopathological examination were performed. Results In acute toxicity study, no treatment related death or toxic signs were observed with NK administration. In the repeated dose study, no significant differences in body weight changes, food / water intake, haematology, clinical biochemistry and electrolytes content were observed between control and NK groups. No gross pathological findings and difference in relative organ weights were observed between control and NK treated rats. Histopathological examination revealed no abnormalities with NK treatment. Conclusion Acute study reveals that the LD50 of NK is greater than 2000mg/kg, b.wt. in fasted female rats and can be classified as Category 5. 28-day repeated oral toxicity demonstrates that the No Observed Adverse Effect Level of NK is greater than 900 mg/kg b.wt./day, p.o in rats

  12. Effect of different single-session educational modalities on improving medical students' ability to demonstrate proper pressurized metered dose inhaler technique.

    Science.gov (United States)

    Dominelli, Giulio S; Dominelli, Paolo B; Rathgeber, Steven L; Webster, Sheila B

    2012-05-01

    Pressurized metered dose inhalers (pMDIs) remain important therapeutic options for obstructive lung diseases. The ability to instruct and evaluate inhaler technique is a crucial skill that all medical professionals should possess; unfortunately, many professionals lack proficiency with pMDIs. We aimed to determine if brief education interventions of differing modalities can positively affect medical students' skills over the long term. The baseline ability of medical students and first year residents to use pMDIs was scored via a 10-point scoring system. Students were randomized to receive no education, one-on-one instruction, or video instruction. Students were then retested immediately after the education and at the 3-month mark for retention of acquired skills. Video, one-on-one and the placebo groups modalities statistically improved the average medical student's score in the immediate retesting (7.5 and 7.4 vs. 4.7, p grades at the immediate recall significantly improved for both modalities. During retention testing, only video education had a statistically significant improvement in pass rate over the control group, as defined by an average score of 7 or better (8 vs. 1, p improve medical students' ability to use pMDIs in short-term testing. However, only video education retained significant improvement compared with control after 3 months. This suggests that compared with traditional one-on-one teaching, video education is an effective means of teaching medical students how to improve their pMDI technique.

  13. Limiting values of radionuclide intake and air concentration and dose conversion factors for inhalation, submersion, and ingestion: Federal guidance report No. 11

    International Nuclear Information System (INIS)

    Eckerman, K.F.; Wolbarst, A.B.; Richardson, A.C.B.

    1988-09-01

    Radiation protection programs for workers are based, in the United States, on a hierarchy of limitations stemming from Federal guidance approved by the President. This guidance, which consists of principles, policies, and numerical primary guides, is used by Federal agencies as the basis for developing and implementing their own regulatory standards. The primary guides are usually expressed in terms of limiting doses to workers. The protection of workers against taking radioactive materials into the body, however, is accomplished largely through the use of regulations based on derived guides expressed in terms of quantities or concentrations of radionuclides. The values of these derived guides are chosen so as to assure that workers in work environments that conform to them are unlikely to receive radiation doses that exceed the primary guides. The purpose of the present report is to set forth derived guides that are consistent with current Federal radiation protection guidance. They are intended to serve as the basis for regulations setting upper bounds on the inhalation and ingestion of, and submersion in, radioactive materials in the workplace. The report also includes tables of exposure-to-dose conversion factors, for general use in assessing average individual committed doses in any population that is adequately characterized by Reference Man. 38 refs

  14. Limiting values of radionuclide intake and air concentration and dose conversion factors for inhalation, submersion, and ingestion: Federal guidance report No. 11

    Energy Technology Data Exchange (ETDEWEB)

    Eckerman, K.F.; Wolbarst, A.B.; Richardson, A.C.B.

    1988-09-01

    Radiation protection programs for workers are based, in the United States, on a hierarchy of limitations stemming from Federal guidance approved by the President. This guidance, which consists of principles, policies, and numerical primary guides, is used by Federal agencies as the basis for developing and implementing their own regulatory standards. The primary guides are usually expressed in terms of limiting doses to workers. The protection of workers against taking radioactive materials into the body, however, is accomplished largely through the use of regulations based on derived guides expressed in terms of quantities or concentrations of radionuclides. The values of these derived guides are chosen so as to assure that workers in work environments that conform to them are unlikely to receive radiation doses that exceed the primary guides. The purpose of the present report is to set forth derived guides that are consistent with current Federal radiation protection guidance. They are intended to serve as the basis for regulations setting upper bounds on the inhalation and ingestion of, and submersion in, radioactive materials in the workplace. The report also includes tables of exposure-to-dose conversion factors, for general use in assessing average individual committed doses in any population that is adequately characterized by Reference Man. 38 refs.

  15. Toxicity of inhaled alpha-emitting radionuclides - Status report

    Energy Technology Data Exchange (ETDEWEB)

    Muggenburg, B A; Mewhinney, J A; Guilmette, R A; Gillett, N A; Diel, J H; Lundgren, D L; Hahn, F F; Boecker, B B; McClellan, R O

    1988-12-01

    The toxicity of inhaled alpha-emitting radionuclides is being investigated in a series of interrelated dose-response studies. Dogs, rodents, and nonhuman primates have been exposed to monodisperse or polydisperse aerosols of the oxides of {sup 239}Pu, {sup 238}Pu, {sup 241}Am, or {sup 244}Cm to measure the relative importance of average organ dose, local dose around particles, specific activity, chemical form, particle size, and number of particles inhaled to the development of biological effects. The influence of animal species, age at exposure, and pre-existing lung disease, as well as the effects of repeated exposure, are also being studied, because they may influence the toxicity of these radionuclides. (author)

  16. A 4-Week Repeated-Dose Oral Toxicity Study of Bojungikgi-Tang in Crl:CD Sprague Dawley Rats

    Directory of Open Access Journals (Sweden)

    Sae-Rom Yoo

    2017-01-01

    Full Text Available Traditional herbal medicines have been used for centuries in Asian countries. However, recent studies have led to increasing concerns about the safety and toxicity of herbal prescriptions. Bojungikgi-tang (BJIGT, a herbal decoction, has been used in Korea to improve physical strength. To establish the safety information, BJIGT water extract was evaluated in a 4-week repeated-dose oral toxicity test in Crl:CD Sprague Dawley rats. BJIGT was orally administered in daily doses of 0, 500, 1000, and 2000 mg/kg/day for 4 weeks via oral gavage in male and female rats. We examined the mortality, clinical signs, body weight change, food intake, organ weights, hematology, serum biochemistry, and urinalysis parameters. No significant changes were observed in mortality, clinical sings, body weight, food intake, organ weights, hematology, serum biochemistry, and urinalysis parameters between the control group and the BJIGT-treated groups in the rats of both sexes. The results indicate that BJIGT did not induce toxic effects at a dose level up to 2000 mg/kg in rats. Thus, this concentration is considered the nonobservable effect dose in rats and is appropriate for a 13-week subchronic toxicity study.

  17. TPP-dendrimer nanocarriers for siRNA delivery to the pulmonary epithelium and their dry powder and metered-dose inhaler formulations.

    Science.gov (United States)

    Bielski, Elizabeth; Zhong, Qian; Mirza, Hamad; Brown, Matthew; Molla, Ashura; Carvajal, Teresa; da Rocha, Sandro R P

    2017-07-15

    The regulation of genes utilizing the RNA interference (RNAi) mechanism via the delivery of synthetic siRNA has great potential in the treatment of a variety of lung diseases. However, the delivery of siRNA to the lungs is challenging due to the poor bioavailability of siRNA when delivered intraveneously, and difficulty in formulating and maintaining the activity of free siRNA when delivered directly to the lungs using inhalation devices. The use of non-viral vectors such as cationic dendrimers can help enhance the stability of siRNA and its delivery to the cell cytosol. Therefore, in this work, we investigate the ability of a triphenylphosphonium (TPP) modified generation 4 poly(amidoamine) (PAMAM) dendrimer (G4NH 2 -TPP) to enhance the in vitro transfection efficiency of siRNA in a model of the pulmonary epithelium and their aerosol formulations in pressurized metered dose inhalers (pMDIs) and dry powder inhalers (DPIs). Complexes of siRNA and G4NH 2 -TPP were prepared with varying TPP densities and increasing N/P ratios. The complexation efficiency was modulated by the presence of the TPP on the dendrimer surface, allowing for a looser complexation compared to unmodified dendrimer as determined by gel electrophoresis and polyanion competition assay. An increase in TPP density and N/P ratio led to an increase in the in vitro gene knockdown of stably green fluorescent protein (eGFP) expressing lung alveolar epithelial (A549) cells. G4NH 2 -12TPP dendriplexes (G4NH 2 PAMAM dendrimers containing 12 TPP molecules on the surface complexed with siRNA) at N/P ratio 30 showed the highest in vitro gene knockdown efficiency. To assess the potential of TPP-dendriplexes for pulmonary use, we also developed micron particle technologies for both pMDIs and DPIs and determined their aerosol characteristics utilizing an Andersen Cascade Impactor (ACI). Mannitol microparticles encapsulating 12TPP-dendriplexes were shown to be effective in producing aerosols suitable for deep lung

  18. Evaluation of the repeated-dose liver micronucleus assay using 2,4-dinitrotoluene: a report of a collaborative study by CSGMT/JEMS.MMS.

    Science.gov (United States)

    Maeda, Akihisa; Tsuchiyama, Hiromi; Asaoka, Yoshiji; Hirakata, Mikito; Miyoshi, Tomoya; Oshida, Keiyu; Miyamoto, Yohei

    2015-03-01

    The liver micronucleus assay using young adult rats has the potential to detect liver carcinogens by repeated dosing, and could be expected to be integrated into repeated-dose toxicity studies using a hepatocyte isolation method without the traditional in situ collagenase perfusion. In this study, to assess the performance of the repeated-dose liver micronucleus assay, 2,4-dinitrotoluene (DNT), which is a rodent liver carcinogen, was administered orally to male rats at doses of 50, 100 and 200 mg/kg/day once daily for 14 or 28 consecutive days, and the frequencies of micronucleated hepatocytes (MNHEPs) and micronucleated immature erythrocytes (MNIMEs) were examined. Significant increases in the MNHEPs were observed at 50 mg/kg/day or more in the 14-day treatment, and 50 and 100 mg/kg/day in the 28-day treatment. These increases were dependent on both the dose and the number of administrations, which indicates the possibility that the MNHEPs accumulate as a result of repeated dosing. In contrast, no increase in the MNIMEs was observed. In conclusion, the repeated-dose liver micronucleus assay using young adult rats is sufficiently sensitive to detect the genotoxicity of 2,4-DNT at a low dose.

  19. Higher lung deposition with Respimat® Soft Mist™ Inhaler than HFA-MDI in COPD patients with poor technique

    Directory of Open Access Journals (Sweden)

    Peter Brand

    2008-08-01

    Full Text Available Peter Brand1, Bettina Hederer2, George Austen3, Helen Dewberry3, Thomas Meyer41RWTH, Aachen, Germany; 2Boehringer Ingelheim, Ingelheim, Germany; 3Boehringer Ingelheim, Bracknell, UK; 4Inamed Research, Gauting, GermanyAbstract: Aerosols delivered by Respimat® Soft Mist™ Inhaler (SMI are slower-moving and longer-lasting than those from pressurized metered-dose inhalers (pMDIs, improving the efficiency of pulmonary drug delivery to patients. In this four-way cross-over study, adults with chronic obstructive pulmonary disease (COPD and with poor pMDI technique received radiolabelled Berodual® (fenoterol hydrobromide 50 µg/ipratropium bromide 20 µg via Respimat® SMI or hydrofluoroalkane (HFA-MDI (randomized order on test days 1 and 2, with no inhaler technique training. The procedure was repeated on test days 3 and 4 after training. Deposition was measured by gamma scintigraphy. All 13 patients entered (9 males, mean age 62 years; FEV1 46% of predicted inhaled too fast at screening (peak inspiratory flow rate [IF]: 69–161 L/min. Whole lung deposition was higher with Respimat® SMI than with pMDI for untrained (37% of delivered dose vs 21% of metered dose and trained patients (53% of delivered vs 21% of metered dose (pSign-Test = 0.15; pANOVA< 0.05. Training also improved inhalation profiles (slower average and peak IF as well as longer breath-hold time. Drug delivery to the lungs with Respimat® SMI is more efficient than with pMDI, even with poor inhaler technique. Teaching patients to hold their breath as well as to inhale slowly and deeply increased further lung deposition using Respimat® SMI.Keywords: chronic obstructive pulmonary disease, drug delivery, inhalation, metered-dose inhaler, poor inhalation technique, training

  20. The ToxBank Data Warehouse: Supporting the Replacement of In Vivo Repeated Dose Systemic Toxicity Testing.

    Science.gov (United States)

    Kohonen, Pekka; Benfenati, Emilio; Bower, David; Ceder, Rebecca; Crump, Michael; Cross, Kevin; Grafström, Roland C; Healy, Lyn; Helma, Christoph; Jeliazkova, Nina; Jeliazkov, Vedrin; Maggioni, Silvia; Miller, Scott; Myatt, Glenn; Rautenberg, Michael; Stacey, Glyn; Willighagen, Egon; Wiseman, Jeff; Hardy, Barry

    2013-01-01

    The aim of the SEURAT-1 (Safety Evaluation Ultimately Replacing Animal Testing-1) research cluster, comprised of seven EU FP7 Health projects co-financed by Cosmetics Europe, is to generate a proof-of-concept to show how the latest technologies, systems toxicology and toxicogenomics can be combined to deliver a test replacement for repeated dose systemic toxicity testing on animals. The SEURAT-1 strategy is to adopt a mode-of-action framework to describe repeated dose toxicity, combining in vitro and in silico methods to derive predictions of in vivo toxicity responses. ToxBank is the cross-cluster infrastructure project whose activities include the development of a data warehouse to provide a web-accessible shared repository of research data and protocols, a physical compounds repository, reference or "gold compounds" for use across the cluster (available via wiki.toxbank.net), and a reference resource for biomaterials. Core technologies used in the data warehouse include the ISA-Tab universal data exchange format, REpresentational State Transfer (REST) web services, the W3C Resource Description Framework (RDF) and the OpenTox standards. We describe the design of the data warehouse based on cluster requirements, the implementation based on open standards, and finally the underlying concepts and initial results of a data analysis utilizing public data related to the gold compounds. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Age dependent systemic exposure to inhaled salbutamol

    DEFF Research Database (Denmark)

    Bønnelykke, Klaus; Jespersen, Jakob Jessing; Bisgaard, Hans

    2007-01-01

    AIMS: To determine the effect of age on systemic exposure to inhaled salbutamol in children. METHODS: Fifty-eight asthmatic children, aged 3-16 years, inhaled 400 microg of salbutamol from a pressurized metered dose inhaler with spacer. The 20 min serum profile was analyzed. RESULTS: Prescribing...

  2. A flow-cytometric NK-cytotoxicity assay adapted for use in rat repeated dose toxicity studies

    International Nuclear Information System (INIS)

    Marcusson-Staahl, Maritha; Cederbrant, Karin

    2003-01-01

    A recent regulatory document for immunotoxicity testing of new pharmaceutical drugs includes cytotoxic natural killer (NK)-cell function as a required parameter in repeated dose toxicity studies. The classical 51 Cr-release assay is the conventional test for cytotoxicity testing but several drawbacks with this assay has increased the demand for new reliable test systems. Here, we describe the optimisation of a flow-cytometric cytotoxicity assay especially adapted for regulatory rat studies in drug development. The test principle is based on target cell labelling with 5-(6)-carboxy-fluorescein succinimidyl ester (CFSE) and subsequent DNA-labelling with propidium iodide (PI) for identification of target cells with compromised cell membranes. The results are expressed as percentage of dead targets on a cell-to-cell basis. The final format of the assay includes 0.5 ml peripheral blood, 1.25x10 5 effector cells per sample, and collection of 500 target events by flow-cytometry. When NKR-P1+ cells were removed from the effector cell population by magnetic depletion the relative proportion decreased from 6 to 0.08%. The corresponding cytotoxic activity decreased from 68 to 8%. Also, the cytotoxic activity showed a significant and positive correlation with the proportion of NK-cells present in the effector cell suspension. Thus, the cytotoxicity measured is almost exclusively exerted by NK-cells. The current flow-cytometric test benefits from using peripheral blood as a source for effector cells since it will not conflict with the use of spleen for histopathological investigations in repeated dose toxicity studies. Additionally, since only a minimal number of effector cells are required per sample repeated testing of the same animal is enabled

  3. [The effect of the inhalation of a single atrovent dose on pulmonary ventilation function and respiratory mechanics in patients with chronic obstructive bronchitis].

    Science.gov (United States)

    Tetenev, F F; Cherniavskaia, G M

    1989-01-01

    A study was made of the action of inhalation of a single atrovent dose in 20 patients with chronic obstructive bronchitis. All the patients demonstrated a considerable abatement or disappearance of dyspnea, and a reduction of the number of dry rales. The vital capacity of the lungs, the volume of forced expiration, maximal pulmonary ventilation, MOCmax, MOC50, and MOC75 substantially increased. The respiratory work diminished on the average by 32.3% primarily due to the lessening of non-elastic lung resistance. The rise of pulmonary static extensibility and reduction of pulmonary elastic propulsion were recorded. In patients with and without clinical signs of bronchospasm, the action of atrovent was identical.

  4. How to use an inhaler - no spacer

    Science.gov (United States)

    ... MDI) administration - no spacer; Bronchial nebulizer; Wheezing - nebulizer; Reactive airway - nebulizer; COPD - ... 66. National Asthma Education and Prevention Program website. How to use a metered-dose inhaler. ...

  5. A long-acting integrase inhibitor protects female macaques from repeated high-dose intravaginal SHIV challenge.

    Science.gov (United States)

    Andrews, Chasity D; Yueh, Yun Lan; Spreen, William R; St Bernard, Leslie; Boente-Carrera, Mar; Rodriguez, Kristina; Gettie, Agegnehu; Russell-Lodrigue, Kasi; Blanchard, James; Ford, Susan; Mohri, Hiroshi; Cheng-Mayer, Cecilia; Hong, Zhi; Ho, David D; Markowitz, Martin

    2015-01-14

    Long-acting GSK1265744 (GSK744 LA) is a strand transfer inhibitor of the HIV/SIV (simian immunodeficiency virus) integrase and was shown to be an effective preexposure prophylaxis (PrEP) agent in a low-dose intrarectal SHIV (simian-human immunodeficiency virus) rhesus macaque challenge model. We examined the pharmacokinetics and efficacy of GSK744 LA as PrEP against repeat high-dose intravaginal SHIV challenge in female rhesus macaques treated with Depo-Provera (depot medroxyprogesterone acetate), which promotes viral transmission vaginally. When Depo-Provera-treated female rhesus macaques were dosed with GSK744 LA (50 mg/kg) monthly, systemic and tissue drug concentrations were lower than previously observed in male rhesus macaques. GSK744 concentrations were fivefold lower on average in cervical tissues than in rectal tissues. Eight female rhesus macaques were treated with GSK744 LA at week 0, and four female rhesus macaques served as controls. All animals received a high-dose challenge of SHIV162P3 at week 1. No infection was detected in GSK744 LA-treated rhesus macaques, whereas viremia was detected 1 to 2 weeks after SHIV challenge in all control animals. The GSK744 LA-treated rhesus macaques were given a second administration of drug at week 4 and further challenged at weeks 5 and 7. GSK744 LA treatment protected six of eight female rhesus macaques against three high-dose SHIV challenges, whereas all control animals became infected after the first challenge (P = 0.0003, log-rank test). These results support further clinical development of GSK744 LA for PrEP. Copyright © 2015, American Association for the Advancement of Science.

  6. Electrostatic Properties of Particles for Inhalation

    OpenAIRE

    Rowland, Martin

    2015-01-01

    Dry powder inhalers (DPIs) and pressurised metered dose inhalers (pMDIs) aredevices used to deliver therapeutic agents to the lungs. Typically, inhaled activepharmaceutical ingredients (APIs) are electrically resistive materials and are prone toaccumulating electrostatic charge. The build-up of charge on inhaled therapeutics hastraditionally been viewed as a nuisance as it may result in problems such as weighingerrors, agglomeration, adhesion to surfaces and poor flow. Energetic processing st...

  7. INREM II: a computer implementation of recent models for estimating the dose equivalent to organs of man from an inhaled or ingested radionuclide

    International Nuclear Information System (INIS)

    Killough, G.G.; Dunning, D.E. Jr.; Pleasant, J.C.

    1978-01-01

    This report describes a computer code, INREM II, which calculates the internal radiation dose equivalent to organs of man which results from the intake of a radionuclide by inhalation or ingestion. Deposition and removal of radioactivity from the respiratory tract is represented by the ICRP Task Group Lung Model. A four-segment catenary model of the GI tract is used to estimate movement of radioactive material that is ingested or swallowed after being cleared from the respiratory tract. Retention of radioactivity in other organs is specified by linear combinations of decaying exponential functions. The formation and decay of radioactive daughters is treated explicitly, with each radionuclide species in the chain having its own uptake and retention parameters, as supplied by the user. The dose equivalent to a target organ is computed as the sum of contributions from each source organ in which radioactivity is assumed to be situated. This calculation utilizes a matrix of S-factors (rem/μCi-day) supplied by the user for the particular choice of source and target organs. Output permits the evaluation of crossfire components of dose when penetrating radiations are present. INREM II is coded in FORTRAN IV and has been compiled and executed on an IBM-360 computer

  8. Comparison of distribution and toxicity following repeated oral dosing of different vanadium oxide nanoparticles in mice

    Energy Technology Data Exchange (ETDEWEB)

    Park, Eun-Jung, E-mail: pejtoxic@hanmail.net [Myunggok Eye Research Institute, Konyang University, Daejeon 302-718 (Korea, Republic of); Lee, Gwang-Hee [School of Civil, Environmental, and Architectural Engineering, Korea University, Seoul 136-713 (Korea, Republic of); Yoon, Cheolho [Seoul Center, Korea Basic Science Institute, Seoul 126-16 (Korea, Republic of); Kim, Dong-Wan, E-mail: dwkim1@korea.ac.kr [School of Civil, Environmental, and Architectural Engineering, Korea University, Seoul 136-713 (Korea, Republic of)

    2016-10-15

    Vanadium is an important ultra-trace element derived from fuel product combustion. With the development of nanotechnology, vanadium oxide nanoparticles (VO NPs) have been considered for application in various fields, thus the possibility of release into the environment and human exposure is also increasing. Considering that verification of bioaccumulation and relevant biological responses are essential for safe application of products, in this study, we aimed to identify the physicochemical properties that determine their health effects by comparing the biological effects and tissue distribution of different types of VO NPs in mice. For this, we prepared five types of VO NPs, commercial (C)-VO{sub 2} and -V{sub 2}O{sub 5} NPs and synthetic (S)-VO{sub 2}, -V{sub 2}O{sub 3,} and -V{sub 2}O{sub 5} NPs. While the hydrodynamic diameter of the two types of C-VO NPs was irregular and impossible to measure, those of the three types of S-VO NPs was in the range of 125–170 nm. The S- and C-V{sub 2}O{sub 5} NPs showed higher dissolution rates compared to other VO NPs. We orally dosed the five types of VO NPs (70 and 210 μg/mouse, approximately 2 and 6 mg/kg) to mice for 28 days and compared their biodistribution and toxic effects. We found that S-V{sub 2}O{sub 5} and S-V{sub 2}O{sub 3} NPs more accumulated in tissues compared to other three types of VO NPs, and the accumulated level was in order of heart>liver>kidney>spleen. Additionally, tissue levels of redox reaction-related elements and electrolytes (Na{sup +}, K{sup +}, and Ca{sup 2+}) were most clearly altered in the heart of treated mice. Notably, all S- and C-VO NPs decreased the number of WBCs at the higher dose, while total protein and albumin levels were reduced at the higher dose of S-V{sub 2}O{sub 5} and S-V{sub 2}O{sub 3} NPs. Taken together, we conclude that the biodistribution and toxic effects of VO NPs depend on their dissolution rates and size (surface area). Additionally, we suggest that further studies

  9. Clinical evaluation of the hypoxic cytotoxin tirapazamine (SR-4233): phase I experience with repeated dose administration during fractionated irradiation

    International Nuclear Information System (INIS)

    Hancock, Steven L.; Spencer, Sharon; Mariscal, Carol; Wooten, Ann; Wheeler, Richard; Brown, J. Martin; Fisher, Cheryl; Roemeling, Reinhard von

    1996-01-01

    Purpose: Regions of chronic or transient hypoxia are common in many human tumors and are thought to limit tumor cell killing and tumor control with conventional irradiation and some chemotherapeutic agents. Tirapazamine (3-amino-1,2,4-benzotriazine-1,4-di-N-oxide) forms a cytotoxic free radical during reductive metabolism in regions of hypoxia. In well oxygenated regions, the tirapazamine radical reacts with molecular oxygen to form the inactive parent drug. This results in markedly greater toxicity for hypoxic cells than for the well oxygenated cells that comprise most normal tissues. Tirapazamine increased the anti-tumor effects of single dose or fractionated irradiation or cis-platin chemotherapy in murine tumors,in vivo . This study evaluated the ability to repeat the administration of Tirapazamine during courses of fractionated irradiation in humans after an earlier phase I trial established a maximum tolerated dose of 390 mg per square meter of body surface area (mg/m 2 ) when given as a single dose with radiotherapy. Materials and Methods: Between December 1993 and August 1995 22 patients with locally advanced or metastatic tumors of varying histology, normal renal, hepatic, and hematologic functions, and Karnofsky performance status ≥ 60 received repeated doses of Tirapazamine during a planned, 6 weeks course of standardly fractionated radiotherapy. After anti-emetic treatment with ondansetron (32 mg) and dexamethasone (16 mg), Tirapazamine was administered during a 2 hour intravenous infusion that ended from 30 to 90 minutes before a radiation treatment. Patients were monitored for acute toxicity during the course of treatment and for a minimum of one month after radiotherapy. Results: The study was initiated with three, biweekly doses of Tirapazamine at 330 mg/m 2 . Four of 7 patients who initiated treatment at this dose refused the second (1 patient) or third dose of Tirapazamine (3 patients). Two of the three patients who received three doses

  10. Chronic cigarette smoke exposure increases the pulmonary retention and radiation dose of 239Pu inhaled as 239PuO2 by F344 rats

    International Nuclear Information System (INIS)

    Finch, G.L.; Lundgren, D.L.; Barr, E.B.; Chen, B.T.; Griffith, W.C.; Hobbs, C.H.; Hoover, M.D.; Nikula, K.J.; Mauderly, J.L.

    1998-01-01

    As a portion of a study to examine how chronic cigarette smoke exposure might alter the risk of lung tumors from inhaled 239 PuO 2 in rats, the effects of smoke exposure on alpha-particle lung dosimetry over the life-span of exposed rats were determined. Male and female rats were exposed to inhaled 239 PuO 2 alone or in combination with cigarette smoke. Animals exposed to filtered air along served as controls for the smoke exposure. Whole-body exposure to mainstream smoke diluted to concentrations of either 100 or 250 mg total particulate matter m -3 began at 6 wk of age and continued for 6 h d -1 , 5 d wk -1 , for 30 mo. A single, pernasal, acute exposure to 239 PuO 2 was given to all rats at 12 wk of age. Exposure to cigarette smoke caused decreased body weight gains in a concentration dependent manner. Lung-to-body weight ratios were increased in smoke-exposed rats. Rats exposed to cigarette smoke before the 239 PuO 2 exposure deposited less 239 Pu in the lung than did controls. Except for male rats exposed to LCS, exposure to smoke retarded the clearance of 239 Pu from the lung compared to control rats through study termination at 870 d after 239 PuO 2 exposure. Radiation doses to lungs were calculated by sex and by exposure group for rats on study for at least 360 d using modeled body weight changes, lung-to-body weight ratios, and standard dosimetric calculations. For both sexes, estimated lifetime radiation doses from the time of 239 PuO 2 exposure to death were 3.8 Gy, 4.4 Gy, or 6.7 Gy for the control, LCS, or HCS exposure groups, respectively. Assuming an approximately linear dose-response relationship between radiation dose and lung neoplasm incidence, approximate increases of 20% or 80% in tumor incidence over controls would be expected in rats exposed to 239 PuO 2 and LCS or 239 PuO 2 and HCS, respectively

  11. Pharmacokinetics of repeated oral doses of amlodipine and amlodipine plus telmisartan in healthy volunteers.

    Science.gov (United States)

    Stangier, J; Su, C A

    2000-12-01

    This open-label, crossover study was performed to establish if there is evidence for interaction between telmisartan, an angiotensin II antagonist, and amlodipine, a class II (dihydropyridine) calcium channel antagonist, on the basis of pharmacokinetics and safety. In a two-way crossover trial, 12 healthy Caucasian males were randomized to receive once daily for 9 days oral amlodipine 10 mg with or without oral telmisartan 120 mg. After a washout period of > or = 13 days, the subjects were switched to the other medication regimen. The geometric means of the primary pharmacokinetic parameters at steady state (day 9) for amlodipine when given alone were the following: maximum plasma concentration (Cmax) 17.7 ng/mL, area under the plasma concentration-time curve (AUC) 331 ng.h/mL, and renal clearance 39.5 mL/min, with 8% of the total amlodipine dose being excreted. When concomitant telmisartan was given, the respective values were 18.7 ng/mL, 352 ng.h/mL, and 43.0 mL/min, with 9.4% of the total amlodipine dose being excreted renally. The limits of the 90% confidence intervals (CIs) for the ratios of these steady-state parameters were 0.97 to 1.14 for Cmax and 0.98 to 1.16 for AUC; both were within the predefined reference range (0.8 to 1.25) for bioequivalence. The high intersubject variability in urinary amlodipine excretion resulted in bioequivalence not being demonstrated for renal clearance. Adverse effects were few, mild to moderate in intensity, and transient whether amlodipine was given alone or with telmisartan. Vital signs, except for blood pressure, and clinical laboratory values were unaffected by either medication. The findings of this study show that concomitant telmisartan and amlodipine may be administered as there is no clinically significant variation in primary pharmacokinetic parameters of amlodipine in the presence of telmisartan, and the safety of the combination is comparable to that of amlodipine alone.

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

    Directory of Open Access Journals (Sweden)

    M. D. Jegoda

    2013-06-01

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

  13. Estimation of inhalation flow profile using audio-based methods to assess inhaler medication adherence

    Science.gov (United States)

    Lacalle Muls, Helena; Costello, Richard W.; Reilly, Richard B.

    2018-01-01

    Asthma and chronic obstructive pulmonary disease (COPD) patients are required to inhale forcefully and deeply to receive medication when using a dry powder inhaler (DPI). There is a clinical need to objectively monitor the inhalation flow profile of DPIs in order to remotely monitor patient inhalation technique. Audio-based methods have been previously employed to accurately estimate flow parameters such as the peak inspiratory flow rate of inhalations, however, these methods required multiple calibration inhalation audio recordings. In this study, an audio-based method is presented that accurately estimates inhalation flow profile using only one calibration inhalation audio recording. Twenty healthy participants were asked to perform 15 inhalations through a placebo Ellipta™ DPI at a range of inspiratory flow rates. Inhalation flow signals were recorded using a pneumotachograph spirometer while inhalation audio signals were recorded simultaneously using the Inhaler Compliance Assessment device attached to the inhaler. The acoustic (amplitude) envelope was estimated from each inhalation audio signal. Using only one recording, linear and power law regression models were employed to determine which model best described the relationship between the inhalation acoustic envelope and flow signal. Each model was then employed to estimate the flow signals of the remaining 14 inhalation audio recordings. This process repeated until each of the 15 recordings were employed to calibrate single models while testing on the remaining 14 recordings. It was observed that power law models generated the highest average flow estimation accuracy across all participants (90.89±0.9% for power law models and 76.63±2.38% for linear models). The method also generated sufficient accuracy in estimating inhalation parameters such as peak inspiratory flow rate and inspiratory capacity within the presence of noise. Estimating inhaler inhalation flow profiles using audio based methods may be

  14. Mapping local cerebral blood flow by means of computerized tomography with a short inhalation of low-dose stable xenon

    International Nuclear Information System (INIS)

    Nakagawara, Jyoji; Karasawa, Jun; Tasawa, Toshiaki; Touho, Hajime; Nakauchi, Mikio; Kagawa, Masa-aki; Asai, Masa-aki; Kuriyama, Yoshihiro; Kikuchi, Haruhiko.

    1986-01-01

    A non-invasive technique has been developed for mapping the local blood-brain partition coefficient (λi), the local build-up rate constant (κi), and the local cerebral blood flow (l-CBF) by means of xenon-enhanced computerized tomography (CT) using a YMS CT 9000 scanner. After denitrogenation for 10 minutes, a 30 % xenon/oxygen mixture is inhaled for 4 - 8 minutes through a rubber face-mask and a delivery system of stable xenon. The time course of local cerebral CT enhancement is utilized in order to calculate, the λi, κi, and l-CBF values. The CT enhancement data during the washin-washout phase are fitted to the mathematical functions, based on Kety's formula, using least-squares curve-fitting analysis. Several case studies of patients with cerebral vascular accidents are presented to demonstrate the characterization of the λi and l-CBF patterns in various tissues; the results are of sufficient quality for the management of patients. The theoretical assumptions underlying stable xenon CT CBF measurements are discussed. (author)

  15. Screening of repeated dose toxicity data present in SCC(NF)P/SCCS safety evaluations of cosmetic ingredients.

    Science.gov (United States)

    Vinken, Mathieu; Pauwels, Marleen; Ates, Gamze; Vivier, Manon; Vanhaecke, Tamara; Rogiers, Vera

    2012-03-01

    Alternative methods, replacing animal testing, are urgently needed in view of the European regulatory changes in the field of cosmetic products and their ingredients. In this context, a joint research initiative called SEURAT was recently raised by the European Commission and COLIPA, representing the European cosmetics industry, with the overall goal of developing an animal-free repeated dose toxicity testing strategy for human safety assessment purposes. Although cosmetic ingredients are usually harmless for the consumer, one of the initial tasks of this research consortium included the identification of organs that could potentially be affected by cosmetic ingredients upon systemic exposure. The strategy that was followed hereof is described in the present paper and relies on the systematic evaluation, by using a self-generated electronic databank, of published reports issued by the scientific committee of DG SANCO responsible for the safety of cosmetic ingredients. By screening of the repeated dose toxicity studies present in these reports, it was found that the liver is potentially the most frequently targeted organ by cosmetic ingredients when orally administered to experimental animals, followed by the kidney and the spleen. Combined listing of altered morphological, histopathological, and biochemical parameters subsequently indicated the possible occurrence of hepatotoxicity, including steatosis and cholestasis, triggered by a limited number of cosmetic compounds. These findings are not only of relevance for the in vitro modeling efforts and choice of compounds to be tested in the SEURAT project cluster, but also demonstrate the importance of using previously generated toxicological data through an electronic databank for addressing specific questions regarding the safety evaluation of cosmetic ingredients.

  16. Zinc oxide nanoparticles: a 90-day repeated-dose dermal toxicity study in rats

    Directory of Open Access Journals (Sweden)

    Ryu HJ

    2014-12-01

    was dose-dependent irritation at the site of application, there were no abnormal findings related to ZnO NPs in other organs. Increased concentrations of ZnO in the liver, small intestine, large intestine, and feces were thought to result from oral ingestion of ZnO NPs via licking. Penetration of ZnO NPs through the skin seemed to be limited via the dermal route. This study demonstrates that there was no observed adverse effect of ZnO NPs up to 1,000 mg/kg body weight when they are applied dermally. Keywords: zinc oxide, nanoparticles, subchronic toxicity, dermal exposure

  17. Treatment with budesonide/formoterol pressurized metered-dose inhaler in patients with asthma: a focus on patient-reported outcomes

    Directory of Open Access Journals (Sweden)

    Richard D O'Connor

    2011-01-01

    Full Text Available Richard D O'ConnorSharp Rees-Stealy Medical Group, San Diego, CA, USAAbstract: In the United States, budesonide/formoterol pressurized metered-dose inhaler (pMDI is approved for treatment of asthma in patients aged ≥12 years whose asthma is not adequately controlled with an inhaled corticosteroid (ICS or whose disease severity clearly warrants treatment with an ICS and a long-acting β2-adrenergic agonist. This article reviews studies of budesonide/formoterol pMDI in patients with persistent asthma, with a particular focus on patient-reported outcomes (eg, perceived onset of effect, patient satisfaction with treatment, health-related quality of life [HRQL], global assessments, sleep quality and quantity, as these measures reflect patient perceptions of asthma control and disease burden. A search of PubMed and respiratory meetings was performed to identify relevant studies. In two pivotal budesonide/formoterol pMDI studies in adolescents and adults, greater efficacy and similar tolerability were shown with budesonide/formoterol pMDI 160/9 µg and 320/9 µg twice daily versus its monocomponents or placebo. In those studies, improvements in HRQL, patient satisfaction, global assessments of asthma control, and quality of sleep also favored budesonide/formoterol pMDI compared with one or both of its monocomponents or placebo. Budesonide/formoterol pMDI has a rapid onset of effect (within 15 minutes that patients can feel, an attribute that may have benefits for treatment adherence. In summary, budesonide/formoterol pMDI is effective and well tolerated and has additional therapeutic benefits that may be important from the patient’s perspective.Keywords: budesonide, formoterol, patient-reported outcomes, efficacy, tolerability, onset of effect

  18. Biological characterization of radiation exposure and dose estimates for inhaled uranium milling effluents. Annual progress report April 1, 1982-March 31, 1983

    International Nuclear Information System (INIS)

    Eidson, A.F.

    1984-05-01

    The problems addressed are the protection of uranium mill workers from occupational exposure to uranium through routine bioassay programs and the assessment of accidental worker exposures. Comparisons of chemical properties and the biological behavior of refined uranium ore (yellowcake) are made to identify important properties that influence uranium distribution patterns among organs. These studies will facilitate calculations of organ doses for specific exposures and associated health risk estimates and will identify important bioassay procedures to improve evaluations of human exposures. A quantitative analytical method for yellowcake was developed based on the infrared absorption of ammonium diuranate and U 3 O 8 mixtures in KBr. The method was applied to yellowcake samples obtained from six operating mills. The composition of yellowcake from the six mills ranged from nearly pure ammonium diuranate to nearly pure U 3 O 8 . The composition of yellowcake samples taken from lots from the same mill was only somewhat less variable. Because uranium mill workers might be exposed to yellowcake either by contamination of a wound or by inhalation, a study of retention and translocation of uranium after subcutaneous implantation in rats was done. The results showed that 49% of the implanted yellowcake cleared from the body with a half-time (T sub 1/2) in the body of 0.3 days, and the remainder was cleared with a T sub 1/2 of 11 to 30 days. Exposures of Beagle dogs by nose-only inhalation to aerosols of commercial yellowcake were completed. Biochemical indicators of kidney dysfunction that appeared in blood and urine 4 to 8 days after exposure to the more soluble yellowcake showed significant changes in dogs, but levels returned to normal by 16 days after exposure. No biochemical evidence of kidney dysfunction was observed in dogs exposed to the less soluble yellowcake form. 18 figures, 9 tables

  19. Long-term dose-response studies of inhaled or injected radionuclides. Biennial report, 1 October 1991--30 September 1993

    Energy Technology Data Exchange (ETDEWEB)

    Boecker, B.B.; Muggenburg, B.A.; Miller, S.C.; Bradley, P.L. [eds.

    1994-01-01

    This report describes the scientific progress in, and current status of, life-span studies of the long-term health risks in Beagle dogs of chronic irradiation from internally deposited radionuclides or from an external source. The reporting period for this document is the 2-year period from October 1, 1991 through September 30, 1993. Studies that were initiated at three different laboratories (Inhalation Toxicology Research Institute, ITRI, University of Utah, and Argonne National Laboratory, ANL) are presented here because they are being completed at ITRI. All living dogs in the Utah-initiated studies were transferred to the ITRI facility for the remainder of their life-span observations and measurements in September 1987. This report is the fourth in a series of reports dealing with the current status and progress of both the Utah and ITRI studies. Other life-span studies involving dogs exposed to gamma radiation from an external source were initiated and conducted for many years at ANL. In 1991, the decision was made to discontinue the chronic irradiation of the remaining living dogs and to transfer all remaining dogs to ITRI for care, clinical observations, and pathological observations at death or euthanasia. This report provides the current status of these dogs. Status reports on the Utah and ITRI studies comprise most of this report. The ITRI-related section presents brief statements of project objectives, the general procedures used in these studies, and some study-specific features for each of the 19 studies being conducted with either beta- or alpha-emitting radionuclides. Dose- and effect-modifying factors being addressed in these studies include total dose, dose rate, LET, solubility, nonuniformity of dose, species, age, sex, health status, and mode of exposure. Recent additions to experimental protocols for studies in which dogs are still alive involve the collection and analysis of tumor tissues using currently available molecular biology techniques.

  20. Toxicity studies of inhaled beta-emitting radionuclides - Status report

    Energy Technology Data Exchange (ETDEWEB)

    Hahn, F F; Boeker, B B; Gillett, N A; Griffith, W C; Lundgren, D L; McClellan, R O; Muggenburg, B A; Snipes, M B

    1988-12-01

    The effects of beta-emitting radionuclides inhaled in either a relatively soluble form ({sup 90}SrCl{sub 2}, {sup 144}CeCl{sub 3}, {sup 91}yl{sub 3}, or {sup 137}CsCl) or in a relatively insoluble form ({sup 90}Y, {sup 91}Y, {sup 144}Ce or {sup 90}Sr in fused aluminosilicate particles [FAP]) have been studied in laboratory animals. The results showed that the total beta dose and the dose-rate pattern can modify both the neoplastic and non-neoplastic effects of inhaled beta-emitting radionuclides. In addition, the solubility and chemical characteristics of the radionuclides influence which organs are affected. Effects are seen primarily in organs where the radionuclide is ultimately accumulated, e.g., lung, bone, liver, or tracheobronchial lymph nodes. In addition, effects may be seen in organs where there is little accumulation, but where the radiation dose may still be high, e.g., nasal epithelium and heart. Studies of inhaled {sup 144}Ce-FAP in four different species showed that, compared to mice and dogs, lung tumor risk factors are very low for Syrian hamsters and high for rats. Studies of mice, Syrian hamsters, rats, and dogs repeatedly exposed to aerosols of {sup 144}Ce-FAP showed that lung tumor incidence correlates better with cumulative dose to the lung than with dose rate. Most of the studies in this program are nearing completion and full analyses are in progress. (author)

  1. Study of four weeks repeated-dose toxic test of Sweet Bee Venom in rats Original Articles

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    Kwon Hae-Yon

    2011-03-01

    Full Text Available Objectives: This study was performed to analyse four weeks repeated -dose toxicity of Sweet Bee Venom (SBV-pure melittin, the major component of honey bee venom in rats. Methods: All experiments were conducted under the regulations of Good Laboratory Practice (GLPat Biotoxtech Company, a non-clinical study authorized institution. Male and female rats of 5 weeks old were chosen for the pilot study of four weeks repeated-dose toxicity and was injected at the level of 0.56 mg/kg body weight (eighty times higher than the clinical application dosage as the high dosage, followed by 0.28 and 0.14 mg/kg as midium and low dosage, respectively. Equal amount of normal saline was injected as the control group every day for four weeks. Results: 1. No mortality was witnessed in all of the experiment groups. 2. All experiment groups appealed pain sense in the treating time compared to the control group, and side effects such as hyperemia and movement disorder were observed around the area of injection in all experiment groups, and the higher dosage in treatment, the higher occurrence in side effects. 3. Concerning weight measurement, neither male nor female groups showed significant changes compared to the control group. 4. Concerning to the CBC and biochemistry, all experiment groups didn't show any significant changes compared to the control group. 5. Concerning weight measurement of organs, experiment groups didn't show any significant changes compared to the control group. 6. To verify abnormalities of organs and tissues, those such as cerebellum, cerebrum, liver, lung, kidney,and spinal cords were removed and we conducted histologocal observation with H-E staining.Concerning the histologocal observation of liver tissues, some fatty changes were observed around portal vein in 0.56 mg/kg experiment group. But another organs were not detected in any abnormalities. 7. The proper high dosage of SBV for the thirteen weeks repeated test in rats may be 0.28 mg

  2. Motion-compensated PET image reconstruction with respiratory-matched attenuation correction using two low-dose inhale and exhale CT images

    International Nuclear Information System (INIS)

    Nam, Woo Hyun; Ahn, Il Jun; Ra, Jong Beom; Kim, Kyeong Min; Kim, Byung Il

    2013-01-01

    Positron emission tomography (PET) is widely used for diagnosis and follow up assessment of radiotherapy. However, thoracic and abdominal PET suffers from false staging and incorrect quantification of the radioactive uptake of lesion(s) due to respiratory motion. Furthermore, respiratory motion-induced mismatch between a computed tomography (CT) attenuation map and PET data often leads to significant artifacts in the reconstructed PET image. To solve these problems, we propose a unified framework for respiratory-matched attenuation correction and motion compensation of respiratory-gated PET. For the attenuation correction, the proposed algorithm manipulates a 4D CT image virtually generated from two low-dose inhale and exhale CT images, rather than a real 4D CT image which significantly increases the radiation burden on a patient. It also utilizes CT-driven motion fields for motion compensation. To realize the proposed algorithm, we propose an improved region-based approach for non-rigid registration between body CT images, and we suggest a selection scheme of 3D CT images that are respiratory-matched to each respiratory-gated sinogram. In this work, the proposed algorithm was evaluated qualitatively and quantitatively by using patient datasets including lung and/or liver lesion(s). Experimental results show that the method can provide much clearer organ boundaries and more accurate lesion information than existing algorithms by utilizing two low-dose CT images. (paper)

  3. The National Environmental Respiratory Center (NERC) experiment in multi-pollutant air quality health research: IV. Vascular effects of repeated inhalation exposure to a mixture of five inorganic gases.

    Science.gov (United States)

    Mauderly, J L; Kracko, D; Brower, J; Doyle-Eisele, M; McDonald, J D; Lund, A K; Seilkop, S K

    2014-09-01

    An experiment was conducted to test the hypothesis that a mixture of five inorganic gases could reproduce certain central vascular effects of repeated inhalation exposure of apolipoprotein E-deficient mice to diesel or gasoline engine exhaust. The hypothesis resulted from preceding multiple additive regression tree (MART) analysis of a composition-concentration-response database of mice exposed by inhalation to the exhausts and other complex mixtures. The five gases were the predictors most important to MART models best fitting the vascular responses. Mice on high-fat diet were exposed 6 h/d, 7 d/week for 50 d to clean air or a mixture containing 30.6 ppm CO, 20.5 ppm NO, 1.4 ppm NO₂, 0.5 ppm SO₂, and 2.0 ppm NH₃ in air. The gas concentrations were below the maxima in the preceding studies but in the range of those in exhaust exposure levels that caused significant effects. Five indicators of stress and pro-atherosclerotic responses were measured in aortic tissue. The exposure increased all five response indicators, with the magnitude of effect and statistical significance varying among the indicators and depending on inclusion or exclusion of an apparent outlying control. With the outlier excluded, three responses approximated predicted values and two fell below predictions. The results generally supported evidence that the five gases drove the effects of exhaust, and thus supported the potential of the MART approach for identifying putative causal components of complex mixtures.

  4. Inhaled plutonium nitrate in dogs

    International Nuclear Information System (INIS)

    Dagle, G.E.

    1987-01-01

    The major objective of this project is to determine dose-effect relationships of inhaled plutonium nitrate in dogs to aid in predicting health effects of accidental exposure in man. For lifespan dose-effect studies, beagle dogs were given a single inhalation exposure to 239 Pu(NO 3 ) 4 , in 1976 and 1977. The earliest biological effect was on the hematopoietic system; lymphopenia and neutropenia occurred at the two highest dose levels. They have also observed radiation pneumonitis, lung cancer, and bone cancer at the three highest dose levels. 1 figure, 3 tables

  5. Inhaled plutonium nitrate in dogs

    International Nuclear Information System (INIS)

    Dagle, G.E.

    1986-01-01

    The major objective of this project is to determine dose-effect relationships of inhaled plutonium nitrate in dogs to aid in predicting health effects of accidental exposure in man. For lifespan dose-effect studies, beagle dogs were given a single inhalation exposure to 239 Pu(NO 3 ) 4 , in 1976 and 1977. The earliest biological effect was on the hematopoietic system; lymphopenia and neutropenia occurred at the two highest dose levels. The authors have also observed radiation pneumonitis, lung cancer, and bone cancer at the three highest dose levels. 1 figure, 4 tables

  6. Inhaled plutonium nitrate in dogs

    International Nuclear Information System (INIS)

    Dagle, G.E.

    1982-01-01

    The major objective of this project is to determine dose-effect relationships of inhaled plutonium nitrate in dogs to aid in the prediction of health effects of accidental exposure in man. For lifespan dose-effect studies, beagle dogs were given a single inhalation exposure to 239 Pu(NO 3 ) 4 , in 1976 and 1977. The earliest biological effect was on the hematopoietic system; as described in previous Annual Reports, lymphopenia and neutropenia occurred at the two highest dose levels. Radiation pneumonitis, lung cancer, and bone cancer have been observed at the highest dose levels

  7. Biomarkers of Dose and Effect of inhaled ozone in resting versus exercising human subjects: comparison with resting rats

    Science.gov (United States)

    Background: Human controlled exposure studies have generally focused on subjects exposed to ozone (O3) while exercising while exposures in rats have been done at rest. We exposed resting subjects to labeled O3 (18O3, 0.4 ppm, for 2 hr) and compared O3 dose and effects with our...

  8. Dose calculations for infants and youths due to the inhalation of radon and its decay products in the normal environment

    International Nuclear Information System (INIS)

    Hofmann, W.; Steinhaeusler, F.

    1977-01-01

    Radon and its progenies in the atmosphere of normal working- and living-rooms contribute to parts of the respiratory tract the highest radiation load from all the natural radioactive environment. The base of todays calculations are the lung model of the ICRP-task groups and the physiological data of the ICRP-Reference Man. Both deal extensively with the problems associated with the adult but much less consideration is given to the physiological properties of the growing organism and the resulting radiation load. Functions for age dependent parameters, comprising geometrical dimensions of lung parts as well as respiratory standards were defined. With the use of a hybrid-computer the modifying influence of several parameters of the ICRP-lung model was investigated for the compartmental deposition of decay products as well as clearance effects. Furthermore typical daily routines for various ages, ranging from newborn to adult, comprising different activities, such resting, light and heavy work and times spent indoors and outdoors were considered; this shows great influence on the minute volume. Considering all these factors dose assessments were performed, which reveiled that the doses in the respiratory tract reach a maximum value for the age between 5 and 10 years. These values exceed the corresponding dose values for adults by factors of 2 and more. Dose calculations are presented for children of various ages and compared with those of male and female adults with different life patterns

  9. Repeated Intramuscular-dose Toxicity Test of Water-soluble Carthami Flos (WCF Pharmacopuncture in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Yoo-min Choi

    2015-03-01

    Full Text Available Objectives: Water-soluble carthami flos (WCF is a new mixture of Carthami flos (CF pharmacopuncture. We conducted a 4-week toxicity test of repeated intramuscular injections of WCF in Sprague-Dawley rats. Methods: Forty male and 40 female rats were divided into 4 groups of 10 male and 10 female SD rats: The control group received 0.5 mL/animal/day of normal saline whereas the three experimental groups received WCF at doses of 0.125, 0.25, and 0.5 mL/animal/day, respectively. For 4 weeks, the solutions were injected into the femoral muscle of the rats alternating from side to side. Clinical signs, body weights, and food consumption were observed; opthalmological examinations and urinalyses were performed. On day 29, blood samples were taken for hematological and clinical chemistry analyses. Then, necropsy was conducted in all animals to observe weights and external and histopathological changes in the bodily organs. All data were tested using a statistical analysis system (SAS. Results: No deaths were observed. Temporary irregular respiration was observed in male rats of the experimental group for the first 10 days. Body weights, food consumptions, opthalmological examinations, urinalyses, clinical chemistry analyses, organ weights and necropsy produced no findings with toxicological meaning. In the hematological analysis, delay of prothrombin time (PT was observed in male rats of the 0.25- and the 0.5-mL/animal/day groups. In the histopathological test, a dose-dependent inflammatory cell infiltration into the fascia and panniculitis in perimuscular tissues was observed in all animals of the experimental groups. However, those symptoms were limited to local injection points. No toxicological meanings, except localized changes, were noted. Conclusion: WCF solution has no significant toxicological meaning, but does produce localized symptoms. No observed adverse effect level (NOAEL of WCF in male and female rats is expected for doses over 0.5 mL/animal/day.

  10. Safety and Pharmacokinetic Profiles of Repeated-Dose Micafungin in Children and Adolescents Treated for Invasive Candidiasis

    Science.gov (United States)

    Benjamin, Daniel K.; Deville, Jaime G.; Azie, Nkechi; Kovanda, Laura; Roy, Mike; Wu, Chunzhang; Arrieta, Antonio

    2013-01-01

    Background Micafungin is an echinocandin with proven efficacy against a broad range of fungal infections, including those caused by Candida species. Objective To evaluate the safety and pharmacokinetics of once-daily 3 mg/kg and 4.5 mg/kg micafungin in children with proven, probable, or suspected invasive candidiasis. Methods Micafungin safety and pharmacokinetics were assessed in two Phase I, open-label, repeat-dose trials. In Study 2101, children aged 2–16 years were grouped by weight to receive 3 mg/kg (≥25 kg) or 4.5 mg/kg (<25 kg) intravenous micafungin for 10–14 days. In Study 2102, children aged 4 months to <2 years received 4.5 mg/kg micafungin. Study protocols were otherwise identical. Results Safety was analyzed in seventy-eight and nine children in Studies 2101 and 2102, respectively. Although adverse events were experienced by most children (2101: n = 62; 2102: n = 9), micafungin-related adverse events were less common (2101: n = 28; 2102: n = 1), and the number of patients discontinuing due to adverse events was low (2101: n = 4; 2102: n = 1). The most common micafungin-related adverse events were infusion-associated symptoms, pyrexia, and hypomagnesemia (Study 2101), and liver function abnormalities (Study 2102). The micafungin pharmacokinetic profile was similar to that seen in other studies conducted in children, but different than that observed in adults. Conclusions In this small cohort of children, once-daily doses of 3 mg/kg and 4.5 mg/kg micafungin were well tolerated. Pharmacokinetic data will be combined in a population pharmacokinetic analysis to support U.S. dosing recommendations in children. PMID:23958810

  11. Repeated dose intramuscular injection of the CIMAvax-EGF vaccine in Sprague Dawley rats induces local and systemic toxicity.

    Science.gov (United States)

    Mancebo, A; Casacó, A; González, B; Ledón, N; Sorlozabal, J; León, A; Gómez, D; González, Y; Bada, A M; González, C; Arteaga, M E; Ramírez, H; Fuentes, D

    2012-05-09

    CIMAvax-EGF consists of a human recombinant epidermal growth factor (EGF), coupled to P64k, a recombinant carrier protein from N. meningitis, and Montanide ISA 51 as adjuvant. The vaccine immunization induces a specific antibody production, inhibiting the EGF/EGF-R interaction through EGF deprivation. The objective of this study was to assess the CIMAvax-EGF toxicity in Sprague Dawley rats after intramuscular administration of repeated doses (6 months) and at the same time to determine if rat is a relevant species for studying CIMAvax-EGF vaccine. Rats were randomly distributed into four groups: control, Montanide ISA 51, treated with 1× and 15× of human total dose of the antigen. Animals were immunized weekly during 9 weeks, plus 9 immunizations every 14 days. Rats were inspected daily for clinical signs. Body weight, food consumption, and rectal temperature were measured during the administration of doses. Blood samples were collected for hematological, serum biochemical determinations and EGF titles at the beginning, three months and at the end of experimentation. Gross necropsy and histological examination of tissues were performed on animals at the end of the assay. Vaccine provoked the apparition of antibodies against EGF in the rats, demonstrating rat species relevance in these studies. Body weight gain, food and water consumption were not affected. CIMAvax-EGF and Montanide ISA 51 produced local damage at the administration site, showing multiple cysts and granulomas. Both vaccine-treated groups showed neutrophil elevation, besides an AST increase probably related to the damage at the administration site. Rectal temperature was found to be significantly higher in 15× treated group after immunizations, probably induced by the inflammatory process at the injection site. In summary, the clinical pathology findings together with the body temperature results, appear to be caused by the inflammatory reaction at the administration site of the vaccine, mainly

  12. A single whole-body low dose X-irradiation does not affect L1, B1 and IAP repeat element DNA methylation longitudinally.

    Directory of Open Access Journals (Sweden)

    Michelle R Newman

    Full Text Available The low dose radioadaptive response has been shown to be protective against high doses of radiation as well as aging-induced genomic instability. We hypothesised that a single whole-body exposure of low dose radiation would induce a radioadaptive response thereby reducing or abrogating aging-related changes in repeat element DNA methylation in mice. Following sham or 10 mGy X-irradiation, serial peripheral blood sampling was performed and differences in Long Interspersed Nucleic Element 1 (L1, B1 and Intracisternal-A-Particle (IAP repeat element methylation between samples were assessed using high resolution melt analysis of PCR amplicons. By 420 days post-irradiation, neither radiation- or aging-related changes in the methylation of peripheral blood, spleen or liver L1, B1 and IAP elements were observed. Analysis of the spleen and liver tissues of cohorts of untreated aging mice showed that the 17-19 month age group exhibited higher repeat element methylation than younger or older mice, with no overall decline in methylation detected with age. This is the first temporal analysis of the effect of low dose radiation on repeat element methylation in mouse peripheral blood and the first to examine the long term effect of this dose on repeat element methylation in a radiosensitive tissue (spleen and a tissue fundamental to the aging process (liver. Our data indicate that the methylation of murine DNA repeat elements can fluctuate with age, but unlike human studies, do not demonstrate an overall aging-related decline. Furthermore, our results indicate that a low dose of ionising radiation does not induce detectable changes to murine repeat element DNA methylation in the tissues and at the time-points examined in this study. This radiation dose is relevant to human diagnostic radiation exposures and suggests that a dose of 10 mGy X-rays, unlike high dose radiation, does not cause significant short or long term changes to repeat element or global DNA

  13. Investigation into the Manufacture and Properties of Inhalable High-Dose Dry Powders Produced by Comilling API and Lactose with Magnesium Stearate.

    Science.gov (United States)

    Lau, Michael; Young, Paul M; Traini, Daniela

    2017-08-01

    The aim of the study was to understand the impact of different concentrations of the additive material, magnesium stearate (MGST), and the active pharmaceutical ingredient (API), respectively, on the physicochemical properties and aerosol performance of comilled formulations for high-dose delivery. Initially, blends of API/lactose with different concentrations of MGST (1-7.5% w/w) were prepared and comilled by the jet-mill apparatus. The optimal concentration of MGST in comilled formulations was investigated, specifically for agglomerate structure and strength, particle size, uniformity of content, surface coverage, and aerosol performance. Secondly, comilled formulations with different API (1-40% w/w) concentrations were prepared and similarly analyzed. Comilled 5% MGST (w/w) formulation resulted in a significant improvement in in vitro aerosol performance due to the reduction in agglomerate size and strength compared to the formulation comilled without MGST. Higher concentrations of MGST (7.5% w/w) led to reduction in aerosol performance likely due to excessive surface coverage of the micronized particles by MGST, which led to failure in uniformity of content and an increase in agglomerate strength and size. Generally, comilled formulations with higher concentrations of API increased the agglomerate strength and size, which subsequently caused a reduction in aerosol performance. High-dose delivery was achieved at API concentration of >20% (w/w). The study provided a platform for the investigation of aerosol performance and physicochemical properties of other API and additive materials in comilled formulations for the emerging field of high-dose delivery by dry powder inhalation.

  14. Radiobiological restrictions and tolerance doses of repeated single-fraction hdr-irradiation of intersecting small liver volumes for recurrent hepatic metastases

    Directory of Open Access Journals (Sweden)

    Wust Peter

    2010-05-01

    Full Text Available Abstract Background To assess radiobiological restrictions and tolerance doses as well as other toxic effects derived from repeated applications of single-fraction high dose rate irradiation of small liver volumes in clinical practice. Methods Twenty patients with liver metastases were treated repeatedly (2 - 4 times at identical or intersecting locations by CT-guided interstitial brachytherapy with varying time intervals. Magnetic resonance imaging using the hepatocyte selective contrast media Gd-BOPTA was performed before and after treatment to determine the volume of hepatocyte function loss (called pseudolesion, and the last acquired MRI data set was merged with the dose distributions of all administered brachytherapies. We calculated the BED (biologically equivalent dose for a single dose d = 2 Gy for different α/β values (2, 3, 10, 20, 100 based on the linear-quadratic model and estimated the tolerance dose for liver parenchyma D90 as the BED exposing 90% of the pseudolesion in MRI. Results The tolerance doses D90 after repeated brachytherapy sessions were found between 22 - 24 Gy and proved only slightly dependent on α/β in the clinically relevant range of α/β = 2 - 10 Gy. Variance analysis showed a significant dependency of D90 with respect to the intervals between the first irradiation and the MRI control (p 90 and the pseudolesion's volume. No symptoms of liver dysfunction or other toxic effects such as abscess formation occurred during the follow-up time, neither acute nor on the long-term. Conclusions Inactivation of liver parenchyma occurs at a BED of approx. 22 - 24 Gy corresponding to a single dose of ~10 Gy (α/β ~ 5 Gy. This tolerance dose is consistent with the large potential to treat oligotopic and/or recurrent liver metastases by CT-guided HDR brachytherapy without radiation-induced liver disease (RILD. Repeated small volume irradiation may be applied safely within the limits of this study.

  15. Asthma Control Can Be Maintained after Fixed-Dose, Budesonide/Formoterol Combination Inhaler Therapy is Stepped Down from Medium to Low Dose

    Directory of Open Access Journals (Sweden)

    Masayuki Hojo

    2013-01-01

    Conclusions: If complete control of asthma, not only of clinical symptoms but also airway inflammation, is achieved by 3-6 months of fixed-dose budesonide/formoterol 4 puffs/day, it should be possible to safely perform step-down to 2 puffs/day.

  16. Inhaled plutonium nitrate in dogs

    International Nuclear Information System (INIS)

    Dagle, G.E.; Cannon, W.C.; Ragan, H.A.; Watson, C.R.; Stevens, D.L.; Cross, F.T.; Dionne, P.J.; Harrington, T.P.

    1978-01-01

    Beagle dogs given a single inhalation exposure to 239 Pu(NO 3 ) 4 are being observed for life-span dose-effect relationships. Lymphopenia occurred at the two highest dosage levels as early as 1 mo following exposure and was associated with neutropenia and reduction in numbers of circulatory monocytes by 4 mo postexposure. Radiation pneumonitis developed in one dog at the highest dosage level at 14 mo postexposure. More rapid translocation to skeleton and liver occurred following inhalation of 238 Pu(NO 3 ) 4 than after 239 Pu(NO 3 ) 4 inhalation

  17. The effect of ethanol on the formation and physico-chemical properties of particles generated from budesonide solution-based pressurized metered-dose inhalers.

    Science.gov (United States)

    Zhu, Bing; Traini, Daniela; Chan, Hak-Kim; Young, Paul M

    2013-11-01

    The aerosol performance of budesonide solution-based pressurized metered-dose inhalers (HFA 134a), with various amounts of ethanol (5-30%, w/w) as co-solvents, was evaluated using impaction and laser diffraction techniques. With the increase of ethanol concentration in a formulation, the mass median aerodynamic diameter was increased and the fine particle fraction showed a significant decline. Although data obtained from laser diffraction oversized that of the impaction measurements, good correlations were established between the two sets of data. Particles emitted from all the five formulations in this study were amorphous, with two different types of morphology - the majority had a smooth surface with a solid core and the others were internally porous with coral-like surface morphology. The addition of ethanol in the formulation decreased the percentage of such irregular-shape particles from 52% to 2.5% approximately, when the ethanol concentration was increased from 5% to 30%, respectively. A hypothesis regarding the possible particle formation mechanisms was also established. Due to the difference of droplet composition from the designed formulation during the atomization process, the two types of particle may have gone through distinct drying processes: both droplets will have a very short period of co-evaporation, droplets with less ethanol may be dried during such period; while the droplets containing more ethanol will undergo an extra condensation stage before the final particle formation.

  18. Inhaled plutonium oxide in dogs

    International Nuclear Information System (INIS)

    Anon.

    1981-01-01

    This project is concerned with long-term experiments to determine the life-span dose-effect relationships of inhaled 239 PuO 2 and 238 PuO 2 in beagles. The data will be used to estimate the health effects of inhaled transuranics. The tissue distribution of plutonium, radiation effects in the lung and hematologic changes in plutonium-exposed beagles with lung tumors were evaluated

  19. Respirable versus inhalable dust sampling

    International Nuclear Information System (INIS)

    Hondros, J.

    1987-01-01

    The ICRP uses a total inhalable dust figure as the basis of calculations on employee lung dose. This paper was written to look at one aspect of the Olympic Dam dust situation, namely, the inhalable versus respirable fraction of the dust cloud. The results of this study will determine whether it is possible to use respirable dust figures, as obtained during routine monitoring to help in the calculations of employee exposure to internal radioactive contaminants

  20. Efficacy and safety of ipratropium bromide/salbutamol sulphate administered in a hydrofluoroalkane metered-dose inhaler for the treatment of COPD

    Directory of Open Access Journals (Sweden)

    Bhattacharya A

    2016-06-01

    Full Text Available Amal Bhattacharya,1 Salil Bhargava,2 Virendra Singh,3 Deepak Talwar,4 Jagdeep Whig,5 Juliet Rebello,6 Shrinivas Purandare,6 Jaideep Gogtay6 1Department of Medicine, MP Shah Medical College, Jamnager, Gujarat, 2Tuberculosis and Chest Diseases, MGM Medical College, Indore, Madhya Pradesh, 3Pulmonary Division, SMS Hospital, Jaipur, Rajasthan, 4Respiratory Diseases, Metro Hospital and Heart Institute, Noida, Uttar Pradesh, 5Department of Medicine, Dayanand Medical College & Hospital, Ludhiana, Punjab, 6Clinical Research Department, Cipla Ltd, Mumbai, Maharashtra, India Background: The use of chlorofluorocarbons (CFCs has contributed to the depletion of the stratospheric ozone layer resulting in serious health concerns. Ipratropium bromide/salbutamol sulphate CFC-pressurized metered-dose inhalers (IB/SAL-CFC pMDI have been in widespread use for many years without any apparent ill consequences. This combination has now been reformulated using the hydrofluoroalkane (HFA propellant. This study sought to establish the clinical noninferiority of a new HFA-containing IB/SAL pMDI to the conventional IB/SAL-CFC pMDI in subjects with mild/moderate COPD.Methods: This was a randomized, double-blind, parallel-group, multicenter study in two consecutive periods: a 14-day run-in period followed by a 85-day treatment period. Eligible mild-to-moderate stable COPD subjects aged 40-75 years were enrolled into the study and entered the run-in period during which subjects withdrew all the bronchodilators, except for salbutamol as rescue medication. Subjects were randomized to 85 days treatment with either IB/SAL-HFA or IB/SAL-CFC, 20 µg qid.Results: Of the 290 randomized patients, 249 completed the study. The primary efficacy variable was the change in forced expiratory volume in one second from predose to 60 minutes after dosing on day 85. At the end of the treatment period, the adjusted mean change in forced expiratory volume in one second at 60 minutes was 123

  1. Biennial Report on Long-Term Dose-Response Studies of Inhaled or Injected Radionuclides, 1991 - 1993

    Science.gov (United States)

    1994-01-01

    and Radon or Thoron in the Body R. D. LJoyd, G. N. Taylor and S. C. Miller D. L Henshaw, et al. (In Indoor Radon and Lung Cancer: Reality or Myth ? [F. T...In Indoor Radon and Lung Cancer: Reality or Myth ? [F. T. Cross, ed.], Battelle Press, Richland, WA, p. 167, 1992a) calculated the dose-rates to bone...82300 5635 D-ENTERITIS 0.59 1.5 1.9 1.6 3.9 5.3 80288 4866 E-LEIONYOMA, VAGINA 0.54 1.5 1.9 1.5 3.8 5.2 79165 4392 E-RENAL FAILURE 0.44 1.1 1.5 1.2

  2. Cellular internalization and transport of biodegradable polyester dendrimers on a model of the pulmonary epithelium and their formulation in pressurized metered-dose inhalers.

    Science.gov (United States)

    Heyder, Rodrigo S; Zhong, Qian; Bazito, Reinaldo C; da Rocha, Sandro R P

    2017-03-30

    The purpose of this study was to evaluate the effect of generation and surface PEGylation of degradable polyester-based dendrimers nanocarriers on their interactions with an in vitro model of the pulmonary epithelium as well as to assess the ability to formulate such carriers in propellant-based, portable oral-inhalation devices to determine their potential for local and systemic delivery of drugs to and through the lungs. Hydroxyl (-OH) terminated polyester dendrimers of generation 3 and 4 (G3, and G4) were synthesized using a divergent approach. G4 was surface-modified with PEG (1,000Da). All dendrimers and their building blocks were determined to be highly compatible with the model pulmonary epithelium, with toxicity profiles much more favorable than non-degradable polyamidoamine dendrimers (PAMAM). The transport of the species from the apical to basolateral side across polarized Calu-3 monolayers showed to be generation and surface-chemistry (PEGylation) dependent. The extent of the transport is modulated by their interaction with the polarized epithelium and their transient opening of the tight junctions. G3 was the one most efficiently internalized by the epithelium, and had a small impact on the integrity of the monolayer. On the other hand, the PEGylated G4 was the one least internalized by the polarized epithelium, and at the same time had a more pronounced transient impact on the cellular junctions, resulting in more efficient transport across the cell monolayer. PEGylation of the dendrimer surface played other roles as well. PEGylation modulated the degradation profile of the dendrimer, slowing the process in a step-wise fashion - first the PEG layer is shed and then the dendrimer starts degrading. PEGylation also helped increase the solvation of the nanocarriers by the hydrofluoroalkane propellant used in pressurized metered-dose inhalers, resulting in formulations with excellent dispersibility and aerosol quality (deep lung deposition of 88

  3. Effects of acute and repeated oral doses of D-tagatose on plasma uric acid in normal and diabetic humans.

    Science.gov (United States)

    Saunders, J P; Donner, T W; Sadler, J H; Levin, G V; Makris, N G

    1999-04-01

    D-tagatose, a stereoisomer of D-fructose, is a naturally occurring ketohexose proposed for use as a low-calorie bulk sweetener. Ingested D-tagatose appears to be poorly absorbed. The absorbed portion is metabolized in the liver by a pathway similar to that of D-fructose. The main purpose of this study was to determine if acute or repeated oral doses of D-tagatose would cause elevations in plasma uric acid (as is seen with fructose) in normal humans and Type 2 diabetics. In addition, effects of subchronic D-tagatose ingestion on fasting plasma phosphorus, magnesium, lipids, and glucose homeostasis were studied. Eight normal subjects and eight subjects with Type 2 diabetes participated in this two-phase study. Each group was comprised of four males and four females. In the first phase, all subjects were given separate 75 g 3-h oral glucose and D-tagatose tolerance tests. Uric acid, phosphorus, and magnesium were determined in blood samples collected from each subject at 0, 30, 60, 120, and 180 min after dose. In the 8-week phase of the study, the normals were randomly placed into two groups which received 75 g of either D-tagatose or sucrose (25 g with each meal) daily for 8 weeks. The diabetics were randomized into two groups which received either 75 g D-tagatose or no supplements of sugar daily for 8 weeks. Uric acid, phosphorus, magnesium, lipids, glycosylated hemoglobin, glucose, and insulin were determined in fasting blood plasma of all subjects at baseline (time zero) and biweekly over the 8 weeks. The 8-week test did not demonstrate an increase in fasting plasma uric acid in response to the daily intake of D-tagatose. However, a transient increase of plasma uric acid levels was observed after single doses of 75 g of D-tagatose in the tolerance test. Plasma uric acid levels were found to rise and peak at 60 min after such dosing. No clinical relevance was attributed to this treatment-related effect because excursions of plasma uric acid levels above the normal

  4. Similar Results in Children with Asthma for Steady State Pharmacokinetic Parameters of Ciclesonide Inhaled with or without Spacer

    Directory of Open Access Journals (Sweden)

    H. Boss

    2010-01-01

    Full Text Available Background Ciclesonide is an inhaled corticosteroid administered by a metered dose inhaler (MDI to treat bronchial asthma. After inhalation, the inactive ciclesonide is converted by esterases in the airways to active metabolite desisobutyryl-ciclesonide (des-CIC. Aim To compare the pharmacokinetic (PK parameters of des-CIC in children after administration of therapeutic dose of ciclesonide with and without spacer (AeroChamber Plus™. Methods Open-label, 3 period, cross over, repeated dose, PK study in 37 children with mild to moderate stable asthma (age: 6–11 y; body weight: 20–53 kg. During each 7-day treatment period, ciclesonide was inhaled once in the morning: A 160 μg MDI with spacer, B 80 μg MDI with spacer, and C 160 μg MDI without spacer. Serum PK parameters of ciclesonide and des-CIC were determined on Day 7 of each period. The primary PK parameters were the AUC τ and C max for des-CIC. Results Inhaling ciclesonide with spacer led to a dose proportional systemic exposure (AUC τ of des-CIC (0.316 μg*h/L for 80 μg and 0.663 μg*h/L for 160 μg. The dose-normalized systemic exposure for des-CIC (based on AUC τ was 27% higher after inhalation of ciclesonide 80 μg or 160 μg with spacer than without spacer; the corresponding C max values for des-CIC were, respectively, 63% and 55% higher with spacer. No clinically relevant abnormalities or adverse drug reactions were observed. Conclusions Inhalation of therapeutic ciclesonide dose with spacer led to a slight increase in the systemic exposure of des-CIC, which does not warrant dose adjustment.

  5. Assessment of inhalation and ingestion doses from exposure to radon gas using passive and active detecting techniques

    Energy Technology Data Exchange (ETDEWEB)

    Ismail, A. H.; Jafaar, M. S. [Universiti Sains Malaysia, 11800 USM, Penang (Malaysia)

    2011-07-01

    The aim of this study was to assess an environmental hazard of radon exhalation rate from the samples of soil and drinking water in selected locations in Iraqi Kurdistan, passive (CR-39NTDs) and active (RAD7) detecting techniques has been employed. Long and short term measurements of emitted radon concentrations were estimated for 124 houses. High and lower radon concentration in soil samples was in the cities of Hajyawa and Er. Tyrawa, respectively. Moreover, for drinking water, high and low radon concentration was in the cities of Similan and Kelak, respectively. A comparison between our results with that mentioned in international reports had been done. Average annual dose equivalent to the bronchial epithelium, stomach and whole body in the cities of Kelak and Similan are estimated, and it was varied from 0.04{+-}0.01 mSv to 0.547{+-}0.018 mSv, (2.832{+-}0.22)x10{sup -5} to (11.972{+-}2.09)x10{sup -5} mSv, and (0.056 {+-}0.01) x10{sup -5} to (0.239{+-}0.01)x10{sup -5} mSv, respectively. This indicated that the effects of dissolved radon on the bronchial epithelium are much than on the stomach and whole body. (authors)

  6. Inhaled Drug Delivery: A Practical Guide to Prescribing Inhaler Devices

    Directory of Open Access Journals (Sweden)

    Pierre Ernst

    1998-01-01

    Full Text Available Direct delivery of medication to the target organ results in a high ratio of local to systemic bioavailability and has made aerosol delivery of respiratory medication the route of choice for the treatment of obstructive lung diseases. The most commonly prescribed device is the pressurized metered dose inhaler (pMDI; its major drawback is the requirement that inspiration and actuation of the device be well coordinated. Other requirements for effective drug delivery include an optimal inspiratory flow, a full inspiration from functional residual capacity and a breath hold of at least 6 s. Available pMDIs are to be gradually phased out due to their use of atmospheric ozone-depleting chlorofluorocarbons (CFCs as propellants. Newer pMDI devices using non-CFC propellants are available; preliminary experience suggests these devices greatly increase systemic bioavailability of inhaled corticosteroids. The newer multidose dry powder inhalation devices (DPIs are breath actuated, thus facilitating coordination with inspiration, and contain fewer ingredients. Furthermore, drug delivery is adequate even at low inspired flows, making their use appropriate in almost all situations. Equivalence of dosing among different devices for inhaled corticosteroids will remain imprecise, requiring the physician to adjust the dose of medication to the lowest dose that provides adequate control of asthma. Asthma education will be needed to instruct patients on the effective use of the numerous inhalation devices available.

  7. A comparative study of indoor radon levels and inhalation dose in some areas of Punjab and Haryana, India

    International Nuclear Information System (INIS)

    Bajwa, B.S.; Singh, Harmanjit; Singh, Joga; Singh, Surinder

    2009-01-01

    Indoor radon concentrations have been measured for two consecutive half-year periods in a wide range of dwellings of some regions of Punjab and Haryana states. The objective was to find correlation between the variations of indoor radon levels with the sub-soil, local geology, type of building materials, etc. of the two regions. So keeping this in view the indoor radon measurements have been carried out in the dwellings of different villages around the Tusham ring complex, Bhiwani District, Haryana, known to be composed of acidic volcanics and the associated granites along with some villages of Amritsar District, Punjab. The indoor radon concentration in the dwellings around Tusham (Haryana) have been found to be varying from 120.5±95 to 915.2±233 Bq m -3 , whereas it ranges from 60.0±37 to 235.6±96 Bq m -3 for the dwellings of Punjab. The 222 Rn concentration observed at most of locations particularly around Tusham ring complex region is higher than that of all the villages studied in Punjab region. Local geology including embedded granitic rocks, sub-soil, etc. as well as building materials having higher radioactive content are the major contributors for the higher indoor radon levels observed in the dwelling around Tusham, where few dwellings have higher radon concentrations than the ICRP, 1993 recommendations. The annual effective dose equivalent has also been estimated for each location of the both regions, which has been found to be varying from 1.0 to 17.2 mSv/y. (author)

  8. Aspergillus fumigatus viability drives allergic responses to inhaled conidia.

    Science.gov (United States)

    Nayak, Ajay P; Croston, Tara L; Lemons, Angela R; Goldsmith, W T; Marshall, Nikki B; Kashon, Michael L; Germolec, Dori R; Beezhold, Donald H; Green, Brett J

    2018-04-13

    Aspergillus fumigatus induced allergic airway disease has been shown to involve conidial germination in vivo but the immunological mechanisms remain uncharacterized. A subchronic murine exposure model was used to examine the immunological mediators that are regulated in response to either culturable or non-culturable A. fumigatus conidia. Female B6C3F1/N mice were repeatedly dosed via inhalation with 1 x 105 viable or heat inactivated conidia (HIC), twice a week for 13 weeks (26 exposures). Control mice inhaled HEPA-filtered air. The influence of A. fumigatus conidial germination on the pulmonary immunopathological outcomes was evaluated by flow cytometry analysis of cellular infiltration in the airways, assessment of lung mRNA expression, and quantitative proteomics and histopathology of whole lung tissue. Repeated inhalation of viable conidia, but not HIC, resulted in allergic inflammation marked by vascular remodeling, extensive eosinophilia, and accumulation of alternatively activated macrophages (AAMs) in the murine airways. More specifically, mice that inhaled viable conidia resulted in a mixed TH1 and TH2 (IL-13) cytokine response. Recruitment of eosinophils corresponded with increased Ccl11 transcripts. Furthermore, genes associated with M2 or alternatively activated macrophage polarization (e.g. Arg1, Chil3 and Retnla) were significantly upregulated in viable A. fumigatus exposed mice. In mice inhaling HIC, CD4+ T cells expressing IFN-γ (TH1) dominated the lymphocytic infiltration. Quantitative proteomics of the lung revealed metabolic reprogramming accompanied by mitochondrial dysfunction and endoplasmic reticulum stress stimulated by oxidative stress from repetitive microbial insult. Our studies demonstrate that A. fumigatus conidial viability in vivo is critical to the immunopathological presentation of chronic fungal allergic disease. Copyright © 2018. Published by Elsevier Inc.

  9. Study on Effectiveness of Low Dose Theophylline as Add-on to Inhaled Corticosteroid for Patients with Sulfur Mustard Induced Bronchiolitis

    Directory of Open Access Journals (Sweden)

    Yunes Panahi

    2013-12-01

    , Saburi A, Shohrati M, Ghanei M. Study on Effectiveness of Low Dose Theophylline as Add-on to Inhaled Corticosteroid for Patients with Sulfur Mustard Induced Bronchiolitis. Asia Pac J Med Toxicol 2013;2:126-130.

  10. Dataset for Phase I randomized clinical trial for safety and tolerability of GET 73 in single and repeated ascending doses including preliminary pharmacokinetic parameters

    Directory of Open Access Journals (Sweden)

    Carolina L. Haass-Koffler

    2017-12-01

    Full Text Available The data in this article outline the methods used for the administration of GET 73 in the first time-in-human manuscript entitled “Phase I randomized clinical trial for the safety, tolerability and preliminary pharmacokinetics of the mGluR5 negative allosteric modulator GET 73 following single and repeated doses in healthy male volunteers” (Haass-Koffler et al., 2017 [1]. Data sets are provided in two different manners. The first series of tables provided includes procedural information about the experiments conducted. The next series of tables provided includes Pharmacokinetic (PK parameters for GET 73 and its main metabolite MET 2. This set of data is comprised by two experiments: Experiment 1 references a single ascending dose administration of GET 73 and Experiment 2 references a repeated ascending dose administration of GET 73. Keywords: Glutamate receptor subtype 5 (mGlu5, Allosteric modulator, GET 73, Safety, Tolerability

  11. Dataset for Phase I randomized clinical trial for safety and tolerability of GET 73 in single and repeated ascending doses including preliminary pharmacokinetic parameters.

    Science.gov (United States)

    Haass-Koffler, Carolina L; Goodyear, Kimberly; Long, Victoria M; Tran, Harrison H; Loche, Antonella; Cacciaglia, Roberto; Swift, Robert M; Leggio, Lorenzo

    2017-12-01

    The data in this article outline the methods used for the administration of GET 73 in the first time-in-human manuscript entitled "Phase I randomized clinical trial for the safety, tolerability and preliminary pharmacokinetics of the mGluR5 negative allosteric modulator GET 73 following single and repeated doses in healthy male volunteers" (Haass-Koffler et al., 2017) [1]. Data sets are provided in two different manners. The first series of tables provided includes procedural information about the experiments conducted. The next series of tables provided includes Pharmacokinetic (PK) parameters for GET 73 and its main metabolite MET 2. This set of data is comprised by two experiments: Experiment 1 references a single ascending dose administration of GET 73 and Experiment 2 references a repeated ascending dose administration of GET 73.

  12. Annual effective dose equivalents arising from inhalation of 222Rn, 220Rn and their decay products in high background radiation area in China

    International Nuclear Information System (INIS)

    Zhang Zhonghou

    1985-01-01

    The author presents the data of on-the-sport investigations in the high background radiation area in Yangjiang County in 1975 and 1981. Monazite sand is contained in the soil of this area. The average concentrations of 222 Rn in the air indoors and out doors of the high background radiation area are 31.8 and 16.4 Bqm -3 respectively, which are equal to 2.9 and 1.5 times the average concentrations in the control area. The average concentrations of 220 Rn in the air indoors and outdoors of the high background area are 167.5 and 18.4 Bqm -3 , corresponding to 9.6 and 4.8 times those of the control area respectively. The average potential alpha energy concentrations for daughters of 222 Rn indoors and outdoors are 0.1 and 0.097 μJm -3 , which are equal to 2.6 and 2.2 times those of the control are respectively. The average potential alpha energy concentrations for daughters of 220 Rn indoors and outdoors are 0.255 and 0.053 μJm -3 , corresponding to 3.7 and 2.7 times those of the control area respectively. The average annual effective dose equivalents arising from inhalation of 222 Rn, 220 Rn and their decay products in high background radiation area are estimated to be 2.8 mSv per caput, in which 40.5% arise from 220 Rn and its decay products. This result is about 3 times that in the neighboring control area

  13. Evaluation of the repeated dose liver micronucleus assay using young adult rats with cyclophosphamide monohydrate: a report of a collaborative study by CSGMT/JEMS.MMS.

    Science.gov (United States)

    Matsumoto, Kazumi; Zaizen, Kazuyo; Miyamoto, Atsushi; Wako, Yumi; Kawasako, Kazufumi; Ishida, Hisao

    2015-03-01

    The repeated dose liver micronucleus (RDLMN) assay using young adult rats has the potential to detect liver carcinogens, and this assay could be integrated into general toxicological studies. In this study, in order to assess the performance of the assay, cyclophosphamide monohydrate (CP) was tested in a 14-day RDLMN assay. Based on the results of the 4-day repeated dose-finding study, 10 mg/kg/day of CP was selected as the highest dose and the lower doses were set at 5, 2.5, 1.25, and 0.625 mg/kg/day for the 14-day RDLMN assay. On the day after the completion of the dosing period, specimens of hepatocytes and bone marrow cells were prepared and the induction of micronuclei was assessed. No changes were observed in the incidences of micronucleated hepatocytes. Nevertheless, the incidences of micronucleated immature erythrocytes in the bone marrow were increased significantly at CP doses of 1.25 mg/kg/day or more. These findings are consistent with reports that CP induces tumors in various tissues but it does not induce liver tumors.

  14. Repeated dose 90-day oral toxicity test of G-7% NANA in rats: An application of new criterion for toxicity determination to test article-induced changes.

    Science.gov (United States)

    Heo, Hye Seon; An, MinJi; Lee, Ji Sun; Kim, Hee Kyong; Park, Yeong-Chul

    2018-06-01

    G-7% NANA is N-acetylneuraminic acid(NANA) containing 7% sialic acid isolated from glycomacropeptide (GMP), a compound of milk. Since NANA is likely to have immunotoxicity, the need to ensure safety for long-term administration has been raised. In this study, a 90-day repeated oral dose toxicity test was performed in rats using G-7% NANA in the dosages of 0, 1250, 2500 and 5000 mg/kg/day.A toxicity determination criterion based on the significant change caused by the administration of the substancewas developed for estimating NOEL, NOAEL and LOAELapplied to this study. When analyzing the immunological markers, no significant changes were observed, even if other significant changes were observed in the high dose group. In accordance with the toxicity determination criterion developed, the NOEL in male and female has been determined as 2500 mg/kg/day, and the NOAEL in females has been determined as 5000 mg/kg/day. The toxicity determination criterion, applied for the first time in the repeated dose toxicity tests, could provide a basis for distinguishing NOEL and NOAEL more clearly; nevertheless, the toxicity determination criterion needs to be supplemented by adding differentiating adverse effects and non-adverse effects based on more experiences of the repeated dose toxicity tests. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Inhalation of uranium ores

    International Nuclear Information System (INIS)

    Stuart, B.O.; Jackson, P.O.

    1975-01-01

    In previous studies the biological dispositions of individual long-lived alpha members of the uranium chain ( 238 U, 234 U and 230 Th) were determined during and following repeated inhalation exposures of rats to pitchblende (26 percent U 3 O 8 ) ore. Although finely dispersed ore in secular equilibrium was inhaled, 230 Th/ 234 U radioactivity ratios in the lungs rose from 1.0 to 2.5 during 8 weeks of exposures and increased to 9.2 by four months after cessation of exposures. Marked non-equilibrium levels were also found in the tracheobronchial lymph nodes, kidneys, liver, and femur. Daily exposures of beagle dogs to high levels of this ore for 8 days resulted in lung 230 Th/ 234 U ratios of >2.0. Daily exposures of dogs to lower levels (0.1 mg/1) for 6 months, with sacrifice 15 months later, resulted in lung and thoracic lymph node 230 Th/ 234 U ratios ranging from 3.6 to 9 and nearly 7, respectively. The lungs of hamsters exposed to carnotite (4 percent U 3 O 8 ) ore in current lifespan studies show 230 Th/ 234 U ratios as high as 2.0 during daily inhalation of this ore in secular equilibrium. Beagle dogs sacrificed after several years of daily inhalations of the same carnotite ore plus radon daughters also showed marked non-equilibrium ratios of 230 Th/ 234 U, ranging from 5.6 to 7.4 in lungs and 6.2 to 9.1 in thoracic lymph nodes. This pattern of higher retention of 230 Th than 234 U in lungs, thoracic lymph nodes, and other tissues is thus consistent for two types of uranium ore among several species and suggests a reevaluation of maximum permissible air concentrations of ore, currently based only on uranium content

  16. Study of a 13-weeks, Repeated, Intramuscular Dose, Toxicity Test of Sweet Bee Venom in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Hyunmin Kang

    2014-06-01

    Full Text Available Objectives:This study was performed to analyze a 13-week repeated dose toxicity test of Sweet Bee Venom (SBV extracted from bee venom and administered in Sprague-Dawley (SD rats. Methods:Male and female 5-week-old SD rats were treated once daily with SBV (high-dosage group: 0.28 mg/kg; medium-dosage group: 0.14 mg/kg; or low-dosage group: 0.07 mg/kg for 13 weeks. Normal saline was administered to the control group in a similar manner (0.2 mL/kg. We conducted clinical observations, body weight measurements, ophthalmic examinations, urinalyses, hematology and biochemistry tests, and histological observations using hematoxylin and eosin (H&E staining to identify any abnormalities caused by the SBV treatment. Results:During this study, no mortality was observed in any of the experimental groups. Hyperemia and a movement disorder were observed around the area of in all groups that received SBV treatment, with a higher occurrence in rats treated with a higher dosage. Male rats receiving in the high-dosage group showed a significant decrease in weight during the treatment period. Compared to the control group, no significant changes in the ophthalmic parameters, the urine analyses, the complete blood cell count (CBC, and the biochemistry in the groups treated with SBV. Compared to the control group, some changes in organ weights were observed in the medium-and the high-dosage groups, but the low-dosage group showed no significant changes. Histological examination of thigh muscle indicated cell infiltration, inflammation, degeneration, and necrosis of muscle fiber, as well as fibrosis, in both the medium- and the high-dosage groups. Fatty liver change was observed in the periportal area of rats receiving medium and high dosages of SBV. No other organ abnormalities were observed. Conclusion:Our findings suggest that the No Observed Adverse Effect Level (NOAEL of SBV is approximately 0.07 mg/kg in male and female SD rats.

  17. Metered dose inhaler use - slideshow

    Science.gov (United States)

    ... Duplication for commercial use must be authorized in writing by ADAM Health Solutions. About MedlinePlus Site Map FAQs Customer Support Get email updates Subscribe to RSS Follow us Disclaimers Copyright ...

  18. Broncodilatadores en la crisis asmática: ¿Aerosol o nebulización? Bronchodilators in acute asthma: metered dose inhalers or wet nebulizations?

    Directory of Open Access Journals (Sweden)

    Dora M. Lombardi

    2006-12-01

    Full Text Available El número de consultas por asma aguda en el Hospital María Ferrer ha aumentado de 3300 consultas anuales en 1980 a 15364 en 2002. Los broncodilatadores de acción corta (salbutamol-ipratropio en nebulizaciones, procedimiento que consume tiempo y recursos humanos, eran el tratamiento inicial en 2002. Para tratar de mejorar el cumplimiento del tratamiento frente al aumento de la demanda, se reemplazaron las nebulizaciones por aerosoles dosificadores. El objetivo de este estudio es evaluar el impacto de este cambio. Comparamos 90 pacientes con crisis asmática tratados con aerosoles en diciembre del 2003 con igual número tratados con nebulizaciones en diciembre del 2002 pareados por sexo, edad, altura, VEF1 teórico y de ingreso. Con aerosoles se observó una reducción significativa del tiempo de permanencia en el Departamento de Emergencia (mediana 3 h (2-4.75 versus 4 h (1-6 p=0.01 y un número mayor de altas en las primeras 2 horas (48% vs. 31% p=0.03. Los pacientes tratados con aerosol recibieron el 87% de las dosis prescriptas, mientras que el otro grupo recibió sólo el 38%. El VEF1 mostró una tendencia a ser mayor al egreso en el grupo que recibió aerosoles, pero la diferencia no fue estadísticamente significativa (78% ± 17% vs. 73% ± 17% p=0.09. El porcentaje de alta final fue similar en los dos grupos (96% vs. 93%. El tratamiento con aerosoles produjo una mejoría más rápida y mejor cumplimiento de las normas de tratamiento indicadas.The number of patients attending our Emergency Department (ED with acute asthma has increased from 3300 patient/year in 1980 to 15364 in 2003. Short acting bronchodilators (albuterol/ipratropium administered in wet nebulizations, a resource consuming procedure, were our main initial treatment in 2002. To improve treatment goals, we switched the method of bronchodilator delivery to metered dose inhalers (MDI in 2003. The purpose of this study is to evaluate the impact of this change in the

  19. Effect of inhaled formoterol and budesonide on exacerbations of asthma

    NARCIS (Netherlands)

    Pauwels, RA; Lofdahl, CG; Postma, DS; Tattersfield, AE; OByrne, P; Barnes, PJ; Ullman, A

    1997-01-01

    Background The role of long-acting, inhaled beta(2)-agonists in treating asthma is uncertain. In a double-blind study, we evaluated the effects of adding inhaled formoterol to both lower and higher doses of the inhaled glucocorticoid budesonide. Methods After a four-week run-in period of treatment

  20. Knowledge of spacer device, peak flow meter and inhaler technique ...

    African Journals Online (AJOL)

    Background: Metered dose inhalers are cornerstone in effective management of bronchial asthma when correctly used. Most studies hitherto have focused on assessing patient's knowledge of inhaler technique. We sought to assess the knowledge of inhaler technique, spacer device and peak flow meter among doctors and ...

  1. Development of sensitisation or tolerance following repeated OVA inhalation in BALB/cJ mice. Dose-dependency and modulation by the Al(OH)3 adjuvant

    DEFF Research Database (Denmark)

    Clausen, Susanne Knoth; Bergqvist, Mette; Poulsen, Lars K.

    2003-01-01

    Anthropogenically induced exposures may, due to their adjuvant effect, promote development of sensitisation to commonly occurring aeroallergens. No generally accepted model exists for determination of adjuvant effect of airborne substances. Therefore, BALB/cJ mice were exposed for 10 consecutive...

  2. Repeated irradiations with γ-rays at a dose of 0.5 Gy may exacerbate asthma

    International Nuclear Information System (INIS)

    Fang, Su-ping; Tago, Fumitoshi; Tanaka, Takashi; Simura, Noriko; Kojima, Shuji; Muto, Yasuko; Goto, Resuke

    2005-01-01

    We previously showed that 0.5 Gy whole-body γ-ray irradiation with a single or small number of repeated exposures inhibits tumor growth in mice, via elevation of the IFNγ/IL-4 ratio concomitantly with a decrease in the percentage of B cells. Here we examined whether repeated 0.5 Gy γ-rays irradiation can improve asthma in an ovalbumin (OVA)-induced asthmatic mouse model. We found that repeated irradiation (10 times) with 0.5 Gy of γ-rays significantly increased total IgE in comparison with the disease-control group. The levels of IL-4 and IL-5 were also significantly higher in the γ-ray-irradiated group, while that of IFN-γ was significantly lower, resulting in a further decrease of the IFN-γ/IL-4 ratio from the normal value. These results indicate that the repeated irradiation with γ-rays may exacerbate asthma, and may have opposite effects on different immune reactions unlike the irradiation with a single or small number of repeated exposures. (author)

  3. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... Evaluation Roadblocks 1A. Focus On: Walking Through the Steps and Standards 2. Getting Started 3. Describing and ... to use your metered dose inhaler. Print the step-by-step instructions and keep them with your ...

  4. Evaluation of repeated dose micronucleus assays of the liver using N-nitrosopyrrolidine: a report of the collaborative study by CSGMT/JEMS.MMS.

    Science.gov (United States)

    Ogawa, Izumi; Hagioa, Soichiro; Furukawa, Satoshi; Abe, Masayoshi; Kuroda, Yusuke; Hayashi, Seigo; Wako, Yumi; Kawasako, Kazufumi

    2015-03-01

    The repeated dose liver micronucleus (RDLMN) assay has the potential to detect liver carcinogens, and can be integrated into a general toxicological study. To assess the performance of the assay, N-nitrosopyrrolidine (NPYR), a genotoxic hepatocarcinogen, was tested in 14- or 28-day RDLMN assays. NPYR was orally administered to rats at a daily dose of 25, 50 or 100 mg/kg. One day after the last administration, a portion of the liver was removed and hepatocyte micronucleus (MN) specimens were prepared by the new method recently established by Narumi et al. In addition, a bone marrow MN assay and a histopathological examination of the liver were conducted. The detection of Phospho-Histone H3 was performed by immunohistochemistry to evaluate the proliferation rate of hepatocytes. The results showed significant increase in the number of micronucleated hepatocytes and Phospho-Histone H3-positive cells from the lowest dose in both 14- and 28-day RDLMN assays. On the other hand, the bone marrow MN assay yielded a negative result, which was in accordance with the existing report of the bone marrow MN assay using mice. Upon histopathological examination, inflammatory lesions and hypertrophy were noted, which may explain the increase in the hepatocyte proliferation and the enhancement of MN induction by NPYR. Our findings indicate that the RDLMN assay could be a useful tool for comprehensive risk assessment of carcinogenicity by providing information on both genotoxicity and histopathology when integrated into a general repeat dosing toxicity assay.

  5. Analgesia induced by repeated exposure to low dose X-rays in mice, and involvement of the accessory olfactory system in modulation of the radiation effects

    International Nuclear Information System (INIS)

    Miyachi, Yukihisa; Yamada, Takeshi

    1997-01-01

    The effects of low-dose X-rays on mouse nociceptive behavior were examined using a formalin injected test which rated the amount of time the animals spent licking the injected hind-paw. Male ICR White Swiss mice showed a marked suppression of licking behavior after repeated low-dose X-irradiation (5 cGy/day, 6 consecutive days). The most profound effect was observed on the day 30 after irradiation. The decline of licking behavior, however, was not observed at all following olfactory bulbectomy or vomeronasal tract cut. The analgesic effects could be observed in writhing animals administered acetic-acid intraperitoneally. Moreover, analgesia was totally blocked by the administration of N-nitro-L-arginine, a nitric oxide synthase inhibitor, to accessory olfactory bulbs prior to the exposure. The present results indicate that the olfactory system plays an important role in modulation of radiation-induced analgesia, and a possible involvement of nitric oxide in the formation of recognition memory subjected to repeated X-rays. Relatively higher doses (5 cGy x 9 days, 5 cGy x 12 days), however, did not induce such effects, namely, the decline of nociceptive response was limited to the animals irradiated with the smaller dose. (author)

  6. A Randomised Controlled Trial of High Dose, Inhaled Budesonide Versus Oral Prednisone in Patients Discharged from the Emergency Department following an Acute Asthma Exacerbation

    Directory of Open Access Journals (Sweden)

    J Mark FitzGerald

    2000-01-01

    Full Text Available OBJECTIVE: Prednisone (PRED is recommended at discharge to reduce the relapse rate following emergency treatment for an asthmatic attack. However, PRED has systemic side effects. Inhaled anti-inflammatory medications, such as budesonide (BUD, are well tolerated. This study was designed to compare the effectiveness of PRED and BUD on relapse rate.

  7. Safety, Tolerability and Pharmacokinetics of Single Doses of Oxytocin Administered via an Inhaled Route in Healthy Females: Randomized, Single-blind, Phase 1 Study

    Directory of Open Access Journals (Sweden)

    Disala Fernando

    2017-08-01

    Interpretation: These data suggest that similar oxytocin systemic exposure can be achieved with IM and IH administration routes, and no safety concerns were identified with either route. The inhalation route may offer the opportunity to increase access to oxytocin for women giving birth in resource-poor settings.

  8. Design and in vitro performance testing of multiple air classifier technology in a new disposable inhaler concept (Twincer (R)) for high powder doses

    NARCIS (Netherlands)

    de Boer, Anne H; Hagedoorn, Paul; Westerman, Elsbeth M; Le Brun, Paul P H; Heijerman, Harry G M; Frijlink, Henderik W

    2006-01-01

    Dry powder inhalation of antibiotics in cystic fibrosis (CF) therapy may be a valuable alternative for wet nebulisation, because it saves time and it improves lung deposition. In this study, it is shown that the use of multiple air classifier technology enables effective dispersion of large amounts

  9. Quantifying the Reproducibility of Heart Position During Treatment and Corresponding Delivered Heart Dose in Voluntary Deep Inhalation Breath Hold for Left Breast Cancer Patients Treated With External Beam Radiotherapy

    International Nuclear Information System (INIS)

    McIntosh, Alyson; Shoushtari, Asal N.; Benedict, Stanley H.; Read, Paul W.; Wijesooriya, Krishni

    2011-01-01

    Purpose: Voluntary deep inhalation breath hold (VDIBH) reduces heart dose during left breast irradiation. We present results of the first study performed to quantify reproducibility of breath hold using bony anatomy, heart position, and heart dose for VDIBH patients at treatment table. Methods and Materials: Data from 10 left breast cancer patients undergoing VDIBH whole-breast irradiation were analyzed. Two computed tomography (CT) scans, free breathing (FB) and VDIBH, were acquired to compare dose to critical structures. Pretreatment weekly kV orthogonal images and tangential ports were acquired. The displacement difference from spinal cord to sternum across the isocenter between coregistered planning Digitally Reconstructed Radiographs (DRRs) and kV imaging of bony thorax is a measure of breath hold reproducibility. The difference between bony coregistration and heart coregistration was the measured heart shift if the patient is aligned to bony anatomy. Results: Percentage of dose reductions from FB to VDIBH: mean heart dose (48%, SD 19%, p = 0.002), mean LAD dose (43%, SD 19%, p = 0.008), and maximum left anterior descending (LAD) dose (60%, SD 22%, p = 0.008). Average breath hold reproducibility using bony anatomy across the isocenter along the anteroposterior (AP) plane from planning to treatment is 1 (range, 0–3; SD, 1) mm. Average heart shifts with respect to bony anatomy between different breath holds are 2 ± 3 mm inferior, 1 ± 2 mm right, and 1 ± 3 mm posterior. Percentage dose changes from planning to delivery: mean heart dose (7%, SD 6%); mean LAD dose, ((9%, SD 7%)S, and maximum LAD dose, (11%, SD 11%) SD 11%, p = 0.008). Conclusion: We observed excellent three-dimensional bony registration between planning and pretreatment imaging. Reduced delivered dose to heart and LAD is maintained throughout VDIBH treatment.

  10. Interactions between cannabidiol and Δ9-THC following acute and repeated dosing: Rebound hyperactivity, sensorimotor gating and epigenetic and neuroadaptive changes in the mesolimbic pathway.

    Science.gov (United States)

    Todd, Stephanie M; Zhou, Cilla; Clarke, David J; Chohan, Tariq W; Bahceci, Dilara; Arnold, Jonathon C

    2017-02-01

    The evidence base for the use of medical cannabis preparations containing specific ratios of cannabidiol (CBD) and Δ 9 -tetrahydrocannabinol (THC) is limited. While there is abundant data on acute interactions between CBD and THC, few studies have assessed the impact of their repeated co-administration. We previously reported that CBD inhibited or potentiated the acute effects of THC dependent on the measure being examined at a 1:1 CBD:THC dose ratio. Further, CBD decreased THC effects on brain regions involved in memory, anxiety and body temperature regulation. Here we extend on these finding by examining over 15 days of treatment whether CBD modulated the repeated effects of THC on behaviour and neuroadaption markers in the mesolimbic dopamine pathway. After acute locomotor suppression, repeated THC caused rebound locomotor hyperactivity that was modestly inhibited by CBD. CBD also slightly reduced the acute effects of THC on sensorimotor gating. These subtle effects were found at a 1:1 CBD:THC dose ratio but were not accentuated by a 5:1 dose ratio. CBD did not alter the trajectory of enduring THC-induced anxiety nor tolerance to the pharmacological effects of THC. There was no evidence of CBD potentiating the behavioural effects of THC. However we demonstrated for the first time that repeated co-administration of CBD and THC increased histone 3 acetylation (H3K9/14ac) in the VTA and ΔFosB expression in the nucleus accumbens. These changes suggest that while CBD may have protective effects acutely, its long-term molecular actions on the brain are more complex and may be supradditive. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  11. A study to evaluate safety and tolerability of repeated doses of tirasemtiv in patients with amyotrophic lateral sclerosis.

    Science.gov (United States)

    Shefner, Jeremy M; Watson, Mary Lou; Meng, Lisa; Wolff, Andrew A

    2013-12-01

    Abstract Tirasemtiv is a fast skeletal muscle activator that increases the sensitivity of the sarcomere to calcium, increasing the efficiency of muscle contraction when the muscle is stimulated at submaximal contraction frequencies. A previous study showed single doses of tirasemtiv to be well tolerated and associated with potentially important improvements in a variety of functional outcomes. This study determined safety of tirasemtiv when given at doses up to 500 mg daily for three weeks. Tirasemtiv was given as a single daily dose up to 375 mg for two weeks, with and without concomitant riluzole. In a separate cohort, an ascending dose protocol evaluated a total dose of 500 mg daily given in two divided doses. Safety and tolerability were assessed, as well as measures of function, muscle strength and endurance. Results showed that tirasemtiv was well tolerated, with dizziness the most common adverse event. Tirasemtiv approximately doubled the serum concentration of riluzole. Trends were noted for improvement in ALSFRS-R, Maximum Minute Ventilation, and Nasal Inspiratory Pressure. In conclusion, tirasemtiv is well tolerated and can be given safely with a reduced dose of riluzole. Positive trends in multiple exploratory outcome measures support the further study of this agent in ALS.

  12. Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 22). Effects of 2- and 4-week administration of theobromine on the testis.

    Science.gov (United States)

    Funabashi, H; Fujioka, M; Kohchi, M; Tateishi, Y; Matsuoka, N

    2000-10-01

    The effects of theobromine, a xanthine derivative, on the testis were compared between rats dosed for 2 and 4 weeks to determine whether a 2-week dosing period is long enough to detect toxicity. Theobromine was administered orally to male Sprague-Dawley rats at dose levels of 250 and 500 mg/kg for 2 weeks starting at the age of 6 or 8 weeks, and for 4 weeks from the age of 6 weeks. Histopathological examination of reproductive organs revealed toxic findings in the testis at 500 mg/kg after 2 weeks of dosing at both ages, and at 250 and 500 mg/kg after 4 weeks of dosing. The primary findings were degeneration/necrosis and desquamation of spermatids and spermatocytes, vacuolization of seminiferous tubules, and multinucleated giant cell formation. These findings were present mainly in stages I-VI and XII-XIV. From these results, it is concluded that the toxic effects of theobromine on the testis can be detected by repeated dosing for 2 weeks as well as for 4 weeks.

  13. Inhalation Toxicology Research Institute annual report, October 1, 1983-September 30, 1984

    International Nuclear Information System (INIS)

    Guilmette, R.A.; Medinsky, M.A.

    1984-12-01

    The report describes research in the following areas: (1) aerosol generation and characterization; (2) deposition and fate of inhaled materials; (3) dose-response relationships for inhaled radionuclides; (4) dose-response relationships for inhaled chemical toxicants; and (5) biological factors that influence dose-response relationships. Project descriptions have been individually entered into the date base

  14. Study on a 4-Week Recovery Test of Sweet Bee Venom after a 13-Week, Repeated, Intramuscular Dose Toxicity Test in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Chungsan Lim

    2014-06-01

    Full Text Available Objectives:This study was performed to check for reversibility in the changes induced by a 13-week, repeated, dose toxicity test of Sweet Bee Venom (SBV in Sprague-Dawley (SD rats. Methods:Fifteen male and 15 female SD rats were treated with 0.28 mg/kg of SBV (high-dosage group and the same numbers of male and female SD rats were treated with 0.2 mL/kg of normal saline (control group for 13 weeks. We selected five male and five female SD rats from the high-dosage group and the same numbers of male and female SD rats from the control group, and we observed these rats for four weeks. We conducted body-weight measurements, ophthalmic examinations, urinalyses and hematology, biochemistry, histology tests. Results:(1 Hyperemia and movement disorder were observed in the 13-week, repeated, dose toxicity test, but these symptoms were not observed during the recovery period. (2 The rats in the high-dose group showed no significant changes in weight compared to the control group. (3 No significant differences in the ophthalmic parameters, urine analyses, complete blood cell counts (CBCs, and biochemistry were observed among the recovery groups. (4 No changes in organ weights were observed during the recovery period. (5 Histological examination of the thigh muscle indicated cell infiltration, inflammation, degeneration, necrosis of muscle fiber, and fibrosis during the treatment period, but these changes were not observed during the recovery period. The fatty liver change that was observed during the toxicity test was not observed during the recovery period. No other organ abnormalities were observed. Conclusion:The changes that occurred during the 13-week, repeated, dose toxicity test are reversible, and SBV can be safely used as a treatment modality.

  15. Dose- and time-dependent changes in tissue levels of tetrabromobisphenol A (TBBPA and its sulfate and glucuronide conjugates following repeated administration to female Wistar Han Rats

    Directory of Open Access Journals (Sweden)

    S.J. Borghoff

    Full Text Available Tetrabromobisphenol A (TBBPA, a nongenotoxic flame retardant, causes uterine tumors in female rats. A proposed mode of action (MoA for these tumors involves an increase in the bioavailability of estradiol as a result of TBBPA inhibiting estrogen sulfotransferases (ES, the enzymes responsible for inactivating and enhancing the elimination of estradiol. The objective of this study was to evaluate the effect of dose and repeated administration of TBBPA on the level of TBBPA, TBBPA-glucuronide (GA and TBBPA-sulfate (S conjugates in plasma, liver and uterus of female Wistar Han rats administered TBBPA (50, 100, 250, 500 or 1000 mg/kg for 28 consecutive days. In accordance with this objective, TBBPA sulfation was used as a surrogate for evaluating the potential for estradiol sulfation to be limited at high dose levels of TBBPA. Blood samples were collected at 4 and 8 h post-dosing on study day 7, 14, and 28, while liver and uterus were collected at the same time points following 28 days of dosing. Tissue samples were analyzed for TBBPA, TBBPA-GA and TBBPA-S by LC–MS/MS. A dose-related increase in the concentration of all three analytes occurred in plasma (day 7, 14, and 28 as well as liver and uterus tissue (day 28 at both 4 and 8 h post dose. The plasma concentration of TBBPA-GA and TBBPA-S was higher in animals dosed for 28 days compared to those dosed for 7 or 14 days showing an increase in systemic circulation of these conjugates with repeated administration. The balance of these conjugates was also different in tissues with TBBPA-S > TBBPA-GA at high doses in the liver and TBBPA-GA > TBBPA-S in both plasma and uterus. In all three tissues the ratio of TBBPA-S/TBBPA-GA showed a decreasing trend with dose, suggesting that at high TBBPA dose levels sulfation of TBBPA becomes limited. This effect was most apparent in the liver and plasma at 28 days of administration. Together these data show that administration of high doses of TBBPA

  16. Low-dose metformin improves pregnancy rate in in vitro fertilization repeaters without polycystic ovary syndrome: prediction of effectiveness by multiple parameters related to insulin resistance.

    Science.gov (United States)

    Jinno, Masao; Kondou, Kenichi; Teruya, Koji

    2010-01-01

    Insulin resistance is associated with aging and stress, both common among patients repeatedly failing to conceive with in vitro fertilization (IVF repeaters). In the present study we examined whether low-dose metformin could improve the outcome in IVF repeaters without polycystic ovary syndrome (PCOS). Study I was a preliminary clinical trial aiming at defining indications for therapy; study II was a prospective randomized study. The studies involved a university hospital and a private infertility clinic. We studied 232 women without PCOS who had failed at least twice to conceive by previous IVF. Metformin (500 mg/ day) was administered for 8 to 12 weeks before and during ovarian stimulation (metformin IVF). In study I, IVF outcomes with metformin (n = 33) were compared to outcomes without metformin of previous IVF in the same subjects. A discriminant score (DS) was determined from nine parameters assessed before metformin administration to predict achievement of ongoing pregnancy by metformin IVF. In study II (n = 199), ongoing pregnancy rates were compared prospectively between groups with/without metformin and with DS above/below 0.6647. Study I. Ongoing pregnancy rate improved significantly with metformin compared with previous IVF, and pregnancy correlated significantly with a DS at an optimal threshold of 0.6647 (sensitivity, 0.90; specificity, 0.91). Study II. Ongoing pregnancy and implantation rates were significantly higher in women with a DS above 0.6647 who received metformin (56% and 33%) compared with those having a DS below 0.6647 with metformin (14% and 11%) and those having a DS above/below 0.6647 without metformin (20% and 7.1%/15% and 11%, respectively). Low-dose metformin improved pregnancy rate in IVF repeaters without PCOS, probably by decreasing insulin resistance. Indication can be determined from insulin-resistance-related multiple parameters assessed before metformin administration.

  17. Needle migration and dosimetric impact in high-dose-rate brachytherapy for prostate cancer evaluated by repeated MRI.

    Science.gov (United States)

    Buus, Simon; Lizondo, Maria; Hokland, Steffen; Rylander, Susanne; Pedersen, Erik M; Tanderup, Kari; Bentzen, Lise

    To quantify needle migration and dosimetric impact in high-dose-rate brachytherapy for prostate cancer and propose a threshold for needle migration. Twenty-four high-risk prostate cancer patients treated with an HDR boost of 2 × 8.5 Gy were included. Patients received an MRI for planning (MRI1), before (MRI2), and after treatment (MRI3). Time from needle insertion to MRI3 was ∼3 hours. Needle migration was evaluated from coregistered images: MRI1-MRI2 and MRI1-MRI3. Dose volume histogram parameters from the treatment plan based on MRI1 were related to parameters based on needle positions in MRI2 or MRI3. Regression was used to model the average needle migration per implant and change in D90 clinical target volume, CTV prostate+3mm . The model fit was used for estimating the dosimetric impact in equivalent dose in 2 Gy fractions for dose levels of 6, 8.5, 10, 15, and 19 Gy. Needle migration was on average 2.2 ± 1.8 mm SD from MRI1-MRI2 and 5.0 ± 3.0 mm SD from MRI1-MRI3. D90 CTV prostate+3mm was robust toward average needle migration ≤3 mm, whereas for migration >3 mm D90 decreased by 4.5% per mm. A 3 mm of needle migration resulted in a decrease of 0.9, 1.7, 2.3, 4.8, and 7.6 equivalent dose in 2 Gy fractions for dose levels of 6, 8.5, 10, 15, and 19 Gy, respectively. Substantial needle migration in high-dose-rate brachytherapy occurs frequently in 1-3 hours following needle insertion. A 3-mm threshold of needle migration is proposed, but 2 mm may be considered for dose levels ≥15 Gy. Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  18. Twelve-week efficacy and safety study of mometasone furoate/formoterol 200/10 microg and 400/10 microg combination treatments in patients with persistent asthma previously receiving high-dose inhaled corticosteroids

    DEFF Research Database (Denmark)

    Weinstein, Steven F; Corren, Jonathan; Murphy, Kevin

    2010-01-01

    A significant unmet medical need exists in patients with uncontrolled asthma. The purpose of this study was to evaluate the efficacy and safety of mometasone furoate/formoterol (MF/F) 400/10 microg versus MF 400 microg administered twice-daily (b.i.d.) via metered-dose inhaler in patients...... with asthma uncontrolled on high-dose inhaled corticosteroids (ICS). In a 12-week, randomized, multicenter, double-blind, parallel-group study, patients (>or=12 years of age) were randomized to MF/F 200/10 microg, MF/F 400/10 microg, or MF 400 microg, b.i.d. after a 2- to 3-week open-label run in with MF 400...... microg b.i.d. The primary end point was mean change in area under the curve from 0 to 12 hours in forced expiratory volume in 1 second (FEV(1) AUC(0-12h)) from baseline to week 12 for MF/F 400/10 microg versus MF 400 microg. Effects of MF/F on asthma control and symptoms were evaluated and adverse events...

  19. Inhaled plutonium oxide in dogs

    International Nuclear Information System (INIS)

    Park, J.F.

    1985-01-01

    This project is concerned with long-term experiments to determine the lifespan dose-effect relationships of inhaled 239 PuO 2 and 238 PuO 2 in beagles. The data will be used to estimate the health effects of inhaled transuranics. Beagle dogs given a single exposure to 239 PuO 2 or 238 PuO 2 aerosols to obtain graded levels of initial lung burdens are being observed for lifespan dose-effect relationships. Mortality due to radiation pneumonitis and lung tumor increased in the four highest dose-level groups exposed to 239 PuO 2 , during the 13-yr postexposure period. During the 10 1/2 years after exposure to 238 PuO 2 , mortality due to lung and/or bone tumors increased in the three highest dose-level groups. Chronic lymphopenia, occurring 0.5 to 2 year after exposure, was the earliest observed effect after inhalation of either 239 PuO 2 or 238 PuO 2 in the four highest dose-level groups that had initial lung burdens greater than or equal to 80 nCi. 3 figures, 6 tables

  20. Development of QSAR models using artificial neural network analysis for risk assessment of repeated-dose, reproductive, and developmental toxicities of cosmetic ingredients.

    Science.gov (United States)

    Hisaki, Tomoka; Aiba Née Kaneko, Maki; Yamaguchi, Masahiko; Sasa, Hitoshi; Kouzuki, Hirokazu

    2015-04-01

    Use of laboratory animals for systemic toxicity testing is subject to strong ethical and regulatory constraints, but few alternatives are yet available. One possible approach to predict systemic toxicity of chemicals in the absence of experimental data is quantitative structure-activity relationship (QSAR) analysis. Here, we present QSAR models for prediction of maximum "no observed effect level" (NOEL) for repeated-dose, developmental and reproductive toxicities. NOEL values of 421 chemicals for repeated-dose toxicity, 315 for reproductive toxicity, and 156 for developmental toxicity were collected from Japan Existing Chemical Data Base (JECDB). Descriptors to predict toxicity were selected based on molecular orbital (MO) calculations, and QSAR models employing multiple independent descriptors as the input layer of an artificial neural network (ANN) were constructed to predict NOEL values. Robustness of the models was indicated by the root-mean-square (RMS) errors after 10-fold cross-validation (0.529 for repeated-dose, 0.508 for reproductive, and 0.558 for developmental toxicity). Evaluation of the models in terms of the percentages of predicted NOELs falling within factors of 2, 5 and 10 of the in-vivo-determined NOELs suggested that the model is applicable to both general chemicals and the subset of chemicals listed in International Nomenclature of Cosmetic Ingredients (INCI). Our results indicate that ANN models using in silico parameters have useful predictive performance, and should contribute to integrated risk assessment of systemic toxicity using a weight-of-evidence approach. Availability of predicted NOELs will allow calculation of the margin of safety, as recommended by the Scientific Committee on Consumer Safety (SCCS).

  1. Effects of annealing on the sensitivity of LiF TLD-100 after repeated use for low dose measurements

    International Nuclear Information System (INIS)

    Ogunleye, O.T.; Richmond, R.G.

    1987-01-01

    The changes in sensitivity of LiF TLD-100 extruded ribbons subjected to repeated use up to 100 times were investigated. Three different annealing regimes were compared. The dosemeters were annealed at 400 0 C followed by (i) a slow or (ii) fast cooling to room temperature or (iii) utilising a 20 s readout process in the reader without a high temperature annealing at 400 0 C. Each of the three groups consisted of two sets of 20 chips each, with one set receiving 500 μ Gy of 90 Sr beta radiation and the other unirradiated. Sensitivity evaluations were performed every five cycles through the first 50 cycles, and on each tenth cycle thereafter. On the average, the fast cooled group maintained their integrity best, while a maximum variation in sensitivity of about 15% was observed in the irradiated set of the slowly cooled group. A permanent increase in sensitivity of at least 10% was observed for the set of dosemeters receiving radiation without annealing. Glow curve analyses showed an increase in the ratio of peaks 4 and 5 with repeated use of this group. (author)

  2. Prediction of response to continuous irradiation at low dose rate for repeated administrations in radiotherapy with beta emitters

    International Nuclear Information System (INIS)

    Calderon, Carlos; Gonzalez, Joaquin; Quesada, Waldo

    2009-01-01

    The absorbed dose to tumors after systemic administration of radiopharmaceuticals is not sufficient to achieve acceptable levels of probability of tumor control without compromising on critical tissue toxicity (kidney and / or bone marrow (BM)). There are reports of trials with multiple administrations, about tolerance level inter-administration intervals to allow recovery of the BM, with good results. The biokinetic behavior of some radiopharmaceuticals known makes possible the application of several administrations with short intervals of time.It is the present work combines two kinetic models of tumor growth and cell kinetics in the BM for predicting the response to continuous irradiation at low dose rate. The estimation of the effects of irradiation on tumor and kidneys was done using a formulation of the linear-quadratic model functions suitable for dose rate and multi-exponential repair. The estimation of the response in WB performed using a compartmental model previously reported. The absorbed dose to organs were calculated using the MIRD formulation taking into account the effect of irradiation cross. Biokinetic data were used for therapeutic radiopharmaceuticals 90Y, 131I and 177Lu, as well as radiobiological parameters reported for experimental animals. The effect on the response by the variation of inter-administration interval in slow-growing tumors and fast, so as the radiosensitive and radioresistant tumors. You can set conditions irradiation to an acceptable level of thrombocytopenia (onset and duration of the minimum in the curve) and renal irradiation below the limit of tolerance. It is possible to design experiments evaluation of therapeutic radiopharmaceuticals with a greater degree of refinement. (author)

  3. Repeated Dose 28-Days Oral Toxicity Study of Carica papaya L. Leaf Extract in Sprague Dawley Rats

    Directory of Open Access Journals (Sweden)

    Hussin Muhammad

    2012-04-01

    Full Text Available Carica papaya L. leaves have been used in ethnomedicine for the treatment of fevers and cancers. Despite its benefits, very few studies on their potential toxicity have been described. The aim of the present study was to characterize the chemical composition of the leaf extract from ‘Sekaki’ C. papaya cultivar by UPLC-TripleTOF-ESI-MS and to investigate the sub-acute oral toxicity in Sprague Dawley rats at doses of 0.01, 0.14 and 2 g/kg by examining the general behavior, clinical signs, hematological parameters, serum biochemistry and histopathology changes. A total of twelve compounds consisting of one piperidine alkaloid, two organic acids, six malic acid derivatives, and four flavonol glycosides were characterized or tentatively identified in the C. papaya leaf extract. In the sub-acute study, the C. papaya extract did not cause mortality nor were treatment-related changes in body weight, food intake, water level, and hematological parameters observed between treatment and control groups. Some biochemical parameters such as the total protein, HDL-cholesterol, AST, ALT and ALP were elevated in a non-dose dependent manner. Histopathological examination of all organs including liver did not reveal morphological alteration. Other parameters showed non-significant differences between treatment and control groups. The present results suggest that C. papaya leaf extract at a dose up to fourteen times the levels employed in practical use in traditional medicine in Malaysia could be considered safe as a medicinal agent.

  4. Lung deposition of inhaled drugs increases with age

    DEFF Research Database (Denmark)

    Onhøj, J; Thorsson, L; Bisgaard, H

    2000-01-01

    Budesonide plasma concentrations after inhalation of a fixed dose of the drug from a pressurized metered dose inhaler (pMDI) with spacer (Nebuchamber) were compared in young children and adults: 26 patients with mild asthma comprising 8 children 2-3 yr, 8 children 4-6 yr, and 10 adults 20-41 yr...

  5. Evaluation of repeated dose micronucleus assays of the liver and gastrointestinal tract using potassium bromate: a report of the collaborative study by CSGMT/JEMS.MMS.

    Science.gov (United States)

    Okada, Emiko; Fujiishi, Yohei; Narumi, Kazunori; Kado, Shoichi; Wako, Yumi; Kawasako, Kazufumi; Kaneko, Kimiyuki; Ohyama, Wakako

    2015-03-01

    The food additive potassium bromate (KBrO3) is known as a renal carcinogen and causes chromosomal aberrations in vitro without metabolic activation and in vivo in hematopoietic and renal cells. As a part of a collaborative study by the Mammalian Mutagenicity Study group, which is a subgroup of the Japanese Environmental Mutagen Society, we administered KBrO3 to rats orally for 4, 14, and 28 days and examined the micronucleated (MNed) cell frequency in the liver, glandular stomach, colon, and bone marrow to confirm whether the genotoxic carcinogen targeting other than liver and gastrointestinal (GI) tract was detected by the repeated dose liver and GI tract micronucleus (MN) assays. In our study, animals treated with KBrO3 showed some signs of toxicity in the kidney and/or stomach. KBrO3 did not increase the frequency of MNed cells in the liver and colon in any of the repeated dose studies. However, KBrO3 increased the frequency of MNed cells in the glandular stomach and bone marrow. Additionally, the MNed cell frequency in the glandular stomach was not significantly affected by the difference in the length of the administration period. These results suggest that performing the MN assay using the glandular stomach, which is the first tissue to contact agents after oral ingestion, is useful for evaluating the genotoxic potential of chemicals and that the glandular stomach MN assay could be integrated into general toxicity studies. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Propose of a model for dose and hazard calculation due the Rn-222, Rn-220 and its short half-life daugthers inhalation

    International Nuclear Information System (INIS)

    Mauricio, C.L.P.

    1982-01-01

    The compartimental dosimetric model is used to simulate, by computer, the interactions of the inhalated radon atom radiations and its short half-life daugthers with cells. The metabolic trajectory of these radionuclides is described by differential equations of continuous medium dynamics, where the elements transform by radioactive decay. This work permits to determine the individual retenction function, beeing useful in radioprotection routines or emergence situations. The results of internal dosimetry are consistent with the new I.C.R.P. - 32 international recommendations. (L.C.) [pt

  7. Proposal of a new model for dose calculation due to the inhalation of Ru-222, Ru-220 and their sons with brief half-life

    International Nuclear Information System (INIS)

    Mauricio, C.L.P.

    1982-06-01

    The consequences of the radiation interactions upon the human body are studied. In order to simulate by computer the radiation interaction of the atoms of radon and thoron atoms and their Sons with a brief half life inhaled with the cells, the compartimental dosimetric model is used. The metabolic pathway of those radionuclides is described by continuous medium dynamic differential equation. The energy transfer processes are seen in details. The individual retention function is determined by bio-analysis. The results of internal dosimetry are consistents with the new international recommendations from ICRP-32. (L.F.S.) [pt

  8. Measurement of activity concentrations of {sup 40}K, 2{sup 32T}h and {sup 238}U in TSP aerosols and the associated inhalation annual effective radiation dose to the public in Gosan site, Jeju

    Energy Technology Data Exchange (ETDEWEB)

    Han, Chung Hun; Park, Youn Hyun; Park, Jae Woo [Jeju National University, Jeju (Korea, Republic of)

    2016-10-15

    Gamma radiation emitted from naturally occurring radioisotopes, such as 40K and the radionuclides from the {sup 232}Th and {sup 238}U series and their decay products, which exist at trace levels in all ground formations, represents the main external source of irradiation to the human body. The objective of the current study is to determine the activity concentrations of 40K, {sup 232}Th and {sup 238}U in airborne TSP and the associated internal radiation dose to the public due to inhalation in Gosan site, Jeju Island, Korea. The atmospheric total suspended particulates (TSP) aerosols were collected at Gosan site of Jeju Island, which is one of the background sites of Korea, during January to April 2013. This study analyzed using ICP-DRC-MS the concentrations of potassium, uranium and thorium, and evaluated the annual effective dose by breathing from the results. The correlations between the studied natural isotopes is a good positive correlation between {sup 232}Th and {sup 238}U, supporting the conclusion that they originated from the same source, mostly the crust. The backward trajectory analysis has confirmed that the 40K, {sup 238}U and {sup 232}Th are delivered as the air masses have moved from the China continent. The inhalation annual effective radiation dose (default mode F) to the public due to natural isotopes of the airborne TSP was in the range 16.195 - 77.051 nSv/y, depending on the age group. Jeju Island with less pollution source and low population density is also one of the best places as a background area in Asia.

  9. Disposition of diiosononyl phthalate and its effects on sexual development of the male fetus following repeated dosing in pregnant rats.

    Science.gov (United States)

    Clewell, Rebecca A; Sochaski, Mark; Edwards, Kendra; Creasy, Dianne M; Willson, Gabrielle; Andersen, Melvin E

    2013-01-01

    Pregnant Sprague-Dawley rats received 50, 250, and 500 mg/kg/day diisononyl phthalate (DiNP) from GD 12 to 19 via corn oil gavage to study the dose response for effects on fetal male rat sexual development as well as metabolite disposition in the dam and fetus. Monoisononyl phthalate (MiNP), mono(carboxy-isooctyl) phthalate (MCiOP), mono(hydroxyl-isononyl) phthalate (MHiNP), mono(oxo-isononyl) phthalate (MOiNP), and monoisononyl phthalate glucuronide (MiNP-G) were found in all measured tissues. MCiOP was the major metabolite, followed in decreasing order by MiNP, MHiNP, MOiNP, and MiNP-G. Percentage of dose absorbed decreased at 750 mg/kg/day. Testosterone concentration in the fetal testes was reduced at 250 and 750 mg/kg/day. Multinucleated germ cells were increased in the testes of rats at 250 and 750 mg/kg/day. The no observed effect level (NOEL) for this study was 50 mg/kg/day based on increased MNGs and reduced testes testosterone concentration in the fetal rat. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Inhaled plutonium oxide in dogs

    International Nuclear Information System (INIS)

    Park, J.F.

    1982-01-01

    This project is concerned with long-term experiments to determine the lifespan dose-effect relationships of inhaled 239 PuO 2 and 238 PuO 2 in beagles. Beagle dogs given a single exposure to 239 PuO 2 or 238 PuO 2 aerosols are being observed for lifespan dose-effect relationships. The 239 Pu body burden of the nine dogs that died of pulmonary-fibrosis-induced respiratory insufficiency during the first 3 yr after exposure was 1 to 12μCi. Nineteen of the dogs exposed to 238 Pu haved died during the first 7-1/2 yr after exposure due to bone and/or lung tumors; their body burdens at death ranged from 0.7 to 10μCi. Chronic lymphopenia was the earliest observed effect after inhalation of 239 PuO 2 or 238 PuO 2

  11. Behavioral sensitization after repeated formaldehyde exposure in rats.

    Science.gov (United States)

    Sorg, B A; Hochstatter, T

    1999-01-01

    Multiple chemical sensitivity (MCS) is a phenomenon whereby individuals report increased sensitivity to chemicals in the environment, and attribute their sensitivities to prior exposure to the same or often structurally unrelated chemicals. A leading hypothesis suggests that MCS is akin to behavioral sensitization observed in rodents after repeated exposure to drugs of abuse or environmental stressors. Sensitization occurring within limbic circuitry of the central nervous system (CNS) may explain the multisymptom complaints in individuals with MCS. The present studies represent the continuing development of an animal model for MCS, the basis of which is the CNS sensitization hypothesis. Three behaviors were assessed in rats repeatedly exposed to formaldehyde (Form) inhalation. In the first series of experiments, rats were given high-dose Form exposure (11 parts per million [ppm]; 1 h/day x 7 days) or low-dose Form exposure (1 ppm; either 1 h/day x 7 days or 1 h/day x 5 days/week x 4 weeks). Within a few days after discontinuing daily Form, cocaine-induced locomotor activity was elevated after high-dose Form or 20 days of low-dose Form inhalation. Approximately 1 month later, cocaine-induced locomotor activity remained significantly elevated in the 20-day Form-exposed rats. The second experiment assessed whether prior exposure to Form (20 days, as above) would alter the ability to condition to an odor (orange oil) paired with footshock. The results suggested a tendency to increase the conditioned fear response to the odor but not the context of the footshock box, and a decreased tendency to extinguish the conditioned fear response to odor. The third experiment examined whether CNS sensitization to daily cocaine or stress would alter subsequent avoidance responding to odor (Form). Daily cocaine significantly elevated approach responses to Form, while daily stress pretreatment produced a trend in the opposite direction, producing greater avoidance of Form. Preliminary

  12. Topographical distribution of decrements and recovery in muscarinic receptors from rat brains repeatedly exposed to sublethal doses of soman

    International Nuclear Information System (INIS)

    Churchill, L.; Pazdernik, T.L.; Jackson, J.L.; Nelson, S.R.; Samson, F.E.; McDonough, J.H. Jr.

    1984-01-01

    [3H]Quinuclidinyl benzilate binding to rat brain muscarinic receptors decreased after repeated exposure to soman, a potent organophosphorus cholinesterase inhibitor. The topographical distribution of this decrement was analyzed by quantitative receptor autoradiography. After 4 weeks of soman, three times a week, quinuclidinyl benzilate binding decreased to 67 to 80% of control in frontal and parietal cortex, caudate-putamen, lateral septum, hippocampal body, dentate gyrus, superior colliculus, nucleus of the fifth nerve, and central grey. Minor or no decreases were observed in thalamic or hypothalamic nuclei, reticular formation, pontine nuclei, inferior colliculus, nucleus of the seventh nerve, and cerebellum. Scatchard analyses of saturation curves using frontal cortex sections from soman-treated rats revealed a decrease in maximal quinuclidinyl benzilate binding from that in control rats and a return toward control levels by 24 days without any significant change in affinity. These brain areas showing significant decrements in muscarinic receptors recovered with a similar time course. An estimate of the time for 50% recovery for some of the brain areas was 14 days for superior colliculus, 16 days for cortex, and 19 days for hippocampal body. The application of quantitative receptor autoradiography to analyze receptor alterations has been valuable in localizing the telencephalon as a region more susceptible to change in receptor concentration

  13. Topographical distribution of decrements and recovery in muscarinic receptors from rat brains repeatedly exposed to sublethal doses of soman

    Energy Technology Data Exchange (ETDEWEB)

    Churchill, L.; Pazdernik, T.L.; Jackson, J.L.; Nelson, S.R.; Samson, F.E.; McDonough, J.H. Jr.

    1984-08-01

    (3H)Quinuclidinyl benzilate binding to rat brain muscarinic receptors decreased after repeated exposure to soman, a potent organophosphorus cholinesterase inhibitor. The topographical distribution of this decrement was analyzed by quantitative receptor autoradiography. After 4 weeks of soman, three times a week, quinuclidinyl benzilate binding decreased to 67 to 80% of control in frontal and parietal cortex, caudate-putamen, lateral septum, hippocampal body, dentate gyrus, superior colliculus, nucleus of the fifth nerve, and central grey. Minor or no decreases were observed in thalamic or hypothalamic nuclei, reticular formation, pontine nuclei, inferior colliculus, nucleus of the seventh nerve, and cerebellum. Scatchard analyses of saturation curves using frontal cortex sections from soman-treated rats revealed a decrease in maximal quinuclidinyl benzilate binding from that in control rats and a return toward control levels by 24 days without any significant change in affinity. These brain areas showing significant decrements in muscarinic receptors recovered with a similar time course. An estimate of the time for 50% recovery for some of the brain areas was 14 days for superior colliculus, 16 days for cortex, and 19 days for hippocampal body. The application of quantitative receptor autoradiography to analyze receptor alterations has been valuable in localizing the telencephalon as a region more susceptible to change in receptor concentration.

  14. Synthetic food coloring and behavior: a dose response effect in a double-blind, placebo-controlled, repeated-measures study.

    Science.gov (United States)

    Rowe, K S; Rowe, K J

    1994-11-01

    To establish whether there is an association between the ingestion of synthetic food colorings and behavioral change in children referred for assessment of "hyperactivity." From approximately 800 children referred to the Royal Children's Hospital (Melbourne) for assessment of suspected hyperactivity, 200 were included in a 6-week open trial of a diet free of synthetic food coloring. The parents of 150 children reported behavioral improvement with the diet, and deterioration on the introduction of foods noted to contain synthetic coloring. A 30-item behavioral rating inventory was devised from an examination of the clinical histories of 50 suspected reactors. Thirty-four other children (23 suspected reactors, 11 uncertain reactors) and 20 control subjects, aged 2 to 14 years, were studied. A 21-day, double-blind, placebo-controlled, repeated-measures study used each child as his or her own control. Placebo, or one of six dose levels of tartrazine (1, 2, 5, 10, 20, 50 mg), was administered randomly each morning, and behavioral ratings were recorded by parents at the end of each 24 hours. The study identified 24 children as clear reactors (19 of 23 "suspected reactors," 3 of 11 "uncertain reactors," and 2 of 20 "control subjects"). They were irritable and restless and had sleep disturbance. Significant reactions were observed at all six dose levels. A dose response effect was obtained. With a dose increase greater than 10 mg, the duration of effect was prolonged. Behavioral changes in irritability, restlessness, and sleep disturbance are associated with the ingestion of tartrazine in some children. A dose response effect was observed.

  15. Ciclesonide Oral Inhalation

    Science.gov (United States)

    ... use ciclesonide inhalation.Ciclesonide inhalation helps to prevent asthma attacks (sudden episodes of shortness of breath, wheezing, and coughing) but will not stop an asthma attack that has already started. Do not use ciclesonide ...

  16. Flunisolide Oral Inhalation

    Science.gov (United States)

    ... use flunisolide inhalation.Flunisolide inhalation helps to prevent asthma attacks (sudden episodes of shortness of breath, wheezing, and coughing) but will not stop an asthma attack that has already started. Do not use flunisolide ...

  17. Physiologic effect of repeated adrenaline (epinephrine) doses during cardiopulmonary resuscitation in the cath lab setting: A randomised porcine study.

    Science.gov (United States)

    Hardig, Bjarne Madsen; Götberg, Michael; Rundgren, Malin; Götberg, Matthias; Zughaft, David; Kopotic, Robert; Wagner, Henrik

    2016-04-01

    This porcine study was designed to explore the effects of repetitive intravenous adrenaline doses on physiologic parameters during CPR. Thirty-six adult pigs were randomised to four injections of: adrenaline 0.02 mg(kgdose)(-1), adrenaline 0.03 mg(kgdose)(-1) or saline control. The effect on systolic, diastolic and mean arterial blood pressure, cerebral perfusion pressure (CePP), end tidal carbon dioxide (ETCO2), arterial oxygen saturation via pulse oximetry (SpO2), cerebral tissue oximetry (SctO2), were analysed immediately prior to each injection and at peak arterial systolic pressure and arterial blood gases were analysed at baseline and after 15 min. In the group given 0.02 mg(kgdose)(-1), there were increases in all arterial blood pressures at all 4 pressure peaks but CePP only increased significantly after peak 1. A decrease in ETCO2 following peak 1 and 2 was observed. SctO2 and SpO2 were lowered following injection 2 and beyond. In the group given a 0.03 mg(kgdose)(-1), all ABP's increased at the first 4 pressure peaks but CePP only following 3 pressure peaks. Lower ETCO2, SctO2 and SpO2 were seen at peak 1 and beyond. In the two adrenaline groups, pH and Base Excess were lower and lactate levels higher compared to baseline as well as compared to the control. Repetitive intravenous adrenaline doses increased ABP's and to some extent also CePP, but significantly decreased organ and brain perfusion. The institutional protocol number: Malmö/Lund Committee for Animal Experiment Ethics, approval reference number: M 192-10. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Safety and PK/PD correlation of TV-1106, a recombinant fused human albumin-growth hormone, following repeat dose administration to monkeys.

    Science.gov (United States)

    Ashkenazi, Nurit; Rosenstock, Moti; Hallak, Hussein; Bassan, Merav; Rasamoelisolo, Michele; Leuschner, Jost; Shinar, Doron

    TV-1106 is a recombinant human albumin genetically fused to growth hormone which is intended to reduce the frequency of injections for GH therapy users. We report the safety, tolerability, pharmacokinetics and pharmacodynamics of repeated subcutaneous injections of TV-1106 in Cynomolgus monkeys. Cynomolgus monkeys received four weekly subcutaneous injections of 0, 5, 10 or 20mg/kg TV-1106 and were monitored for safety signals throughout the study. Serum levels of TV-1106 and insulin-like growth factor 1 (IGF-1) were assayed. Treated animals showed no adverse effects or histopathological changes. TV-1106 serum concentrations showed sustained exposure to the drug. Exposure increased in a dose-dependent manner with peak concentrations at approximately 24h post-dosing and elimination half-lives in the range of 12 to 24h. IGF-1 serum concentrations were elevated throughout the entire study duration, indicative of the pharmacological response. There was a clear correlation between change in IGF-1 levels and dose or exposure to TV-1106. The safety, pharmacokinetic and pharmacodynamic findings support the further development of TV-1106 as a once-weekly administered treatment for patients with GHD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. [Toxicity studies of landiolol hydrochloride (ONO-1101) (2). 4-week repeated dose intravenous toxicity study in rats with 4-week recovery test].

    Science.gov (United States)

    Yamaguchi, K; Yanagi, H; Shimizu, K; Sakai, M; Nishibata, K; Oida, H; Shinomiya, K; Suzuki, Y; Yonezawa, H; Fujita, T

    1997-12-01

    4-week repeated dose toxicity study with 4-week recovery test of landiolol hydrochloride (ONO-1101), a novel ultra short acting beta-blocker, was conducted in Sprague-Dawley (SD) rats. ONO-1101 was administered intravenously to rats of both sexes at a dose level of 0 (control), 12.5, 25, 50 or 100 mg/kg/day. In the 100 mg/kg/day group, bradypnea or dyspnea was seen in all animals, pale in ear, eye and foot, tremor, reddish lacrimation and loss of righting reflex were also observed in some animals right after administration, and then those signs disappeared within 1 min after administration. During the treatment period, 3/20 animals of each sex in the 100 mg/kg/day showed clonic convulsion and died within 2 min after administration. No clinical changes were seen in the 50 mg/kg/day group or lower. Histopathological findings showed atrophy of the submaxillary gland in females and vessel-wall thickening and perivascular fibrosis of the injection site (tail) in both sexes at 100 mg/kg/day, however those changes were reversible. ONO-1101 did not effect on body weight, food consumption, ophthalmology, urinalysis, hematology, blood chemistry, organ weights or necropsy at any doses. These results indicate that the no-adverse-effect level of ONO-1101 in rats is 50 mg/kg/day for both sexes in this study.

  20. Teaching inhaler use in chronic obstructive pulmonary disease patients.

    Science.gov (United States)

    Lareau, Suzanne C; Hodder, Richard

    2012-02-01

    To review barriers to the successful use of inhalers in patients with chronic obstructive pulmonary disease (COPD), and the role of the nurse practitioner (NP) in facilitating optimum inhaler use. Review of the national and international scientific literature. Pharmacologic treatment of COPD patients comprises mainly inhaled medications. Incorrect use of inhalers is very common in these individuals. Some of the consequences of poor inhaler technique include reduced therapeutic dosing, medication adherence, and disease stability, which can lead to increased morbidity, decreased quality of life, and a high burden on the healthcare system. Knowledgeable evaluation and frequent reassessment of inhaler use coupled with education of patients, caregivers, and healthcare professionals can significantly improve the benefits COPD patients derive from inhaled therapy. Patient education is vital for correct use of inhalers and to ensure the effectiveness of inhaled medications. The NP has a critical role in assessing potential barriers to successful learning by the patient and improving inhaler technique and medication management. The NP can also facilitate success with inhaled medications by providing up-to-date inhaler education for other healthcare team members, who may then act as patient educators. ©2011 The Author(s) Journal compilation ©2011 American Academy of Nurse Practitioners.

  1. Hydrazine inhalation hepatotoxicity.

    Science.gov (United States)

    Kao, Yung Hsiang; Chong, C H; Ng, W T; Lim, D

    2007-10-01

    Abstract Hydrazine is a hazardous chemical commonly used as a reactant in rocket and jet fuel cells. Animal studies have demonstrated hepatic changes after hydrazine inhalation. Human case reports of hydrazine inhalation hepatotoxicity are rare. We report a case of mild hepatotoxicity following brief hydrazine vapour inhalation in a healthy young man, which resolved completely on expectant management.

  2. A 90-day repeated-dose toxicity study of dietary alpha linolenic acid-enriched diacylglycerol oil in rats.

    Science.gov (United States)

    Bushita, Hiroto; Ito, Yuichi; Saito, Tetsuji; Nukada, Yuko; Ikeda, Naohiro; Nakagiri, Hideaki; Saito, Kazutoshi; Morita, Osamu

    2018-05-31

    Diets supplemented with alpha-linolenic acid (ALA)-enriched diacylglycerol (DAG) oil-which mainly consists of oleic and linolenic, linoleic acids-have potential health benefits in terms of preventing or managing obesity. Although safety of DAG oil has been extensively investigated, toxicity of ALA-DAG oil has not been well understood. Hence, the present study was conducted to clarify the potential adverse effects, if any, of ALA-DAG oil in rats (10/sex/group) fed diets containing 1.375%, 2.75%, or 5.5% ALA-DAG oil for 90 days. Compared to control rats fed rapeseed oil or ALA-triacylglycerol oil (flaxseed oil), rats receiving ALA-DAG oil did not reveal any toxicologically significant treatment-related changes as evaluated by clinical signs, functional observational battery, body weight, food consumption, ophthalmology, urinalysis, hematology, clinical chemistry, organ weight, necropsy and histopathology. The no observed adverse effect levels for dietary exposure to ALA-DAG oil for male and female rats were 2916 and 3326 mg/kg body weight/day, respectively, the highest dose tested. The findings from this study suggest that consumption of ALA-DAG oil is unlikely to cause adverse effects. Copyright © 2018. Published by Elsevier Inc.

  3. Safety of sucrose esters from Physalis peruviana L. in a 28-day repeated-dose study in mice.

    Science.gov (United States)

    Ocampo, Yanet C; Caro, Daneiva C; Rivera, David E; Franco, Luis A

    2017-06-01

    Although extracts and consumed foods from Physalis species contain sucrose esters from their glandular trichomes, there is no experimental data available on their toxicological effects. As peruvioses A and B isolated from Physalis peruviana L. calyces have proved to be effective anti-inflammatory and immunomodulatory compounds, this work aimed to investigate their sub-acute toxicity study and genotoxicity. For this, CD-1(ICR) mice were treated intraperitoneally with peruvioses at doses of 2.5, 5, and 10mg/kg/day for 28 consecutive days, to simulate therapeutic and over-therapeutic dosage levels. At the end of the treatment, animals were sacrificed and their organs weighted, and blood and tissue samples were collected. Toxicological endpoints included clinical signs; food consumption; body and organ weights; hematological and biochemical parameters; as well as macroscopic and microscopic examination of tissues. The results showed no significant differences between treated animals and control group at macroscopic, histological, molecular, and biochemical levels. In addition, a combination of mammalian erythrocyte micronucleus test, comet assay in peripheral blood cells, and Ames test, did not reveal genotoxic effects induced by peruvioses. Taken together, our data suggests that peruvioses A and B can be safely employed to treat inflammatory diseases. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. Development of immunity against viral and bacterial antigens after repeated exposures to suberythemal doses of ultraviolet light

    Directory of Open Access Journals (Sweden)

    S. A. Snopov

    2012-01-01

    Full Text Available The effects of ultraviolet (UV radiation on human infectious immunity are not well studied. On the one hand, solar and artificial UU sources have been shown to change cytokine levels in human skin, lymphocyte subpopulation counts in parepheral blood, lymphocyte DNA synthesis and prolifarative response to mitogens. On the other hand, there are just only one or two observations suggesting an influence of UV radiation on human infection course. For instance, UV irradiations have been reported to induce a reccurence of orofacial vesicular lesions caused by herpes siplex virus. Moreover, there is a lack of data concerning immune effects of suberythtemal doses of UV in spite of a long history of using them by Russian prophylactic medicine. In this work we questioned whether such suberythemal UV exposures can affect the immune responses of children to infectious conjunctivitis, to simultaneous measles and polio vaccinations and to simultaneous polio and diphtheria-tetanus vaccinations. In peripheral blood of vaccinated children we examined leukocyte counts (monocytes, neutrophils, eosinophils, lymphocytes, percentages of lymphocyte subpopulations (CD3+, CD20+, CD4+, CD8+, CD25+, HLADR+, concentrations of cytokines (IL-1 beta, TNF-alpha, IFN- amma и IL-10, DNA-synthetic activity of lymphocytes and titres of antibodies against measles and diphtheria toxin. We observed no local or systemic reactions to the vaccines in the UV-group while a moderate rise in body temperature occured in several children from unexposed group. In the blood of childeren from UV-group we found increases in CD25+ и HLADR+ cell percentages, IL- 1 beta and IL-10 concentrations, PWMinduced DNA synthesis in mononuclears, and no decreases in formation of antibodies against measles and diphreria. We concluded that suberythemal UV exposures of children modulated their further responses to imminisations perhaps through the activation of a T helper 2-like

  5. A method for determining an indicator of effective dose calculation due to inhalation of Radon and its progeny from in vivo measurements; Um metodo para determinar um indicador para calcular dose efetiva devida a inalacao de Radonio e seus descendentes utilizando medicoes in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Estrada, Julio Jose da Silva

    1994-07-01

    Direct measurement of the absolved dose to lung tissue from inhalation of radon and its progeny is not possible and must be calculated using dosimetric models, taking into consideration the several parameters upon which the dose calculation depends. To asses the dose due to inhalation of radon and its progeny, it is necessary to estimate the cumulative exposure. Historically, this has been done using WLM values estimated with measurements of radon concentration in air. The radon concentration in air varies significantly, however, in space with time, and the exposed individual is also constantly moving around. This makes it almost impossible to obtain a precise estimate of an individual's inhalation exposure. This work describes a pilot study to calculate lung dose from the deposition of radon progeny, via estimates of cumulative exposure derived from in vivo measurements of {sup 210} Pb, in subjects exposed to above-average radon and its progeny concentrations in their home environments. The measurements were performed in a whole body counter. With this technique, the exposed individuals become, in affect, their own samplers and dosimeters and the estimate of cumulative exposure is not affected by the variation of the atmospheric concentration of radon and its progeny in time and space. Forty individuals identified as living in homes with radon levels ranging from about 740 Bq/m{sup 3} to 150.000 Bq/m{sup 3} were measured. Also, additional 34 measurements were made on personnel from NYUMC/NIEM who live in a residential area surrounding the laboratory in which the levels of radon have been shown to be at below average values. To realize these measurements a methodology was developed to determine the subject's background, using a head phantom made with a cubic plastic container containing known amounts of potassium and calcium dissolved in four liters of water. The effective doses calculated from the in vivo measurements are compared to effective doses estimated, for

  6. A method for determining an indicator of effective dose calculation due to inhalation of Radon and its progeny from in vivo measurements; Um metodo para determinar um indicador para calcular dose efetiva devida a inalacao de Radonio e seus descendentes utilizando medicoes in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Estrada, Julio Jose da Silva

    1994-07-01

    Direct measurement of the absolved dose to lung tissue from inhalation of radon and its progeny is not possible and must be calculated using dosimetric models, taking into consideration the several parameters upon which the dose calculation depends. To asses the dose due to inhalation of radon and its progeny, it is necessary to estimate the cumulative exposure. Historically, this has been done using WLM values estimated with measurements of radon concentration in air. The radon concentration in air varies significantly, however, in space with time, and the exposed individual is also constantly moving around. This makes it almost impossible to obtain a precise estimate of an individual's inhalation exposure. This work describes a pilot study to calculate lung dose from the deposition of radon progeny, via estimates of cumulative exposure derived from in vivo measurements of {sup 210} Pb, in subjects exposed to above-average radon and its progeny concentrations in their home environments. The measurements were performed in a whole body counter. With this technique, the exposed individuals become, in affect, their own samplers and dosimeters and the estimate of cumulative exposure is not affected by the variation of the atmospheric concentration of radon and its progeny in time and space. Forty individuals identified as living in homes with radon levels ranging from about 740 Bq/m{sup 3} to 150.000 Bq/m{sup 3} were measured. Also, additional 34 measurements were made on personnel from NYUMC/NIEM who live in a residential area surrounding the laboratory in which the levels of radon have been shown to be at below average values. To realize these measurements a methodology was developed to determine the subject's background, using a head phantom made with a cubic plastic container containing known amounts of potassium and calcium dissolved in four liters of water. The effective doses calculated from the in vivo measurements are compared to effective doses

  7. Impact of Single or Repeated Dose Intranasal Zinc-free Insulin in Young and Aged F344 Rats on Cognition, Signaling, and Brain Metabolism.

    Science.gov (United States)

    Anderson, Katie L; Frazier, Hilaree N; Maimaiti, Shaniya; Bakshi, Vikas V; Majeed, Zana R; Brewer, Lawrence D; Porter, Nada M; Lin, Ai-Ling; Thibault, Olivier

    2017-02-01

    Novel therapies have turned to delivering compounds to the brain using nasal sprays, bypassing the blood brain barrier, and enriching treatment options for brain aging and/or Alzheimer's disease. We conducted a series of in vivo experiments to test the impact of intranasal Apidra, a zinc-free insulin formulation, on the brain of young and aged F344 rats. Both single acute and repeated daily doses were compared to test the hypothesis that insulin could improve memory recall in aged memory-deficient animals. We quantified insulin signaling in different brain regions and at different times following delivery. We measured cerebral blood flow (CBF) using MRI and also characterized several brain metabolite levels using MR spectroscopy. We show that neither acute nor chronic Apidra improved memory or recall in young or aged animals. Within 2 hours of a single dose, increased insulin signaling was seen in ventral areas of the aged brains only. Although chronic Apidra was able to offset reduced CBF with aging, it also caused significant reductions in markers of neuronal integrity. Our data suggest that this zinc-free insulin formulation may actually hasten cognitive decline with age when used chronically. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Comparative analysis of transcriptomic responses to repeated-dose exposure to 2-MCPD and 3-MCPD in rat kidney, liver and testis.

    Science.gov (United States)

    Buhrke, Thorsten; Schultrich, Katharina; Braeuning, Albert; Lampen, Alfonso

    2017-08-01

    3-Chloro-1,2-propanediol (3-MCPD) and its isomer 2-chloro-1,3-propanediol (2-MCPD) are heat-induced food contaminants present in oil- and fat-containing foodstuff. Kidney and testes are among the main target organs of 3-MCPD. Almost no data on 2-MCPD toxicity are available. Here, transcriptomic responses following repeated-dose exposure of rats to non-toxic doses of 10 mg/kg body weight per day 2-MCPD or 3-MCPD for 28 days were characterized by microarray analysis of kidney, liver, and testes. 3-MCPD exerted more pronounced effects than 2-MCPD in all organs. The limited overlap between the datasets indicates that 2-MCPD and 3-MCPD do not share the same molecular mechanisms of toxicity. By combining transcriptomic data with datasets on proteomic regulation by 3-MCPD, a comprehensive view on 3-MCPD-induced regulation of glucose utilization and oxidative stress response was developed. Bioinformatic analyses revealed that Nrf2 (nuclear factor (erythroid-derived 2)-like 2) signaling is likely to be involved in mediating the oxidative stress response to 3-MCPD. In summary, this study for the first time presents data on alterations in global gene expression by two important food contaminants, 2-MCPD and 3-MCPD. Data demonstrate profound differences between the effects of the two compounds and substantially broaden our knowledge on molecular details of 3-MCPD-induced disturbance of glucose utilization and redox balance. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Inalador dosimetrado com espaçador artesanal versus nebulizador no tratamento da crise de sibilância na criança Metered-dose inhaler with home-made spacer versus nebulizers to treat moderate wheezing attacks in children

    Directory of Open Access Journals (Sweden)

    Liana Consuelo Santana Vilarinho

    2003-10-01

    oximetria. A comparação dos parâmetros clínicos e de saturação de oxigênio, entre os grupos, não mostrou diferença significativa após as doses de salbutamol, havendo equivalência clínica entre doses diferentes (três vezes menor no grupo IDE, em relação ao grupo NEB; os tempos de preparo e administração da medicação e o custo do tratamento foram significativamente menores no grupo IDE. O grau de satisfação das famílias foi semelhante nos dois grupos. CONCLUSÃO: O inalador dosimetrado com espaçador artesanal pode ser utilizado na admini stração de salbutamol a crianças em crise de sibilância, com algumas vantagens em relação ao nebulizador.OBJECTIVE: To compare the effectiveness of salbutamol administration by metered-dose inhaler with a home-made spacer versus jet nebulizer in children with moderate wheezing attacks. MATERIAL AND METHODS: A randomized, single-blinded trial was performed with a convenience sample of children presenting wheezing. The children were enrolled in an emergency room and randomly assigned to one of two treatment groups: home-made spacer group or nebulizer group. Clinical scores and oxygen saturation were recorded at baseline and 15 minutes after salbutamol administration. Treatment with salbutamol (100 µg/3 kg in the spacer group, and 250 µg/3 kg in the nebulizer group was repeated at 20-minute intervals, until the child was considered to have improved significantly, with no need of any further dose, or until three doses were delivered. Treatment cost, time spent to prepare and deliver the drug, and level of parental satisfaction with the treatment were recorded. RESULTS: Fifty-four children with age between 22 days and 11.7 years were enrolled - 27 in each group. Baseline and demographic characteristics were similar for both groups. The spacer was as effective as the nebulizer in terms of clinical score and oxygen saturation. The different doses (100 µg/3 kg with the spacer, and 250 µg/3 kg with the nebulizer were

  10. The influence of exercise and dehydration on the urine concentrations of salbutamol after inhaled administration of 1600 µg salbutamol as a single dose in relation to doping analysis

    DEFF Research Database (Denmark)

    Haase, Christoffer Bjerre; Backer, Vibeke; Kalsen, Anders

    2016-01-01

    The present study investigated the influence of exercise and dehydration on the urine concentrations of salbutamol after inhalation of that maximal permitted (1600 µg) on the 2015 World Anti-Doping Agency (WADA) prohibited list. Thirteen healthy males participated in the study. Urine concentrations...... of salbutamol were measured during three conditions: exercise (EX), exercise+dehydration (EXD), and rest (R). Exercise consisted of 75 min cycling at 60% of VO2max and a 20-km time-trial. Fluid intake was 2300, 270, and 1100 mL during EX, EXD, and R, respectively. Urine samples of salbutamol were collected 0.......0±0.7 ng/mL) than EX(3.8±0.8 ng/mL) and EXD(3.6±0.8 ng/mL). AUC was lower for R (14.1±2.8 ng/mL·∙h) than EX (16.9±2.9 ng/mL·∙h)(Pdehydration affect urine concentrations of salbutamol and increase the risk of Adverse Analytical Findings...

  11. Inhaled medication and inhalation devices for lung disease in patients with cystic fibrosis: A European consensus

    DEFF Research Database (Denmark)

    Heijerman, Harry; Westerman, Elsbeth; Conway, Steven

    2009-01-01

    , mucolytics/mucous mobilizers, anti-inflammatory drugs, bronchodilators and combinations of solutions. Additionally, we review the current knowledge on devices for inhalation therapy with regard to optimal particle sizes and characteristics of wet nebulisers, dry powder and metered dose inhalers. Finally, we...... review the current status of inhaled medication in CF, including the mechanisms of action of the various drugs, their modes of administration and indications, their effects on lung function, exacerbation rates, survival and quality of life, as well as side effects. Specifically we address antibiotics...

  12. Evaluation of Inhaler Techniques Among Asthma Patients Seen in ...

    African Journals Online (AJOL)

    Background: An Adequate and an effective dose of inhalation drugs can be administered only if the correct inhaler‑specific technique is followed by asthma patients. There is paucity of data on this subject among Nigerians and Africans. Aims: This observational study was to assess the inhaler techniques among asthma ...

  13. Inhalant allergies in children.

    Science.gov (United States)

    Mims, James W; Veling, Maria C

    2011-06-01

    Children with chronic or recurrent upper respiratory inflammatory disease (rhinitis) should be considered for inhalant allergies. Risk factors for inhalant allergies in children include a first-degree relative with allergies, food allergy in infancy, and atopic dermatitis. Although inhalant allergies are rare in infancy, inhalant allergies are common in older children and impair quality of life and productivity. Differentiating between viral and allergic rhinitis can be challenging in children, but the child's age, history, and risk factors can provide helpful information. Allergic rhinitis is a risk factor for asthma, and if one is present, medical consideration of the other is warranted. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Inhalant Abuse and Dextromethorphan.

    Science.gov (United States)

    Storck, Michael; Black, Laura; Liddell, Morgan

    2016-07-01

    Inhalant abuse is the intentional inhalation of a volatile substance for the purpose of achieving an altered mental state. As an important, yet underrecognized form of substance abuse, inhalant abuse crosses all demographic, ethnic, and socioeconomic boundaries, causing significant morbidity and mortality in school-aged and older children. This review presents current perspectives on epidemiology, detection, and clinical challenges of inhalant abuse and offers advice regarding the medical and mental health providers' roles in the prevention and management of this substance abuse problem. Also discussed is the misuse of a specific "over-the-counter" dissociative, dextromethorphan. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Study of the intervention effect of Laminaria japonica polysaccharides on testis tissue in male rats exposed by repeated low-dose ionizing radiation

    International Nuclear Information System (INIS)

    Liu Jun; Luo Qiong; Cui Xiaoyan; Yang Mingliang; Yan Jun

    2010-01-01

    Objective: To investigate the effect of the Laminaria japonica polysaccharides (LJP) intervention on the male rats' testicular tissue oxidative damage which was caused by repeated low-dose local ionizing radiation. Methods: Male Wistar rats were randomly divided into control group, model group and LJP intervention group. The rats in the LJP intervention group was given with LJP. The rats in each group were exposed to 60 Co γ-ray local irradiation 7 d after adaptability breeding, once per day for 20 times in 4 weeks. Each rat was irradiated with the total dose of 2.3 Gy. The rats were killed at 1, 7 and 14 d post-irradiation, respectively. The testis and the epididymis were taken out. The contents of MDA and GSH, and the activities of SOD, LDH and GSH-Px were measured using spectrophotometer. The amorphous of testicular tissue was observed and the sperm count and viability were analyzed. Results: As compared with those in the model group, the content of MDA decreased in testicular tissue in the LJP group (t=3.66-5.03, P<0.01), while the GSH content increased. The activities of SOD, LDH and GSH-Px (t=2.77-25.52, P<0.05) and the sperm count and viability increased (t=3.11-23.08, P<0.01). Each index was more close to that in the control group 14 d post-irradiation. Conclusions: LJP can promote the recovery of testicular tissue oxidative damage caused by chronic local ionizing radiation. It has a role in promoting the spermatogenic function of male rate. (authors)

  16. Objective measurement of inhaler inhalation flow profile using acoustic methods

    Energy Technology Data Exchange (ETDEWEB)

    Lacalle, H.; Taylor, T.E.; Marco, S.; Reilly, R.B.

    2016-07-01

    Patients with asthma and chronic obstructive pulmonary diseases (COPD) are mostly treated with inhalers that deliver medication directly to their airways. Drug delivery from dry powder inhalers (DPIs) is very much reliant on the inhalation manoeuvre, specifically the peak inspiratory flow rate (PIFR), inspiratory capacity (IC) and inhalation rise time (IRT) of the inhalation. It has been widely reported that patients may not follow correct inhalation technique while using their inhaler. In this study, a novel acoustic method is proposed to accurately estimate inhalation flow profile using only one inhalation recording for calibration. An Ellipta DPI was placed inside an airtight container with a spirometer connected in order to measure inhalation flow parameters. An acoustic recording device (Inhaler Compliance Assessment (INCA)) was also attached to the DPI. Inhalation audio and flow signals were recorded simultaneously. The data were collected from 20 healthy subjects while performing inhaler inhalations at a range of inspiratory flow rates. A power law regression model was computed to obtain the relationship between the acoustic envelope of the inhalation and flow profile of each recording. Each model was tested on the remaining audio signals to estimate flow profile. The average estimation error was found to be 10.5±0.3% for estimating flow profile from audio signals. Inhalation flow profile parameters (PIFR, IC and IRT) could then be measured from the estimated flow profile with high accuracy giving information on user inhalation technique. This method may assist in improving patient inhaler adherence and overall disease control. (Author)

  17. Effectiveness of the different methods of inhalation drugs delivery in children with bronchial asthma

    Directory of Open Access Journals (Sweden)

    S.M. Nedelska

    2017-02-01

    Full Text Available Aim of the work — to evaluate the effectiveness of inhalation technique when using different types of inhalers (dry powder inhalers — Turbuhaler, Diskus, metered-dose inhalers, breath-actuated inhalers — Easyhaler. Materials and methods. 45 patients aged 6–17 years underwent the evaluation of inhalation technique accuracy with the use of In-Check-Dial — apparatus, which imitates the airway resistance that should be overcome during inspiration through different inhaler types, and measure inspiration velocity. Incidence of mistakes was studied in different age groups. Results. 80 % of children aged 6–7 years made mistakes while using Turbuhaler, 73.3 % — metered-dose inhaler, 60 % — Easyhaler. There were no mistakes in patients making inhalation by means of Diskhaler. 100 % of children aged 12–14 years incorrectly used metered-dose inhaler. Easyhaler was incorrectly used in 66.6 % of cases, Diskhaler — in 26.6 %. Among elder group, incidence of mistakes when making inhalations through Turbuhaler was lower — 40 % in 12–14-year-old group and 25 % — in 15–17-year-old (р < 0.05. Children of 15–17 years old are able to use Turbuhaler and Diskus (mistakes in 33.3 and 46.6 %, respectively. At the same time, none of the patients have done the correct inhalation by means of metered-dose inhaler, 93.3 % of the patients have mistakes when using Easyhaler. Conclusions. The incidence of mistakes depends on the age and inhaler type and reaches 26–100 %. Minimal quantity of mistakes is seen for Diskus (in all age groups, maxi­mal — for metered-dose inhaler. For the purpose of optimal inhaler choice in a child with bronchial asthma, it is advisable to measure the inspiratory flow with the help of In-Check-Dial before therapy administration.

  18. Biotransformation of 2,3,3,3-tetrafluoropropene (HFO-1234yf) in male, pregnant and non-pregnant female rabbits after single high dose inhalation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, Tobias [Institut für Toxikologie, Universität Würzburg, Versbacher Str. 9, 97078 Würzburg (Germany); Bertermann, Rüdiger [Institut für Anorganische Chemie, Universität Würzburg, Am Hubland, 97074 Würzburg (Germany); Rusch, George M. [Honeywell, P.O. Box 1057, Morristown, NJ 07962–1057 (United States); Hoffman, Gary M. [Huntingdon Life Sciences., East Millstone, NJ (United States); Dekant, Wolfgang, E-mail: dekant@toxi.uni-wuerzburg.de [Institut für Toxikologie, Universität Würzburg, Versbacher Str. 9, 97078 Würzburg (Germany)

    2012-08-15

    2,3,3,3-Tetrafluoropropene (HFO-1234yf) is a novel refrigerant intended for use in mobile air conditioning. It showed a low potential for toxicity in rodents studies with most NOAELs well above 10,000 ppm in guideline compliant toxicity studies. However, a developmental toxicity study in rabbits showed mortality at exposure levels of 5,500 ppm and above. No lethality was observed at exposure levels of 2,500 and 4,000 ppm. Nevertheless, increased subacute inflammatory heart lesions were observed in rabbits at all exposure levels. Since the lethality in pregnant animals may be due to altered biotransformation of HFO-1234yf and to evaluate the potential risk to pregnant women facing a car crash, this study compared the acute toxicity and biotransformation of HFO-1234yf in male, female and pregnant female rabbits. Animals were exposed to 50,000 ppm and 100,000 ppm for 1 h. For metabolite identification by {sup 19}F NMR and LC/MS-MS, urine was collected for 48 h after inhalation exposure. In all samples, the predominant metabolites were S-(3,3,3-trifluoro-2-hydroxypropanyl)-mercaptolactic acid and N-acetyl-S-(3,3,3-trifluoro-2-hydroxypropanyl)-L-cysteine. Since no major differences in urinary metabolite pattern were observed between the groups, only N-acetyl-S-(3,3,3-trifluoro-2-hydroxypropanyl)-L-cysteine excretion was quantified. No significant differences in recovery between non-pregnant (43.10 ± 22.35 μmol) and pregnant female (50.47 ± 19.72 μmol) rabbits were observed, male rabbits exposed to 100,000 ppm for one hour excreted 86.40 ± 38.87 μmol. Lethality and clinical signs of toxicity were not observed in any group. The results suggest that the lethality of HFO-1234yf in pregnant rabbits unlikely is due to changes in biotransformation patterns or capacity in pregnant rabbits. -- Highlights: ► No lethality and clinical signs were observed. ► No differences in metabolic pattern between pregnant and non-pregnant rabbits. ► Rapid and similar metabolite

  19. Biotransformation of 2,3,3,3-tetrafluoropropene (HFO-1234yf) in male, pregnant and non-pregnant female rabbits after single high dose inhalation exposure

    International Nuclear Information System (INIS)

    Schmidt, Tobias; Bertermann, Rüdiger; Rusch, George M.; Hoffman, Gary M.; Dekant, Wolfgang

    2012-01-01

    2,3,3,3-Tetrafluoropropene (HFO-1234yf) is a novel refrigerant intended for use in mobile air conditioning. It showed a low potential for toxicity in rodents studies with most NOAELs well above 10,000 ppm in guideline compliant toxicity studies. However, a developmental toxicity study in rabbits showed mortality at exposure levels of 5,500 ppm and above. No lethality was observed at exposure levels of 2,500 and 4,000 ppm. Nevertheless, increased subacute inflammatory heart lesions were observed in rabbits at all exposure levels. Since the lethality in pregnant animals may be due to altered biotransformation of HFO-1234yf and to evaluate the potential risk to pregnant women facing a car crash, this study compared the acute toxicity and biotransformation of HFO-1234yf in male, female and pregnant female rabbits. Animals were exposed to 50,000 ppm and 100,000 ppm for 1 h. For metabolite identification by 19 F NMR and LC/MS-MS, urine was collected for 48 h after inhalation exposure. In all samples, the predominant metabolites were S-(3,3,3-trifluoro-2-hydroxypropanyl)-mercaptolactic acid and N-acetyl-S-(3,3,3-trifluoro-2-hydroxypropanyl)-L-cysteine. Since no major differences in urinary metabolite pattern were observed between the groups, only N-acetyl-S-(3,3,3-trifluoro-2-hydroxypropanyl)-L-cysteine excretion was quantified. No significant differences in recovery between non-pregnant (43.10 ± 22.35 μmol) and pregnant female (50.47 ± 19.72 μmol) rabbits were observed, male rabbits exposed to 100,000 ppm for one hour excreted 86.40 ± 38.87 μmol. Lethality and clinical signs of toxicity were not observed in any group. The results suggest that the lethality of HFO-1234yf in pregnant rabbits unlikely is due to changes in biotransformation patterns or capacity in pregnant rabbits. -- Highlights: ► No lethality and clinical signs were observed. ► No differences in metabolic pattern between pregnant and non-pregnant rabbits. ► Rapid and similar metabolite

  20. Differential effects of repeated low dose treatment with the cannabinoid agonist WIN 55,212-2 in experimental models of bone cancer pain and neuropathic pain

    DEFF Research Database (Denmark)

    Hald, Andreas; Ding, Ming; Egerod, Kristoffer Lihme

    2008-01-01

    Pain due to bone malignancies is one of the most difficult types of cancer pain to fully control and may further decrease the patients' quality of life. Animal models of chronic pain conditions resulting from peripheral inflammatory reactions or nerve injuries are responsive to treatment with can......Pain due to bone malignancies is one of the most difficult types of cancer pain to fully control and may further decrease the patients' quality of life. Animal models of chronic pain conditions resulting from peripheral inflammatory reactions or nerve injuries are responsive to treatment...... with cannabinoid agonists. However, the use of cannabinoid agonists in humans may be hampered by CNS related side effects and development of tolerance. In the present study, we investigated the effect of repeated low dose administration of the synthetic cannabinoid agonist WIN 55,212-2 on bone cancer pain...... and neuropathic pain in mice. In addition, we investigated the development of CNS related side effects and tolerance. We found that 0.5 mg/kg/day for 18 days reduced pain related behavior and expression of spinal glial fibrillary acidic protein in the bone cancer pain model but not in the neuropathic pain model...

  1. Propossal of a model for the calculation of doses and of the risk due to inhalation and ingestion of radionuclides from nuclear facilities

    International Nuclear Information System (INIS)

    Bertelli Neto, L.

    1980-10-01

    An improvement of existing models for the various body components and simulates the human body metabolic behaviour as a whole, are presented. It takes into account the uptake of material, via nose or mouth, up to its excretion by urine or faeces. It has an aditional choice for calculation, which permits the evaluation of the quantity of material that has settled inside the organism, using the data obtained from the quantitative analysis of the excreta. The simulation of the metabolic process leads to the possibility of dose and detriment estimation as well as the corresponding mortality and genetic risks. Metabolic tests were made for physiological comparison and for the determination of the whole body dose equivalent. Tests were made, using different intake and excretion activities, to verify the validity of the proposed model. (E.G.) [pt

  2. Design and application of a new modular adapter for laser diffraction characterization of inhalation aerosols

    NARCIS (Netherlands)

    de Boer, Anne; Gjaltema, D; Hagedoorn, P; Schaller, M; Witt, W; Frijlink, H W

    2002-01-01

    An inhaler adapter has been designed for the characterization of the aerosol clouds from medical aerosol generators such as nebulizers, dry powder inhalers (dpis) and metered dose inhalers (mdis) with laser diffraction technology. The adapter has a pre-separator, for separation of large particles

  3. Real-life characteristics of asthma inhaler device use in South Korea

    NARCIS (Netherlands)

    Wan Yau Ming, S.; Rhee, C.K.; Park, H.Y.; Yoo, K.H.; Kim, D.K.; Van Boven, J.F.; Price, D.; Park, H.S.

    2016-01-01

    Background and Aims: Historically, dry powder inhalers (DPIs) were considered to provide better airway distribution, easier identification of empty devices, and easier handling when compared to pressurized metered dose inhalers (pMDIs). Prior research into the major handling errors with inhaler

  4. A Phase I randomized clinical trial testing the safety, tolerability and preliminary pharmacokinetics of the mGluR5 negative allosteric modulator GET 73 following single and repeated doses in healthy volunteers.

    Science.gov (United States)

    Haass-Koffler, Carolina L; Goodyear, Kimberly; Long, Victoria M; Tran, Harrison H; Loche, Antonella; Cacciaglia, Roberto; Swift, Robert M; Leggio, Lorenzo

    2017-11-15

    Preclinical work suggests that the metabotropic glutamate receptor subtype 5 (mGlu5) may represent a novel target to treat neuropsychiatric disorders, including alcohol use disorder and obesity. The goal of this first-in-man study was to evaluate the safety, tolerability and pharmacokinetics (PK) of GET 73 (PubChem SID: 329974174), a novel mGluR5 negative allosteric modulator. This was a double-blind, placebo-controlled, ascending dose, Phase I study conducted in healthy male volunteers in two experiments. GET 73 was administered as single ascending doses (N=48; Experiment 1; 10, 30, 100, 300, 450, 600-mg) or multiple ascending doses (N=32; Experiment 2; 100, 300, 450, 450-mg twice a day). Primary endpoints were the incidence of adverse events (AEs) among drug conditions and drug tolerability. The secondary endpoints were the PK parameters of GET 73 and its metabolite MET 2. Single GET 73 doses of up to 600-mg and repeated ascending doses of up to 450-mg twice/day were safe and well-tolerated. There were no serious or severe AEs. All AEs were mild or moderate in severity. Total GET 73 exposure increased with each increased GET 73 dose. A dose-related increase in mean maximum plasma drug concentration was observed after repeated dosing. Maximum plasma drug concentrations occurred between 0.5 and 2.05h after administration in all groups for both single and repeated doses. This first-in-human study indicates that GET 73, as single or multiple ascending doses, is safe and well-tolerated when administered to healthy male volunteers. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... Facebook Tweet Share Compartir You can control your asthma and avoid an attack by taking your medicine exactly as your doctor ... and by avoiding things that can cause an attack. Watch a video to follow ... keep them with your Asthma Action Plan. Using a metered dose inhaler with ...

  6. Report of the panel on inhaled actinides

    International Nuclear Information System (INIS)

    Anon.

    1978-01-01

    Some topics discussed are as follows: assessment of risks to man of inhaling actinides; use of estimates for developing protection standards; epidemiology of lung cancer in exposed human populations; development of respiratory tract models; and effects in animals: dose- and effect-modifying factors

  7. Inhalants in Peru.

    Science.gov (United States)

    Lerner, R; Ferrando, D

    1995-01-01

    In Peru, the prevalence and consequences of inhalant abuse appear to be low in the general population and high among marginalized children. Inhalant use ranks third in lifetime prevalence after alcohol and tobacco. Most of the use appears to be infrequent. Among marginalized children, that is, children working in the streets but living at home or children living in the street, the problem of inhalant abuse is a serious problem. Among children working in the streets but living at home, the lifetime prevalence rate for inhalant abuse is high, ranging from 15 to 45 percent depending on the study being cited. For children living in the streets, the use of inhalant is even more severe. As mentioned earlier in this chapter, most of these street children use inhalants on a daily basis. The lack of research on the problem of inhalant abuse is a serious impediment to development of intervention programs and strategies to address this problem in Peru. Epidemiologic and ethnographic research on the nature and extent of inhalant abuse are obvious prerequisites to targeted treatment and preventive intervention programs. The urgent need for current and valid data is underscored by the unique vulnerability of the youthful population at risk and the undisputed harm that results from chronic abuse of inhalants. Nonetheless, it is important to mention several programs that work with street children. Some, such as the Information and Education Center for the Prevention of Drug Abuse, Generation, and Centro Integracion de Menores en Abandono have shelters where street children are offered transition to a less marginal lifestyle. Teams of street educators provide the children with practical solutions and gain their confidence, as well as offer them alternative socialization experiences to help them survive the streets and avoid the often repressive and counterproductive environments typical of many institutions. Most of the children who go through these programs tend to abandon

  8. Hidrofluoralcano como propelente dos aerossóis pressurizados de dose medida: histórico, deposição pulmonar, farmacocinética, eficácia e segurança Hydrofluoroalkane as a propellant for pressurized metered-dose inhalers: history, pulmonary deposition, pharmacokinetics, efficacy and safety

    Directory of Open Access Journals (Sweden)

    Cássio C. Ibiapina

    2004-12-01

    Full Text Available OBJETIVO: Rever a literatura sobre o hidrofluoralcano como propelente dos inaladores de dose medida contendo medicamentos empregados na asma. FONTES DOS DADOS: O levantamento bibliográfico foi realizado em bancos de dados eletrônicos - MEDLINE, MDConsult, HighWire, Medscape e LILACS - e por pesquisa direta - referentes aos últimos 15 anos -, utilizando-se as seguintes palavras-chaves: hidrofluoralcano, asma e infância. SÍNTESE DOS DADOS: Foram selecionados 43 artigos originais abordando a questão da substituição do clorofluorcarbono pelo hidrofluoralcano. Este gás mostrou-se como uma alternativa de propelente segura, com deposição pulmonar de 50 a 60% e eficácia significativa quando comparado com placebo (p OBJECTIVE: To review the literature about hydrofluoroalkane as a propellent of pressurized metered-dose inhalers containing anti-asthma drugs. SOURCES OF DATA: Bibliographic search in electronic databases (MEDLINE, MDConsult, HighWire, Medscape and LILACS and direct search referring to the past 15 years, using the key words hydrofluoroalkane, asthma and childhood were carried out. SUMMARY OF THE FINDINGS: 43 original articles on the replacement of clorofluorcarbon by hydrofluoralkane were selected. Hydrofluoralkane showed to be a safe propellent, with pulmonary deposition ranging from 50 to 60%, and to have significant efficacy, when compared with placebo (p < 0.003 in controlled clinical trials. Most works using hydrofluoralkane included beclomethasone diproprionate. Approximate annual cost of a treatment with beclomethasone diproprionate/hydrofluoralkane was lower than with beclomethasone diproprionate/clorofluorcarbon. Some studies assessed salbutamol, fluticasone, flunisolide and the association fluticasone-salmeterol, with hydrofluoralkane as propellent in pressurized metered-dose inhalers. CONCLUSIONS: Efficacy and safety of hydrofluoralkane as propellent of bronchodilators and inhaled corticosteroids in adults was evidenced

  9. Inhalation of a dry powder ciprofloxacin formulation in healthy subjects: a phase I study.

    Science.gov (United States)

    Stass, Heino; Nagelschmitz, Johannes; Willmann, Stefan; Delesen, Heinz; Gupta, Abhishek; Baumann, Sybille

    2013-06-01

    Oral and intravenous formulations of ciprofloxacin have established efficacy and safety profiles in respiratory infections. A dry powder for inhalation (DPI) that uses Novartis' PulmoSphere™ technology has been developed to deliver high concentrations of ciprofloxacin to the lung with low systemic exposure using a portable and convenient passive dry powder inhaler (Novartis' T-326 inhaler). The primary objective was to investigate the safety and tolerability of ciprofloxacin DPI in healthy male subjects, with a secondary objective to investigate the pharmacokinetics of ciprofloxacin after ciprofloxacin DPI administration. This was a phase I, single-dose, single-site, randomized, single-blind, placebo-controlled, crossover study conducted in the hospital setting. Subjects were followed up for safety for approximately 2 weeks. Six healthy male subjects, aged 27-42 years with no history of pulmonary disease, repeated bronchitis or respiratory allergies were enrolled. In randomized order and separated by a 1-week washout period, subjects inhaled a single dose of ciprofloxacin DPI 32.5 mg or placebo from the T-326 inhaler. Primary safety parameters included vital signs, electrocardiogram, laboratory tests, adverse events and lung function (total specific resistance, thoracic gas volume and forced expiratory volume in 1 s). Plasma concentration-time data were used to calculate pharmacokinetic parameters. Ciprofloxacin DPI was well tolerated with no clinically relevant adverse effects on lung function. Estimates of lung deposition derived from physiology-based pharmacokinetic modelling suggest that approximately 40 % of the total dose of ciprofloxacin DPI reached the trachea/bronchi and alveolar space. Systemic ciprofloxacin was detected soon after inhalation [peak concentration in plasma (C(max)) 56.42 μg/L, median time to C max 0.625 h], but total systemic exposure was minimal (area under the plasma concentration-time curve 354.4 μg·h/L). Terminal elimination half

  10. Effect of budesonide/formoterol pressurized metered-dose inhaler on exacerbations versus formoterol in chronic obstructive pulmonary disease: The 6-month, randomized RISE (Revealing the Impact of Symbicort in reducing Exacerbations in COPD) study.

    Science.gov (United States)

    Ferguson, Gary T; Tashkin, Donald P; Skärby, Tor; Jorup, Carin; Sandin, Kristina; Greenwood, Michael; Pemberton, Kristine; Trudo, Frank

    2017-11-01

    Prevention of exacerbations is a primary goal for chronic obstructive pulmonary disease (COPD) therapy. This randomized, double-blind, double-dummy, parallel-group, multicenter study evaluated the effect of budesonide/formoterol pressurized metered-dose inhaler (pMDI) versus formoterol dry powder inhaler (DPI) on reducing COPD exacerbations. 1219 patients aged ≥40 years with moderate-to-very-severe COPD (per lung function) and a history of ≥1 COPD exacerbation received budesonide/formoterol pMDI 320/9 μg twice daily (BID) during a 4-week run-in. Patients were then randomized 1:1 to receive budesonide/formoterol pMDI 320/9 μg BID (n = 606) or formoterol DPI 9 μg BID (n = 613) for 26 weeks. Exacerbations were identified using predefined criteria for symptom worsening and treatment with systemic corticosteroids and/or antibiotics and/or hospitalization. The primary endpoint was annual rate of exacerbations. Budesonide/formoterol pMDI resulted in a 24% reduction in annual rate of exacerbations (0.85 vs 1.12; rate ratio: 0.76 [95% CI: 0.62, 0.92]; P = 0.006), and a significant risk reduction for time to first exacerbation (hazard ratio: 0.78 [95% CI: 0.64, 0.96]; P = 0.016) versus formoterol DPI. The most commonly reported adverse events (AEs; ≥3%) in budesonide/formoterol and formoterol groups were COPD (4.5% vs 8.6%) and nasopharyngitis (5.0% vs 5.2%). Pneumonia AEs were reported in 0.5% and 1.0% of budesonide/formoterol-treated and formoterol-treated patients, respectively. Budesonide/formoterol pMDI is an effective treatment option for reducing exacerbation rates in COPD patients with moderate-to-very-severe airflow limitation and history of exacerbations. No increase in pneumonia was observed with budesonide/formoterol; safety data were consistent with its established profile. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Collaborative work on evaluation of ovarian toxicity. 13) Two- or four-week repeated dose studies and fertility study of PPAR alpha/gamma dual agonist in female rats.

    Science.gov (United States)

    Sato, Norihiro; Uchida, Keisuke; Nakajima, Mikio; Watanabe, Atsushi; Kohira, Terutomo

    2009-01-01

    The main focus of this study was to determine the optimal dosing period in a repeated dose toxicity study based on toxic effects as assessed by ovarian morphological changes. To assess morphological and functional changes induced in the ovary by a peroxisome proliferator-activated receptor (PPAR) alpha/gamma dual agonist, the compound was administered to female rats at dose levels of 0, 4, 20, and 100 mg/kg/day in a repeated dose toxicity study for 2 or 4 weeks, and from 2 weeks prior to mating to Day 7 of pregnancy in a female fertility study. In the repeated dose toxicity study, an increase in atresia of large follicles, a decrease in corpora lutea, and an increase in stromal cells were observed in the treated groups. In addition, the granulosa cell exfoliations into antrum of large follicles and corpora lutea with retained oocyte are morphological characteristics induced by this compound, and they might be related with abnormal condition of ovulation. In the female fertility study, the pregnancy rate tended to decrease in the 100 mg/kg/day group. At necropsy, decreases in the number of corpora lutea, implantations and live embryos were noted in the 20 and 100 mg/kg/day group. No changes were observed in animals given 4 mg/kg/day. These findings indicated that histopathological changes in the ovary are important endpoints for evaluation of drugs inducing ovarian damage. In conclusion, a 2-week administration period is sufficient to detect ovarian toxicity of this test compound in the repeated dose toxicity study.

  12. Effect of inhaled formyl-methionyl-leucyl-phenylalanine on airway function.

    Science.gov (United States)

    Berend, N; Peters, M J; Armour, C L; Black, J L; Ward, H E

    1988-01-01

    Formyl-methionyl-leucyl-phenylalanine (FMLP), a synthetic, acylated tripeptide analogous to bacterial chemotactic factors, has been shown to cause bronchoconstriction in guinea pig, rabbit, and human airways in vitro. To determine whether FMLP causes bronchoconstriction in man in vivo, a preliminary study was undertaken in which five non-smokers (mean age 35 years, FEV1 94% (SEM 5%) predicted) and five smokers (mean age 34 years, FEV1 93% (6%) predicted) inhaled aerosols of FMLP. None of the subjects showed airway hyperresponsiveness to histamine (the provocative concentrations of histamine causing a fall of greater than or equal to 20% in FEV1 (PC20) were over 8 mg/ml). FMLP dissolved in 50% dimethylsulphoxide and 50% saline in concentrations of 0, 0.06, 0.12, 0.25, 0.5, 1.0, 2.0, and 4.0 mg/ml was administered to the subjects by means of a French-Rosenthal dosimeter, FEV1 being recorded after inhalation of each concentration. Dose dependent falls in FEV1 occurred in five non-smokers (geometric mean 1.76, 95% confidence limits 0.87-3.53 mg/ml) and three smokers (0.23, 0.07-0.78 mg/ml), with two smokers not responding by 20% to the highest concentration of FMLP. On a separate day the FMLP dose-response curves were repeated after nebulisation of 500 micrograms of ipratropium bromide. The PC20 FMLP in the responders more than doubled. In six additional normal subjects a histamine inhalation test was performed before and four and 24 hours after inhalation of FMLP. All subjects remained unresponsive to histamine. These results show that FMLP is a potent bronchoconstrictor in some non-asthmatic individuals in vivo and this may be important in bronchoconstriction related to infection in patients with chronic obstructive lung disease.

  13. Pharmacokinetics and Bioavailability of Inhaled Esketamine in Healthy Volunteers.

    Science.gov (United States)

    Jonkman, Kelly; Duma, Andreas; Olofsen, Erik; Henthorn, Thomas; van Velzen, Monique; Mooren, René; Siebers, Liesbeth; van den Beukel, Jojanneke; Aarts, Leon; Niesters, Marieke; Dahan, Albert

    2017-10-01

    Esketamine is traditionally administered via intravenous or intramuscular routes. In this study we developed a pharmacokinetic model of inhalation of nebulized esketamine with special emphasis on pulmonary absorption and bioavailability. Three increasing doses of inhaled esketamine (dose escalation from 25 to 100 mg) were applied followed by a single intravenous dose (20 mg) in 19 healthy volunteers using a nebulizer system and arterial concentrations of esketamine and esnorketamine were obtained. A multicompartmental pharmacokinetic model was developed using population nonlinear mixed-effects analyses. The pharmacokinetic model consisted of three esketamine, two esnorketamine disposition and three metabolism compartments. The inhalation data were best described by adding two absorption pathways, an immediate and a slower pathway, with rate constant 0.05 ± 0.01 min (median ± SE of the estimate). The amount of esketamine inhaled was reduced due to dose-independent and dose-dependent reduced bioavailability. The former was 70% ± 5%, and the latter was described by a sigmoid EMAX model characterized by the plasma concentration at which absorption was impaired by 50% (406 ± 46 ng/ml). Over the concentration range tested, up to 50% of inhaled esketamine is lost due to the reduced dose-independent and dose-dependent bioavailability. We successfully modeled the inhalation of nebulized esketamine in healthy volunteers. Nebulized esketamine is inhaled with a substantial reduction in bioavailability. Although the reduction in dose-independent bioavailability is best explained by retention of drug and particle exhalation, the reduction in dose-dependent bioavailability is probably due to sedation-related loss of drug into the air.

  14. Olodaterol Oral Inhalation

    Science.gov (United States)

    ... in a class of medications called long-acting beta-agonists (LABAs). It works by relaxing and opening ... the inhaler upright with the yellow cap closed. Turn the clear base in the direction of the ...

  15. Pirbuterol Acetate Oral Inhalation

    Science.gov (United States)

    ... Pirbuterol is in a class of medications called beta-agonist bronchodilators. It works by relaxing and opening ... cleaning. Once a week, remove the mouthpiece cover, turn the inhaler upside down and wipe the mouthpiece ...

  16. Cromolyn Oral Inhalation

    Science.gov (United States)

    ... your doctor.Cromolyn oral inhalation helps to prevent asthma attacks (sudden episodes of shortness of breath, wheezing, and coughing) but will not stop an asthma attack that has already started. Your doctor will prescribe ...

  17. Ipratropium Oral Inhalation

    Science.gov (United States)

    ... with the clear end pointing upward. Place the metal canister inside the clear end of the inhaler. ... do not discard it in an incinerator or fire.Unneeded medications should be disposed of in special ...

  18. Nicotine Oral Inhalation

    Science.gov (United States)

    ... with a smoking cessation program, which may include support groups, counseling, or specific behavioral change techniques. Nicotine inhalation ... and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or ...

  19. Inhalation exposure to chloramine T induces DNA damage and inflammation in lung of Sprague-Dawley rats.

    Science.gov (United States)

    Shim, Ilseob; Seo, Gyun-Baek; Oh, Eunha; Lee, Mimi; Kwon, Jung-Taek; Sul, Donggeun; Lee, Byung-Woo; Yoon, Byung-Il; Kim, Pilje; Choi, Kyunghee; Kim, Hyun-Mi

    2013-01-01

    Chloramine T has been widely used as a disinfectant in many areas such as kitchens, laboratories and hospitals. It has been also used as a biocide in air fresheners and deodorants which are consumer products; however, little is known about its toxic effects by inhalation route. This study was performed to identify the subacute inhalation toxicity of chloramine T under whole-body inhalation exposure conditions. Male and female groups of rats were exposed to chloramine T at concentrations of 0.2, 0.9 and 4.0 mg/m³ for 6 hr/day, 5 days/week during 4 weeks. After 28-day repeated inhalation of chloramine T, there were dose-dependently significant DNA damage in the rat tissues evaluated and inflammation was histopathologically noted around the terminal airways of the lung in both genders. As a result of the expression of three types of antioxidant enzymes (SOD-2, GPx-1, PRX-1) in rat's lung after exposure, there was no significant change of all antioxidant enzymes in the male and female rats. The results showed that no observed adverse effect level (NOAEL) was 0.2 mg/m³ in male rats and 0.9 mg/m³ in female rats under the present experimental condition.

  20. Radioactive gas inhalator

    International Nuclear Information System (INIS)

    LeMon, D.E.

    1975-01-01

    An ''inhalator'', or more particularly an apparatus for permitting a patient to inhale a radioactive gas in order to provide a diagnostic test of the patient's lung area, is described. The disclosed apparatus provides a simple, trouble-free mechanism for achieving this result; and, furthermore, provides an improved testing method. Moreover, the disclosed apparatus has the capability of gradually introducing the test condition in a manner that makes it easy for the patient to become acclimated to it. (U.S.)

  1. Inhalation Toxicology Research Institute. Annual report, October 1, 1981-September 30, 1982

    International Nuclear Information System (INIS)

    Snipes, M.B.; Marshall, T.C.; Martinez, B.S.

    1982-12-01

    Studies are presented of the effect on man of airborne particulates and gaseous emissions associated with the production of energy. Included in the report from the Inhalation Toxicology Research Institute are papers on: (1) the physical and chemical characterization of energy technology aerosols; (2) laboratory studies of aerosol generation and characterization; (3) in vitro predictors of toxicity; (4) disposition and fate of inhaled materials; (5) dose-response relationships for inhaled radionuclides; (6) dose-response relationships for inhaled chemical toxicants; (7) biological factors which influence dose-response relationships; and (8) risk assessment

  2. Serological analysis of human anti-human antibody responses in colon cancer patients treated with repeated doses of humanized monoclonal antibody A33.

    Science.gov (United States)

    Ritter, G; Cohen, L S; Williams, C; Richards, E C; Old, L J; Welt, S

    2001-09-15

    Mouse monoclonal antibody A33 (mAb A33) recognizes a M(r) 43,000 cell surface glycoprotein (designated A33) expressed in human colonic epithelium and colon cancer but absent from most other normal tissues. In patients, mAb A33 localizes with high specificity to colon cancer and is retained for up to 6 weeks in the cancer but cleared rapidly from normal colon (5-6 days). As a carrier of (125)I or (131)I, mAb A33 has shown antitumor activity. Induction of strong human anti-mouse antibody (immunoglobulin; HAMA) responses in patients, however, limits the use of the murine mAb A33 to very few injections. A humanized version of this antibody (huAb A33) has been prepared for Phase I and II clinical studies in patients with colon cancer. In those studies, immunogenicity of huAb A33 has been monitored using a novel, highly sensitive BIACORE method, which allows measurement of human anti-human antibodies (HAHAs) without the use of secondary reagents. We found that 63% (26 of 41) of the patients treated with repeated doses of huAb A33 developed HAHAs against a conformational antigenic determinant located in the V(L) and V(H) regions of huAb A33. Detailed serological analysis showed two distinct types of HAHAs. HAHA of type I (49% of patients) was characterized by an early onset with peak HAHA levels after 2 weeks of treatment, which declined with ongoing huAb A33 treatment. HAHA of type II (17% of patients) was characterized by a typically later onset of HAHA than in type I and by progressively increasing HAHA levels with each subsequent huAb A33 administration. Colon cancer patients with type I HAHAs did not develop infusion-related adverse events. In contrast, HAHA of type II was indicative of infusion-related adverse events. By using this new method, we were able to distinguish these two types of HAHAs in patients while on antibody treatment, allowing patients to be removed from study prior to the onset of severe infusion-related adverse events.

  3. Quintupling Inhaled Glucocorticoids to Prevent Childhood Asthma Exacerbations.

    Science.gov (United States)

    Jackson, Daniel J; Bacharier, Leonard B; Mauger, David T; Boehmer, Susan; Beigelman, Avraham; Chmiel, James F; Fitzpatrick, Anne M; Gaffin, Jonathan M; Morgan, Wayne J; Peters, Stephen P; Phipatanakul, Wanda; Sheehan, William J; Cabana, Michael D; Holguin, Fernando; Martinez, Fernando D; Pongracic, Jacqueline A; Baxi, Sachin N; Benson, Mindy; Blake, Kathryn; Covar, Ronina; Gentile, Deborah A; Israel, Elliot; Krishnan, Jerry A; Kumar, Harsha V; Lang, Jason E; Lazarus, Stephen C; Lima, John J; Long, Dayna; Ly, Ngoc; Marbin, Jyothi; Moy, James N; Myers, Ross E; Olin, J Tod; Raissy, Hengameh H; Robison, Rachel G; Ross, Kristie; Sorkness, Christine A; Lemanske, Robert F

    2018-03-08

    Asthma exacerbations occur frequently despite the regular use of asthma-controller therapies, such as inhaled glucocorticoids. Clinicians commonly increase the doses of inhaled glucocorticoids at early signs of loss of asthma control. However, data on the safety and efficacy of this strategy in children are limited. We studied 254 children, 5 to 11 years of age, who had mild-to-moderate persistent asthma and had had at least one asthma exacerbation treated with systemic glucocorticoids in the previous year. Children were treated for 48 weeks with maintenance low-dose inhaled glucocorticoids (fluticasone propionate at a dose of 44 μg per inhalation, two inhalations twice daily) and were randomly assigned to either continue the same dose (low-dose group) or use a quintupled dose (high-dose group; fluticasone at a dose of 220 μg per inhalation, two inhalations twice daily) for 7 days at the early signs of loss of asthma control ("yellow zone"). Treatment was provided in a double-blind fashion. The primary outcome was the rate of severe asthma exacerbations treated with systemic glucocorticoids. The rate of severe asthma exacerbations treated with systemic glucocorticoids did not differ significantly between groups (0.48 exacerbations per year in the high-dose group and 0.37 exacerbations per year in the low-dose group; relative rate, 1.3; 95% confidence interval, 0.8 to 2.1; P=0.30). The time to the first exacerbation, the rate of treatment failure, symptom scores, and albuterol use during yellow-zone episodes did not differ significantly between groups. The total glucocorticoid exposure was 16% higher in the high-dose group than in the low-dose group. The difference in linear growth between the high-dose group and the low-dose group was -0.23 cm per year (P=0.06). In children with mild-to-moderate persistent asthma treated with daily inhaled glucocorticoids, quintupling the dose at the early signs of loss of asthma control did not reduce the rate of severe asthma

  4. Fine particle mass from the Diskus inhaler and Turbuhaler inhaler in children with asthma

    DEFF Research Database (Denmark)

    Bisgaard, H; Klug, B; Sumby, B S

    1998-01-01

    (1) from the 8 yr old children, respectively. Similar particle fractions from the Budesonide Turbuhaler were 35 (9), 21 (10) and 7 (5) from 4 yr old children and 30 (7), 32 (9) and 12 (6) from 8 yr old children. In conclusion, the Diskus inhaler provides an improved dose consistency through...

  5. Biological effects of repeated exposure of beagle dogs to relatively insoluble aerosols of 144Ce. IV

    International Nuclear Information System (INIS)

    Boecker, B.B.; Hahn, F.F.; Hanika-Rebar, C.; McClellan, R.O.; Mauderly, J.L.; Pickrell, J.A.

    1977-01-01

    This experiment is being conducted to study the behavior and long-term biological effects in Beagle dogs of 144 Ce inhaled in fused aluminosilicate particles in repeated inhalation exposures for comparison with similar data from dogs that were exposed only once to a similar aerosol. Four groups of nine dogs each were exposed once every eight weeks for two years (13 exposures) to achieve specified exposure goals. The 144 Ce-exposed dogs received increasing or relatively constant beta radiation dose rates in contrast to the steadily decreasing dose rate seen after a single inhalation exposure. Exposures in the first and second groups were planned to yield a cumulative absorbed dose to lung of approximately equal to 35,000 rads and those in the third group approximately equal to 17,000 rads within two years after the first exposure. Singly exposed dogs that had died with pulmonary tumors when this experiment was initiated had cumulative doses to death of 29,000 to 61,000 rads. All 13 exposures have been completed. One dog in the 4.5-μCi 144 Ce/kg body weight group died at 771 days after first exposure with emaciation, adrenal cortical degeneration and bone marrow aplasia. One control dog died accidentally during anesthesia. During the past year, two additional dogs have died. One dog in the repeated 2.5-μCi 144 Ce/kg body weight group died at 1256 days after the first exposure with radiation pneumonitis and pulmonary fibrosis and a control dog died at 1052 days with autoimmune hemolytic anemia. The remaining 32 dogs appear to be in good physical condition except for a persistent lymphopenia at approximately equal to 4 years after the first exposure. They are being maintained for life span observations

  6. Neural Plasticity Associated with Hippocampal PKA-CREB and NMDA Signaling Is Involved in the Antidepressant Effect of Repeated Low Dose of Yueju Pill on Chronic Mouse Model of Learned Helplessness

    Directory of Open Access Journals (Sweden)

    Zhilu Zou

    2017-01-01

    Full Text Available Yueju pill is a traditional Chinese medicine formulated to treat syndromes of mood disorders. Here, we investigated the therapeutic effect of repeated low dose of Yueju in the animal model mimicking clinical long-term depression condition and the role of neural plasticity associated with PKA- (protein kinase A- CREB (cAMP response element binding protein and NMDA (N-methyl-D-aspartate signaling. We showed that a single low dose of Yueju demonstrated antidepressant effects in tests of tail suspension, forced swim, and novelty-suppressed feeding. A chronic learned helplessness (LH protocol resulted in a long-term depressive-like condition. Repeated administration of Yueju following chronic LH remarkably alleviated all of depressive-like symptoms measured, whereas conventional antidepressant fluoxetine only showed a minor improvement. In the hippocampus, Yueju and fluoxetine both normalized brain-derived neurotrophic factor (BDNF and PKA level. Only Yueju, not fluoxetine, rescued the deficits in CREB signaling. The chronic LH upregulated the expression of NMDA receptor subunits NR1, NR2A, and NR2B, which were all attenuated by Yueju. Furthermore, intracerebraventricular administration of NMDA blunted the antidepressant effect of Yueju. These findings supported the antidepressant efficacy of repeated routine low dose of Yueju in a long-term depression model and the critical role of CREB and NMDA signaling.

  7. Neural Plasticity Associated with Hippocampal PKA-CREB and NMDA Signaling Is Involved in the Antidepressant Effect of Repeated Low Dose of Yueju Pill on Chronic Mouse Model of Learned Helplessness.

    Science.gov (United States)

    Zou, Zhilu; Chen, Yin; Shen, Qinqin; Guo, Xiaoyan; Zhang, Yuxuan; Chen, Gang

    2017-01-01

    Yueju pill is a traditional Chinese medicine formulated to treat syndromes of mood disorders. Here, we investigated the therapeutic effect of repeated low dose of Yueju in the animal model mimicking clinical long-term depression condition and the role of neural plasticity associated with PKA- (protein kinase A-) CREB (cAMP response element binding protein) and NMDA (N-methyl-D-aspartate) signaling. We showed that a single low dose of Yueju demonstrated antidepressant effects in tests of tail suspension, forced swim, and novelty-suppressed feeding. A chronic learned helplessness (LH) protocol resulted in a long-term depressive-like condition. Repeated administration of Yueju following chronic LH remarkably alleviated all of depressive-like symptoms measured, whereas conventional antidepressant fluoxetine only showed a minor improvement. In the hippocampus, Yueju and fluoxetine both normalized brain-derived neurotrophic factor (BDNF) and PKA level. Only Yueju, not fluoxetine, rescued the deficits in CREB signaling. The chronic LH upregulated the expression of NMDA receptor subunits NR1, NR2A, and NR2B, which were all attenuated by Yueju. Furthermore, intracerebraventricular administration of NMDA blunted the antidepressant effect of Yueju. These findings supported the antidepressant efficacy of repeated routine low dose of Yueju in a long-term depression model and the critical role of CREB and NMDA signaling.

  8. Deployment Repeatability

    Science.gov (United States)

    2016-04-01

    evaluating the deployment repeatability builds upon the testing or analysis of deployment kinematics (Chapter 6) and adds repetition. Introduction...material yield or failure during a test. For the purposes of this chapter, zero shift will refer to permanent changes in the structure, while reversible ...the content of other chapters in this book: Gravity Compensation (Chapter 4) and Deployment Kinematics and Dynamics (Chapter 6). Repeating the

  9. Inhaled americium dioxide

    International Nuclear Information System (INIS)

    Park, J.F.

    1982-01-01

    This project includes experiments to determine the effects of Zn-DTPA therapy on the retention, translocation and biological effects of inhaled 241 AmO 2 . Beagle dogs that received inhalation exposure to 241 AmO 2 developed leukopenia, clincial chemistry changes associated with hepatocellular damage, and were euthanized due to respiratory insufficiency caused by radiation pneumonitis 120 to 131 days after pulmonary deposition of 22 to 65 μCi 241 Am. Another group of dogs that received inhalation exposure to 241 AmO 2 and were treated daily with Zn-DTPA had initial pulmonary deposition of 19 to 26 μCi 241 Am. These dogs did not develop respiratory insufficiency, and hematologic and clinical chemistry changes were less severe than in the non-DTPA-treated dogs

  10. Inhaled Steroids: First Line Treatment of Adult Asthma

    Directory of Open Access Journals (Sweden)

    André Cartier

    1995-01-01

    Full Text Available Corticosteroids are the most potent inhaled anti-inflammatory drugs for asthma treatment. This paper reviews the clinical evidence supporting the early use of inhaled steroids in asthma as a first line treatment. Inhaled steroids can probably alter the course of asthma, especially in mild asthmatics. Once they have been shown to improve control of asthma and even if the need for beta2-agonists is virtually nil, their use should be continued at low doses (ie, equivalent to 400 to 500 μg of budesonide or beclomethasone for at least one year before attempting to reduce the dosage.

  11. Dose-Response for Multiple Biomarkers of Exposure and Genotoxic Effect Following Repeated Treatment of Rats with the Alkylating Agents, MMS and MNU.

    Science.gov (United States)

    Ji, Zhiying; LeBaron, Matthew J; Schisler, Melissa R; Zhang, Fagen; Bartels, Michael J; Gollapudi, B Bhaskar; Pottenger, Lynn H

    2016-05-01

    The nature of the dose-response relationship for various in vivo endpoints of exposure and effect were investigated using the alkylating agents, methyl methanesulfonate (MMS) and methylnitrosourea (MNU). Six male F344 rats/group were dosed orally with 0, 0.5, 1, 5, 25 or 50mg/kg bw/day (mkd) of MMS, or 0, 0.01, 0.1, 1, 5, 10, 25 or 50 mkd of MNU, for 4 consecutive days and sacrificed 24h after the last dose. The dose-responses for multiple biomarkers of exposure and genotoxic effect were investigated. In MMS-treated rats, the hemoglobin adduct level, a systemic exposure biomarker, increased linearly with dose (r (2) = 0.9990, P agents. © The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Inhalation toxicology of 241Am(NO3)3

    International Nuclear Information System (INIS)

    Ballou, J.E.; Gies, R.A.; Beasley, A.H.

    1980-01-01

    Inhaled 241 Am(NO 3 ) 3 was rapidly cleared from the lung (90% in 30 days) and translocated principally to skeleton. Although the estimated radiation dose to lung was twofold greater than the bone dose, the principal treatment-related lesion appeared to be osteosarcoma of the skeleton

  13. Repeated dose 28-day oral toxicity study in Wistar rats with a mixture of five pesticides often found as residues in food: alphacypermethrin, bromopropylate, carbendazim, chlorpyrifos and mancozeb

    DEFF Research Database (Denmark)

    Jacobsen, H.; Østergaard, G.; Lam, Henrik Rye

    2004-01-01

    Six dose groups of 8 male and female rats respectively received a daily dose equivalent to 0, 0.15, 0.006, 0.03, 0.15 or 0.3 mg/kg b.w./day chlorpyrifos (groups 1-6) and the last four dose groups (groups 3-6) received in addition daily doses equivalent to 18 mg/kg b.w./day alphacypermethrin, 30 mg...... of acetylcholinesterase activity in plasma and brain by chlorpyrifos was not enhanced by coadministration of the other four pesticides. Effects were seen in liver, thyroid, thymus and blood in the combination groups. However, identification of the pesticide(s) responsible for these changes would require further studies...

  14. A 28-day repeat dose toxicity study of steroidal glycoalkaloids, alpha-solanine and alpha-chaconine in the Syrian Golden hamster

    DEFF Research Database (Denmark)

    Langkilde, Søren; Mandimika, T.; Schrøder, Malene

    2009-01-01

    of the glycoalkaloids. The Syrian Golden hamster was given daily doses of alpha-solanine and alpha-chaconine by gavage for 28 days. Doses of up to 33.3 mg total glycoalkaloids/kg body weight were applied in ratios of 1:3.7 and 1:70 (alpha-solanine:alpha-chaconine). Administration of the highest doses of both ratios...... intestines of the hamsters administered the highest doses of the glycoalkaloid treatments. In general, more differential gene expression was observed in the epithelial scrapings of the hamsters fed the ratio of 1:3.7. Mostly, pathways involved in lipid and energy metabolism were affected by the ratio of 1:3.7....

  15. Randomized, controlled, assessor-blind clinical trial to assess the efficacy of single- versus repeated-dose albendazole to treat ascaris lumbricoides, trichuris trichiura, and hookworm infection.

    Science.gov (United States)

    Adegnika, Ayola A; Zinsou, Jeannot F; Issifou, Saadou; Ateba-Ngoa, Ulysse; Kassa, Roland F; Feugap, Eliane N; Honkpehedji, Yabo J; Dejon Agobe, Jean-Claude; Kenguele, Hilaire M; Massinga-Loembe, Marguerite; Agnandji, Selidji T; Mordmüller, Benjamin; Ramharter, Michael; Yazdanbakhsh, Maria; Kremsner, Peter G; Lell, Bertrand

    2014-05-01

    In many regions where soil-transmitted helminth infections are endemic, single-dose albendazole is used in mass drug administration programs to control infections. There are little data on the efficacy of the standard single-dose administration compared to that of alternative regimens. We conducted a randomized, controlled, assessor-blinded clinical trial to determine the efficacies of standard and extended albendazole treatment against soil-transmitted helminth infection in Gabon. A total of 175 children were included. Adequate cure rates and egg reduction rates above 85% were found with a single dose of albendazole for Ascaris infection, 85% (95% confidence interval [CI], 73, 96) and 93.8% (CI, 87.6, 100), respectively, while two doses were necessary for hookworm infestation (92% [CI, 78, 100] and 92% [CI, 78, 100], respectively). However, while a 3-day regimen was not sufficient to cure Trichuris (cure rate, 83% [CI, 73, 93]), this regimen reduced the number of eggs up to 90.6% (CI, 83.1, 100). The rate ratios of two- and three-dose regimens compared to a single-dose treatment were 1.7 (CI, 1.1, 2.5) and 2.1 (CI, 1.5, 2.9) for Trichuris and 1.7 (CI, 1.0, 2.9) and 1.7 (CI, 1.0, 2.9) for hookworm. Albendazole was safe and well tolerated in all regimens. A single-dose albendazole treatment considerably reduces Ascaris infection but has only a moderate effect on hookworm and Trichuris infections. The single-dose option may still be the preferred regimen because it balances efficacy, safety, and compliance during mass drug administration, keeping in mind that asymptomatic low-level helminth carriage may also have beneficial effects. (This study has been registered at ClinicalTrials.gov under registration number NCT01192802.).

  16. Inhaler technique maintenance: gaining an understanding from the patient's perspective.

    Science.gov (United States)

    Ovchinikova, Ludmila; Smith, Lorraine; Bosnic-Anticevich, Sinthia

    2011-08-01

    The aim of this study was to determine the patient-, education-, and device-related factors that predict inhaler technique maintenance. Thirty-one community pharmacists were trained to deliver inhaler technique education to people with asthma. Pharmacists evaluated (based on published checklists), and where appropriate, delivered inhaler technique education to patients (participants) in the community pharmacy at baseline (Visit 1) and 1 month later (Visit 2). Data were collected on participant demographics, asthma history, current asthma control, history of inhaler technique education, and a range of psychosocial aspects of disease management (including adherence to medication, motivation for correct technique, beliefs regarding the importance of maintaining correct technique, and necessity and concern beliefs regarding preventer therapy). Stepwise backward logistic regression was used to identify the predictors of inhaler technique maintenance at 1 month. In total 145 and 127 participants completed Visits 1 and 2, respectively. At baseline, 17% of patients (n = 24) demonstrated correct technique (score 11/11) which increased to 100% (n = 139) after remedial education by pharmacists. At follow-up, 61% (n = 77) of patients demonstrated correct technique. The predictors of inhaler technique maintenance based on the logistic regression model (X(2) (3, N = 125) = 16.22, p = .001) were use of a dry powder inhaler over a pressurized metered-dose inhaler (OR 2.6), having better asthma control at baseline (OR 2.3), and being more motivated to practice correct inhaler technique (OR 1.2). Contrary to what is typically recommended in previous research, correct inhaler technique maintenance may involve more than repetition of instructions. This study found that past technique education factors had no bearing on technique maintenance, whereas patient psychosocial factors (motivation) did.

  17. Inhalation drug delivery devices: technology update

    Directory of Open Access Journals (Sweden)

    Ibrahim M

    2015-02-01

    Full Text Available Mariam Ibrahim, Rahul Verma, Lucila Garcia-ContrerasDepartment of Pharmaceutical Sciences, College of Pharmacy, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USAAbstract: The pulmonary route of administration has proven to be effective in local and systemic delivery of miscellaneous drugs and biopharmaceuticals to treat pulmonary and non-pulmonary diseases. A successful pulmonary administration requires a harmonic interaction between the drug formulation, the inhaler device, and the patient. However, the biggest single problem that accounts for the lack of desired effect or adverse outcomes is the incorrect use of the device due to lack of training in how to use the device or how to coordinate actuation and aerosol inhalation. This review summarizes the structural and mechanical features of aerosol delivery devices with respect to mechanisms of aerosol generation, their use with different formulations, and their advantages and limitations. A technological update of the current state-of-the-art designs proposed to overcome current challenges of existing devices is also provided.Keywords: pulmonary delivery, asthma, nebulizers, metered dose inhaler, dry powder inhaler

  18. Lung dosimetry for inhaled radon progeny

    International Nuclear Information System (INIS)

    Hofmann, W.

    1986-01-01

    Lung cancer risk assessment for inhaled radon progeny requires a detailed knowledge of the dose distribution pattern throughout the human respiratory tract. Current lung dosimetry models take into acocunt aerosol deposition in a formalized airway structrue, modification of the initial deposition pattern by clearance mechanisms, and the energy deposited by alpha particles in sensitive cells of the bronchial epithelium. The resulting dose distribution pattern depends on the characteristics of the inhaled aerosol and the breathing pattern. Special emphasis has been laid on the age dependency of the anatomical structure of the human lung and the resulting doses, as well as on the rediological significance of enhanced aerosol deposition at bronchial bifuraction. The biological variability inherent in all morphometric, physiological and histological parameters involved in lung dosimetry suggests the application of stochastic modelling techniques. Examples for the use of Monte Carlo methods presented here are the random walk of inhaled particles through a random airway geometry, and the influence of the intra-subject variability of radiation doses on radiation protection standards. At the cellular level the concept of absorbed dose loses its significance and has to be replaced by microdosimetric concepts, such as internal microdosimtry or track structure theory. An image-analysis model allows us to construct specific energy distributions in sensitive lung cells. Application of a track structure model of alpha particle interaction with bronchial epithelial cells permits the calculation of probabilities for inactivation, transformation, and tumor induction. The latter has been used to analyse lung cancer risk at low doses in Chinese high background areas

  19. A 13-week repeated dose study of three 3-monochloropropane-1,2-diol fatty acid esters in F344 rats.

    Science.gov (United States)

    Onami, Saeko; Cho, Young-Man; Toyoda, Takeshi; Mizuta, Yasuko; Yoshida, Midori; Nishikawa, Akiyoshi; Ogawa, Kumiko

    2014-04-01

    3-monochloropropane-1,2-diol (3-MCPD), a rat renal and testicular carcinogen, has been reported to occur in various foods and food ingredients as free or esterified forms. Since reports about toxicity of 3-MCPD esters are limited, we conducted a 13-week rat subchronic toxicity study of 3-MCPD esters (palmitate diester: CDP, palmitate monoester: CMP, oleate diester: CDO). We administered a carcinogenic dose (3.6 × 10(-4) mol/kg B.W./day) of 3-MCPD or these esters at equimolar concentrations and two 1/4 lower doses by gavage with olive oil as a vehicle five times a week for 13 weeks to F344 male and female rats. As a result, five out of ten 3-MCPD-treated females died from acute renal tubular necrosis, but none of the ester-treated rats. Decreased HGB was observed in all high-dose 3-MCPD fatty acid ester-treated rats, except CDO-treated males. The absolute and relative kidney weights were significantly increased in the ester-treated rats at medium and high doses. Relative liver weights were significantly increased in the esters-treated rat at high dose, except for CMP females. Significant increase in apoptotic epithelial cells in the initial segment of the epididymis of high-dose ester-treated males was also observed. The results suggested that although acute renal toxicity was lower than 3-MCPD, these three 3-MCPD fatty acid esters have the potential to exert subchronic toxicity to the rat kidneys and epididymis, to a similar degree as 3-MCPD under the present conditions. NOAELs (no-observed-adverse-effect levels) of CDP, CMP and CDO were suggested to be 14, 8 and 15 mg/kg B.W./day, respectively.

  20. Repeating Marx

    DEFF Research Database (Denmark)

    Fuchs, Christian; Monticelli, Lara

    2018-01-01

    This introduction sets out the context of the special issue “Karl Marx @ 200: Debating Capitalism & Perspectives for the Future of Radical Theory”, which was published on the occasion of Marx’s bicentenary on 5 May 2018. First, we give a brief overview of contemporary capitalism’s development...... and its crises. Second, we argue that it is important to repeat Marx today. Third, we reflect on lessons learned from 200 years of struggles for alternatives to capitalism. Fourth, we give an overview of the contributions in this special issue. Taken together, the contributions in this special issue show...... that Marx’s theory and politics remain key inspirations for understanding exploitation and domination in 21st-century society and for struggles that aim to overcome these phenomena and establishing a just and fair society. We need to repeat Marx today....

  1. Deployment Repeatability

    Science.gov (United States)

    2016-08-31

    large cohort of trials to spot unusual cases. However, deployment repeatability is inherently a nonlinear phenomenon, which makes modeling difficult...and GEMS tip position were both tracked during ground testing by a laser target tracking system. Earlier SAILMAST testing in 2005 [8] used...recalls the strategy used by SRTM, where a constellation of lights was installed at the tip of the boom and a modified star tracker was used to track tip

  2. Efficacy and safety of various repeat treatment dosing regimens of rituximab in patients with active rheumatoid arthritis: results of a Phase III randomized study (MIRROR)

    NARCIS (Netherlands)

    Rubbert-Roth, Andrea; Tak, Paul P.; Zerbini, Cristiano; Tremblay, Jean-Luc; Carreño, Luis; Armstrong, Gillian; Collinson, Neil; Shaw, Tim M.

    2010-01-01

    Methods. Patients with active RA despite stable MTX (10-25 mg/week) were randomly assigned to one of the three treatment regimens comprising two courses of RTX given 24 weeks apart: 2 x 500 and 2 x 500 mg; 2 x 500 and 2 x 1000 mg (dose escalation); and 2 x 1000 and 2 x 1000 mg. The primary endpoint

  3. Dose-escalated CHOP plus etoposide (MegaCHOEP) followed by repeated stem cell transplantation for primary treatment of aggressive high-risk non-Hodgkin lymphoma

    NARCIS (Netherlands)

    Glass, B; Kloess, M; Bentz, M; Schlimok, G; Berdel, WE; Feller, A; Trumper, L; Loeffler, M; Pfreundschuh, M; Schmitz, N

    2006-01-01

    Feasibility, safety, and efficacy of a 4-course high-dose chemotherapy (HDT) protocol including autologous stem cell transplantation (SCT) after courses 2, 3, and 4 was investigated in 110 patients, aged 18 to 60 years, with primary diagnosis of aggressive NHL (aNHL), and lactic dehydrogenase (LDH)

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  5. Food hypersensitivity by inhalation

    Directory of Open Access Journals (Sweden)

    Bahna Sami L

    2009-02-01

    Full Text Available Abstract Though not widely recognized, food hypersensitivity by inhalation can cause major morbidity in affected individuals. The exposure is usually more obvious and often substantial in occupational environments but frequently occurs in non-occupational settings, such as homes, schools, restaurants, grocery stores, and commercial flights. The exposure can be trivial, as in mere smelling or being in the vicinity of the food. The clinical manifestations can vary from a benign respiratory or cutaneous reaction to a systemic one that can be life-threatening. In addition to strict avoidance, such highly-sensitive subjects should carry self-injectable epinephrine and wear MedicAlert® identification. Asthma is a strong predisposing factor and should be well-controlled. It is of great significance that food inhalation can cause de novo sensitization.

  6. Inhaled transuranics in rodents

    International Nuclear Information System (INIS)

    Sanders, C.L.

    1983-01-01

    This project examines the interactions of external and internal radiation from mixtures of radionuclides present within the nuclear fuel inventory. The objective of the project is to evaluate the effects of mixed radiation insults, using key radiation sources as indicative of overall processes that may occur following release of nuclear fuel into the air. Previously initiated studies of immunological effects of plutonium inhalation are also being completed as part of this project

  7. Self-reported osteoporosis prevention in inhaled corticosteroid users in community pharmacy setting

    Directory of Open Access Journals (Sweden)

    Valerie Chan

    2015-05-01

    Full Text Available Objectives: The use of inhaled corticosteroids is the standard maintenance therapy in asthma therapy and as adjunct therapy in moderate to severe chronic obstructive pulmonary disease. A dose-related increase in fracture risk is associated with inhaled corticosteroid use; there is an inverse relationship between bone mineral density and duration and cumulative dose of inhaled corticosteroid. Adequate intake of calcium and vitamin D are cornerstones of osteoporosis prevention. The objectives are to assess whether the proportion of patients receiving inhaled corticosteroids are taking calcium and vitamin D; the association between long-term inhaled corticosteroid use and abnormal bone mineral density or fractures; and how many qualified patients received bone mineral density scans. Methods: Patients who filled a prescription for inhaled corticosteroids at selected community pharmacies across Alberta were recruited for a survey of their osteoporosis prevention activities. Results: A total of 256 patients from 12 community pharmacies were included. The average age was 60 ± 17.4 years with 65% female. There were 21%, 51%, and 28% of patients on high, medium, and low dose inhaled corticosteroids, respectively. Only 17% of patients >50 years old received recommended calcium and vitamin D supplementation and 87 (73% of the qualified patients received bone mineral density scan. Conclusion: Osteoporosis prevention in inhaled corticosteroid users is currently poorly addressed. More promotion is needed to raise pharmacist awareness of the risks of inhaled corticosteroids.

  8. Action of 50 R X-ray doses on the breeding function of C3H strain mice - effect of splitting the dose, action of repeated irradiations on successive generations

    International Nuclear Information System (INIS)

    Alix, D.

    1965-01-01

    X-rays exposure effect was studied on C3H strain mice, at the standpoint of the effects produced on breeding function. The method used with this purpose was the following: single doses 20 - 30 - 40 and 50 R/dose, fractional doses: 50 R/total dose, divided in 2 - 5 - 10 or 25 irradiations distributed in one month duration. The offsprings were irradiated at the same doses than the parents, consanguinity being maintained. Statistical treatment of results was carried out, that led at the following conclusions: 1) Couples receiving single exposure of 50 R or two exposures of 25 R at one month interval give comparable results. Fractional doses do not involve the slightest diminution of X-rays effect. 2) 30 R exposure brings about a decrease in fertility, with an increase in abortions. Fertility of 20 R irradiated couples remains below controls. 3) After ten times 5 R and twenty-five 2 R, the number of abortions is the largest. Ovarian function is particularly sensitive to X-rays; one may think that twenty-five 2 R give injuries conditioning non-viability of conception products, smaller doses should produce mutations and yield births of altered genotype individuals. (author) [fr

  9. Action of thrice- and five-times repeated exposures of rats to a low dose of X-rays on the carbonhydrate-energy metabolism of the brain

    Energy Technology Data Exchange (ETDEWEB)

    Mironova, T M; Cherkasova, L S; Fomichenko, V G [AN Belorusskoj SSR, Minsk. Inst. Fiziologii

    1975-01-01

    Rats have been subjected to whole-body X-irradiation either 3 times with 2- and 3-day intervals and the total dose of 40 R or 5 times with 3-day intervals and the total dose of 50 R. One day after the end of the 3 times irradiation course the following concentrational changes have been observed in brain hemispheres: increase in the biologically active glycogen-protein complex and creatine phosphate, and decrease in glucose-1-phosphate; after the 5 times irradiation course the changes have not been significant, though an elevated corticosterone level in blood has been noted in both cases. 9 to 15 days after the quintuple irradiation a discoordination of glycogenolysis processes against the background of lowered corticosterone level has been observed. The trend towards restitution of metabolism becomes apparent at the normal hormone level. The glycogenlipid complex has probably an adaptive function.

  10. A 14-day repeated-dose oral toxicological evaluation of an isothiocyanate-enriched hydro-alcoholic extract from Moringa oleifera Lam. seeds in rats.

    Science.gov (United States)

    Kim, Youjin; Jaja-Chimedza, Asha; Merrill, Daniel; Mendes, Odete; Raskin, Ilya

    2018-01-01

    A 14-d short-term oral toxicity study in rats evaluated the safety of moringa isothiocyanate-1 (MIC-1)-enriched hydro-alcoholic moringa seeds extract (MSE). Rats (5 males/5 females per group) were gavaged daily for 14 d with the vehicle control or MSE, at 78 (low), 257 (mid-low), 772 (mid-high), or 2571 (high) mg/kg bw/d, standardized to MIC-1 (30, 100, 300, or 1000 mg/kg bw/d, respectively). Toxicological endpoints included body weight and weight gain, food consumption and feed efficiency, clinical observations, hematology, gross necropsy and histopathology, and relative organ weights. Mortality was only observed in the high dose group animals, both male and female, representing decreases in body weight/weight gain and food consumption/feed efficiency. Irregular respiratory patterns and piloerection were major clinical observations found primarily in the mid-high and high dose group animals. In the high dose group, gastrointestinal distention and stomach discoloration were observed in non-surviving males and females, and degeneration and necrosis of the testicular germinal cells and epididymal cells were also observed in a non-surviving male. Increased liver weights were found in females in the mid-high and high dose groups. Animals in the low and mid-low groups did not exhibit adverse effects of MSE (100 mg/kg bw/d MIC-1). A no observed adverse effect level (NOAEL) of the standardized MSE was determined as 257 mg/kg bw/d providing 100 mg/kg bw/d MIC-1.

  11. Inhalation Toxicology Research Institute annual report, October 1, 1982-September 30, 1983

    International Nuclear Information System (INIS)

    1983-12-01

    The mission of the Inhalation Toxicology Research Institute (ITRI) is to investigate the nature and magnitude of human health effects that might result from inhalation of airborne materials encountered in the work place, special attention is directed toward airborne particulate and gaseous emissions released by various energy technologies or from national defense activities. Included are five papers on the physical and chemical characterization of energy technology aerosols, 10 papers on laboratory studies of aerosol generation and characterization, 11 papers on in vitro predictors of toxicity, 12 papers on disposition and fate of inhaled materials, 24 papers on dose-response relationships for inhaled radionuclides, 3 papers on dose-response relationships for inhaled chemical toxicants, 8 papers on biological factors that influence dose-response relationships, and 4 papers are concerned with risk assessment

  12. Liquid chromatography tandem mass spectrometry determination of total budesonide levels in dog plasma after inhalation exposure.

    Science.gov (United States)

    Berg, Seija; Melamies, Marika; Rajamäki, Minna; Vainio, Outi; Peltonen, Kimmo

    2012-01-01

    A sensitive and selective method to quantify budesonide in dog plasma samples was developed and fully validated. Liquid-liquid extraction was followed by solid-phase extraction and liquid chromatography-tandem mass spectrometry with electrospray ionization. After reconstitution of the analytes in the mobile phase, samples were analysed by reversed-phase liquid chromatography with isocratic elution. d8-Budesonide was used as an internal standard, and characteristic transitions of d8-budesonide and budesonide were used for quantification. The method was validated with respect to selectivity, specificity, linearity, recovery, repeatability, reproducibility and limits of detection and quantification. The validated method was successfully applied to monitor the plasma levels of budesonide in dogs exposed to clinical doses of inhaled and intravenous drug.

  13. Quantitative biokinetic analysis of radioactively labelled, inhaled Titanium dioxide Nanoparticles in a rat model

    Energy Technology Data Exchange (ETDEWEB)

    Kreyling, Wolfgang G.; Wenk, Alexander; Semmler-Behnke, Manuela [Helmholtz Zentrum Muenchen, Deutsches Forschungszentrum fuer Gesundheit und Umwelt GmbH (Germany). Inst. fuer Lungenbiologie und Erkrankungen, Netzwerk Nanopartikel und Gesundheit

    2010-09-15

    The aim of this project was the determination of the biokinetics of TiO{sub 2} nanoparticles (NP) in the whole body of healthy adult rats after NP administration to the respiratory tract - either via inhalation or instillation. We developed an own methodology to freshly synthesize and aerosolize TiO{sub 2}-NP in our lab for the use of inhalation studies. These NP underwent a detailed physical and chemical characterization providing pure polycrystalline anatase TiO{sub 2}-NP of about 20 nm (geometric standard deviation 1.6) and a specific surface area of 270 m{sup 2}/g. In addition, we developed techniques for sufficiently stable radioactive {sup 48}V labelling of the TiO{sub 2} NP. The kinetics of solubility of {sup 48}V was thoroughly determined. The methodology of quantitative biokinetics allows for a quantitative balance of the retained and excreted NP in control of the administered NP dose and provides a much more precise determination of NP fractions and concentrations of NP in organs and tissues of interest as compared to spotting biokinetics studies. Small fractions of TiO{sub 2}-NP translocate across the air-blood-barrier and accumulate in secondary target organs, soft tissue and skeleton. The amount of translocated TiO{sub 2}-NP is approximately 2% of TiO{sub 2}-NP deposited in the lungs. A prominent fraction of these translocated TiO{sub 2}-NP was found in the remainder. Smaller amounts of TiO{sub 2}-NP accumulate in secondary organs following particular kinetics. TiO{sub 2}-NP translocation was grossly accomplished within the first 2-4 hours after inhalation followed by retention in all organs and tissues studied without any detectable clearance of these biopersistent TiO{sub 2}-NP within 28 days. Therefore, our data suggest crossing of the air-blood-barrier of the lungs and subsequent accumulation in secondary organs and tissues depends on the NP material and its physico-chemical properties. Furthermore, we extrapolate that during repeated or chronic

  14. Quantitative biokinetic analysis of radioactively labelled, inhaled Titanium dioxide Nanoparticles in a rat model

    International Nuclear Information System (INIS)

    Kreyling, Wolfgang G.; Wenk, Alexander; Semmler-Behnke, Manuela

    2010-01-01

    The aim of this project was the determination of the biokinetics of TiO 2 nanoparticles (NP) in the whole body of healthy adult rats after NP administration to the respiratory tract - either via inhalation or instillation. We developed an own methodology to freshly synthesize and aerosolize TiO 2 -NP in our lab for the use of inhalation studies. These NP underwent a detailed physical and chemical characterization providing pure polycrystalline anatase TiO 2 -NP of about 20 nm (geometric standard deviation 1.6) and a specific surface area of 270 m 2 /g. In addition, we developed techniques for sufficiently stable radioactive 48 V labelling of the TiO 2 NP. The kinetics of solubility of 48 V was thoroughly determined. The methodology of quantitative biokinetics allows for a quantitative balance of the retained and excreted NP in control of the administered NP dose and provides a much more precise determination of NP fractions and concentrations of NP in organs and tissues of interest as compared to spotting biokinetics studies. Small fractions of TiO 2 -NP translocate across the air-blood-barrier and accumulate in secondary target organs, soft tissue and skeleton. The amount of translocated TiO 2 -NP is approximately 2% of TiO 2 -NP deposited in the lungs. A prominent fraction of these translocated TiO 2 -NP was found in the remainder. Smaller amounts of TiO 2 -NP accumulate in secondary organs following particular kinetics. TiO 2 -NP translocation was grossly accomplished within the first 2-4 hours after inhalation followed by retention in all organs and tissues studied without any detectable clearance of these biopersistent TiO 2 -NP within 28 days. Therefore, our data suggest crossing of the air-blood-barrier of the lungs and subsequent accumulation in secondary organs and tissues depends on the NP material and its physico-chemical properties. Furthermore, we extrapolate that during repeated or chronic exposure to insoluble NP the translocated fraction of NP will

  15. Genotoxicity of Silver Nanoparticles in Lung Cells of Sprague Dawley Rats after 12 Weeks of Inhalation Exposure

    Directory of Open Access Journals (Sweden)

    Hyun Sun Cho

    2013-11-01

    Full Text Available Due to the widespread use of silver nanoparticles in consumer products, the toxicity of silver nanoparticles has also been studied in relation to their application. However, most genotoxicity studies of silver nanoparticles have been performed in vitro. Therefore, this study evaluated the DNA damage to lung cells caused by repeated inhalation of silver nanoparticles. Male Sprague Dawley rats were exposed to silver nanoparticles for 12 weeks in a whole-body inhalation chamber. The animals were divided into one control group and three dose groups that were exposed to silver nanoparticles (14–15 nm diameter at concentrations of 0.66 × 106 particles/cm3 (49 μg/m3, low dose, 1.41 × 106 particles/cm3 (117 μg/m3, middle dose, and 3.24 × 106 particles /cm3 (381 μg/m3, high dose, respectively, for six hours/day over 12 weeks. The rats were sacrificed after the 12-week exposure period and the DNA damage assessed using a Comet assay of cells obtained from the right lungs. The olive tail moment values were 2.93 ± 0.19, 3.81 ± 0.23, 3.40 ± 0.22, and 5.16 ± 0.32 for the control, low-, middle-, and high-dose groups, respectively. Although no dose-dependent results were observed, a significant increase in the level of DNA damage was noted for the high-dose group.

  16. Identification of inhaler technique errors with a routine procedure in Portuguese community pharmacy

    Directory of Open Access Journals (Sweden)

    Castel-Branco MM

    2017-12-01

    Full Text Available Background: A correct selection of drugs prescribed, but also the choice of the appropriate inhaler device, is crucial for the control of respiratory diseases. Objective: To evaluate the inhaler technique and identify potential errors of patients when treated with inhalers by testing a routinary procedure to be implemented in any community pharmacy. Methods: Adults with asthma/COPD and under inhalation therapy were invited to demonstrate how they use their inhalers. After direct observation it was registered whether all the sequential steps included in the summary of product characteristics (SmPC were performed. Results: The study involved 67 patients from 4 community pharmacies (Portugal central region: 34 (50.7% males, 65.4 (SD=18.28 years old, 42 (62.7% with COPD, and 23 (34.3% using more than one inhaler. The 67 patients used 95 inhalers, comprising: 57 (60.0% multiple dose DPI (dry powder inhalers, 18 (18.9% single dose DPI, 16 (16.8% pMDI (pressurized metered dose inhalers, 2 (2.1% pMDI+spacer and 2 (2.1% SMI (soft mist inhalers. No errors were made only by 9 (13.4% patients. In the 75 DPIs techniques, the most frequent errors were ‘no previous forced expiration’ (46=61.3% and ‘no 10s apnea after inhalation’ (51=68.0%; in the 16 pMDIs techniques common errors were ‘lack of hand-lung coordination’ (7=43.8 %, ‘no previous forced exhalation’ (8=50.0% and ‘no apnea after inhalation’ (10=62.5%. After inhaling from 56 devices containing corticosteroids, 34 (60.7% of the patients did not wash their mouth. Conclusion: The study demonstrated the possibility of performing this procedure routinely in Portuguese community pharmacies and also its utility, since 58 (87% of patients had at least one error during the inhalers use.

  17. The effect of inhaled fluticasone propionate in the treatment of young asthmatic children

    DEFF Research Database (Denmark)

    Bisgaard, H; Gillies, J; Groenewald, M

    1999-01-01

    The response in asthmatic young children to inhaled steroids within the usual pediatric dose range is unknown. We therefore evaluated the dose-related response in young children with moderate asthma to inhaled fluticasone propionate (FP) (delivered via the Babyhaler spacer device) within the pedi......The response in asthmatic young children to inhaled steroids within the usual pediatric dose range is unknown. We therefore evaluated the dose-related response in young children with moderate asthma to inhaled fluticasone propionate (FP) (delivered via the Babyhaler spacer device) within...... the pediatric dose range. A total of 237 children (mean age 28 mo, range 12 to 47) with moderate asthmatic symptoms were studied in this multicenter, randomized, double-blind, parallel group, placebo-controlled study of 12 wk treatment following a 4-wk run-in period. The median use of rescue medication was 1...

  18. The effect of exercise on the absorption of inhaled human insulin in healthy volunteers

    DEFF Research Database (Denmark)

    Petersen, Astrid Heide; Kohler, Gerd; Korsatko, Stefan

    2008-01-01

    overall absorption. Aims To investigate the effect of moderate exercise on the absorption of inhaled insulin. Methods A single-centre, randomized, open-label, three-period cross-over trial was carried out in 12 nonsmoking healthy subjects. A dose of 3.5 mg inhaled human insulin was administered via...

  19. The effect of body posture during medication inhalation on exercise induced bronchoconstriction in asthmatic children

    NARCIS (Netherlands)

    Visser, R.; Wind, M.; de Graaf, B.J.; de Jong, F.H.; van der Palen, Jacobus Adrianus Maria; Thio, B.J.

    2015-01-01

    RATIONALE: Inhaling medication in a standard body posture leads to impaction of particles in the sharp angle of the upper airway. Stretching the upper airway by extending the neck in a forward leaning body posture may improve pulmonary deposition. A single dose of inhaled corticosteroids (ICS)

  20. Internal dose estimates

    International Nuclear Information System (INIS)

    Wrenn, M.E.

    1977-01-01

    Internal doses, the procedures for making them and their significance has been reviewed. Effects of uranium, radium, lead-210, polonium-210, thorium in man are analysed based on data from tables and plots. Dosimetry of some ingested nuclides and inhalation dose due to radon-222, radon-220 and their daugther products are discussed [pt

  1. Exposures from external radiation and from inhalation of resuspended material

    International Nuclear Information System (INIS)

    Jacob, P.; Roth, P.; Golikov, V.; Balonov, M.; Erkin, V.; Likhtariov, I.; Garger, E.; Kashparov, V.

    1996-01-01

    In the modelling of external exposures due to cesium released during the reactor accident of Chernobyl, gamma dose rates in air over open undisturbed sites are considered to be different according to the unsoluble fraction in the deposit. This is taken into account by forming different classes according to the distance from the Chernobyl NPP. The effect of the different migration behavior in these distance classes on the gamma dose rate in air is found to increase with time. Predictions of gamma dose rates in air are based on measurements of the nuclear weapons tests fallout. Various population groups in the CIS countries are defined according to their place of residence (rural or urban), their occupation or age (indoor resp. outdoor workers, pensioners, school-children, or preschool-children), and their kind of residence (wooden, brick, or multi-storey house). Model results for various population groups are compared with the results of TLD-measurements of individual external exposures. For the calculation of inhalation doses, the new ICRP model for the respiratory tract was used. The dose assessments were conducted for measured size resolved activity distributions of resuspended material, obtained at different locations and for several kinds of agricultural operations. Inhalation doses vary considerably with respect to different kinds of work. Tractor drivers receive much higher doses than other agricultural workers, especially when the cabin window of the tractor is open. Effective doses due to the inhalation of resuspended plutonium are assessed to be a few μSv per initial deposit of one kBq/m 2 . Inhalation doses from 137 Cs are usually smaller by an order of magnitude than the doses from Pu, provided a high solubility is assumed for resuspended Cs

  2. Inhalational and dermal exposures during spray application of biocides.

    Science.gov (United States)

    Berger-Preiss, Edith; Boehncke, Andrea; Könnecker, Gustav; Mangelsdorf, Inge; Holthenrich, Dagmar; Koch, Wolfgang

    2005-01-01

    Data on inhalational and potential dermal exposures during spray application of liquid biocidal products were generated. On the one hand, model experiments with different spraying devices using fluorescent tracers were carried out to investigate the influence of parameters relevant to the exposure (e.g. spraying equipment, nozzle size, direction of application). On the other hand, measurements were performed at selected workplaces (during disinfection operations in food and feed areas; pest control operations for private, public and veterinary hygiene; wood protection and antifouling applications) after application of biocidal products such as Empire 20, Responsar SC, Omexan-forte, Actellic, Perma-forte; Fendona SC, Pyrethrum mist; CBM 8, Aldekol Des 03, TAD CID, Basileum, Basilit. The measurements taken in the model rooms demonstrated dependence of the inhalation exposure on the type of spraying device used, in the following order: "spraying with low pressure" < "airless spraying" < "fogging" indicating that the particle diameter of the released spray droplets is the most important parameter. In addition inhalation exposure was lowest when the spraying direction was downward. Also for the potential dermal exposure, the spraying direction was of particular importance: overhead spraying caused the highest contamination of body surfaces. The data of inhalational and potential dermal exposures gained through workplace measurements showed considerable variation. During spraying procedures with low-pressure equipments, dose rates of active substances inhaled by the operators ranged from 7 to 230 microg active substance (a.s.)/h. An increase in inhaled dose rates (6-33 mg a.s./h) was observed after use of high application volumes/time unit during wood protection applications indoors. Spraying in the veterinary sector using medium-pressure sprayers led to inhaled dose rates between 2 and 24mga.s./h. The highest inhaled dose rates were measured during fogging (114 mg a

  3. Factors related to the incorrect use of inhalers by asthma patients

    Directory of Open Access Journals (Sweden)

    Paulo de Tarso Roth Dalcin

    2014-01-01

    Full Text Available OBJECTIVE: To evaluate inhaler technique in outpatients with asthma and to determine associations between the correctness of that technique and the level of asthma control. METHODS: This was a cross-sectional study involving patients > 14 years of age with physician-diagnosed asthma. The patients were recruited from the Asthma Outpatient Clinic of the Hospital de Clínicas de Porto Alegre, in the city of Porto Alegre, Brazil. The patients completed two questionnaires (a general questionnaire and an asthma control questionnaire based on the 2011 Global Initiative for Asthma guidelines, demonstrated their inhaler technique, and performed pulmonary function tests. Incorrect inhaler technique was defined as the incorrect execution of at least two of the predefined steps. RESULTS: We included 268 patients. Of those, 81 (30.2% showed incorrect inhaler technique, which was associated with poor asthma control (p = 0.002. Logistic regression analysis identified the following factors associated with incorrect inhaler technique: being widowed (OR = 5.01; 95% CI, 1.74-14.41; p = 0.003; using metered dose inhalers (OR = 1.58; 95% CI, 1.35-1.85; p 2 comorbidities (OR = 3.80; 95% CI, 1.03-14.02; p = 0.045. CONCLUSIONS: In the sample studied, incorrect inhaler technique was associated with poor asthma control. Widowhood, use of metered dose inhalers, low socioeconomic level, and the presence of > 2 comorbidities were associated with incorrect inhaler technique.

  4. Argemone oil, an edible oil adulterant, induces systemic immunosuppression in Balb/c mice in an oral 28 days repeated dose toxicity study.

    Science.gov (United States)

    Mandal, Payal; Tewari, Prachi; Kumar, Sachin; Yadav, Sarika; Ayanur, Anjaneya; Chaturvedi, Rajnish K; Das, Mukul; Tripathi, Anurag

    2018-05-01

    Consumption of edible oils contaminated with Argemone oil (AO) leads to a clinical condition called "Epidemic dropsy". Earlier studies have reported that metabolism and oxidative stress primarily contributes to AO toxicity, however, the involvement of immune system has not been assessed so far. Therefore, the present study was undertaken to systematically assess the effect of AO exposure on the function of immune system in Balb/c mice. The repeated exposure of AO for 28 days caused prominent regression of spleen and thymus; severe inflammatory changes in spleen depicted by the loss of distinct follicles, increased megakaryocyte infiltration, and enhanced expression levels of inflammatory markers (iNOS & COX-2). At the functional level, AO exposure significantly abrogated the mixed lymphocyte reaction and mitogen-stimulated lymphoproliferative activity of T and B cells, which is reflective of profound lymphocyte dysfunction upon antigen exposure. In concordance with the loss in functional activity of lymphocytes in AO exposed animals, it was found the AO altered the relative percentage of CD3 + , CD4 + , and CD28  +  T cells. Further, there was a marked decrease in the relative distribution of cells with prominent MHC I and CD1d expression in AO exposed splenocytes. Moreover, reduced levels of immune stimulatory cytokines (TNF-α, IFN-γ, IL-2, IL-4, and IL-6), and increased levels of immunosuppressive cytokine IL-10 were detected in the serum of AO treated mice. Along with T and B cells, AO exposure also affected the phenotype and activation status of macrophages suggesting the inclination towards "alternative activation of macrophages". Altogether, these functional changes in the immune cells are contributing factors in AO induced immunosuppression. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Long-term Outcomes With Planned Multistage Reduced Dose Repeat Stereotactic Radiosurgery for Treatment of Inoperable High-Grade Arteriovenous Malformations: An Observational Retrospective Cohort Study.

    Science.gov (United States)

    Marciscano, Ariel E; Huang, Judy; Tamargo, Rafael J; Hu, Chen; Khattab, Mohamed H; Aggarwal, Sameer; Lim, Michael; Redmond, Kristin J; Rigamonti, Daniele; Kleinberg, Lawrence R

    2017-07-01

    There is no consensus regarding the optimal management of inoperable high-grade arteriovenous malformations (AVMs). This long-term study of 42 patients with high-grade AVMs reports obliteration and adverse event (AE) rates using planned multistage repeat stereotactic radiosurgery (SRS). To evaluate the efficacy and safety of multistage SRS with treatment of the entire AVM nidus at each treatment session to achieve complete obliteration of high-grade AVMs. Patients with high-grade Spetzler-Martin (S-M) III-V AVMs treated with at least 2 multistage SRS treatments from 1989 to 2013. Clinical outcomes of obliteration rate, minor/major AEs, and treatment characteristics were collected. Forty-two patients met inclusion criteria (n = 26, S-M III; n = 13, S-M IV; n = 3, S-M V) with a median follow-up was 9.5 yr after first SRS. Median number of SRS treatment stages was 2, and median interval between stages was 3.5 yr. Twenty-two patients underwent pre-SRS embolization. Complete AVM obliteration rate was 38%, and the median time to obliteration was 9.7 yr. On multivariate analysis, higher S-M grade was significantly associated ( P = .04) failure to achieve obliteration. Twenty-seven post-SRS AEs were observed, and the post-SRS intracranial hemorrhage rate was 0.027 events per patient year. Treatment of high-grade AVMs with multistage SRS achieves AVM obliteration in a meaningful proportion of patients with acceptable AE rates. Lower obliteration rates were associated with higher S-M grade and pre-SRS embolization. This approach should be considered with caution, as partial obliteration does not protect from hemorrhage. Copyright © 2017 by the Congress of Neurological Surgeons

  6. Calculating radiation exposure and dose

    International Nuclear Information System (INIS)

    Hondros, J.

    1987-01-01

    This paper discusses the methods and procedures used to calculate the radiation exposures and radiation doses to designated employees of the Olympic Dam Project. Each of the three major exposure pathways are examined. These are: gamma irradiation, radon daughter inhalation and radioactive dust inhalation. A further section presents ICRP methodology for combining individual pathway exposures to give a total dose figure. Computer programs used for calculations and data storage are also presented briefly

  7. Inhaled Surfactant Therapy in Newborns in Artificial Lung Ventilation

    Directory of Open Access Journals (Sweden)

    S. A. Perepelitsa

    2014-01-01

    Full Text Available Objective: to evaluate the efficiency of inhaled surfactant therapy in neonatal infants with respiratory failure.Subjects and methods. The trial enrolled 13 premature neonatal infants; their mean gestational age was 31.8±2.8 weeks and the birth weight was 1825±600.9 g. They had a oneminute Apgar score of 4.3±1.4. All the neonates needed mechanical ventilation (MV atbirth because the leading clinical sign was respiratory failure caused by acute intranatal hypoxia, neonatal amniotic fluid aspiration, respiratory distress syndrome (RDS, and cerebral ischemia. Curosurf was injected in a dose of 174.7±21 mg/kg in the infants with neonatal RDS at 35 minutes of life. All the babies included in the study were noted to have severe disease and prolonged MV. After stabilization of their status, the neonates received combination therapy involving surfactantBL inhalation to reduce the duration of MV. The dose of the agent was 75 mg. Results. After surfactantBL inhalation, effective spontaneous respiration occurred in 69.2% of the newborn infants; successful extubation was carried out. The median duration ofMV after surfactant BL inhalation was 22 hours (4—68 hours. There were no reintubated cases after inhalation therapy. Following surfactantBL inhalation, 4 (30.8% patients remained to be on MV as a control regimen; 3 of them had highfre quency MV. SurfactantBL inhalation made it possible to change the respiratory support regimen and to reduce MV parame ters in these babies. 

  8. Systemic and immunotoxicity of pristine and PEGylated multi-walled carbon nanotubes in an intravenous 28 days repeated dose toxicity study.

    Science.gov (United States)

    Zhang, Ting; Tang, Meng; Zhang, Shanshan; Hu, Yuanyuan; Li, Han; Zhang, Tao; Xue, Yuying; Pu, Yuepu

    2017-01-01

    The numerous increasing use of carbon nanotubes (CNTs) derived from nanotechnology has raised concerns about their biosafety and potential toxicity. CNTs cause immunologic dysfunction and limit the application of CNTs in biomedicine. The immunological responses induced by pristine multi-walled carbon nanotubes (p-MWCNTs) and PEGylated multi-walled carbon nanotubes (MWCNTs-PEG) on BALB/c mice via an intravenous administration were investigated. The results reflect that the p-MWCNTs induced significant increases in spleen, thymus, and lung weight. Mice treated with p-MWCNTs showed altered lymphocyte populations (CD3 + , CD4 + , CD8 + , and CD19 + ) in peripheral blood and increased serum IgM and IgG levels, and splenic macrophage ultrastructure indicated mitochondria swelling. p-MWCNTs inhibited humoral and cellular immunity function and were associated with decreased immune responses against sheep erythrocytes and serum hemolysis level. Natural killer (NK) activity was not modified by two types of MWCNTs. In comparison with two types of MWCNTs, for a same dose, p-MWCNTs caused higher levels of inflammation and immunosuppression than MWCNTs-PEG. The results of immunological function suggested that after intravenous administration with p-MWCNTs caused more damage to systemic immunity than MWCNTs-PEG. Here, we demonstrated that a surface functional modification on MWCNTs reduces their immune perturbations in vivo. The chemistry-modified MWCNTs change their preferred immune response in vivo and reduce the immunotoxicity of p-MWCNTs.

  9. Opportunities for inhaler device selection in elderly patients with asthma or COPD

    Directory of Open Access Journals (Sweden)

    Barrons R

    2015-12-01

    Full Text Available Robert Barrons,1 James Wheeler,2 J Andrew Woods1 1Wingate University School of Pharmacy, Wingate, NC, USA; 2University of Tennessee Health Science Center, Nashville, TN, USA Abstract: An anticipated surge in the elderly population will be accompanied by a rise in aging patients with asthma or COPD. Clinician selection of inhalers needs to address the unique challenges to elderly patients. These challenges to the use of inhalers include diminished physical and cognitive abilities, as well as cost reimbursement issues associated with polypharmacy and the Medicare gap. Clinicians should consider patient preferences for an inhaler device that provides ease of administration, and addresses conveniences such as portability, visual, and auditory indicators of dosing completion. The addition of spacer devices resolves hand-breath coordination difficulty with pressurized metered dose inhalers, but reduces overall inhaler convenience. Soft mist inhalers (Respimat® improve ease of administration, but use may be limited by cost and formulary availability. Multiple dose dry powder inhalers provide convenience and simplified use by requiring only one to two steps prior to administration, but concerns of peak inspiratory flow requirements remain among patients with advanced age and severity of COPD. If unaddressed, these challenges to inhaler selection contribute to inappropriate use of inhalers in 41% to 69% of patients, accompanied by at least 51% non-adherence to treatment. Clinicians must first avail themselves of reputable educational resources regarding new inhaler developments and administration, for competent patient instruction. Patient education should include a checklist of inhaler technique, with physical demonstration of each device by the patient and provider. Device demonstration significantly improves inhaler technique and identifies the need for nebulization therapy. Clinician and patient knowledge of available inhalers and their

  10. Whole-body nanoparticle aerosol inhalation exposures.

    Science.gov (United States)

    Yi, Jinghai; Chen, Bean T; Schwegler-Berry, Diane; Frazer, Dave; Castranova, Vince; McBride, Carroll; Knuckles, Travis L; Stapleton, Phoebe A; Minarchick, Valerie C; Nurkiewicz, Timothy R

    2013-05-07

    Inhalation is the most likely exposure route for individuals working with aerosolizable engineered nano-materials (ENM). To properly perform nanoparticle inhalation toxicology studies, the aerosols in a chamber housing the experimental animals must have: 1) a steady concentration maintained at a desired level for the entire exposure period; 2) a homogenous composition free of contaminants; and 3) a stable size distribution with a geometric mean diameter generation of aerosols containing nanoparticles is quite challenging because nanoparticles easily agglomerate. This is largely due to very strong inter-particle forces and the formation of large fractal structures in tens or hundreds of microns in size (6), which are difficult to be broken up. Several common aerosol generators, including nebulizers, fluidized beds, Venturi aspirators and the Wright dust feed, were tested; however, none were able to produce nanoparticle aerosols which satisfy all criteria (5). A whole-body nanoparticle aerosol inhalation exposure system was fabricated, validated and utilized for nano-TiO2 inhalation toxicology studies. Critical components: 1) novel nano-TiO2 aerosol generator; 2) 0.5 m(3) whole-body inhalation exposure chamber; and 3) monitor and control system. Nano-TiO2 aerosols generated from bulk dry nano-TiO2 powders (primary diameter of 21 nm, bulk density of 3.8 g/cm(3)) were delivered into the exposure chamber at a flow rate of 90 LPM (10.8 air changes/hr). Particle size distribution and mass concentration profiles were measured continuously with a scanning mobility particle sizer (SMPS), and an electric low pressure impactor (ELPI). The aerosol mass concentration (C) was verified gravimetrically (mg/m(3)). The mass (M) of the collected particles was determined as M = (Mpost-Mpre), where Mpre and Mpost are masses of the filter before and after sampling (mg). The mass concentration was calculated as C = M/(Q*t), where Q is sampling flowrate (m(3)/min), and t is the sampling

  11. Exubera. Inhale therapeutic systems.

    Science.gov (United States)

    Bindra, Sanjit; Cefalu, William T

    2002-05-01

    Inhale, in colaboration with Pfizer and Aventis Pharma (formerly Hoechst Marion Roussel; HMR), is developing an insulin formulation utilizing its pulmonary delivery technology for macromolecules for the potential treatment of type I and II diabetes. By July 2001, the phase III program had been completed and the companies had begun to assemble data for MAA and NDA filings; however, it was already clear at this time that additional data might be required for filing. By December 2001, it had been decided that the NDA should include an increased level of controlled, long-term pulmonary safety data in diabetic patients and a major study was planned to be completed in 2002, with the NDA filed thereafter (during 2002). US-05997848 was issued to Inhale Therapeutic Systems in December 1999, and corresponds to WO-09524183, filed in February 1995. Equivalent applications have appeared to date in Australia, Brazil, Canada, China, Czech Republic, Europe, Finland, Hungary, Japan, Norway, New Zealand, Poland and South Africa. This family of applications is specific to pulmonary delivery of insulin. In February 1999, Lehman Brothers gave this inhaled insulin a 60% probability of reaching market, with a possible launch date of 2001. The analysts estimated peak sales at $3 billion in 2011. In May 2000, Aventis predicted that estimated peak sales would be in excess of $1 billion. In February 2000, Merrill Lynch expected product launch in 2002 and predicted that it would be a multibillion-dollar product. Analysts Merril Lynch predicted, in September and November 2000, that the product would be launched by 2002, with sales in that year of e75 million, rising to euro 500 million in 2004. In April 2001, Merrill Lynch predicted that filing for this drug would occur in 2001. Following the report of the potential delay in regulatory filing, issued in July 2001, Deutsche Banc Alex Brown predicted a filing would take place in the fourth quarter of 2002 and launch would take place in the first

  12. Compared biokinetic and biological studies of chronic and acute inhalations of uranium compounds in the rat

    International Nuclear Information System (INIS)

    Monleau, M.

    2005-12-01

    Uranium is a natural, radioactive heavy metal, widely used in the nuclear industry in various chemical and isotopic forms. Its use in the fuel cycle involves the risk of radiological exposure for the workers, mainly via the inhalation of uranium particles. According to the workplace configuration, uranium contaminations can be acute or repeated, involve various chemical forms and different levels of enrichment, as well as involving one or several components. The dosimetric concepts and models available for workers' radiological protection, as well as most of the studies of the biological effects, correspond to acute exposure situations. Moreover the processes leading to pathological effects are little known in vivo. In this context, the main question is to know whether exposures due to repeated inhalation by rats induce the element kinetics and toxicity, which may be different from those observed after an acute exposure. In this study, comparison of the experimental and theoretical biokinetics of an insoluble uranium repeatedly inhaled over three weeks shows that a chronic contamination is correctly modelled, except for bone retention, by the sum of acute, successive and independent incorporations. Moreover, the kinetics of a soluble uranium inhaled irregularly can be modified by previous repeated exposure to an insoluble uranium. In certain cases therefore, exposure to uranium could modify its biokinetics during later exposures. At a toxicological level, the study demonstrates that the uranium particles inhaled repeatedly induce behavioural disruptions and genotoxic effects resulting in various sorts of DNA damage, in several cell types and certainly depending on the quantity inhaled. Exposures involving several uraniferous components produce a synergy effect. Moreover, repeated inhalations worsen the genotoxic effects in comparison to an acute exposure. This work demonstrates the importance of not ignoring the effects of the repetition of uranium exposure. It

  13. Practice makes perfect: self-reported adherence a positive marker of inhaler technique maintenance.

    Science.gov (United States)

    Azzi, Elizabeth; Srour, Pamela; Armour, Carol; Rand, Cynthia; Bosnic-Anticevich, Sinthia

    2017-04-24

    Poor inhaler technique and non-adherence to treatment are major problems in the management of asthma. Patients can be taught how to achieve good inhaler technique, however maintenance remains problematic, with 50% of patients unable to demonstrate correct technique. The aim of this study was to determine the clinical, patient-related and/or device-related factors that predict inhaler technique maintenance. Data from a quality-controlled longitudinal community care dataset was utilized. 238 patients using preventer medications where included. Data consisted of patient demographics, clinical data, medication-related factors and patient-reported outcomes. Mixed effects logistic regression was used to identify predictors of inhaler technique maintenance at 1 month. The variables found to be independently associated with inhaler technique maintenance using logistic regression (Χ 2 (3,n = 238) = 33.24, p < 0.000) were inhaler technique at Visit 1 (OR 7.1), device type (metered dose inhaler and dry powder inhalers) (OR 2.2) and self-reported adherent behavior in the prior 7 days (OR 1.3). This research is the first to unequivocally establish a predictive relationship between inhaler technique maintenance and actual patient adherence, reinforcing the notion that inhaler technique maintenance is more than just a physical skill. Inhaler technique maintenance has an underlying behavioral component, which future studies need to investigate. BEHAVIORAL ELEMENT TO CORRECT LONG-TERM INHALER TECHNIQUES: Patients who consciously make an effort to perfect asthma inhaler technique will maintain their skills long-term. Elizabeth Azzi at the University of Sydney, Australia, and co-workers further add evidence that there is a strong behavioral component to patients retaining correct inhaler technique over time. Poor inhaler technique can limit asthma control, affecting quality of life and increasing the chances of severe exacerbations. Azzi's team followed 238 patients to

  14. Systemic and immunotoxicity of pristine and PEGylated multi-walled carbon nanotubes in an intravenous 28 days repeated dose toxicity study

    Directory of Open Access Journals (Sweden)

    Zhang T

    2017-02-01

    Full Text Available Ting Zhang,1–3 Meng Tang,1–3 Shanshan Zhang,1–3 Yuanyuan Hu,1–3 Han Li,4 Tao Zhang,4 Yuying Xue,1–3 Yuepu Pu1–3 1Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China; 2Jiangsu key Laboratory for Biomaterials and Devices, Southeast University, Nanjing, China; 3Collaborative Innovation Center of Suzhou Nano Science and Technology, Suzhou, China; 4Department of Material Science and Engineering, National Key Laboratory of Solid State Microstructures, Nanjing University, Nanjing, China Abstract: The numerous increasing use of carbon nanotubes (CNTs derived from nanotechnology has raised concerns about their biosafety and potential toxicity. CNTs cause immunologic dysfunction and limit the application of CNTs in biomedicine. The immunological responses induced by pristine multi-walled carbon nanotubes (p-MWCNTs and PEGylated multi-walled carbon nanotubes (MWCNTs-PEG on BALB/c mice via an intravenous administration were investigated. The results reflect that the p-MWCNTs induced significant increases in spleen, thymus, and lung weight. Mice treated with p-MWCNTs showed altered lymphocyte populations (CD3+, CD4+, CD8+, and CD19+ in peripheral blood and increased serum IgM and IgG levels, and splenic macrophage ultrastructure indicated mitochondria swelling. p-MWCNTs inhibited humoral and cellular immunity function and were associated with decreased immune responses against sheep erythrocytes and serum hemolysis level. Natural killer (NK activity was not modified by two types of MWCNTs. In comparison with two types of MWCNTs, for a same dose, p-MWCNTs caused higher levels of inflammation and immunosuppression than MWCNTs-PEG. The results of immunological function suggested that after intravenous administration with p-MWCNTs caused more damage to systemic immunity than MWCNTs- PEG. Here, we demonstrated that a surface functional modification on MWCNTs reduces

  15. Repeat dose of gonadotropin-releasing hormone agonist trigger in polycystic ovarian syndrome undergoing In Vitro fertilization cycles provides a better cycle outcome - a proof-of-concept study

    Directory of Open Access Journals (Sweden)

    Krishna Deepika

    2017-01-01

    Full Text Available Objective: Is a single dose of gonadotropin-releasing hormone agonist (GnRHa trigger to induce final oocyte maturation in polycystic ovarian syndrome (PCOS undergoing in vitro fertilization (IVF cycles with GnRH antagonist protocol sufficient to provide optimal oocyte maturity? Design: This is a prospective, randomized, double-blind, proof-of-concept study. Setting: This study was carried out at a tertiary care center. Material and Methods: A total of 125 patients diagnosed with PCOS defined as per the ESHRE/ASRM Rotterdam criteria (2003 undergoing IVF in antagonist protocol were randomized into two groups. Group A: single dose of GnRHa 0.2 mg, 35 h prior to oocyte retrieval, and Group B: 0.2 mg GnRHa 35 h prior to oocyte retrieval + repeat dose of 0.1 mg 12 h following the 1st dose. 12 h post-trigger, luteinizing hormone (LH, progesterone (P4, and follicle-stimulating hormone (FSH values were estimated. Statistical Analysis: Continuous variables were expressed as mean ± standard deviation and categorical variables as proportions where applicable. Independent sample t-test was used for continuous variables which were normally distributed and Mann–Whitney U-test for data not normally distributed. Chi-square test or Fisher's exact test was used for categorical variables where appropriate. Odds ratio (OR with 95% confidence intervals (CIs was calculated. In addition, receiver operating characteristic curve was used to evaluate the post-trigger LH, P4, and FSH values at 12 h as predictors of oocyte maturity. Main Outcome Measures: Primary outcome: maturity rate of the oocytes. Secondary outcomes: oocyte yield, fertilization rate, availability of good quality embryos on day 3, blastocyst conversion, OHSS rates, post-trigger serum LH (IU/L, FSH (IU/L, and P4 (ng/mL levels implantation rate and clinical pregnancy rate. Results: A higher number of mature (metaphase II oocytes were obtained in Group B compared to Group A (OR of 0.47; CI: 0.38–0

  16. Formulation and evaluation of CFC free inhalers for beclomethasone dipropionate

    Directory of Open Access Journals (Sweden)

    Gopala Krishna Murthy Talasila

    2013-06-01

    Full Text Available Beclomethasone dipropionate CFC free inhalation formulations were developed with a view to treat asthma prophylactically. Dry powder inhalers (DPI for beclomethasone dipropionate were prepared with different grades of lactose monohydrate. The influence of carrier and overages on performance of DPI was studied. Metered dose inhalers (MDI with HFA based propellants were formulated with various doses, overages and different concentrations of alcohol. Formulated DPI and MDI were evaluated for various official and unofficial quality control tests. The influence of over doses on valve delivery, effect of overages on emitted dose and influence of alcohol on spray pattern from MDI were studied. The better fine particle fraction and emitted dose were obtained from the DPI formulated with 10:90 ratio of fine lactose: coarse lactose and with 20% w/w overages. The studies on MDI revealed that the 15% of overdoses are required for effective valve delivery and 20% overages are required for 100% drug delivery. 5-10%v/v alcohol was found to be preferable to get optimum emitted dose and fine particle fraction.

  17. Evaluating inhaler use technique in COPD patients

    Directory of Open Access Journals (Sweden)

    Pothirat C

    2015-07-01

    Full Text Available Chaicharn Pothirat, Warawut Chaiwong, Nittaya Phetsuk, Sangnual Pisalthanapuna, Nonglak Chetsadaphan, Woranoot Choomuang Division of Pulmonary, Critical Care and Allergy, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Background: Poor inhalation techniques are associated with decreased medication delivery and poor disease control in chronic obstructive pulmonary disease (COPD. The purpose of this study was to evaluate techniques for using inhaler devices in COPD patients.Methods: A prospective cross-sectional study was conducted to assess patient compliance with correct techniques for using inhaler devices across four regimens, ie, the pressurized metered-dose inhaler (pMDI, the pMDI with a spacer, the Accuhaler®, and the Handihaler®. The percentage of compliance with essential steps of correct device usage for each regimen was recorded without prior notification when COPD patients presented for a routine visit, and 1 month after receiving face-to-face training. We compared the percentage of compliance between the devices and risk factors related to incorrect techniques using logistic regression analysis. Percentage of patient compliance with correct techniques was compared between the two visits using the chi-square test. Statistical significance was set at P<0.05.Results: A total of 103 COPD patients (mean age 71.2±9.2 years, males 64.1%, low education level 82.5%, and percent predicted forced expiratory volume in 1 second 51.9±22.5 were evaluated. Seventy-seven patients (74.8% performed at least one step incorrectly. Patients using the Handihaler had the lowest compliance failure (42.5%, and the odds ratio for failure with the other devices compared with the Handihaler were 4.6 (95% confidence interval [CI] 1.8–11.8 for the pMDI, 3.1 (95% CI 1.2–8.2 for the pMDI with a spacer, and 2.4 (95% CI 1.1–5.2 for the Accuhaler. Low education level was the single most important factor related

  18. Inhaled Loxapine for Agitation in Intoxicated Patients: A Case Series.

    Science.gov (United States)

    Roncero, Carlos; Ros-Cucurull, Elena; Palma-Álvarez, Raúl Felipe; Abad, Alfonso Carlos; Fadeuilhe, Christian; Casas, Miquel; Grau-López, Lara

    Episodes of agitation are frequent in intoxicated patients who have a substance use disorder, a psychiatric disorder or both (dual diagnosis). For managing the agitation, it is necessary to act promptly in a safe environment and addressing any underlying etiology. Inhaled loxapine improves symptoms of agitation in adults with psychiatric disorders (eg, schizophrenia) within 10 minutes of administration. Recently, some reports have documented the usefulness of loxapine in dual diagnoses patients with agitation. However, the efficacy of loxapine in intoxicated patients has not been deeply addressed. This report describes a case series of 12 patients (with addiction or dual disorder) who received inhaled loxapine for symptoms of psychomotor agitation during intoxication with different substances (eg, alcohol, cannabis, or cocaine) at 1 center in Spain. Data from 12 patients were reviewed, 5 patients were attended at the emergency room, 4 at the addiction and dual diagnosis unit, and 3 were treated during hospitalization for detoxification. All patients were under effects of substances. They had substance use disorder (including cannabis, cocaine, alcohol, hypnotics, and hallucinogens), and almost all (90%) presented 1 or more psychiatric disorders. One dose of inhaled loxapine was effective in 9 patients (75%), and in 3 patients, a second dose was required. Only mild dizziness was reported in 1 patient after the second dose. The acute agitation was effectively and quickly managed with inhaled loxapine in all intoxicated patients and enabled the appropriate clinical evaluation of the agitated state and the patient's management.

  19. Health effects of inhaled gasoline engine emissions.

    Science.gov (United States)

    McDonald, Jacob D; Reed, Matthew D; Campen, Matthew J; Barrett, Edward G; Seagrave, JeanClare; Mauderly, Joe L

    2007-01-01

    Despite their prevalence in the environment, and the myriad studies that have shown associations between morbidity or mortality with proximity to roadways (proxy for motor vehicle exposures), relatively little is known about the toxicity of gasoline engine emissions (GEE). We review the studies conducted on GEE to date, and summarize the findings from each of these studies. While there have been several studies, most of the studies were conducted prior to 1980 and thus were not conducted with contemporary engines, fuels, and driving cycles. In addition, many of the biological assays conducted during those studies did not include many of the assays that are conducted on contemporary inhalation exposures to air pollutants, including cardiovascular responses and others. None of the exposures from these earlier studies were characterized at the level of detail that would be considered adequate today. A recent GEE study was conducted as part of the National Environmental Respiratory Center (www.nercenter.org). In this study several in-use mid-mileage General Motors (Chevrolet S-10) vehicles were purchased and utilized for inhalation exposures. An exposure protocol was developed where engines were operated with a repeating California Unified Driving Cycle with one cold start per day. Two separate engines were used to provide two cold starts over a 6-h inhalation period. The exposure atmospheres were characterized in detail, including detailed chemical and physical analysis of the gas, vapor, and particle phase. Multiple rodent biological models were studied, including general toxicity and inflammation (e.g., serum chemistry, lung lavage cell counts/differentials, cytokine/chemokine analysis, histopathology), asthma (adult and in utero exposures with pulmonary function and biochemical analysis), cardiovascular effects (biochemical and electrocardiograph changes in susceptible rodent models), and susceptibility to infection (Pseudomonas bacteria challenge). GEE resulted in

  20. Effect of inhaled corticosteroid use on weight (BMI) in pediatric patients with moderate-severe asthma.

    Science.gov (United States)

    Han, Jennifer; Nguyen, John; Kim, Yuna; Geng, Bob; Romanowski, Gale; Alejandro, Lawrence; Proudfoot, James; Xu, Ronghui; Leibel, Sydney

    2018-04-19

    Assess the relationship between inhaled corticosteroid use (ICS) and weight (BMI) in pediatric patients with moderate-severe asthma. Assess if the number of emergency department (ED) visits correlates with overall BMI trajectory. Assess the trend of prescribing biologic therapy in pediatric patients with moderate-severe asthma and determine its relationship with weight (BMI). A retrospective chart review was performed on 93 pediatric patients with moderate-severe asthma to determine the relationship between ICS use and weight (BMI), biologic therapy and BMI, and number of ED visits and BMI trajectory. A mixed effects model was employed with the correlation between repeated measures accounted for through the random effects. There is a statistically significant increase of 0.369 kg/m 2 in BMI trajectory per year in subjects on high-dose steroids compared to an increase of 0.195 kg/m 2 in the low dose group (p BMI of subjects initiated on biologic therapy (omalizumab or mepolizumab) had a statistically significant decrease in BMI trajectory of 0.818 kg/m 2 per year (p BMI trajectory (p BMI trajectory; the higher the dose, the greater the projected BMI increase per year. Initiation of biologic therapy decreased BMI trajectory over time. Lastly, those with frequent ED visits had a higher BMI trend. Future prospective studies are warranted that further evaluate the potential metabolic impacts of ICS and assess the effects of biologic therapy on BMI.

  1. In vitro tests for aerosol deposition. III: effect of inhaler insertion angle on aerosol deposition.

    Science.gov (United States)

    Delvadia, Renish R; Longest, P Worth; Hindle, Michael; Byron, Peter R

    2013-06-01

    Inhaler orientation with respect to a patient's mouth may be an important variable determining the efficiency of aerosol lung delivery. The effect of insertion angle on regional deposition was evaluated for a series of inhalers using concurrent in vitro and computational fluid dynamics (CFD) analysis. Geometrically realistic physical mouth-throat (MT) and upper tracheobronchial (TB) models were constructed to connect different inhalers at a series of insertion angles relative to the horizontal plane of the model. These models were used to assess albuterol sulfate deposition from the Novolizer(®) dry powder inhaler (DPI), Proventil(®) HFA pressurized metered dose inhaler (MDI), and Respimat(®) Soft Mist™ Inhaler (SMI) following the actuation of a single dose. Drug deposition from Novolizer DPI was studied for Salbulin(®) and an experimental "drug only" formulation. Albuterol sulfate was recovered and quantified from the device and the MT and TB regions. Significant differences in MT and total lung dose (TLD) of albuterol sulfate deposition were not observed for Salbulin Novolizer DPI and Respimat SMI inserted at different angles. In contrast, drug-only Novolizer DPI and Proventil HFA MDI showed a significant difference in MT and TLD deposition using different insertion angles. For drug-only Novolizer DPI and Proventil HFA MDI, the lowest and the highest MT depositions were observed at +10° and -20°, respectively; for Respimat SMI and Salbulin Novolizer DPI, these angles were -10° and +10°, and +20° and -20°, respectively. CFD simulations were in agreement with the experimental results and illustrated shifts in local particle deposition associated with changes in insertion angle. The effect of inhaler orientation at the inhaler-mouth interface on MT aerosol deposition appeared to be dependent on velocity, aerosol size, and formulation. These findings not only demonstrate the need for patient education on correct inhaler orientation, but provide important

  2. Inhaled Corticosteroids (ICSs) and Pregnancy

    Science.gov (United States)

    ... of the airways in the lungs and reduce mucus production so that asthma attacks are less likely. ... of medicine that would be in the breast milk following inhalation is likely too small to cause ...

  3. Effect of novel inhaler technique reminder labels on the retention of inhaler technique skills in asthma: a single-blind randomized controlled trial.

    Science.gov (United States)

    Basheti, Iman A; Obeidat, Nathir M; Reddel, Helen K

    2017-02-09

    Inhaler technique can be corrected with training, but skills drop off quickly without repeated training. The aim of our study was to explore the effect of novel inhaler technique labels on the retention of correct inhaler technique. In this single-blind randomized parallel-group active-controlled study, clinical pharmacists enrolled asthma patients using controller medication by Accuhaler [Diskus] or Turbuhaler. Inhaler technique was assessed using published checklists (score 0-9). Symptom control was assessed by asthma control test. Patients were randomized into active (ACCa; THa) and control (ACCc; THc) groups. All patients received a "Show-and-Tell" inhaler technique counseling service. Active patients also received inhaler labels highlighting their initial errors. Baseline data were available for 95 patients, 68% females, mean age 44.9 (SD 15.2) years. Mean inhaler scores were ACCa:5.3 ± 1.0; THa:4.7 ± 0.9, ACCc:5.5 ± 1.1; THc:4.2 ± 1.0. Asthma was poorly controlled (mean ACT scores ACCa:13.9 ± 4.3; THa:12.1 ± 3.9; ACCc:12.7 ± 3.3; THc:14.3 ± 3.7). After training, all patients had correct technique (score 9/9). After 3 months, there was significantly less decline in inhaler technique scores for active than control groups (mean difference: Accuhaler -1.04 (95% confidence interval -1.92, -0.16, P = 0.022); Turbuhaler -1.61 (-2.63, -0.59, P = 0.003). Symptom control improved significantly, with no significant difference between active and control patients, but active patients used less reliever medication (active 2.19 (SD 1.78) vs. control 3.42 (1.83) puffs/day, P = 0.002). After inhaler training, novel inhaler technique labels improve retention of correct inhaler technique skills with dry powder inhalers. Inhaler technique labels represent a simple, scalable intervention that has the potential to extend the benefit of inhaler training on asthma outcomes. REMINDER LABELS IMPROVE INHALER TECHNIQUE: Personalized

  4. Subchronic inhalation toxicity of gold nanoparticles

    Directory of Open Access Journals (Sweden)

    Chung Yong

    2011-05-01

    Full Text Available Abstract Background Gold nanoparticles are widely used in consumer products, including cosmetics, food packaging, beverages, toothpaste, automobiles, and lubricants. With this increase in consumer products containing gold nanoparticles, the potential for worker exposure to gold nanoparticles will also increase. Only a few studies have produced data on the in vivo toxicology of gold nanoparticles, meaning that the absorption, distribution, metabolism, and excretion (ADME of gold nanoparticles remain unclear. Results The toxicity of gold nanoparticles was studied in Sprague Dawley rats by inhalation. Seven-week-old rats, weighing approximately 200 g (males and 145 g (females, were divided into 4 groups (10 rats in each group: fresh-air control, low-dose (2.36 × 104 particle/cm3, 0.04 μg/m3, middle-dose (2.36 × 105 particle/cm3, 0.38 μg/m3, and high-dose (1.85 × 106 particle/cm3, 20.02 μg/m3. The animals were exposed to gold nanoparticles (average diameter 4-5 nm for 6 hours/day, 5 days/week, for 90-days in a whole-body inhalation chamber. In addition to mortality and clinical observations, body weight, food consumption, and lung function were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, blood samples were collected for hematology and clinical chemistry tests, and organ weights were measured. Cellular differential counts and cytotoxicity measurements, such as albumin, lactate dehydrogenase (LDH, and total protein were also monitored in a cellular bronchoalveolar lavage (BAL fluid. Among lung function test measurements, tidal volume and minute volume showed a tendency to decrease comparing control and dose groups during the 90-days of exposure. Although no statistically significant differences were found in cellular differential counts, histopathologic examination showed minimal alveoli, an inflammatory infiltrate with a mixed cell type, and increased macrophages in the high-dose rats. Tissue

  5. Synergistic combination of hyperoxygenation and radiotherapy by repeated assessments of tumor pO2 with EPR oximetry

    International Nuclear Information System (INIS)

    Hou, H.; Dong, R.; Lariviere, J.P.; Mupparaju, S.P.; Swartz, H.M.; Khan, N.

    2011-01-01

    The effect of hyperoxygenation with carbogen (95% O 2 +5% CO 2 ) inhalation on radiation-induced fibrosarcoma (RIF-1) tumor pO 2 and its consequence on growth inhibition with fractionated radiotherapy is reported. The temporal changes in the tumor pO 2 were assessed by in vivo Electron Paramagnetic Resonance (EPR) oximetry in mice breathing 30% O 2 or carbogen and the tumors were irradiated with 4 Gy/day for 5 consecutive days; a protocol that emulates the clinical application of carbogen. The RIF-1 tumors were hypoxic with a tissue pO 2 of 5-9 mmHg. Carbogen (CB) breathing significantly increased tumor pO 2 , with a maximum increase at 22.9-31.2 min on days 1-5, however, the magnitude of increase in pO 2 declined on day 5. Radiotherapy during carbogen inhalation (CB/RT) resulted in a significant tumor growth inhibition from day 3 to day 6 as compared to 30%O 2 /RT and carbogen (CB/Sham RT) groups. The results provide unambiguous quantitative information on the effect of carbogen inhalation on tumor pO 2 over the course of 5 days. Tumor growth inhibition in the CB/RT group confirms that the tumor oxygenation with carbogen was radiobiologically significant. Repeated tumor pO 2 measurements by EPR oximetry can provide temporal information that could be used to improve therapeutic outcomes by scheduling doses at times of improved tumor oxygenation. (author)

  6. Synergistic combination of hyperoxygenation and radiotherapy by repeated assessments of tumor pO2 with EPR oximetry

    Science.gov (United States)

    HOU, Huagang; DONG, Ruhong; LARIVIERE, Jean P.; MUPPARAJU, Sriram P.; SWARTZ, Harold M.; KHAN, Nadeem

    2013-01-01

    The effect of hyperoxygenation with carbogen (95% O2 + 5% CO2) inhalation on RIF-1 tumor pO2 and its consequence on growth inhibition with fractionated radiotherapy is reported. The temporal changes in the tumor pO2 were assessed by in vivo Electron Paramagnetic Resonance (EPR) oximetry in mice breathing 30% O2 or carbogen and the tumors were irradiated with 4 Gy/day for 5 consecutive days; a protocol that emulates the clinical application of carbogen. The RIF-1 tumors were hypoxic with a tissue pO2 of 5 – 9 mm Hg. Carbogen (CB) breathing significantly increased tumor pO2, with a maximum increase at 22.9 – 31.2 min on days 1 – 5, however, the magnitude of increase in pO2 declined on day 5. Radiotherapy during carbogen inhalation (CB/RT) resulted in a significant tumor growth inhibition from day 3 to day 6 as compared to 30%O2/RT and carbogen (CB/Sham RT) groups. The results provide unambiguous quantitative information on the effect of carbogen inhalation on tumor pO2 over the course of 5 days. Tumor growth inhibition in the CB/RT group confirms that the tumor oxygenation with carbogen was radiobiologically significant. Repeated tumor pO2 measurements by EPR oximetry can provide temporal information that could be used to improve therapeutic outcomes by scheduling doses at times of improved tumor oxygenation. PMID:21799293

  7. Lung cancer and inhaled uranium ore dust in rats

    International Nuclear Information System (INIS)

    Mitchel, R.E.J.; Jackson, J.S.

    1997-01-01

    Using a nose only inhalation system, 187 nine week old male Sprague-Dawley rats were exposed to two different concentrations of natural uranium ore dust aerosol (44% U) without significant radon content. Inhalation exposures averaged about 4.2 h/day, 5 days/week for 65 weeks at which point lung uranium burdens in the two groups averaged 0.9 and 1.9 mg/g dry weight. Animals (63) exposed to the air stream without dust served as controls. After inhalation exposure ceased, the rats were allowed to live for their natural lifetime, a maximum of about 900 days after the start of dust inhalation. Lung uranium burdens were measured at the time of death of each animal. Lung burdens were found to decline exponentially after dust inhalation ceased, and the rate of decline was independent of the initial lung burden. All lungs were examined at necropsy and histologically for lung tumors. Lung tumors of lung origin were observed in both exposed groups and in the control group. The frequency of primary malignant lung tumors was 0.016, 0.175 and 0.328 and primary non-malignant lung tumors 0.016, 0.135 and 0.131 in the control low and high aerosol exposed groups respectively. Absorbed dose to the lung was calculated for each animal in the study. The average maximum doses for all the animals exposed to the low or high concentration of dust aerosol were 0.87 Gy and 1.64 Gy respectively. The average risk of malignant lung tumors from inhaled natural uranium ore dust was therefore about 0.20 tumors/animal/Gy. For animals with lung tumors, the average doses were 0.98 and 1.90 in the exposed groups. In both exposed groups, the frequency of primary malignant or non-malignant lung tumors was significantly greater than in the control group (p < 0.02) and the frequency of primary malignant lung tumors in the two exposed group were significantly different from each other (p = 0.05). The frequency of primary lung tumors (malignant and non-malignant) was calculated as a function of dose

  8. Measurement of regional cerebral blood flow with the Xenon-133 inhalation procedure in patients with cerebrovascular disease

    Energy Technology Data Exchange (ETDEWEB)

    Hartmann, A.

    1985-10-01

    Measurement of regional cerebral blood flow with inhalation of Xenon-133 and recording of regional clearance curves by stationary external detectors permits repeated estimation of bilateral cortical blood flow in resting position and after different activating procedures. Measurements can be performed on an outpatient basis, measurements in critical ill patients are possible as well. Compared to Xenon-133 single photon emission computerized tomography smaller doses can be used. Compared to Iodine-123 amphetamie SPECT actual flow calculation without arterial puncture is possible. Drawbacks of the technique are the two-dimensional imaging, unsufficient indication of the look through phenomenon and non-perfused tissue with zero-flow. However, measurement of rCBF with this technique are helpful in individual diagnosis of the following diseases: transient ischemic attacks with prolonged ischemia, communicating hydrocephalus with normal intracranial pressure, follow up studies in hemodilution, evaluation of patients with polyarterial vascular disease in respect to neurosurgical or vasculosurgical intervention, subarachnoid hemorrhage and head trauma. (orig.).

  9. ASSESSING THE HEALTH EFFECTS AND RISKS ASSOCIATED WITH CHILDREN’S INHALATION EXPOSURES – ASTHMA AND ALLERGY

    Science.gov (United States)

    Adults and children may have different reactions to inhalation exposures, which may be the result of differences in inhaled or target tissue doses following similar exposures, and/or due to growth and development of the lung which continues postnatally in distinct stages. Because...

  10. Experimental study of the combined effects of inhalation of radon daughter products and tobacco smoke

    International Nuclear Information System (INIS)

    Chameaud, J.; Perraud, R.; Chretien, J.; Masse, R.; Lafuma, J.

    1979-01-01

    For 10 years, over 500 lung cancers have been induced in rats by inhalations of radon daughter products at various concentrations and cumulated doses. Considering several points and the dose-effect relationship especially, such cancers can be compared with human cancers. This type of experiments, fully mastered, has made it possible to undertake under good conditions the study of the co-carcinogenic effect of various inhaled pollutants such as tobacco smoke. In a first experiment, 100 rats were exposed to a 4000WLM cumulated dose of radon daughter products, knowing that this level induces some 30% of lung cancers. 50 animals were then administered tobacco smoke by inhalation in a fume box during 5 months (350 h.) In the group inhaling radon only, 17 cancers appeared; in the radon -tobacco group 32 cancers bigger and more invasive were observed. Under the same conditions, tobacco smoke was inhaled by rats previously exposed to lower doses of radon daughter products (2 groups of 30 rats, 500 and 100 WLM respectively). Again, the number of cancers observed was higher that the number of cancers expected if the rats had inhaled radon only. This co-carcinogenic and potentiating action of tobacco was clearly demonstrated. Further experiments are considered in order to determine the processes involved

  11. Hematologic effects of inhaled plutonium in beagles

    International Nuclear Information System (INIS)

    Ragan, H.A.; Buschbom, R.L.; Park, J.F.; Dagle, G.E.; Weller, R.E.

    1986-01-01

    Beagle dogs were exposed, by inhalation, 5 to 11 years ago, to aerosols of 239 PuO 2 , 238 PuO 2 , or 239 Pu(NO 3 ) 4 , at six dose levels resulting in initial lung burdens ranging from ∼2 to ∼5500 nCi. Translocation of the plutonium to extrapulmonary sites was related to the physical-chemical characteristics of the plutonium compound. The highly insoluble 239 PuO 2 was retained primarily in the lung and associated lymph nodes, whereas 239 Pu(NO 3 ) 4 was much more soluble and translocated relatively rapidly to the skeleton and other extrapulmonary tissues. The 238 PuO 2 was intermediate in solubility and translocation characteristics. The hematologic effects of plutonium inhalation were most pronounced on lymphocyte populations. Evidence suggests that these effects result from irradiation of lymphocytes via the pulmonary lymph nodes with insoluble 239 PuO 2 , and via these same lymph nodes, extrapulmonary lymph nodes, and bone marrow lymphocytes with the more soluble forms, i.e., 238 PuO 2 and 239 Pu(NO 3 ) 4 . There is no evidence suggesting that these exposures increase the risk of developing myeloid or lymphoid neoplasia. 8 refs., 4 figs., 3 tabs

  12. Lovelace ITRI studies on the toxicity of inhaled radionuclides in beagle dogs

    International Nuclear Information System (INIS)

    McClellan, R.O.; Boecker, B.B.; Hahn, F.F.; Muggenburg, B.A.

    1986-01-01

    This paper reviews 19 studies conducted by the Lovelace ITRI on the toxicity of inhaled radionuclides in beagle dogs. These studies provide information to estimate potential health effects in accidentally exposed people. Specific radionuclides ( 90 Sr, 90 Y, 91 Y, 137 Cs, 144 Ce, 238 Pu, and 239 Pu), chemical forms, and particle sizes were selected for study because they are abundant in nuclear operations and deliver a wide range of radiation dose patterns. Depending upon the aerosol, one or more of the following organs or tissues received the significant irradiation: lung, nasal cavity, lung-associated lymph nodes, whole body, liver, or skeleton, with the radiation dose delivered over durations of time ranging from a few days to several years. In eight studies monodisperse particles of either 238 PuO 2 or 239 PuO 2 were used to evaluate the influence of particle number and total dose on lung cancer induction. Most studies involved single, brief exposures of young adult dogs, but two studies used immature dogs, two used aged dogs, and two studies involved repeated brief exposures. For each aerosol two types of studies were conducted. One was used to evaluate the time course of retention of radioactivity in various tissues of the body for calculating radiation doses. The second was used to determine health effects in animals exposed to achieve different initial lung burdens and observed for the remainder of their life spans. Initial lung burdens were selected to produce early morbidity and mortality at the highest levels and an excess of late-occurring diseases such as cancer at the lowest levels. The latter dogs have had an excess incidence of cancer, especially of the lung, lung-associated lymph nodes, nasal cavity, skeleton, and liver. Relationships between radiation doses to various tissues and effects have been evaluated for individual studies

  13. Development of Respimat® Soft Mist™ Inhaler and its clinical utility in respiratory disorders

    Directory of Open Access Journals (Sweden)

    Dalby RN

    2011-09-01

    Full Text Available Richard N Dalby1, Joachim Eicher2, Bernd Zierenberg21Department of Pharmaceutical Sciences, University of Maryland, Baltimore, MD, USA; 2Boehringer Ingelheim, Ingelheim, GermanyAbstract: The Respimat® Soft Mist™ Inhaler (SMI (Boehringer Ingelheim International GmbH, Ingelheim, Germany was developed in response to the need for a pocket-sized device that can generate a single-breath, inhalable aerosol from a drug solution using a patient-independent, reproducible, and environmentally friendly energy supply. This paper describes the design and evolution of this innovative device from a laboratory concept model and the challenges that were overcome during its development and scaleup to mass production. A key technical breakthrough was the uniblock, a component combining filters and nozzles and made of silicon and glass, through which drug solution is forced using mechanical power. This allows two converging jets of solution to collide at a controlled angle, generating a fine aerosol of inhalable droplets. The mechanical energy comes from a spring which is tensioned by twisting the base of the device before use. Additional features of the Respimat® SMI include a dose indicator and a lockout mechanism to avoid the problems of tailing-off of dose size seen with pressurized metered dose inhalers. The Respimat® SMI aerosol cloud has a unique range of technical properties. The high fine particle fraction allied with the low velocity and long generation time of the aerosol translate into a higher fraction of the emitted dose being deposited in the lungs compared with aerosols from pressurized metered dose inhalers and dry powder inhalers. These advantages are realized in clinical trials in adults and children with obstructive lung diseases, which have shown that the efficacy and safety of a pressurized metered dose inhaler formulation of a combination bronchodilator can be matched by a Respimat® SMI formulation containing only one half or one quarter

  14. A method for rapid estimation of internal dose to members of the public from inhalation of mixed fission products (based on the ICRP 1994 human respiratory tract model for radiological protection)

    International Nuclear Information System (INIS)

    Hou Jieli

    1999-01-01

    Based on the computing principle given in ICRP-30, a method had been given by the author for fast estimating internal dose from an intake of mixed fission products after nuclear accident. Following the ICRP-66 Human respiratory tract model published in 1994, the method was reconstructed. The doses of 1 Bq intake of mixed fission products (its AMAD = 1 μm, decay rate coefficient n = 0.2∼2.0) during the period of 1∼15 d after an accident were calculated. It is lower slightly based on ICRP 1994 respiratory tract model than that based on ICRP-30 model

  15. The relative effectiveness of inhaled alpha- and beta-emitting radionuclides in producing lung cancer

    International Nuclear Information System (INIS)

    Boecker, B.B.; Hahn, F.F.; Muggenburg, B.A.; Guilmetter, R.A.; Griffith, W.C.; McClellan, R.O.

    1988-01-01

    Proper assessment of a long-term human health risks associated with inhaled radionuclides requires knowledge of dose to critical cells and tissues and relationships between dose and effect for different biological end points. Results from epidemiological studies of exposed human populations provided important information for such assessments. However, because the types of exposures are limited, these results need to be supplemented with more detailed information on dosimetry and biological effects available through studies in laboratory animals and in vitro systems. To provide health risk information for inhaled fission product and actinide aerosols, life-span studies are being conducted using beagle dogs and other species at the Lovelace Inhalation Toxicology Research Institute (ITRI). Results of two life-span studies in dogs involving inhalation of the beta emitter 91 Y in fused aluminosilicate particles or the alpha emitter 239 PuO 2 are reported here

  16. Evaluation of factors that allow the clinician to taper inhaled corticosteroids in childhood asthma

    Directory of Open Access Journals (Sweden)

    Kentaro Matsuda

    1999-01-01

    Full Text Available Inhaled corticosteroids are potent and effective treatment agents for controlling symptoms of childhood asthma. However, there are no predictive factors that help to determine which patients with asthma are likely to be tapered off inhaled corticosteroids successfully. We examined whether any factor or combination of factors could help the clinician safely discontinue inhaled steroid therapy. Thirty-six asthmatic children whose symptoms were stable on low-dose beclomethasone dipropionate (BDP were divided by parental choice into two groups: maintenance BDP (n = 11 and no BDP (n = 25. Methacholine inhalation tests were performed at the beginning of the study and after 1 month. Twelve children (48% who had BDP discontinued developed exacerbations after 2–3 months, whereas there were no problems in the maintenance group. The no BDP group was retrospectively divided into two subgroups: exacerbation (+ and (−. The threshold to methacholine in the exacerbation (+ subgroup decreased significantly in advance of clinical symptoms. The two subgroups were analyzed statistically by two-group discriminant function analysis. The change in threshold to methacholine, the dose and potency of drugs, duration of asthma and gender (female correlated with exacerbation. These results suggest that discontinuation of inhaled steroids should be done carefully, even in stable asthmatic children. The methacholine inhalation test, gender, drugs and history may be used as references for discontinuing inhaled steroids.

  17. Pentoxifylline does not alter the response to inhaled grain dust.

    Science.gov (United States)

    Jagielo, P J; Watt, J L; Quinn, T J; Knapp, H R; Schwartz, D A

    1997-05-01

    Pentoxifylline (PTX) has been shown to reduce sepsis-induced neutrophil sequestration in the lung and inhibit endotoxin-mediated release of tumor necrosis factor-alpha (TNF-alpha). Previously, we have shown that endotoxin appears to be the principal agent in grain dust causing airway inflammation and airflow obstruction following grain dust inhalation. To determine whether PTX affects the physiologic and inflammatory events following acute grain dust inhalation, 10 healthy, nonsmoking subjects with normal airway reactivity were treated with PTX or placebo (PL) followed by corn dust extract (CDE) inhalation (0.08 mL/kg), using a single-blinded, crossover design. Subjects received PTX (1,200 mg/d) or PL for 4 days prior to CDE inhalation and 400 mg PTX or PL on the exposure day. Both respiratory symptoms and declines in FEV1 and FVC occurred following CDE exposure in both groups, but there were no significant differences in the frequency of symptoms or percent declines from baseline in the FEV1 and FVC at any of the time points measured in the study. Elevations in peripheral blood leukocyte and neutrophil concentrations and BAL total cell, neutrophil, TNF-alpha, and interleukin-8 concentrations were measured 4 h following exposure to CDE in both the PTX- and PL-treated subjects, but no significant differences were found between treatment groups. These results suggest that pretreatment with PTX prior to inhalation of CDE, in the doses used in this study, does not alter the acute physiologic or inflammatory events following exposure to inhaled CDE.

  18. Oral versus inhaled antibiotics for bronchiectasis.

    Science.gov (United States)

    Spencer, Sally; Felix, Lambert M; Milan, Stephen J; Normansell, Rebecca; Goeminne, Pieter C; Chalmers, James D; Donovan, Tim

    2018-03-27

    Bronchiectasis is a chronic inflammatory disease characterised by a recurrent cycle of respiratory bacterial infections associated with cough, sputum production and impaired quality of life. Antibiotics are the main therapeutic option for managing bronchiectasis exacerbations. Evidence suggests that inhaled antibiotics may be associated with more effective eradication of infective organisms and a lower risk of developing antibiotic resistance when compared with orally administered antibiotics. However, it is currently unclear whether antibiotics are more effective when administered orally or by inhalation. To determine the comparative efficacy and safety of oral versus inhaled antibiotics in the treatment of adults and children with bronchiectasis. We identified studies through searches of the Cochrane Airways Group's Specialised Register (CAGR), which is maintained by the Information Specialist for the group. The Register contains trial reports identified through systematic searches of bibliographic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, AMED, and PsycINFO, and handsearching of respiratory journals and meeting abstracts. We also searched ClinicalTrials.gov and the WHO trials portal. We searched all databases in March 2018 and imposed no restrictions on language of publication. We planned to include studies which compared oral antibiotics with inhaled antibiotics. We would have considered short-term use (less than four weeks) for treating acute exacerbations separately from longer-term use as a prophylactic (4 weeks or more). We would have considered both intraclass and interclass comparisons. We planned to exclude studies if the participants received continuous or high-dose antibiotics immediately before the start of the trial, or if they have received a diagnosis of cystic fibrosis (CF), sarcoidosis, active allergic bronchopulmonary aspergillosis or active non-tuberculous Mycobacterial infection

  19. Inhaled mannitol for cystic fibrosis.

    Science.gov (United States)

    Nevitt, Sarah J; Thornton, Judith; Murray, Clare S; Dwyer, Tiffany

    2018-02-09

    Several agents are used to clear secretions from the airways of people with cystic fibrosis. Mannitol increases mucociliary clearance, but its exact mechanism of action is unknown. The dry powder formulation of mannitol may be more convenient and easier to use compared with established agents which require delivery via a nebuliser. Phase III trials of inhaled dry powder mannitol for the treatment of cystic fibrosis have been completed and it is now available in Australia and some countries in Europe. This is an update of a previous review. To assess whether inhaled dry powder mannitol is well tolerated, whether it improves the quality of life and respiratory function in people with cystic fibrosis and which adverse events are associated with the treatment. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic databases, handsearching relevant journals and abstracts from conferences.Date of last search: 28 September 2017. All randomised controlled studies comparing mannitol with placebo, active inhaled comparators (for example, hypertonic saline or dornase alfa) or with no treatment. Authors independently assessed studies for inclusion, carried out data extraction and assessed the risk of bias in included studies. The quality of the evidence was assessed using GRADE. Six studies (reported in 50 publications) were included with a total of 784 participants.Duration of treatment in the included studies ranged from 12 days to six months, with open-label treatment for an additional six months in two of the studies. Five studies compared mannitol with control (a very low dose of mannitol or non-respirable mannitol) and the final study compared mannitol to dornase alfa alone and to mannitol plus dornase alfa. Two large studies had a similar parallel design and provided data for 600 participants, which could be pooled where data for a particular outcome and time point were

  20. Changes in body water distribution during treatment with inhaled steroid in pre-school children

    DEFF Research Database (Denmark)

    Heitmann, B L; Anhøj, Jacob; Bisgaard, A M

    2004-01-01

    .i.d. delivered via Babyhaler, budesonide pressurized metered dose inhaler (pMDI) 200 microg b.i.d. delivered via Nebuchamber and placebo. Spacers were primed before use. In total, 40 children aged 1-3 years, with mild intermittent asthma were included. Twenty-five of the children completed all three treatments...... overall this effect was not statistically significant (0.1 growth during inhaled steroid treatment seems to partly reflect generalized changes...

  1. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... for Control Triggers Indoors In the Workplace Outdoors Management Asthma Action Plan Flu Shots Inhalers Data, Statistics, ... How to Use Your Asthma Inhaler Recommend on Facebook Tweet Share Compartir You can control your asthma ...

  2. Pathology associated with inhaled plutonium in beagles

    International Nuclear Information System (INIS)

    Dagle, G.E.; Park, J.F.; Weller, R.E.; Ragan, H.A.; Stevens, D.L.

    1986-01-01

    The pathology associated with the inhalation of plutonium was studied in beagle dogs given a single exposure to aerosols of 239 PuO 2 , 238 PuO 2 , or 239 Pu(NO 3 ) 4 . The temporal-spatial relationships between plutonium deposition and the development of lesions in dogs were evaluated up to 11 years, 8 years, or 5 years, respectively, after exposures, resulting in initial lung burdens ranging from ∼2 to ∼5500 nCi. Exposure of the lung to high dose levels produced a spectrum of progressively more severe morphological changes, ranging from radiation pneumonitis to fibrosis. Lung tumors occurred at exposure levels that did not result in early death from radiation pneumonitis or fibrosis. Bronchiolar-alveolar carcinomas, papillary adenocarcinomas, epidermoid carcinomas, and combined epidermoid and adenocarcinomas were observed. Sclerosing tracheobronchial lymphadenitis, radiation osteodystrophy, osteosarcoma, and hepatic adenomatous hyperplasia were the principal extrapulmonary lesions resulting from translocation of plutonium. 15 refs., 2 tabs

  3. Evaluation of the repeated-dose liver micronucleus assay using N-nitrosomorpholine in young adult rats: report on collaborative study by the Collaborative Study Group for the Micronucleus Test (CSGMT)/Japanese Environmental Mutagen Society (JEMS)-Mammalian Mutagenicity Study (MMS) Group.

    Science.gov (United States)

    Hayashi, Aya; Kosaka, Mizuki; Kimura, Aoi; Wako, Yumi; Kawasako, Kazufumi; Hamada, Shuichi

    2015-03-01

    The present study was conducted to evaluate the suitability of a repeated-dose liver micronucleus (LMN) assay in young adult rats as a collaborative study by the Mammalian mutagenicity study (MMS) group. All procedures were performed in accordance with the standard protocols of the MMS Group. Six-week-old male Crl:CD(SD) rats (5 animals/group) received oral doses of the hepatocarcinogen N-nitrosomorpholine (NMOR) at 0 (control), 5, 10, and 30mg/kg/day (10mL/kg) for 14 days. Control animals received vehicle (water). Hepatocytes were collected from the liver 24h after the last dose, and the number of micronucleated hepatocytes (MNHEPs) was determined by microscopy. The number of micronucleated immature erythrocytes (MNIMEs) in the femoral bone marrow was also determined. The liver was examined using histopathologic methods after formalin fixation. The results showed statistically significant and dose-dependent increases in the number of MNHEPs in the liver at doses of 10mg/kg and greater when compared with the vehicle control. However, no significant increase was noted in the number of MNIMEs in the bone marrow at doses of up to 30mg/kg. Histopathology of the liver revealed hypertrophy and single cell necrosis of hepatocytes at doses of 5mg/kg and above. These results showed that the induction of micronuclei by NMOR was detected by the repeated-dose LMN assay, but not by the repeated-dose bone marrow micronucleus assay. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Radiation Dose to Post-Chernobyl Cleanup Workers

    Science.gov (United States)

    Radiation dose calculation for post-Chernobyl Cleanup Workers in Ukraine - both external radiation exposure due to fallout and internal doses due to inhalation (I131 intake) or ingestion of contaminated foodstuffs.