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Sample records for physiologically based biokinetic

  1. Physiologically Based Biokinetic (PBBK) Modeling of Safrole Bioactivation and Detoxification in Humans as Compared With Rats

    NARCIS (Netherlands)

    Martati, E.; Boersma, M.G.; Spenkelink, A.; Khadka, D.B.; Bladeren, van P.J.; Rietjens, I.; Punt, A.

    2012-01-01

    A physiologically based biokinetic (PBBK) model for the alkenylbenzene safrole in humans was developed based on in vitro- and in silico-derived kinetic parameters. With the model obtained, the time- and dose-dependent formation of the proximate and ultimate carcinogenic metabolites, 1'-hydroxysafrol

  2. Physiologically based biokinetic (PBBK) model for safrole bioactivation and detoxification in rats

    NARCIS (Netherlands)

    Martati, E.; Boersma, M.G.; Spenkelink, A.; Khadka, D.B.; Punt, A.; Vervoort, J.J.M.; Bladeren, van P.J.; Rietjens, I.

    2011-01-01

    A physiologically based biokinetic (PBBK) model for alkenylbenzene safrole in rats was developed using in vitro metabolic parameters determined using relevant tissue fractions. The performance of the model was evaluated by comparison of the predicted levels of 1,2-dihydroxy-4-allylbenzene and 1'-hyd

  3. Physiologically based biokinetic (PBBK) modeling of safrole bioactivation and detoxification in humans as compared with rats.

    Science.gov (United States)

    Martati, Erryana; Boersma, Marelle G; Spenkelink, Albertus; Khadka, Dambar B; van Bladeren, Peter J; Rietjens, Ivonne M C M; Punt, Ans

    2012-08-01

    A physiologically based biokinetic (PBBK) model for the alkenylbenzene safrole in humans was developed based on in vitro- and in silico-derived kinetic parameters. With the model obtained, the time- and dose-dependent formation of the proximate and ultimate carcinogenic metabolites, 1-hydroxysafrole and 1-sulfooxysafrole in human liver were estimated and compared with previously predicted levels of these metabolites in rat liver. In addition, Monte Carlo simulations were performed to predict interindividual variation in the formation of these metabolites in the overall population. For the evaluation of the model performance, a comparison was made between the predicted total amount of urinary metabolites of safrole and the reported total levels of metabolites in the urine of humans exposed to safrole, which adequately matched. The model results revealed no dose-dependent shifts in safrole metabolism and no relative increase in bioactivation at dose levels up to 100mg/kg body weight/day. Species differences were mainly observed in the detoxification pathways of 1-hydroxysafrole, with the formation of 1-oxosafrole being a main detoxification pathway of 1-hydroxysafrole in humans but a minor pathway in rats, and glucuronidation of 1-hydroxysafrole being less important in humans than in rats. The formation of 1-sulfooxysafrole was predicted to vary 4- to 17-fold in the population (fold difference between the 95th and median, and 95th and 5th percentile, respectively), with the median being three to five times higher in human than in rat liver. Comparison of the PBBK results for safrole with those previously obtained for the related alkenylbenzenes estragole and methyleugenol revealed that differences in 1-sulfooxy metabolite formation are limited, being only twofold to fivefold.

  4. Physiologically based biokinetic (PBBK) model for safrole bioactivation and detoxification in rats.

    Science.gov (United States)

    Martati, E; Boersma, M G; Spenkelink, A; Khadka, D B; Punt, A; Vervoort, J; van Bladeren, P J; Rietjens, I M C M

    2011-06-20

    A physiologically based biokinetic (PBBK) model for alkenylbenzene safrole in rats was developed using in vitro metabolic parameters determined using relevant tissue fractions. The performance of the model was evaluated by comparison of the predicted levels of 1,2-dihydroxy-4-allylbenzene and 1'-hydroxysafrole glucuronide to levels of these metabolites reported in the literature to be excreted in the urine of rats exposed to safrole and by comparison of the predicted amount of total urinary safrole metabolites to the reported levels of safrole metabolites in the urine of safrole exposed rats. These comparisons revealed that the predictions adequately match observed experimental values. Next, the model was used to predict the relative extent of bioactivation and detoxification of safrole at different oral doses. At low as well as high doses, P450 mediated oxidation of safrole mainly occurs in the liver in which 1,2-dihydroxy-4-allylbenzene was predicted to be the major P450 metabolite of safrole. A dose dependent shift in P450 mediated oxidation leading to a relative increase in bioactivation at high doses was not observed. Comparison of the results obtained for safrole with the results previously obtained with PBBK models for the related alkenylbenzenes estragole and methyleugenol revealed that the overall differences in bioactivation of the three alkenylbenzenes to their ultimate carcinogenic 1'-sulfooxy metabolites are limited. This is in line with the generally less than 4-fold difference in their level of DNA binding in in vitro and in vivo studies and their almost similar BMDL(10) values (lower confidence limit of the benchmark dose that gives 10% increase in tumor incidence over background level) obtained in in vivo carcinogenicity studies. It is concluded that in spite of differences in the rates of specific metabolic conversions, overall the levels of bioactivation of the three alkenylbenzenes are comparable which is in line with their comparable

  5. A physiological biokinetic model for the [7(N)-{sup 3}H]-cholesterol dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Adriano dos Santos; Martins, Joao Francisco Trencher; Velo, Alexandre Franca; Hamada, Margarida M.; Mesquita, Carlos Henrique de, E-mail: adriano_oliveira@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2015-07-01

    Cardiovascular diseases (CVD) are a major source of deaths worldwide according to WHO (World Health Organization). It is well-known that the change of the level of plasma lipoproteins, which are responsible for the cholesterol transport in the bloodstream, is a main cause of these diseases. For this reason, to know the biokinetic parameters of plasma lipoproteins and quantifies them is important to correct and deepen the understanding of associated diseases. The main objective of this work is to provide a biokinetic model in order to estimate the radiometric dose, due to the intake of [7(N){sup -3}H] –Cholesterol in physiological issues, in metabolic studies. The internal dosimetry is important to know the biological effects of radiation. The model was based on Schwartz et al (2004), using parameters for the plasmatic lipoproteins and ICRP 30 (1979) gastrointestinal tract; the dose in the compartments were calculated using the MIRD methodology and the compartmental analysis by Matlab® software. The coefficients were estimated for an adult phantom with a body mass of 73.3 kg. (author)

  6. A biokinetic model for zinc for use in radiation protection

    Energy Technology Data Exchange (ETDEWEB)

    Leggett, R.W., E-mail: rwl@ornl.gov

    2012-03-15

    The physiology of the essential trace element zinc has been studied extensively in human subjects using kinetic analysis of time-dependent measurements of administered zinc tracers. A number of biokinetic models describing zinc exchange between plasma and tissues and endogenous excretion of zinc have been derived as fits to data for specific study groups. More rudimentary biokinetic models for zinc have been developed to estimate radiation doses from internally deposited radioisotopes of zinc. The latter models are designed to provide broadly accurate estimates of cumulative decays of zinc radioisotopes in tissues and are not intended as realistic descriptions of the directions of movement of zinc in the body. This paper reviews biokinetic data for zinc and proposes a physiologically meaningful biokinetic model for systemic zinc for use in radiation protection. The proposed model bears some resemblance to zinc models developed in physiological studies but depicts a finer division of systemic zinc and is based on a broader spectrum of data than previous models. The proposed model and the model for zinc currently recommended by the International Commission on Radiological Protection yield reasonably similar estimates of total-body retention and effective dose for internally deposited radioisotopes of zinc but much different systemic distributions of activity and much different dose estimates for some individual tissues, particularly the liver. - Highlights: Black-Right-Pointing-Pointer Zinc is an essential trace element with numerous functions in the human body. Black-Right-Pointing-Pointer Several biokinetic models for zinc have been developed from tracer studies on humans. Black-Right-Pointing-Pointer More rudimentary biokinetic models for zinc have been developed in radiation protection. Black-Right-Pointing-Pointer Biokinetic data for zinc are reviewed and a new biokinetic model is proposed for radiation protection. Black-Right-Pointing-Pointer The proposed model

  7. Computer-aided biokinetic modelling combined with in vitro data

    NARCIS (Netherlands)

    Ommen, B. van; Jongh, J. de; Sandt, J. van de; Blaauboer, B.; Hissink, E.; Bogaards, J.; Bladeren, P. van

    1995-01-01

    Within the framework of in vitro alternatives for in vivo safety assessment, the kinetic behaviour of a compound can be described by biokinetic models. These models, with emphasis on the physiologically based pharmacokinetic models, need a variety of biological, physicochemical and biochemical param

  8. The CONRAD approach to biokinetic modeling of DTPA decorporation therapy.

    Science.gov (United States)

    Breustedt, Bastian; Blanchardon, Eric; Bérard, Philippe; Fritsch, Paul; Giussani, Augusto; Lopez, Maria Antonia; Luciani, Andrea; Nosske, Dietmar; Piechowski, Jean; Schimmelpfeng, Jutta; Sérandour, Anne-Laure

    2010-10-01

    Diethylene Triamine Pentaacetic Acid (DTPA) is used for decorporation of plutonium because it is known to be able to enhance its urinary excretion for several days after treatment by forming stable Pu-DTPA complexes. The decorporation prevents accumulation in organs and results in a dosimetric benefit, which is difficult to quantify from bioassay data using existing models. The development of a biokinetic model describing the mechanisms of actinide decorporation by administration of DTPA was initiated as a task in the European COordinated Network on RAdiation Dosimetry (CONRAD). The systemic biokinetic model from Leggett et al. and the biokinetic model for DTPA compounds of International Commission on Radiological Protection Publication 53 were the starting points. A new model for biokinetics of administered DTPA based on physiological interpretation of 14C-labeled DTPA studies from literature was proposed by the group. Plutonium and DTPA biokinetics were modeled separately. The systems were connected by means of a second order kinetics process describing the chelation process of plutonium atoms and DTPA molecules to Pu-DTPA complexes. It was assumed that chelation only occurs in the blood and in systemic compartment ST0 (representing rapid turnover soft tissues), and that Pu-DTPA complexes and administered forms of DTPA share the same biokinetic behavior. First applications of the CONRAD approach showed that the enhancement of plutonium urinary excretion after administration of DTPA was strongly influenced by the chelation rate constant. Setting it to a high value resulted in a good fit to the observed data. However, the model was not yet satisfactory since the effects of repeated DTPA administration in a short time period cannot be predicted in a realistic way. In order to introduce more physiological knowledge into the model several questions still have to be answered. Further detailed studies of human contamination cases and experimental data will be needed in

  9. A biokinetic model for zinc for use in radiation protection

    Energy Technology Data Exchange (ETDEWEB)

    Leggett, Richard Wayne [ORNL

    2012-01-01

    The physiology of the essential trace element zinc has been studied extensively in human subjects using kinetic analysis of time-dependent measurements of administered zinc tracers. A number of biokinetic models describing zinc exchange between plasma and tissues and loss of systemic zinc in excreta have been developed from the derived data. More rudimentary biokinetic models for zinc have been developed to estimate radiation doses from internally deposited radioisotopes of zinc. The latter models are designed to provide broadly accurate estimates of cumulative decays of zinc radioisotopes in tissues and are not intended as realistic descriptions of the directions of movement of zinc in the body. This paper reviews biokinetic data for zinc and proposes a physiologically meaningful biokinetic model for systemic zinc for use in radiation protection. The proposed model bears some resemblance to zinc models developed in physiological studies but depicts a finer division of systemic zinc and is based on a broader spectrum of data than previous models. The proposed model and current radiation protection model for zinc yield broadly similar estimates of effective dose from internally deposited radioisotopes of zinc but substantially different dose estimates for several individual tissues, particularly the liver.

  10. Molecular Biomarker-Based Biokinetic Modeling of a PCE-Dechlorinating and Methanogenic Mixed Culture

    Energy Technology Data Exchange (ETDEWEB)

    Heavner, Gretchen L. W.; Rowe, Annette R.; Mansfeldt, Cresten B.; Pan, Ju Khuan; Gossett, James M.; Richardson, Ruth E.

    2013-04-16

    Bioremediation of chlorinated ethenes via anaerobic reductive dechlorination relies upon the activity of specific microbial population-most notably Dehalococcoides (DHC) strains. In the lab and field Dehalococcoides grow most robustly in mixed communities which usually contain both fermenters and methanogens. Recently, researchers have been developing quantitative molecular biomarkers to aid in field site diagnostics and it is hoped that these biomarkers could aid in the modeling of anaerobic reductive dechlorination. A comprehensive biokinetic model of a community containing Dehalococcoides mccartyi (formerly D. ethenogenes) was updated to describe continuously fed reactors with specific biomass levels based on quantitative PCR (qPCR)-based population data (DNA and RNA). The model was calibrated and validated with subsets of chemical and molecular biological data from various continuous feed experiments (n = 24) with different loading rates of the electron acceptor (1.5 to 482 μeeq/L-h), types of electron acceptor (PCE, TCE, cis-DCE) and electron donor to electron acceptor ratios. The resulting model predicted the sum of dechlorination products vinyl chloride (VC) and ethene (ETH) well. However, VC alone was under-predicted and ETH was over predicted. Consequently, competitive inhibition among chlorinated ethenes was examined and then added to the model. Additionally, as 16S rRNA gene copy numbers did not provide accurate model fits in all cases, we examined whether an improved fit could be obtained if mRNA levels for key functional enzymes could be used to infer respiration rates. The resulting empirically derived mRNA “adjustment factors” were added to the model for both DHC and the main methanogen in the culture (a Methanosaeta species) to provide a more nuanced prediction of activity. Results of this study suggest that at higher feeding rates competitive inhibition is important and mRNA provides a more accurate indicator of a population’s instantaneous

  11. A systemic biokinetic model for polonium.

    Science.gov (United States)

    Leggett, R W; Eckerman, K F

    2001-07-25

    Although the biokinetics of polonium has been studied extensively, interpretation of the data is complicated by potential differences with species and route of exposure and the questionable reliability of much of the reported excretion data for man. A study was undertaken to identify the data that are most likely to represent the typical behavior of polonium and apply those data to construct an improved, physiologically realistic systemic biokinetic model for polonium in man. Such a model is needed for interpretation of urinary excretion data for workers exposed to 210Po and reconstruction of the radiation doses received by those workers. This paper reviews the database on the biokinetics of polonium and describes a new systemic biokinetic model for polonium in man.

  12. The Biokinetic Spectrum for Temperature.

    Directory of Open Access Journals (Sweden)

    Ross Corkrey

    Full Text Available We identify and describe the distribution of temperature-dependent specific growth rates for life on Earth, which we term the biokinetic spectrum for temperature. The spectrum has the potential to provide for more robust modeling in thermal ecology since any conclusions derived from it will be based on observed data rather than using theoretical assumptions. It may also provide constraints for systems biology model predictions and provide insights in physiology. The spectrum has a Δ-shape with a sharp peak at around 42°C. At higher temperatures up to 60°C there was a gap of attenuated growth rates. We found another peak at 67°C and a steady decline in maximum rates thereafter. By using Bayesian quantile regression to summarise and explore the data we were able to conclude that the gap represented an actual biological transition between mesophiles and thermophiles that we term the Mesophile-Thermophile Gap (MTG. We have not identified any organism that grows above the maximum rate of the spectrum. We used a thermodynamic model to recover the Δ-shape, suggesting that the growth rate limits arise from a trade-off between activity and stability of proteins. The spectrum provides underpinning principles that will find utility in models concerned with the thermal responses of biological processes.

  13. a Biokinetic Model for CESIUM-137 in the Fetus

    Science.gov (United States)

    Jones, Karen Lynn

    1995-01-01

    Previously, there was no method to determine the dose to the embryo, fetus, fetal organs or placenta from radionuclides within the embryo, fetus, or placenta. In the past, the dose to the fetus was assumed to be equivalent to the dose to the uterus. Watson estimated specific absorbed fractions from various maternal organs to the uterine contents which included the fetus, placenta, and amniotic fluid and Sikov estimated the absorbed dose to the embryo/fetus after assuming 1 uCi of radioactivity was made available to the maternal blood.^{1,2} However, this method did not allow for the calculation of a dose to individual fetal organs or the placenta. The radiation dose to the embryo or fetus from Cs-137 in the fetus and placenta due to a chronic ingestion by the mother was determined. The fraction of Cs-137 in the maternal plasma crossing the placenta to the fetal plasma was estimated. The absorbed dose from Cs-137 in each modelled fetal organ was estimated. Since there has been more research regarding potassium in the human body, and particularly in the pregnant woman, a biokinetic model for potassium was developed first and used as a basis and confirmation of the cesium model. Available pertinent information in physiology, embryology, biokinetics, and radiation dosimetry was utilized. Due to the rapid growth of the fetus and placenta, the pregnancy was divided into four gestational periods. The numerous physiological changes that occurred during pregnancy were considered and an appropriate biokinetic model was developed for each of the gestational periods. The amount of cesium in the placenta, embryo, and fetus was estimated for each period. The dose to the fetus from cesium deposited in the embryo or fetus and in the placenta was determined for each period using Medical Internal Radiation Dosimetry (MIRD) methodology. An uncertainty analysis was also performed to account for the variability of the parameters in the biokinetic model based on the experimental data

  14. Biokinetics of cesium in Perna viridis

    Energy Technology Data Exchange (ETDEWEB)

    Yu, P.K.N.; Lam, P.K.S.; Ng, B.K.P.; Li, A.M.Y.

    2000-02-01

    The biokinetics of Cs in four compartments in the green-lipped mussel Perna viridis, namely, gill, viscera, adductor muscle, and foot, were studied. First-order linear differential equations were set up for these four compartments, and their solutions were used to fit the experimental data. The parameters governing the biokinetics, which depend on the elimination rate from each compartment and the transfer coefficient between compartments, were found. These are useful in understanding the physiology of Perna viridis, in predicting the activity of cesium in each compartment of Perna viridis from a contamination history, or in using Perna viridis as a sentinel organism for surveying and monitoring radioactive contamination. The results showed that the viscera should be represented by more than one compartment. Concentration factors for the four compartments and for Perna viridis were also determined, and these agreed well with reported values in the literature.

  15. Biokinetic modeling and in vitro-in vivo extrapolations.

    NARCIS (Netherlands)

    Blaauboer, B.J.

    2010-01-01

    The introduction of in vitro methodologies in the toxicological risk assessment process requires a number of prerequisites regarding both the toxicodynamics and the biokinetics of the compounds under study. In vitro systems will need to be relevant for measuring those structural and physiological ch

  16. Biokinetic modeling and in vitro-in vivo extrapolations.

    NARCIS (Netherlands)

    Blaauboer, B.J.|info:eu-repo/dai/nl/068359802

    2010-01-01

    The introduction of in vitro methodologies in the toxicological risk assessment process requires a number of prerequisites regarding both the toxicodynamics and the biokinetics of the compounds under study. In vitro systems will need to be relevant for measuring those structural and physiological

  17. A biokinetic and dosimetric model for ionic indium in humans

    Science.gov (United States)

    Andersson, Martin; Mattsson, Sören; Johansson, Lennart; Leide-Svegborn, Sigrid

    2017-08-01

    This paper reviews biokinetic data for ionic indium, and proposes a biokinetic model for systemic indium in adult humans. The development of parameter values focuses on human data and indium in the form of ionic indium(III), as indium chloride and indium arsenide. The model presented for systemic indium is defined by five different pools: plasma, bone marrow, liver, kidneys and other soft tissues. The model is based on two subsystems: one corresponding to indium bound to transferrin and one where indium is transported back to the plasma, binds to red blood cell transferrin and is then excreted through the kidneys to the urinary bladder. Absorbed doses to several organs and the effective dose are calculated for 111In- and 113mIn-ions. The proposed biokinetic model is compared with previously published biokinetic indium models published by the ICRP. The absorbed doses are calculated using the ICRP/ICRU adult reference phantoms and the effective dose is estimated according to ICRP Publication 103. The effective doses for 111In and 113mIn are 0.25 mSv MBq-1 and 0.013 mSv MBq-1 respectively. The updated biokinetic and dosimetric models presented in this paper take into account human data and new animal data, which represent more detailed and presumably more accurate dosimetric data than that underlying previous models for indium.

  18. Developing a physiologically based approach for modeling plutonium decorporation therapy with DTPA.

    Science.gov (United States)

    Kastl, Manuel; Giussani, Augusto; Blanchardon, Eric; Breustedt, Bastian; Fritsch, Paul; Hoeschen, Christoph; Lopez, Maria Antonia

    2014-11-01

    To develop a physiologically based compartmental approach for modeling plutonium decorporation therapy with the chelating agent Diethylenetriaminepentaacetic acid (Ca-DTPA/Zn-DTPA). Model calculations were performed using the software package SAAM II (©The Epsilon Group, Charlottesville, Virginia, USA). The Luciani/Polig compartmental model with age-dependent description of the bone recycling processes was used for the biokinetics of plutonium. The Luciani/Polig model was slightly modified in order to account for the speciation of plutonium in blood and for the different affinities for DTPA of the present chemical species. The introduction of two separate blood compartments, describing low-molecular-weight complexes of plutonium (Pu-LW) and transferrin-bound plutonium (Pu-Tf), respectively, and one additional compartment describing plutonium in the interstitial fluids was performed successfully. The next step of the work is the modeling of the chelation process, coupling the physiologically modified structure with the biokinetic model for DTPA. RESULTS of animal studies performed under controlled conditions will enable to better understand the principles of the involved mechanisms.

  19. Biokinetics of Plutonium in Nonhuman Primates.

    Science.gov (United States)

    Poudel, Deepesh; Guilmette, Raymond A; Gesell, Thomas F; Harris, Jason T; Brey, Richard R

    2016-10-01

    A major source of data on metabolism, excretion and retention of plutonium comes from experimental animal studies. Although old world monkeys are one of the closest living relatives to humans, certain physiological differences do exist between these nonhuman primates and humans. The objective of this paper was to describe the metabolism of plutonium in nonhuman primates using the bioassay and retention data obtained from macaque monkeys injected with plutonium citrate. A biokinetic model for nonhuman primates was developed by adapting the basic model structure and adapting the transfer rates described for metabolism of plutonium in adult humans. Significant changes to the parameters were necessary to explain the shorter retention of plutonium in liver and skeleton of the nonhuman primates, differences in liver to bone partitioning ratio, and significantly higher excretion of plutonium in feces compared to that in humans.

  20. Reliability of Current Biokinetic and Dosimetric Models for Radionuclides: A Pilot Study

    Energy Technology Data Exchange (ETDEWEB)

    Leggett, Richard Wayne [ORNL; Eckerman, Keith F [ORNL; Meck, Robert A. [U.S. Nuclear Regulatory Commission

    2008-10-01

    studied radionuclides. (4) The biokinetics of a radionuclide in the human body typically represents the greatest source of uncertainty or variability in dose per unit intake. (5) Characterization of uncertainty in dose per unit exposure is generally a more straightforward problem for external exposure than for intake of a radionuclide. (6) For many radionuclides the most important outcome of a large-scale critical evaluation of databases and biokinetic models for radionuclides is expected to be the improvement of current models. Many of the current models do not fully or accurately reflect available radiobiological or physiological information, either because the models are outdated or because they were based on selective or uncritical use of data or inadequate model structures. In such cases the models should be replaced with physiologically realistic models that incorporate a wider spectrum of information.

  1. Linear parameter estimation of rational biokinetic functions

    NARCIS (Netherlands)

    Doeswijk, T.G.; Keesman, K.J.

    2009-01-01

    For rational biokinetic functions such as the Michaelis-Menten equation, in general, a nonlinear least-squares method is a good estimator. However, a major drawback of a nonlinear least-squares estimator is that it can end up in a local minimum. Rearranging and linearizing rational biokinetic

  2. PHYSIOLOGY OF ACID BASE BALANCE

    Directory of Open Access Journals (Sweden)

    Awati

    2014-12-01

    Full Text Available Acid-base, electrolyte, and metabolic disturbances are common in the intensive care unit. Almost all critically ill patients often suffer from compound acid-base and electrolyte disorders. Successful evaluation and management of such patients requires recognition of common patterns (e.g., metabolic acidosis and the ability to dissect one disorder from another. The intensivists needs to identify and correct these condition with the easiest available tools as they are the associated with multiorgan failure. Understanding the elements of normal physiology in these areas is very important so as to diagnose the pathological condition and take adequate measures as early as possible. Arterial blood gas analysis is one such tool for early detection of acid base disorder. Physiology of acid base is complex and here is the attempt to simplify it in our day to day application for the benefit of critically ill patients.

  3. Human biokinetic data and a new compartmental model of zirconium - A tracer study with enriched stable isotopes

    Energy Technology Data Exchange (ETDEWEB)

    Greiter, Matthias B., E-mail: matthias.greiter@helmholtz-muenchen.de; Giussani, Augusto, E-mail: AGiussani@BfS.de; Hoellriegl, Vera, E-mail: vera.hoellriegl@helmholtz-muenchen.de; Li Weibo, E-mail: wli@helmholtz-muenchen.de; Oeh, Uwe, E-mail: uwe.oeh@helmholtz-muenchen.de

    2011-09-01

    Biokinetic models describing the uptake, distribution and excretion of trace elements are an essential tool in nutrition, toxicology, or internal dosimetry of radionuclides. Zirconium, especially its radioisotope {sup 95}Zr, is relevant to radiation protection due to its production in uranium fission and neutron activation of nuclear fuel cladding material. We present a comprehensive set of human data from a tracer study with stable isotopes of zirconium. The data are used to refine a biokinetic model of zirconium. Six female and seven male healthy adult volunteers participated in the study. It includes 16 complete double tracer investigations with oral ingestion and intravenous injection, and seven supplemental investigations. Tracer concentrations were measured in blood plasma and urine collected up to 100 d after tracer administration. The four data sets (two chemical tracer forms in plasma and urine) each encompass 105-240 measured concentration values above detection limits. Total fractional absorption of ingested zirconium was found to be 0.001 for zirconium in citrate-buffered drinking solution and 0.007 for zirconium oxalate solution. Biokinetic models were developed based on the linear first-order kinetic compartmental model approach used by the International Commission on Radiological Protection (ICRP). The main differences of the optimized systemic model of zirconium to the current ICRP model are (1) recycling into the transfer compartment made necessary by the observed tracer clearance from plasma, (2) different parameters related to fractional absorption for each form of the ingested tracer, and (3) a physiologically based excretion pathway to urine. The study considerably expands the knowledge on the biokinetics of zirconium, which was until now dominated by data from animal studies. The proposed systemic model improves the existing ICRP model, yet is based on the same principles and fits well into the ICRP radiation protection approach. - Research

  4. Towards a consensus-based biokinetic model for green microalgae – The ASM-A

    DEFF Research Database (Denmark)

    Wágner, Dorottya Sarolta; Valverde Pérez, Borja; Sæbø, Mariann

    2016-01-01

    Cultivation of microalgae in open ponds and closed photobioreactors (PBRs) using wastewater resources offers an opportunity for biochemical nutrient recovery. Effective reactor system design and process control of PBRs requires process models. Several models with different complexities have been...... of microalgae. Model parameters were estimated using laboratory-scale batch and sequenced batch experiments using the novel Latin Hypercube Sampling based Simplex (LHSS) method. The model was evaluated using independent data obtained in a 24-L PBR operated in sequenced batch mode. Identifiability of the model...

  5. Towards a consensus-based biokinetic model for green microalgae - The ASM-A.

    Science.gov (United States)

    Wágner, Dorottya S; Valverde-Pérez, Borja; Sæbø, Mariann; Bregua de la Sotilla, Marta; Van Wagenen, Jonathan; Smets, Barth F; Plósz, Benedek Gy

    2016-10-15

    Cultivation of microalgae in open ponds and closed photobioreactors (PBRs) using wastewater resources offers an opportunity for biochemical nutrient recovery. Effective reactor system design and process control of PBRs requires process models. Several models with different complexities have been developed to predict microalgal growth. However, none of these models can effectively describe all the relevant processes when microalgal growth is coupled with nutrient removal and recovery from wastewaters. Here, we present a mathematical model developed to simulate green microalgal growth (ASM-A) using the systematic approach of the activated sludge modelling (ASM) framework. The process model - identified based on a literature review and using new experimental data - accounts for factors influencing photoautotrophic and heterotrophic microalgal growth, nutrient uptake and storage (i.e. Droop model) and decay of microalgae. Model parameters were estimated using laboratory-scale batch and sequenced batch experiments using the novel Latin Hypercube Sampling based Simplex (LHSS) method. The model was evaluated using independent data obtained in a 24-L PBR operated in sequenced batch mode. Identifiability of the model was assessed. The model can effectively describe microalgal biomass growth, ammonia and phosphate concentrations as well as the phosphorus storage using a set of average parameter values estimated with the experimental data. A statistical analysis of simulation and measured data suggests that culture history and substrate availability can introduce significant variability on parameter values for predicting the reaction rates for bulk nitrate and the intracellularly stored nitrogen state-variables, thereby requiring scenario specific model calibration. ASM-A was identified using standard cultivation medium and it can provide a platform for extensions accounting for factors influencing algal growth and nutrient storage using wastewater resources.

  6. The STATFLUX code: a statistical method for calculation of flow and set of parameters, based on the Multiple-Compartment Biokinetical Model

    Science.gov (United States)

    Garcia, F.; Mesa, J.; Arruda-Neto, J. D. T.; Helene, O.; Vanin, V.; Milian, F.; Deppman, A.; Rodrigues, T. E.; Rodriguez, O.

    2007-03-01

    The code STATFLUX, implementing a new and simple statistical procedure for the calculation of transfer coefficients in radionuclide transport to animals and plants, is proposed. The method is based on the general multiple-compartment model, which uses a system of linear equations involving geometrical volume considerations. Flow parameters were estimated by employing two different least-squares procedures: Derivative and Gauss-Marquardt methods, with the available experimental data of radionuclide concentrations as the input functions of time. The solution of the inverse problem, which relates a given set of flow parameter with the time evolution of concentration functions, is achieved via a Monte Carlo simulation procedure. Program summaryTitle of program:STATFLUX Catalogue identifier:ADYS_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ADYS_v1_0 Program obtainable from: CPC Program Library, Queen's University of Belfast, N. Ireland Licensing provisions: none Computer for which the program is designed and others on which it has been tested:Micro-computer with Intel Pentium III, 3.0 GHz Installation:Laboratory of Linear Accelerator, Department of Experimental Physics, University of São Paulo, Brazil Operating system:Windows 2000 and Windows XP Programming language used:Fortran-77 as implemented in Microsoft Fortran 4.0. NOTE: Microsoft Fortran includes non-standard features which are used in this program. Standard Fortran compilers such as, g77, f77, ifort and NAG95, are not able to compile the code and therefore it has not been possible for the CPC Program Library to test the program. Memory required to execute with typical data:8 Mbytes of RAM memory and 100 MB of Hard disk memory No. of bits in a word:16 No. of lines in distributed program, including test data, etc.:6912 No. of bytes in distributed program, including test data, etc.:229 541 Distribution format:tar.gz Nature of the physical problem:The investigation of transport mechanisms for

  7. Comparison of ICRP 67 and Other Plutonium Systemic Model Predictions with the Biokinetic Data from Nonhuman Primates.

    Science.gov (United States)

    Poudel, Deepesh; Krage, Eric Stephen; Brey, Richard Ray; Guilmette, Raymond A

    2016-04-01

    Despite the presence of a relatively large amount of human data available on the metabolism of plutonium, the experimental animal data is still important in constructing and parameterizing the biokinetic models. Recognizing this importance, the biokinetic data obtained from studies done by P.W. Durbin in nonhuman primates (NHP) were evaluated against the ICRP 67 systemic model and the two human models developed thereafter. The default transfer rates recommended for adult humans in these models predict the urinary excretion in NHP to a certain extent. However, they were unable to describe the fecal excretion rates several days post intake and the activities in skeleton and liver at the time of the death. These inconsistencies between the human reference models and the NHP biokinetic data are the result of metabolic and physiological differences between the species, as demonstrated by early biokinetic studies.

  8. In silico methods for physiologically based biokinetic models describing bioactivation and detoxification of coumarin and estragole: Implications for risk assessment

    NARCIS (Netherlands)

    Rietjens, I.; Punt, A.; Schilter, B.; Scholz, G.; Delatour, T.; Bladeren, van P.J.

    2010-01-01

    In chemical safety assessment, information on adverse effects after chronic exposure to low levels of hazardous compounds is essential for estimating human risks. Results from in vitro studies are often not directly applicable to the in vivo situation, and in vivo animal studies often have to be per

  9. Providing a theoretical basis for nanotoxicity risk analysis departing from traditional physiologically-based pharmacokinetic (PBPK) modeling

    Science.gov (United States)

    Yamamoto, Dirk P.

    The same novel properties of engineered nanoparticles that make them attractive may also present unique exposure risks. But, the traditional physiologically-based pharmacokinetic (PBPK) modeling assumption of instantaneous equilibration likely does not apply to nanoparticles. This simulation-based research begins with development of a model that includes diffusion, active transport, and carrier mediated transport. An eigenvalue analysis methodology was developed to examine model behavior to focus future research. Simulations using the physico-chemical properties of size, shape, surface coating, and surface charge were performed and an equation was determined which estimates area under the curve for arterial blood concentration, which is a surrogate of nanoparticle dose. Results show that the cellular transport processes modeled in this research greatly affect the biokinetics of nanoparticles. Evidence suggests that the equation used to estimate area under the curve for arterial blood concentration can be written in terms of nanoparticle size only. The new paradigm established by this research leverages traditional in vitro, in vivo, and PBPK modeling, but includes area under the curve to bridge animal testing results to humans. This new paradigm allows toxicologists and policymakers to then assess risk to a given exposure and assist in setting appropriate exposure limits for nanoparticles. This research provides critical understanding of nanoparticle biokinetics and allows estimation of total exposure at any toxicological endpoint in the body. This effort is a significant contribution as it highlights future research needs and demonstrates how modeling can be used as a tool to advance nanoparticle risk assessment.

  10. A biokinetic model for nickel released from cardiovascular devices.

    Science.gov (United States)

    Saylor, David M; Adidharma, Lingga; Fisher, Jeffrey W; Brown, Ronald P

    2016-10-01

    Many alloys used in cardiovascular device applications contain high levels of nickel, which if released in sufficient quantities, can lead to adverse health effects. While nickel release from these devices is typically characterized through the use of in-vitro immersion tests, it is unclear if the rate at which nickel is released from a device during in-vitro testing is representative of the release rate following implantation in the body. To address this uncertainty, we have developed a novel biokinetic model that combines a traditional toxicokinetic compartment model with a physics-based model to estimate nickel release from an implanted device. This model links the rate of in-vitro nickel release from a cardiovascular device to serum nickel concentrations, an easily measured endpoint, to estimate the rate and extent of in-vivo nickel release from an implanted device. The model was initially parameterized using data in the literature on in-vitro nickel release from a nickel-containing alloy (nitinol) and baseline serum nickel levels in humans. The results of this first step were then used to validate specific components of the model. The remaining unknown quantities were fit using serum values reported in patients following implantation with nitinol atrial occluder devices. The model is not only consistent with levels of nickel in serum and urine of patients following treatment with the atrial occluders, but also the optimized parameters in the model were all physiologically plausible. The congruity of the model with available data suggests that it can provide a framework to interpret nickel biomonitoring data and use data from in-vitro nickel immersion tests to estimate in-vivo nickel release from implanted cardiovascular devices.

  11. Deposition and biokinetics of inhaled nanoparticles

    Directory of Open Access Journals (Sweden)

    Kreyling Wolfgang G

    2010-01-01

    Full Text Available Abstract Particle biokinetics is important in hazard identification and characterization of inhaled particles. Such studies intend to convert external to internal exposure or biologically effective dose, and may help to set limits in that way. Here we focus on the biokinetics of inhaled nanometer sized particles in comparison to micrometer sized ones. The presented approach ranges from inhaled particle deposition probability and retention in the respiratory tract to biokinetics and clearance of particles out of the respiratory tract. Particle transport into the blood circulation (translocation, towards secondary target organs and tissues (accumulation, and out of the body (clearance is considered. The macroscopically assessed amount of particles in the respiratory tract and secondary target organs provides dose estimates for toxicological studies on the level of the whole organism. Complementary, microscopic analyses at the individual particle level provide detailed information about which cells and subcellular components are the target of inhaled particles. These studies contribute to shed light on mechanisms and modes of action eventually leading to adverse health effects by inhaled nanoparticles. We review current methods for macroscopic and microscopic analyses of particle deposition, retention and clearance. Existing macroscopic knowledge on particle biokinetics and microscopic views on particle organ interactions are discussed comparing nanometer and micrometer sized particles. We emphasize the importance for quantitative analyses and the use of particle doses derived from real world exposures.

  12. Deposition and biokinetics of inhaled nanoparticles

    Science.gov (United States)

    2010-01-01

    Particle biokinetics is important in hazard identification and characterization of inhaled particles. Such studies intend to convert external to internal exposure or biologically effective dose, and may help to set limits in that way. Here we focus on the biokinetics of inhaled nanometer sized particles in comparison to micrometer sized ones. The presented approach ranges from inhaled particle deposition probability and retention in the respiratory tract to biokinetics and clearance of particles out of the respiratory tract. Particle transport into the blood circulation (translocation), towards secondary target organs and tissues (accumulation), and out of the body (clearance) is considered. The macroscopically assessed amount of particles in the respiratory tract and secondary target organs provides dose estimates for toxicological studies on the level of the whole organism. Complementary, microscopic analyses at the individual particle level provide detailed information about which cells and subcellular components are the target of inhaled particles. These studies contribute to shed light on mechanisms and modes of action eventually leading to adverse health effects by inhaled nanoparticles. We review current methods for macroscopic and microscopic analyses of particle deposition, retention and clearance. Existing macroscopic knowledge on particle biokinetics and microscopic views on particle organ interactions are discussed comparing nanometer and micrometer sized particles. We emphasize the importance for quantitative analyses and the use of particle doses derived from real world exposures. PMID:20205860

  13. Development of the Plutonium-DTPA Biokinetic Model.

    Science.gov (United States)

    Konzen, Kevin; Brey, Richard

    2015-06-01

    Estimating radionuclide intakes from bioassays following chelation treatment presents a challenge to the dosimetrist due to the observed excretion enhancement of the particular radionuclide of concern where no standard biokinetic model exists. This document provides a Pu-DTPA biokinetic model that may be used for making such determination for plutonium intakes. The Pu-DTPA biokinetic model is intended to supplement the standard recommended biokinetic models. The model was used to evaluate several chelation strategies that resulted in providing recommendations for effective treatment. These recommendations supported early treatment for soluble particle inhalations and an initial 3-day series of DTPA treatments for wounds. Several late chelation strategies were also compared where reduced treatment frequencies proved to be as effective as multiple treatments. The Pu-DTPA biokinetic model can be used to assist in estimating initial intakes of transuranic radionuclides and for studying the effects of different treatment strategies.

  14. Estimating biokinetic coefficients in the PACT™ system.

    Science.gov (United States)

    Shen, Zhiyao; Arbuckle, Wm Brian

    2016-02-01

    When powdered activated carbon (PAC) is continuously added to the aeration tank of an activated sludge reactor, the modification is called a PACT™ process (for powdered activated carbon treatment). The PAC provides many benefits, but complicates the determination of biological phenomena. Determination of bio-oxidation kinetics in a PACT system is a key to fully understanding enhanced biological mechanisms resulting from PAC addition. A model is developed to account for the main mechanisms involved in the PACT system -- adsorption, air stripping and bio-oxidation. The model enables the investigation of biokinetic information, including possible synergistic effects. Six parallel reactors were used to treat a synthetic waste; three activated sludge and three PACT. The PACT reactors provided significantly reduced effluent TOC (total organic carbon). Biokinetic coefficients were obtained from steady-state data using averaged reactor data and by using all data (22 points for each reactor). As expected, the PACT reactors resulted in a substantial reduction in the effluent concentration of non-biodegradable total organic carbon. The Monod equation's half-saturation coefficient (Ks) was reduced significantly in the PACT reactors, resulting in higher growth rates at lower concentrations. The maximum specific substrate utilization (qm) rate was also reduced about 25% using the averaged data and remained unchanged using all the data. The substrate utilization values are affected by errors in biomass determination and more research is needed to accurately determine biomass.

  15. Biokinetic study of free {sup 177}Lu in NIH mice

    Energy Technology Data Exchange (ETDEWEB)

    Villarreal Jimenez, V.; Crudo, J., E-mail: josierys@yahoo.com [Comision Nacional de Energia Atomica (CNEA), Buenos Aires (Argentina); Rojo, A.M.; Deluca, G.M. [Autoridad Regulatoria Nuclear (ARN), Buenos Aires (Argentina)

    2008-07-01

    Full text: {sup 177}Lu has been identified, by the scientific community, as a radionuclide with interesting advantages compared with {sup 90}Y and other beta emitters used in nuclear medicine. This paper analyses the free {sup 177}Lu biokinetic behavior in NIH male mice from activity measurements performed by the Radiopharmacy Division of CNEA (Comision Nacional de Energia Atomica) in the frame of an IAEA (International Atomic Energy Agency) Coordinated Research Project. The study of experimental data is a previous condition that allows drawing the activity-time curves for organs and to know the biodistribution of {sup 177}Lu. The cumulated activity in organs of interest in NIH male mice are calculated and critical organs are identified. The organs selected for analysis in this paper are the liver, kidneys, spleen, stomach, intestine, lungs, skeleton and red marrow. The last one is estimated from the activity measured in blood based on a recognized method published by Sgouros (2000). The results has been extrapolated to human assuming the same biokinetic behaviour as mice being the applicability of the different extrapolation methods also discussed. The direct extrapolation from mice data was the method of election from a radiological protection point of view. The measurement procedures, the data processing, the extrapolation techniques and the analysis performed in this study will contribute as a basis for future research of this group in the area of antibodies and other radiopharmaceutical labeled with {sup 177}Lu. The cumulated activity calculated in each organ is relevant because it makes possible to perform the dose assessment through the application of appropriate dose coefficients. It is a necessary step in order to evaluate the toxicity risk that is required in a pre-clinical study. (author)

  16. Biokinetic models for radionuclides in experimental animals; Modelos biocineticos de radionucleidos en animales de experimentacion

    Energy Technology Data Exchange (ETDEWEB)

    Morcillo, M. A. [Ciemat. Madrid (Spain)

    2003-07-01

    The biokinetic models for many radionuclides are, to a large extent, based on data obtained in experimental animals. The methods used in the experimental development of a biokinetic model can be classified in two groups (i) those applied during the experimental work, which include the activity determination of a given radionuclide at different times and in different biological media such as blood, serum, organs/tissues, urine, bile and faeces and (ii) those methods used for the analysis and study of the experimental data, based in mathematical tools. Some of these methods are reviewed,with special emphasis in the whole body macro autoradiography. To conclude, the contribution that this type of studies can have in two fields of radiation protection is discussed, namely optimization of dosimetric evaluations and decorporation of radionuclides. (Author)

  17. MEGen: A Physiologically Based Pharmacokinetic Model Generator

    Directory of Open Access Journals (Sweden)

    George D Loizou

    2011-11-01

    Full Text Available Physiologically based pharmacokinetic models are being used in an increasing number of different areas. These not only include the human safety assessment of pharmaceuticals, pesticides, biocides and environmental chemicals but also for food animal, wild mammal and avian risk assessment. The value of PBPK models is that they are tools for estimating tissue dosimetry by integrating in vitro and in vivo mechanistic, pharmacokinetic and toxicological information through their explicit mathematical description of important anatomical, physiological and biochemical determinants of chemical uptake, disposition and elimination. However, PBPK models are perceived as complex, data hungry, resource intensive and time consuming. In addition, model validation and verification are hindered by the relative complexity of the equations. To begin to address these issues a freely available web application for the rapid construction and documentation of bespoke PBPK models is under development. Here we present an overview of the current capabilities of MEGen, a model equation generator and parameter database and discuss future developments.

  18. The biokinetics of inorganic cobalt in the human body.

    Science.gov (United States)

    Leggett, R W

    2008-01-25

    This paper reviews information on the biological behavior of inorganic cobalt in humans and laboratory animals and proposes a model of the systemic biokinetics of inorganic cobalt in adult humans. The model was developed as part of an effort to update the models of the International Commission on Radiological Protection (ICRP) for addressing intakes of radionuclides by workers but is also applicable to environmental or medical exposures to inorganic forms of radiocobalt. The model can be used in conjunction with any respiratory, gastrointestinal, or wound model that provides predictions of the time-dependent feed of cobalt to blood. In contrast to the ICRP's current systemic model for cobalt, which is a simple open catenary system, the proposed model is constructed within a physiologically realistic framework that depicts recycling of cobalt between blood and tissues and transfer from blood to excretion pathways. Compared with the ICRP's current model, the proposed model yields similar predictions of whole-body retention but substantially different predictions of the systemic distribution of cobalt as a function of time after uptake to blood.

  19. Integration of Life-Stage Physiologically Based ...

    Science.gov (United States)

    A Life-stage Physiologically-Based Pharmacokinetic (PBPK) model was developed to include descriptions of several life-stage events such as pregnancy, fetal development, the neonate and child growth. The overall modeling strategy was used for in vitro to in vivo (IVIVE) extrapolation to help contextualize activity in ToxCast assays that were mapped to an adverse outcome pathway (AOP) for embryonic vascular disruption. Using life-stage PBPK models, we estimated maternal exposures that would yield fetal blood levels equivalent to in vitro activity from ToxCast assays with critical vascular signaling targets. The resulting in vivo dose estimates were then compared to life-time exposures using literature data or exposure models (SHEDS-LITE) to derive AOP-based Margins of Exposure (ME). This computational framework was applied to a list of five chemicals with varying activity against the putative Vascular Disruption AOP. The idea of linking biological information related to toxicity (using AOPs), high throughput in vitro data (ToxCast), and age-varying physiological and biochemical information to estimate AOP-based MEs is novel and can be used to help regulators in realistically assessing chemicals based on toxicity, dosimetry, and real-life exposures. Developing fetuses and infants are especially sensitive to toxicity caused by exposure to xenobiotics. The time and dose to which a developing target tissue is exposed during pregnancy or via lactation after birth are c

  20. Biokinetics and bioavailability protocol for organic pollutants in soil to enhance bioremediation

    Energy Technology Data Exchange (ETDEWEB)

    Tabak, H.H. [Environmental Protection Agency, Cincinnati, OH (United States); Govind, R.; Fu, C.; Yan, X.; Gao, C.; Pfanstiel, S. [Univ. of Cincinnati, OH (United States). Dept. of Chemical Engineering

    1995-12-31

    Bioremediation of polluted soil requires a fundamental understanding of biodegradation kinetics and the physicochemical factors that control the rate of biodegradation. A systematic multi-level protocol based on three types of bioreactor systems, was developed to determine the biokinetic parameters of the suspended and immobilized microbiota and the transport and diffusivity parameters of soil contaminants and oxygen in the soil matrix. In the soil slurry reactor, significant biodegradation occurs in the aqueous phase by the suspended and immobilized microbiota and to some extent by the soil immobilized biofilms. The soil slurry reactor data were used to derive the biokinetic parameters for the suspended and immobilized microorganisms. The wafer reactor data were used to obtain additional information on biokinetic and transport parameters with oxygen limitation. The porous tube reactor data provided quantitative determination of oxygen diffusivity. In the soil tube reactor, oxygen limitation occurs inside the tube due to the diffusional resistance and oxygen consumption due to biodegradation. Soil slurry, soil wafer and soil tube reactor systems are used in conjunction with respirometers to quantitatively assess biodegradation rates in dispersed and intact soil systems. Modeling procedures, applied to the 3 experimental schemes proved useful for determining the biokinetic, transport and diffusivity parameters for phenol and polycyclic aromatic hydrocarbons (PAHs) in soil. Heterogeneous solid phase diffusion models developed for predicting adsorption and desorption rates of PAHs in low and high organic carbon soils were shown to be superior to the homogeneous surface diffusion models. Adsorption and desorption experiments were conducted to obtain nonlinear isotherms described by the Freundlich isotherm equation. A dual mode isotherm was used to describe adsorption in high organic soils.

  1. Laboratory-scale in situ bioremediation in heterogeneous porous media: biokinetics-limited scenario.

    Science.gov (United States)

    Song, Xin; Hong, Eunyoung; Seagren, Eric A

    2014-03-01

    Subsurface heterogeneities influence interfacial mass-transfer processes and affect the application of in situ bioremediation by impacting the availability of substrates to the microorganisms. However, for difficult-to-degrade compounds, and/or cases with inhibitory biodegradation conditions, slow biokinetics may also limit the overall bioremediation rate, or be as limiting as mass-transfer processes. In this work, a quantitative framework based on a set of dimensionless coefficients was used to capture the effects of the competing interfacial and biokinetic processes and define the overall rate-limiting process. An integrated numerical modeling and experimental approach was used to evaluate application of the quantitative framework for a scenario in which slow-biokinetics limited the overall bioremediation rate of a polycyclic aromatic hydrocarbon (naphthalene). Numerical modeling was conducted to simulate the groundwater flow and naphthalene transport and verify the system parameters, which were used in the quantitative framework application. The experiments examined the movement and biodegradation of naphthalene in a saturated, heterogeneous intermediate-scale flow cell with two layers of contrasting hydraulic conductivities. These experiments were conducted in two phases: Phase I, simulating an inhibited slow biodegradation; and Phase II, simulating an engineered bioremediation, with system perturbations selected to enhance the slow biodegradation rate. In Phase II, two engineered perturbations to the system were selected to examine their ability to enhance in situ biodegradation. In the first perturbation, nitrogen and phosphorus in excess of the required stoichiometric amounts were spiked into the influent solution to mimic a common remedial action taken in the field. The results showed that this perturbation had a moderate positive impact, consistent with slow biokinetics being the overall rate-limiting process. However, the second perturbation, which was to

  2. Laboratory-scale in situ bioremediation in heterogeneous porous media: Biokinetics-limited scenario

    Science.gov (United States)

    Song, Xin; Hong, Eunyoung; Seagren, Eric A.

    2014-03-01

    Subsurface heterogeneities influence interfacial mass-transfer processes and affect the application of in situ bioremediation by impacting the availability of substrates to the microorganisms. However, for difficult-to-degrade compounds, and/or cases with inhibitory biodegradation conditions, slow biokinetics may also limit the overall bioremediation rate, or be as limiting as mass-transfer processes. In this work, a quantitative framework based on a set of dimensionless coefficients was used to capture the effects of the competing interfacial and biokinetic processes and define the overall rate-limiting process. An integrated numerical modeling and experimental approach was used to evaluate application of the quantitative framework for a scenario in which slow-biokinetics limited the overall bioremediation rate of a polycyclic aromatic hydrocarbon (naphthalene). Numerical modeling was conducted to simulate the groundwater flow and naphthalene transport and verify the system parameters, which were used in the quantitative framework application. The experiments examined the movement and biodegradation of naphthalene in a saturated, heterogeneous intermediate-scale flow cell with two layers of contrasting hydraulic conductivities. These experiments were conducted in two phases: Phase I, simulating an inhibited slow biodegradation; and Phase II, simulating an engineered bioremediation, with system perturbations selected to enhance the slow biodegradation rate. In Phase II, two engineered perturbations to the system were selected to examine their ability to enhance in situ biodegradation. In the first perturbation, nitrogen and phosphorus in excess of the required stoichiometric amounts were spiked into the influent solution to mimic a common remedial action taken in the field. The results showed that this perturbation had a moderate positive impact, consistent with slow biokinetics being the overall rate-limiting process. However, the second perturbation, which was to

  3. Physiologically based biokinetic (PBBK) modeling and validation of dose-, species-, interindividual- and matrix dependent effects on the bioactivation and detoxification of safrole

    NARCIS (Netherlands)

    Martati, E.

    2013-01-01

    Keywords: safrole, PBBK model, DNA adduct, mace  Safrole has been demonstrated to be carcinogenic in rodent studies at high doses of the pure compound. The use of pure safrole in foodshas already been prohibited. As a result, the main exposu

  4. Physiological Bases of Bulimia, and Antidepressant Treatment.

    Science.gov (United States)

    Getzfeld, Andrew R.

    This paper reviews the literature on the physiological causes of bulimia and investigates the rationale behind the usage of antidepressant medication in the treatment of bulimia nervosa. No definite conclusions can be stated regarding the physiology of bulimia, but a number of hypotheses are suggested. It appears that the hypothalamus is involved…

  5. Physiologically Based Pharmacokinetic (PBPK) Modeling of ...

    Science.gov (United States)

    Background: Quantitative estimation of toxicokinetic variability in the human population is a persistent challenge in risk assessment of environmental chemicals. Traditionally, inter-individual differences in the population are accounted for by default assumptions or, in rare cases, are based on human toxicokinetic data.Objectives: To evaluate the utility of genetically diverse mouse strains for estimating toxicokinetic population variability for risk assessment, using trichloroethylene (TCE) metabolism as a case study. Methods: We used data on oxidative and glutathione conjugation metabolism of TCE in 16 inbred and one hybrid mouse strains to calibrate and extend existing physiologically-based pharmacokinetic (PBPK) models. We added one-compartment models for glutathione metabolites and a two-compartment model for dichloroacetic acid (DCA). A Bayesian population analysis of inter-strain variability was used to quantify variability in TCE metabolism. Results: Concentration-time profiles for TCE metabolism to oxidative and glutathione conjugation metabolites varied across strains. Median predictions for the metabolic flux through oxidation was less variable (5-fold range) than that through glutathione conjugation (10-fold range). For oxidative metabolites, median predictions of trichloroacetic acid production was less variable (2-fold range) than DCA production (5-fold range), although uncertainty bounds for DCA exceeded the predicted variability. Conclusions:

  6. Human physiologically based pharmacokinetic model for propofol

    Directory of Open Access Journals (Sweden)

    Schnider Thomas W

    2005-04-01

    Full Text Available Abstract Background Propofol is widely used for both short-term anesthesia and long-term sedation. It has unusual pharmacokinetics because of its high lipid solubility. The standard approach to describing the pharmacokinetics is by a multi-compartmental model. This paper presents the first detailed human physiologically based pharmacokinetic (PBPK model for propofol. Methods PKQuest, a freely distributed software routine http://www.pkquest.com, was used for all the calculations. The "standard human" PBPK parameters developed in previous applications is used. It is assumed that the blood and tissue binding is determined by simple partition into the tissue lipid, which is characterized by two previously determined set of parameters: 1 the value of the propofol oil/water partition coefficient; 2 the lipid fraction in the blood and tissues. The model was fit to the individual experimental data of Schnider et. al., Anesthesiology, 1998; 88:1170 in which an initial bolus dose was followed 60 minutes later by a one hour constant infusion. Results The PBPK model provides a good description of the experimental data over a large range of input dosage, subject age and fat fraction. Only one adjustable parameter (the liver clearance is required to describe the constant infusion phase for each individual subject. In order to fit the bolus injection phase, for 10 or the 24 subjects it was necessary to assume that a fraction of the bolus dose was sequestered and then slowly released from the lungs (characterized by two additional parameters. The average weighted residual error (WRE of the PBPK model fit to the both the bolus and infusion phases was 15%; similar to the WRE for just the constant infusion phase obtained by Schnider et. al. using a 6-parameter NONMEM compartmental model. Conclusion A PBPK model using standard human parameters and a simple description of tissue binding provides a good description of human propofol kinetics. The major advantage of a

  7. Teaching Acid/Base Physiology in the Laboratory

    Science.gov (United States)

    Friis, Ulla G.; Plovsing, Ronni; Hansen, Klaus; Laursen, Bent G.; Wallstedt, Birgitta

    2010-01-01

    Acid/base homeostasis is one of the most difficult subdisciplines of physiology for medical students to master. A different approach, where theory and practice are linked, might help students develop a deeper understanding of acid/base homeostasis. We therefore set out to develop a laboratory exercise in acid/base physiology that would provide…

  8. Teaching Acid/Base Physiology in the Laboratory

    Science.gov (United States)

    Friis, Ulla G.; Plovsing, Ronni; Hansen, Klaus; Laursen, Bent G.; Wallstedt, Birgitta

    2010-01-01

    Acid/base homeostasis is one of the most difficult subdisciplines of physiology for medical students to master. A different approach, where theory and practice are linked, might help students develop a deeper understanding of acid/base homeostasis. We therefore set out to develop a laboratory exercise in acid/base physiology that would provide…

  9. Physiology

    Science.gov (United States)

    Kay, Ian

    2008-01-01

    Underlying recent developments in health care and new treatments for disease are advances in basic medical sciences. This edition of "Webwatch" focuses on sites dealing with basic medical sciences, with particular attention given to physiology. There is a vast amount of information on the web related to physiology. The sites that are included here…

  10. The biokinetic of incorporates radionuclides; Die Biokinetik von inkorporierten Radionukliden

    Energy Technology Data Exchange (ETDEWEB)

    Breustedt, Bastian [Karlsruher Institut fuer Technologie (KIT), Eggenstein-Leopoldshafen (Germany). Inst. fuer Strahlenforschung; Giussani, Augusto [Bundesamt fuer Strahlenschutz, Oberschleissheim (Germany). Arbeitsgruppe ' ' Externe und interne Dosimetrie, Biokinetik' '

    2017-08-01

    Incorporated radionuclides from nuclear accidents, fission product releases or nuclear medical administration are distributed in the human body in organs and tissue, absorbed 9or excreted. The interpretation of incorporation monitoring results and the estimation of the internal doses that cannot be measured directly need mathematical methods and the formulation of biokinetic models.

  11. Optimization of biomass and biokinetic constant in Mazut biodegradation by indigenous bacteria BBRC10061

    Science.gov (United States)

    2014-01-01

    Optimization based on appropriate parameters can be applied to improve a process. Mazut degradation as a critical issue in environment requires optimization to be efficiently done. To provide biodegradation conditions, experiments were designed on the least interactions among levels of parameters consisting of pH, Tween 80, glucose, phosphorous source, nitrogen source, and time. Kinetic constants and biomass were calculated based on 16 assays, designed using Taguchi method, which constructed various mazut biodegradation conditions. Kinetics of mazut degradation by newly isolated bacteria Enterobacter cloacae closely followed second order kinetic model. Results of the 16 experiments showed that biomass was in the range of 0.019 OD600 to 2.75 OD600, and biokinetic constant was in the range of 0.2 × 10-5 L/ (mg day) to 10-4 L/ (mg day). Optimal level for each parameter was obtained through data analysis. For optimal biomass equal to 2.75 OD600, optimal pH, Tween80, glucose, phosphorous source, and time were 8.3, 4 g/L, 4 g/L, 9 g/L, and 10 days, respectively. For biokinetic constant equal to 1.2 × 10-4 L/ (mg day), optimal pH, Tween80, glucose, phosphorous source, and nitrogen source were 8.3, 1 g/L, 4 g/L, 1 g/L, and 9 g/L, respectively. The optimum levels for biomass and biokinetic constant were the same except the levels of the Tween 80, and phosphorous source. Consequently, mazut may be more degraded with adjusting the conditions on the optimum condition. PMID:25013725

  12. Clinical review: Reunification of acid–base physiology

    OpenAIRE

    2005-01-01

    Recent advances in acid–base physiology and in the epidemiology of acid–base disorders have refined our understanding of the basic control mechanisms that determine blood pH in health and disease. These refinements have also brought parity between the newer, quantitative and older, descriptive approaches to acid–base physiology. This review explores how the new and older approaches to acid–base physiology can be reconciled and combined to result in a powerful bedside tool. A case based tutori...

  13. Validation of biokinetic models for strontium. Analysis of the Techa River and Chernobyl data

    Energy Technology Data Exchange (ETDEWEB)

    Tolstykh, E.I.; Degteva, M.O.; Kozheurov, V.P. [Urals Research Center for Radiation Medicine, Chelyabinsk (Russian Federation); Repin, V.S.; Novak, N.Y.; Berkovski, V.; Nosske, D.

    2000-05-01

    The ICRP models used in radiation protection to estimate doses resulting from internal irradiation are based on biokinetic models for different radionuclides. Strontium-90 was one of the main sources of environmental contamination due to accidents in the ''Mayak'' plutonium production complex (Southern Urals, 1949-1956) and the Chernobyl accident (1986). Over 800 measurements of bone-autopsy, and 31,000 Whole body Counter {sup 90}Sr measurements for Techa River population were made at URCRM (Chelyabinsk). Measurements of {sup 90}Sr contents in skeleton were performed for residents of the area contaminated due to Chernobyl accident (RPI, Kiev). These unique data allowed to validate the predictions of {sup 90}Sr biokinetic models at different times after ingestion, and in the case of complicated rate of intake. Model validation can be considered as best approach for quantifying the reliability of the model's predictions. Available data on {sup 90}Sr content in human skeleton were analyzed. {sup 90}Sr measurements cover the long period after start of intake: from 2 to 45 years after contamination (Techa River data). Model predictions for all age groups were compared with Techa River and Chernobyl data. For adult persons calculated and measured values of {sup 90}Sr body content were found to be very close, especially over the first 15 years after the major intake. After the majority of measured people had attained the age of 45 years and changes of calcium metabolism resulted in a significant increase of strontium elimination rate. The particularities of bone mineral turnover in old persons are not considered in the framework of the ICRP model. The latter feature resulted in a divergence between the model curve and the results of {sup 90}Sr measurements for old persons. For children and adolescents the differences between calculated values and measured {sup 90}Sr body contents are more significant. The comparison of different strontium

  14. Strontium biokinetic model for the pregnant woman and fetus: application to Techa River studies.

    Science.gov (United States)

    Shagina, N B; Fell, T P; Tolstykh, E I; Harrison, J D; Degteva, M O

    2015-09-01

    A biokinetic model for strontium (Sr) for the pregnant woman and fetus (Sr-PWF model) has been developed for use in the quantification of doses from internal radiation exposures following maternal ingestion of Sr radioisotopes before or during pregnancy. The model relates in particular to the population of the Techa River villages exposed to significant amounts of ingested Sr radioisotopes as a result of releases of liquid radioactive wastes from the Mayak plutonium production facility (Russia) in the early 1950s. The biokinetic model for Sr metabolism in the pregnant woman was based on a biokinetic model for the adult female modified to account for changes in mineral metabolism during pregnancy. The model for non-pregnant females of all ages was developed earlier with the use of extensive data on (90)Sr-body measurements in the Techa Riverside residents. To determine changes in model parameter values to take account of changing mineral metabolism during pregnancy, data from longitudinal studies of calcium homeostasis during human pregnancy were analysed and applied. Exchanges between maternal and fetal circulations and retention in fetal skeleton and soft tissues were modelled as adaptations of previously published models, taking account of data on Sr and calcium (Ca) metabolism obtained in Russia (Southern Urals and Moscow) relating to dietary calcium intakes, calcium contents in maternal and fetal skeletons and strontium transfer to the fetus. The model was validated using independent data on (90)Sr in the fetal skeleton from global fallout as well as unique data on (90)Sr-body burden in mothers and their still-born children for Techa River residents. While the Sr-PWF model has been developed specifically for ingestion of Sr isotopes by Techa River residents, it is also more widely applicable to maternal ingestion of Sr radioisotopes at different times before and during pregnancy and different ages of pregnant women in a general population.

  15. Different biokinetics of nanomedicines linking to their toxicity; an overview

    Directory of Open Access Journals (Sweden)

    Abdollahi Mohammad

    2013-02-01

    Full Text Available Abstract In spite of the extreme rise to the knowledge of nanotechnology in pharmaceutical sciences, there are currently limited experimental works studying the interactions between nanoparticles (NPs and the biological system. Adjustment of size and surface area plays the main role in the reaction between NPs and cells leading to their increased entrance into cells through skin, gastrointestinal and respiratory system. Moreover, change in physicochemical reactivity of NPs causes them to interact with circulatory and cellular proteins differentially leading to the altered parameters of their biokinetics, including adsorption, distribution, translocation, transformation, and elimination. A direct relationship between the surface area, reactive oxygen species generating capability, and proinflammatory effects of NPs have been found in respiratory tract toxicity. Additionally, complement-mediated hypersensitivity reactions to liposomes and other lipid-based nanodrugs have been well defined. Inhalation studies of some NPs have confirmed the translocation of inhaled materials to extra pulmonary organs such as central nervous system (CNS via olfactory neurons and induction of inflammatory response. Injectable uncoated NPs have a tendency to remain on the injection site while the poly ethanol glycol (PEG-coated NPs can be notably drained from the injection site to get as far as the lymph nodes where they accumulate. This confirms the existence of channels within the extracellular matrix for NPs to move along. Furthermore, induction of DNA strand breaks and formation of micronuclei have been recorded for exposure to some NPs such as single-walled carbon nanotubes. In the recent years, most of the studies have simply outlined better efficacy of nanodrugs, but few discussed their possible toxic reactions specially if used chronically. Therefore, we emphasize that this part of the nanoscience must not be undermined and toxicologists must be sensitive to

  16. The physiological and biochemical bases of functional brain imaging

    OpenAIRE

    2007-01-01

    Functional brain imaging is based on the display of computer-derived images of changes in physiological and/or biochemical functions altered by activation or depression of local functional activities in the brain. This article reviews the physiological and biochemical mechanisms involved.

  17. ICRP 67 Biokinetic Models for AM-241 Applied to Nonhuman Primates.

    Science.gov (United States)

    Alomairy, Nada A; Brey, Richard R; Guilmette, Raymond A

    2017-05-01

    Between 1960 and 1985, Patricia Durbin and colleagues performed studies on the distribution of intravenously and intramuscularly injected Am citrate with dosages ranging from 16 to 32 kBq kg in 30 male and female non-human primates (NHP). Dr. Durbin died unexpectedly in March of 2009, leaving much of the extensive serial blood, bioassay, and autopsy data from these NHP studies unanalyzed. As part of the experimental design, serial blood samples were taken, and urine and feces samples were collected separately for the duration of the study. The measurements of urine, fecal excretion, blood samples, and organ burden data obtained from the animals were used to evaluate the transfer rates of the ICRP 67 biokinetic model for Am. Seven cases, in which the primates were administered Am citrate by intravenous injection, were evaluated using the ICRP 67 systemic model. There were differences ranging from 51.4% underestimated to 102.7% overestimated activity between the predicted intake, which was calculated using IMBA Professional Plus software and based upon the urine bioassay data and the actual activity. The difference between the predicted activity at the time of death in the liver and skeleton using IMBA professional software and the value of the measured activity at the time of death were also compared. Generally, the ratios of predicted activity in the liver and skeleton at the time of death to the measured activity were consistently more than 1. However, the ratios were less than 1 in the skeleton for animals that were sacrificed 2,199 and 973 d post injection. The posterior probability distributions for model parameters derived using WeLMoS method were inconsistent with the ICRP 67 default parameters. The prediction made based on the posterior probability distributions for model parameters derived using WeLMoS gave the best fit to these data; however, the modified parameters overestimated the activity in almost all cases. The difference between the predicted Am

  18. Age and gender specific biokinetic model for strontium in humans

    Energy Technology Data Exchange (ETDEWEB)

    Shagina, N. B.; Tolstykh, E. I.; Degteva, M. O.; Anspaugh, L. R.; Napier, Bruce A.

    2015-03-01

    A biokinetic model for strontium in humans is necessary for quantification of internal doses due to strontium radioisotopes. The ICRP-recommended biokinetic model for strontium has limitation for use in a population study, because it is not gender specific and does not cover all age ranges. The extensive Techa River data set on 90Sr in humans (tens of thousands of measurements) is a unique source of data on long-term strontium retention for men and women of all ages at intake. These, as well as published data, were used for evaluation of age- and gender-specific parameters for a new compartment biokinetic model for strontium (Sr-AGe model). The Sr-AGe model has similar structure as the ICRP model for the alkaline earth elements. The following parameters were mainly reevaluated: gastro-intestinal absorption and parameters related to the processes of bone formation and resorption defining calcium and strontium transfers in skeletal compartments. The Sr-AGe model satisfactorily describes available data sets on strontium retention for different kinds of intake (dietary and intravenous) at different ages (0–80 years old) and demonstrates good agreement with data sets for different ethnic groups. The Sr-AGe model can be used for dose assessment in epidemiological studies of general population exposed to ingested strontium radioisotopes.

  19. A generic biokinetic model for noble gases with application to radon

    Energy Technology Data Exchange (ETDEWEB)

    Leggett, Richard Wayne [ORNL; Marsh, James [Health Protection Agency of Great Britain; Gregoratto, Demetrio [Health Protection Agency of Great Britain; Blanchardon, Eric [IRSN

    2013-01-01

    The International Commission for Radiological Protection (ICRP) currently uses a dose conversion coefficient to calculate effective dose per unit exposure to radon and its progeny. The coefficient is derived by dividing the detriment associated with unit exposure to radon, as estimated from epidemiological studies, by the detriment per unit effective dose, as estimated mainly from atomic bomb survivor data and animal studies. In a recent statement the ICRP indicated that future guidance on exposure to radon and its progeny will be developed in the same way as guidance for any other radionuclide. That is, intake of radon and progeny will be limited on the basis of effective dose coefficients derived from biokinetic and dosimetric models. This paper proposes a biokinetic model for systemic (absorbed) radon for use in the calculation of dose coefficients for inhaled or ingested radon. The model is based largely on physical laws governing transfer of a non-reactive and soluble gas between materials. Model predictions are shown to be consistent with results of controlled studies of the fate of internally deposited radon in human subjects.

  20. Human insulin dynamics in women: a physiologically based model.

    Science.gov (United States)

    Weiss, Michael; Tura, Andrea; Kautzky-Willer, Alexandra; Pacini, Giovanni; D'Argenio, David Z

    2016-02-01

    Currently available models of insulin dynamics are mostly based on the classical compartmental structure and, thus, their physiological utility is limited. In this work, we describe the development of a physiologically based model and its application to data from 154 patients who underwent an insulin-modified intravenous glucose tolerance test (IM-IVGTT). To determine the time profile of endogenous insulin delivery without using C-peptide data and to evaluate the transcapillary transport of insulin, the hepatosplanchnic, renal, and peripheral beds were incorporated into the circulatory model as separate subsystems. Physiologically reasonable population mean estimates were obtained for all estimated model parameters, including plasma volume, interstitial volume of the peripheral circulation (mainly skeletal muscle), uptake clearance into the interstitial space, hepatic and renal clearance, as well as total insulin delivery into plasma. The results indicate that, at a population level, the proposed physiologically based model provides a useful description of insulin disposition, which allows for the assessment of muscle insulin uptake.

  1. Teaching acid/base physiology in the laboratory

    DEFF Research Database (Denmark)

    Friis, Ulla G; Plovsing, Ronni; Hansen, Klaus;

    2010-01-01

    Acid/base homeostasis is one of the most difficult subdisciplines of physiology for medical students to master. A different approach, where theory and practice are linked, might help students develop a deeper understanding of acid/base homeostasis. We therefore set out to develop a laboratory...... exercise in acid/base physiology that would provide students with unambiguous and reproducible data that clearly would illustrate the theory in practice. The laboratory exercise was developed to include both metabolic acidosis and respiratory alkalosis. Data were collected from 56 groups of medical...

  2. The Application of Internal Dose Measures, Biokinetics, and Biomonitoring Data in the Risk Assessment of Dioxin-Like Compounds

    NARCIS (Netherlands)

    Aylward, L.L.

    2009-01-01

    This thesis presents a series of investigations into the biokinetic behavior of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds and the application of biokinetic modeling and biomonitoring data in quantitative risk assessment for these compounds. The biokinetic properties of TCDD an

  3. Refined biokinetic model for humans exposed to cobalt dietary supplements and other sources of systemic cobalt exposure.

    Science.gov (United States)

    Unice, Kenneth M; Kerger, Brent D; Paustenbach, Dennis J; Finley, Brent L; Tvermoes, Brooke E

    2014-06-05

    An updated biokinetic model for human exposures to cobalt (Co) was developed based on a comprehensive set of human pharmacokinetics data collected from five male and five female volunteers who ingested ∼1 mg Co/day of a Co supplement for 3 months. Three key experimental observations from the human dosing studies were incorporated into the model: (1) an increase in the measured fraction of large molecular serum protein bound Co from 95% during dosing to 99% after dosing; (2) a linear decrease in Co red blood cell concentration after dosing; and (3) Co renal clearance consistent with estimated glomerular filtration rates and free Co²⁺ concentration. The model was refined by adding compartments accounting for (1) albumin bound Co in intravascular fluid (serum); (2) albumin bound Co in extravascular fluid with physiologic exchange rates of albumin bound Co between extravascular and intravascular fluid; and (3) a novel sequential cascade of compartments representing red blood cell ages between 1 and 120 days. Reasonable agreement between the modeled and measured urine, serum, and whole blood concentrations were observed (r>0.84, slope=0.79-1.0) with gastrointestinal absorption rates between 9% and 66%. In addition, model predictions agreed well with data from several external studies representing healthy human volunteers, dialysis patients, anephric patients, a Co-poisoning incident and whole body retention studies. Our revised model considerably improves the state of knowledge on human Co kinetics, and should be helpful for evaluating elevated blood Co concentrations in currently exposed populations, such as metal-on-metal (MoM) hip implant patients. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. Wearable Systems for Service based on Physiological Signals.

    Science.gov (United States)

    Ryoo, Dong-Wan; Kim, Young-Sung; Lee, Jeun-Woo

    2005-01-01

    Many researches for useful status information on humans have been done using the bio-signals. The bio-signal acquisition systems can be used to connect a user and a ubiquitous computing environment. The ubiquitous computing environment has to give various services anywhere, anytime. Consequently, ubiquitous computing requires new technology, such as a new user interface, dynamic service mechanism based on context and mobility support, which is different from technology used in desktop environment. To do this, we developed a wearable system, which can sense physiological data, determine emotional status and execute service based on the emotion. In this paper, we described wearable systems for personalized service based on physiological signals. The wearable system is composed of three subsystems, the physiological data sensing subsystem, the human status awareness subsystem and the service management subsystem. The physiological data sensing subsystem senses PPG, GSR and SKT signals from the data glove and sends the data to a wearable system using Bluetooth. The human status awareness subsystem in the wearable system receives the data from bio-sensors and determines emotional status using nonlinear mapping and rule-base. After determining emotion, the service management subsystem activates proper service automatically, and the service management subsystem can provide personalized service for users based on acquired bio-signals. Also, we presented various feature extraction using bio-signals such as PPG, GSR, SKT considering mobility, and emotion recognition of human status for the ubiquitous computing service.

  5. Successful Implementation of Inquiry-Based Physiology Laboratories in Undergraduate Major and Nonmajor Courses

    Science.gov (United States)

    Casotti, G.; Rieser-Danner, L.; Knabb, M. T.

    2008-01-01

    Recent evidence has demonstrated that inquiry-based physiology laboratories improve students' critical- and analytical-thinking skills. We implemented inquiry-based learning into three physiology courses: Comparative Vertebrate Physiology (majors), Human Physiology (majors), and Human Anatomy and Physiology (nonmajors). The aims of our curricular…

  6. Successful Implementation of Inquiry-Based Physiology Laboratories in Undergraduate Major and Nonmajor Courses

    Science.gov (United States)

    Casotti, G.; Rieser-Danner, L.; Knabb, M. T.

    2008-01-01

    Recent evidence has demonstrated that inquiry-based physiology laboratories improve students' critical- and analytical-thinking skills. We implemented inquiry-based learning into three physiology courses: Comparative Vertebrate Physiology (majors), Human Physiology (majors), and Human Anatomy and Physiology (nonmajors). The aims of our curricular…

  7. Physiologically based kinetic modeling of the bioactivation of myristicin

    NARCIS (Netherlands)

    Al-Malahmeh, Amer J.; Al-Ajlouni, Abdelmajeed; Wesseling, Sebastiaan; Soffers, Ans E.M.F.; Al-Subeihi, A.; Kiwamoto, Reiko; Vervoort, Jacques; Rietjens, Ivonne M.C.M.

    2016-01-01

    The present study describes physiologically based kinetic (PBK) models for the alkenylbenzene myristicin that were developed by extension of the PBK models for the structurally related alkenylbenzene safrole in rat and human. The newly developed myristicin models revealed that the formation of th

  8. Biokinetics and dosimetric studies about {sup 99m}Tc(V)DMSA distribution

    Energy Technology Data Exchange (ETDEWEB)

    Correia, M.B.L.; Magnata, S.S.L.P.; Silva, I.M.S.; Lima, F.F.; Catanho, M.T.J.A., E-mail: marilialiborio@ig.com.br, E-mail: sfmagnata@terra.com.br, E-mail: isvania@gmail.com, E-mail: fima@cnen.gov.br, E-mail: mariajansem@terra.com.br [Centro Regional de Ciencias Nucleares (CRCN/CNEN-PE), Recife, PE (Brazil)

    2008-07-01

    Research for radiodiagnostic agents should considerate biological critical parameters as half-life effective, target/not target uptake ratio and metabolites that together will determinate the biokinetic. Each parameter give own contribution in the absorbed dose. The dimercaptosuccinic acid (DMSA) labeled with {sup 99m}Tc(VN) is a radiopharmaceutical which has well established role in medullar thyroid carcinoma and has been proposed in complementary evaluation of bone metastasis. The aim of this work was study the biokinetics and dosimetry of {sup 99m}Tc(V)-DMSA by animal model. The {sup 99m}Tc(V)-DMSA was prepared by (III)DMSA kit alkalized. The methodology used mice, 70 days old, both males and females. The animals (n=5) received {sup 99m}Tc(V)DMSA administered IV (tail vein). After determinate times (30 min, 1h, 5h and 12h) the animals were sacrificed, the organs (blood, lungs, kidneys, muscle and bone) were excised and the activities were measured by a gamma counter. The results were evaluated based on %activity/g and the absorbed dose was estimated by extrapolation of data from animal to human, using the residence time to each organ in the MIRDOSE 3.0 program. The results show that the majority of organs reaches the top uptake at 30 min, the kidney has the greatest uptake in this time, (4.81 ± 1.38) % activity per gram, while the bone presents its highest uptake at 1h (5.49 ± 0.47)% activity per gram, after 1h all the organs had activity exponential decrease. About the absorbed dose estimated to human scale, the preliminary results showed higher value to bone, being the soft tissue dose relatively low. These dose values, however, are submitted to biological implications which are under studying yet. The biokinetic profile of {sup 99m}Tc(V)-DMSA, prepared from a DMSA kit by IPEN, was well established, allowing quantifying of residence time, while the dosimetric model presented preliminary data which directs to new analyzes.

  9. A biokinetic study of {sup 209}Po in man

    Energy Technology Data Exchange (ETDEWEB)

    Henricsson, C.F.; Ranebo, Y. [Department of Medical Radiation Physics, Clinical Sciences in Lund, Lund University, Skane University Hospital in Lund (Sweden); Hansson, M. [Medical Radiation Physics, Department of Clinical Sciences in Malmoe, Lund University, Skane University Hospital in Malmoe (Sweden); Raeaef, C.L., E-mail: Christopher.Raaf@med.lu.se [Medical Radiation Physics, Department of Clinical Sciences in Malmoe, Lund University, Skane University Hospital in Malmoe (Sweden); Holm, E. [Norwegian Radiation Protection Authority, Osteras (Norway)

    2012-10-15

    Five adult volunteers participated in a biokinetic study of radioactive polonium. Portions of about 10 Bq of {sup 209}Po were orally administrated to four of the volunteers in a single ingestion. The fifth volunteer ingested a daily amount of 53 mBq of 209Po for 243 d to study the time to achieve equilibrium between intake and excretion for protracted intakes. For the subjects ingesting single intakes of {sup 209}Po complete sampling of urine and feces was subsequently collected the first few days upon the ingestion. The samples were processed with radiochemical extraction and analyzed with alpha spectrometry. In the study, the maximum daily excretion rates in feces were 18-50% of the ingested activity, observed within 3 d after intake. Regarding the urine excretion, the daily excretion peaked, on average, at 0.15-1% of the ingested activity within two days upon intake. These results indicate an average gastro-intestinal uptake fraction of 0.46 {+-} 0.08, which agrees well with earlier biokinetic studies of polonium in man. -- Highlights: Black-Right-Pointing-Pointer Human metabolism of an oral intake of polonium. Black-Right-Pointing-Pointer 4 individuals were administrated about 10 Bq polonium-209. Black-Right-Pointing-Pointer Gastro-intestinal uptake fraction, if orally administrated polonium-209 was investigated. Black-Right-Pointing-Pointer The biological half-time of polonium in human body was studied.

  10. An Earth-Based Model of Microgravity Pulmonary Physiology

    Science.gov (United States)

    Hirschl, Ronald B.; Bull, Joseph L.; Grothberg, James B.

    2004-01-01

    There are currently only two practical methods of achieving micro G for experimentation: parabolic flight in an aircraft or space flight, both of which have limitations. As a result, there are many important aspects of pulmonary physiology that have not been investigated in micro G. We propose to develop an earth-based animal model of micro G by using liquid ventilation, which will allow us to fill the lungs with perfluorocarbon, and submersing the animal in water such that the density of the lungs is the same as the surrounding environment. By so doing, we will eliminate the effects of gravity on respiration. We will first validate the model by comparing measures of pulmonary physiology, including cardiac output, central venous pressures, lung volumes, and pulmonary mechanics, to previous space flight and parabolic flight measurements. After validating the model, we will investigate the impact of micro G on aspects of lung physiology that have not been previously measured. These will include pulmonary blood flow distribution, ventilation distribution, pulmonary capillary wedge pressure, ventilation-perfusion matching, and pleural pressures and flows. We expect that this earth-based model of micro G will enhance our knowledge and understanding of lung physiology in space which will increase in importance as space flights increase in time and distance.

  11. A physiologically based model for tramadol pharmacokinetics in horses.

    Science.gov (United States)

    Abbiati, Roberto Andrea; Cagnardi, Petra; Ravasio, Giuliano; Villa, Roberto; Manca, Davide

    2017-09-21

    This work proposes an application of a minimal complexity physiologically based pharmacokinetic model to predict tramadol concentration vs time profiles in horses. Tramadol is an opioid analgesic also used for veterinary treatments. Researchers and medical doctors can profit from the application of mathematical models as supporting tools to optimize the pharmacological treatment of animal species. The proposed model is based on physiology but adopts the minimal compartmental architecture necessary to describe the experimental data. The model features a system of ordinary differential equations, where most of the model parameters are either assigned or individualized for a given horse, using literature data and correlations. Conversely, residual parameters, whose value is unknown, are regressed exploiting experimental data. The model proved capable of simulating pharmacokinetic profiles with accuracy. In addition, it provides further insights on un-observable tramadol data, as for instance tramadol concentration in the liver or hepatic metabolism and renal excretion extent. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Emotion recognition based on physiological changes in music listening.

    Science.gov (United States)

    Kim, Jonghwa; André, Elisabeth

    2008-12-01

    Little attention has been paid so far to physiological signals for emotion recognition compared to audiovisual emotion channels such as facial expression or speech. This paper investigates the potential of physiological signals as reliable channels for emotion recognition. All essential stages of an automatic recognition system are discussed, from the recording of a physiological dataset to a feature-based multiclass classification. In order to collect a physiological dataset from multiple subjects over many weeks, we used a musical induction method which spontaneously leads subjects to real emotional states, without any deliberate lab setting. Four-channel biosensors were used to measure electromyogram, electrocardiogram, skin conductivity and respiration changes. A wide range of physiological features from various analysis domains, including time/frequency, entropy, geometric analysis, subband spectra, multiscale entropy, etc., is proposed in order to find the best emotion-relevant features and to correlate them with emotional states. The best features extracted are specified in detail and their effectiveness is proven by classification results. Classification of four musical emotions (positive/high arousal, negative/high arousal, negative/low arousal, positive/low arousal) is performed by using an extended linear discriminant analysis (pLDA). Furthermore, by exploiting a dichotomic property of the 2D emotion model, we develop a novel scheme of emotion-specific multilevel dichotomous classification (EMDC) and compare its performance with direct multiclass classification using the pLDA. Improved recognition accuracy of 95\\% and 70\\% for subject-dependent and subject-independent classification, respectively, is achieved by using the EMDC scheme.

  13. Investigation of biokinetics of radioiodine with a population kinetics approach.

    Science.gov (United States)

    Janzen, T; Giussani, A; Canzi, C; Gerundini, P; Oeh, U; Hoeschen, C

    2010-01-01

    The dosimetric studies required for planning individually tailored radioiodine therapy of benign thyroid pathologies may be too complex and time-demanding for many ordinary nuclear medicine departments. In this work, a preliminary population kinetics approach was applied to a model structure for iodine biokinetics in order to identify those model features that actually need to be individually investigated, in order to simplify the protocol for data collection in patients. Data from 29 patients undergoing radioiodine therapy for the treatment of the autonomous nodule syndrome were used in the analysis. The greatest inter-individual variations were observed in the parameters describing the transformation of iodide into organic iodine in the thyroid and in the kinetics of the organic form.

  14. Biokinetics of zinc oxide nanoparticles: toxicokinetics, biological fates, and protein interaction

    Directory of Open Access Journals (Sweden)

    Choi SJ

    2014-12-01

    Full Text Available Soo-Jin Choi,1 Jin-Ho Choy2 1Department of Food Science and Technology, Seoul Women's University, 2Center for Intelligent Nano Bio Materials (CINBM, Department of Bioinspired Science and Department of Chemistry and Nanoscience, Ewha Womans University, Seoul, South Korea Abstract: Biokinetic studies of zinc oxide (ZnO nanoparticles involve systematic and quantitative analyses of absorption, distribution, metabolism, and excretion in plasma and tissues of whole animals after exposure. A full understanding of the biokinetics provides basic information about nanoparticle entry into systemic circulation, target organs of accumulation and toxicity, and elimination time, which is important for predicting the long-term toxic potential of nanoparticles. Biokinetic behaviors can be dependent on physicochemical properties, dissolution property in biological fluids, and nanoparticle–protein interaction. Moreover, the determination of biological fates of ZnO nanoparticles in the systemic circulation and tissues is critical in interpreting biokinetic behaviors and predicting toxicity potential as well as mechanism. This review focuses on physicochemical factors affecting the biokinetics of ZnO nanoparticles, in concert with understanding bioavailable fates and their interaction with proteins. Keywords: ZnO nanoparticles, biokinetics, distribution, excretion, fate, interaction

  15. Field-based physiological testing of wheelchair athletes.

    Science.gov (United States)

    Goosey-Tolfrey, Victoria L; Leicht, Christof A

    2013-02-01

    The volume of literature on field-based physiological testing of wheelchair sports, such as basketball, rugby and tennis, is considerably smaller when compared with that available for individuals and team athletes in able-bodied (AB) sports. In analogy to the AB literature, it is recognized that performance in wheelchair sports not only relies on fitness, but also sport-specific skills, experience and technical proficiency. However, in contrast to AB sports, two major components contribute towards 'wheeled sports' performance, which are the athlete and the wheelchair. It is the interaction of these two that enable wheelchair propulsion and the sporting movements required within a given sport. Like any other athlete, participants of wheelchair sports are looking for efficient ways to train and/or analyse their technique and fitness to improve their performance. Consequently, laboratory and/or field-based physiological monitoring tools used at regular intervals at key time points throughout the year must be considered to help with training evaluation. The present review examines methods available in the literature to assess wheelchair sports fitness in a field-based environment, with special attention on outcome variables, validity and reliability issues, and non-physiological influences on performance. It also lays out the context of field-based testing by providing details about the Paralympic court sports and the impacts of a disability on sporting performance. Due to the limited availability of specialized equipment for testing wheelchair-dependent participants in the laboratory, the adoption of field-based testing has become the preferred option by team coaches of wheelchair athletes. An obvious advantage of field-based testing is that large groups of athletes can be tested in less time. Furthermore, athletes are tested in their natural environment (using their normal sports wheelchair set-up and floor surface), potentially making the results of such testing

  16. Physiology-based face recognition in the thermal infrared spectrum.

    Science.gov (United States)

    Buddharaju, Pradeep; Pavlidis, Ioannis T; Tsiamyrtzis, Panagiotis; Bazakos, Mike

    2007-04-01

    The current dominant approaches to face recognition rely on facial characteristics that are on or over the skin. Some of these characteristics have low permanency can be altered, and their phenomenology varies significantly with environmental factors (e.g., lighting). Many methodologies have been developed to address these problems to various degrees. However, the current framework of face recognition research has a potential weakness due to its very nature. We present a novel framework for face recognition based on physiological information. The motivation behind this effort is to capitalize on the permanency of innate characteristics that are under the skin. To establish feasibility, we propose a specific methodology to capture facial physiological patterns using the bioheat information contained in thermal imagery. First, the algorithm delineates the human face from the background using the Bayesian framework. Then, it localizes the superficial blood vessel network using image morphology. The extracted vascular network produces contour shapes that are characteristic to each individual. The branching points of the skeletonized vascular network are referred to as Thermal Minutia Points (TMPs) and constitute the feature database. To render the method robust to facial pose variations, we collect for each subject to be stored in the database five different pose images (center, midleft profile, left profile, midright profile, and right profile). During the classification stage, the algorithm first estimates the pose of the test image. Then, it matches the local and global TMP structures extracted from the test image with those of the corresponding pose images in the database. We have conducted experiments on a multipose database of thermal facial images collected in our laboratory, as well as on the time-gap database of the University of Notre Dame. The good experimental results show that the proposed methodology has merit, especially with respect to the problem of

  17. Biokinetic food chain modeling of waterborne selenium pulses into aquatic food chains: Implications for water quality criteria.

    Science.gov (United States)

    DeForest, David K; Pargee, Suzanne; Claytor, Carrie; Canton, Steven P; Brix, Kevin V

    2016-04-01

    We evaluated the use of biokinetic models to predict selenium (Se) bioaccumulation into model food chains after short-term pulses of selenate or selenite into water. Both periphyton- and phytoplankton-based food chains were modeled, with Se trophically transferred to invertebrates and then to fish. Whole-body fish Se concentrations were predicted based on 1) the background waterborne Se concentration, 2) the magnitude of the Se pulse, and 3) the duration of the Se pulse. The models were used to evaluate whether the US Environmental Protection Agency's (USEPA's) existing acute Se criteria and their recently proposed intermittent Se criteria would be protective of a whole-body fish Se tissue-based criterion of 8.1 μg g(-1) dry wt. Based on a background waterborne Se concentration of 1 μg L(-1) and pulse durations of 1 d and 4 d, the Se pulse concentrations predicted to result in a whole-body fish Se concentration of 8.1 μg g(-1) dry wt in the most conservative model food chains were 144 and 35 μg L(-1), respectively, for selenate and 57 and 16 μg L(-1), respectively, for selenite. These concentrations fall within the range of various acute Se criteria recommended by the USEPA based on direct waterborne toxicity, suggesting that these criteria may not always be protective against bioaccumulation-based toxicity that could occur after short-term pulses. Regarding the USEPA's draft intermittent Se criteria, the biokinetic modeling indicates that they may be overly protective for selenate pulses but potentially underprotective for selenite pulses. Predictions of whole-body fish Se concentrations were highly dependent on whether the food chain was periphyton- or phytoplankton-based, because the latter had much greater Se uptake rate constants. Overall, biokinetic modeling provides an approach for developing acute Se criteria that are protective against bioaccumulation-based toxicity after trophic transfer, and it is also a useful tool for evaluating averaging

  18. Nasal Physiology

    Science.gov (United States)

    ... Caregivers Contact ARS HOME ANATOMY Nasal Anatomy Sinus Anatomy Nasal Physiology Nasal Endoscopy Skull Base Anatomy Virtual Anatomy Disclosure ... Patient Education About this Website Font Size + - Home > ANATOMY > Nasal Physiology Nasal Anatomy Sinus Anatomy Nasal Physiology Nasal Endoscopy ...

  19. Measurement and Modeling of Algal Biokinetics in Highly EutrophicWaters

    Energy Technology Data Exchange (ETDEWEB)

    Stringfellow, William T.; Borglin, Sharon E.; Hanlon, Jeremy S.

    2006-04-04

    Excessive growth of suspended algae in eutrophic surface waters can contribute to the degradation of water quality. The objective of this study was to understand the fundamental processes limiting algal growth in highly nutrient-rich agricultural drainage water. Studies examining algal biokinetics (growth rates, yields, and decay) were conducted in a twenty-eight mile long, hydraulically simple, open channel. Algae biokinetics were found to follow a growth limited model,despite monitoring data demonstrating the presence of nutrients at concentrations far in excess of those expected to be limiting. A mechanistic algal biokinetic model was written to assist in data interpretation. Results from the mechanistic model suggested that at different times, soluble phosphate, minerals, and inorganic carbon could limit growth rates, but that growth yield was most likely limited by zooplankton grazing. The implication of these finding for control of algal growth are discussed.

  20. Emotion of Physiological Signals Classification Based on TS Feature Selection

    Institute of Scientific and Technical Information of China (English)

    Wang Yujing; Mo Jianlin

    2015-01-01

    This paper propose a method of TS-MLP about emotion recognition of physiological signal.It can recognize emotion successfully by Tabu search which selects features of emotion’s physiological signals and multilayer perceptron that is used to classify emotion.Simulation shows that it has achieved good emotion classification performance.

  1. Impact of varying electron donors on the molecular microbial ecology and biokinetics of methylotrophic denitrifying bacteria.

    Science.gov (United States)

    Baytshtok, Vladimir; Lu, Huijie; Park, Hongkeun; Kim, Sungpyo; Yu, Ran; Chandran, Kartik

    2009-04-15

    The goal of this study was to identify bacterial populations that assimilated methanol in a denitrifying sequencing batch reactor (SBR), using stable isotope probing (SIP) of (13)C labeled DNA and quantitatively track changes in these populations upon changing the electron donor from methanol to ethanol in the SBR feed. Based on SIP derived (13)C 16S rRNA gene clone libraries, dominant SBR methylotrophic bacteria were related to Methyloversatilis spp. and Hyphomicrobium spp. These methylotrophic populations were quantified via newly developed real-time PCR assays. Upon switching the electron donor from methanol to ethanol, Hyphomicrobium spp. concentrations decreased significantly in accordance with their obligately methylotrophic nutritional mode. In contrast, Methyloversatilis spp. concentrations were relatively unchanged, in accordance with their ability to assimilate both methanol and ethanol. Direct assimilation of ethanol by Methyloversatilis spp. but not Hyphomicrobium spp. was also confirmed via SIP. The reduction in methylotrophic bacterial concentration upon switching to ethanol was paralleled by a significant decrease in the methanol supported denitrification biokinetics of the SBR on nitrate. In sum, the results of this study demonstrate that the metabolic capabilities (methanol assimilation and metabolism) and substrate specificity (obligately or facultatively methylotrophic) of two distinct methylotrophic bacterial populations contributed to their survival or washout in denitrifying bioreactors. 2008 Wiley Periodicals, Inc.

  2. Validating an important aspect of the new ICRP biokinetic model of thorium.

    Science.gov (United States)

    Roth, P; Höllriegl, V; Li, W B; Oeh, U; Schramel, P

    2005-03-01

    The daily urinary excretion of Th (Th) was estimated in 11 adult German subjects who were not exposed occupationally to thorium and its related compounds. Thirty-one urine samples were collected over 24-h periods on different occasions from these subjects and were analyzed using high resolution sector field inductively coupled plasma mass spectrometry (HR-SF-ICP-MS). Using this instrument a limit of detection of 20 pg L for thorium in the reagent blank was achieved. The median (mean) daily urinary thorium excretion was obtained as 1.0 (1.8) ng. This was in good agreement with the mean value of 1.5 ng Th (6 microBq) reported by another group for German population, but is significantly lower in comparison to the daily excretion range of 3.6 to 105 ng reported from other countries. The expected daily urinary excretion of thorium for the adult German population was also calculated by applying the new ICRP biokinetic model of thorium assuming reference intake values. The expected urinary thorium excretion rate for this age group is about 0.1 ng per day. Even if a small contribution from the inhalation is considered, the calculated value will be much lower than the measured values. The reason for the disagreement appears to be the use of a low gastrointestinal absorption factor (f1) of 5 x 10 in the ICRP model. Based on the present study, a higher f1 factor might be proposed separately for dietary incorporated thorium.

  3. In vivo validation and physiologically based biokinetic modeling of the inhibition of SULT-mediated estragole DNA adduct formation in the liver of male Sprague-Dawley rats by the basil flavonoid nevadensin

    NARCIS (Netherlands)

    Alhusainy, W.; Paini, A.; Berg, van den J.H.J.; Punt, A.; Scholz, G.; Schilter, B.; Bladeren, van P.J.; Taylor, S.; Adams, T.B.; Rietjens, I.

    2013-01-01

    ScopeThe present work investigates whether the previous observation that the basil flavonoid nevadensin is able to inhibit sulfotransferase (SULT)-mediated estragole DNA adduct formation in primary rat hepatocytes could be validated in vivo. Methods and resultsEstragole and nevadensin were co-admini

  4. Optimizing nanomedicine pharmacokinetics using physiologically based pharmacokinetics modelling.

    Science.gov (United States)

    Moss, Darren Michael; Siccardi, Marco

    2014-09-01

    The delivery of therapeutic agents is characterized by numerous challenges including poor absorption, low penetration in target tissues and non-specific dissemination in organs, leading to toxicity or poor drug exposure. Several nanomedicine strategies have emerged as an advanced approach to enhance drug delivery and improve the treatment of several diseases. Numerous processes mediate the pharmacokinetics of nanoformulations, with the absorption, distribution, metabolism and elimination (ADME) being poorly understood and often differing substantially from traditional formulations. Understanding how nanoformulation composition and physicochemical properties influence drug distribution in the human body is of central importance when developing future treatment strategies. A helpful pharmacological tool to simulate the distribution of nanoformulations is represented by physiologically based pharmacokinetics (PBPK) modelling, which integrates system data describing a population of interest with drug/nanoparticle in vitro data through a mathematical description of ADME. The application of PBPK models for nanomedicine is in its infancy and characterized by several challenges. The integration of property-distribution relationships in PBPK models may benefit nanomedicine research, giving opportunities for innovative development of nanotechnologies. PBPK modelling has the potential to improve our understanding of the mechanisms underpinning nanoformulation disposition and allow for more rapid and accurate determination of their kinetics. This review provides an overview of the current knowledge of nanomedicine distribution and the use of PBPK modelling in the characterization of nanoformulations with optimal pharmacokinetics.

  5. Wildlife toxicity extrapolations: Allometry versus physiologically-based toxicokinetics

    Energy Technology Data Exchange (ETDEWEB)

    Fairbrother, A. [Ecological Planning and Toxicology Inc., Corvallis, OR (United States); Berg, M. van den [Univ. of Utrecht (Netherlands). Research Inst. of Toxicology

    1995-12-31

    Ecotoxicological assessments must rely on the extrapolation of toxicity data from a few indicator species to many species of concern. Data are available from laboratory studies (e.g., quail, mallards, rainbow trout, fathead minnow) and some planned or serendipitous field studies of a broader, but by no means comprehensive, suite of species. Yet all ecological risk assessments begin with an estimate of risk based on information gleaned from the literature. The authors are then confronted with the necessity of extrapolating toxicity information from a limited number of indicator species to all organisms of interest. This is a particularly acute problem when trying to estimate hazards to wildlife in terrestrial systems as there is an extreme paucity of data for most chemicals in all but a handful of species. The question arises of how interspecific extrapolations should be made. Should extrapolations be limited to animals within the same class, order, family or genus? Alteratively, should extrapolations be made along trophic levels or physiologic similarities rather than by taxonomic classification? In other words, is an avian carnivore more like a mammalian carnivore or an avian granivore in its response to a toxic substance? Can general rules be set or does the type of extrapolation depend upon the class of chemical and its mode of uptake and toxicologic effect?

  6. Development of concept-based physiology lessons for biomedical engineering undergraduate students.

    Science.gov (United States)

    Nelson, Regina K; Chesler, Naomi C; Strang, Kevin T

    2013-06-01

    Physiology is a core requirement in the undergraduate biomedical engineering curriculum. In one or two introductory physiology courses, engineering students must learn physiology sufficiently to support learning in their subsequent engineering courses and careers. As preparation for future learning, physiology instruction centered on concepts may help engineering students to further develop their physiology and biomedical engineering knowledge. Following the Backward Design instructional model, a series of seven concept-based lessons was developed for undergraduate engineering students. These online lessons were created as prerequisite physiology training to prepare students to engage in a collaborative engineering challenge activity. This work is presented as an example of how to convert standard, organ system-based physiology content into concept-based content lessons.

  7. Internal Dose Calculations with the New Biokinetic Models of the ICRP

    Energy Technology Data Exchange (ETDEWEB)

    Silverman, I.; Shamai, Y.; Schlesinger, T.; Biran, T

    1999-07-01

    During the past decade, the ICRP made major revisions in its recommendations regarding protection from ionising radiation and advised the use of new models for estimating doses due to intake of radionuclides. A new Internal Dosimetry code (InDose) is presented which employs all the new biokinetic models together with the new respiratory tract (RT) model and the gastrointestinal tract (GI) model. The code makes use of a generalised form of these new biokinetic models which enables the use of any of them. The code has been used to assess intakes and doses for the 3rd European Intercomparison Exercise on Internal Dose Assessment. A detailed study of one of the test cases of this exercise is presented. Our code using the new plutonium biokinetic model and LUDEP gave similar results. InDose, however, provides a way to insert consistent changes in the models in orderto make estimations under non-standard conditions. The new biokinetic model has been found to give better agreement with measured data than the old (ICRP 30) model. (author)

  8. Distribution and biokinetic analysis of {sup 210}Pb and {sup 210}Po in poultry due to ingestion of dicalcium phosphate

    Energy Technology Data Exchange (ETDEWEB)

    Casacuberta, N., E-mail: Nuria.Casacuberta@uab.es [Departament de Fisica and Institut de Ciencia i Tecnologia Ambientals, Universitat Autonoma de Barcelona, 08193 Bellaterra (Spain); Traversa, F.L. [Departament d' Electronica, Escola Tecnica Superior d' Enginyeria, Universitat Autonoma de Barcelona, 08193 Bellaterra (Spain); Masque, P.; Garcia-Orellana, J. [Departament de Fisica and Institut de Ciencia i Tecnologia Ambientals, Universitat Autonoma de Barcelona, 08193 Bellaterra (Spain); Anguita, M.; Gasa, J. [Departament de Ciencia Animal i dels Aliments, Universitat Autonoma de Barcelona, 08193 Bellaterra (Spain); Garcia-Tenorio, R. [Universidad de Sevilla, Avda. Reina Mercedes s/n, 41012 Sevilla (Spain)

    2010-09-15

    Dicalcium phosphate (DCP) is used as a calcium supplement for food producing animals (i.e., cattle, poultry and pig). When DCP is produced via wet acid digestion of the phosphate rock and depending on the acid used in the industrial process, the final product can result in enhanced {sup 210}Pb and {sup 210}Po specific activities ({approx} 2000 Bq.kg{sup -1}). Both {sup 210}Pb and {sup 210}Po are of great interest because their contribution to the dose received by ingestion is potentially large. The aims of this work are to examine the accumulation of {sup 210}Pb and {sup 210}Po in chicken tissues during the first 42 days of life and to build a suitable single-compartment biokinetic model to understand the behavior of both radionuclides within the entire animal using the experimental results. Three commercial corn-soybean-based diets containing different amounts and sources of DCP were fed to broilers during a period of 42 days. The results show that diets containing enhanced concentrations of {sup 210}Pb and {sup 210}Po lead to larger specific accumulation in broiler tissues compared to the blank diet. Radionuclides do not accumulate homogeneously within the animal body: {sup 210}Pb follows the calcium pathways to some extent and accumulates largely in bones, while {sup 210}Po accumulates to a large extent in liver and kidneys. However, the total amount of radionuclide accumulation in tissues is small compared to the amounts excreted in feces. The single-compartment non-linear biokinetic model proposed here for {sup 210}Pb and {sup 210}Po in the whole animal takes into account the size evolution and is self-consistent in that no fitting parameterization of intake and excretions rates is required.

  9. Distribution and biokinetic analysis of 210Pb and 210Po in poultry due to ingestion of dicalcium phosphate.

    Science.gov (United States)

    Casacuberta, N; Traversa, F L; Masqué, P; Garcia-Orellana, J; Anguita, M; Gasa, J; Garcia-Tenorio, R

    2010-09-15

    Dicalcium phosphate (DCP) is used as a calcium supplement for food producing animals (i.e., cattle, poultry and pig). When DCP is produced via wet acid digestion of the phosphate rock and depending on the acid used in the industrial process, the final product can result in enhanced (210)Pb and (210)Po specific activities (approximately 2000 Bq.kg(-1)). Both (210)Pb and (210)Po are of great interest because their contribution to the dose received by ingestion is potentially large. The aims of this work are to examine the accumulation of (210)Pb and (210)Po in chicken tissues during the first 42 days of life and to build a suitable single-compartment biokinetic model to understand the behavior of both radionuclides within the entire animal using the experimental results. Three commercial corn-soybean-based diets containing different amounts and sources of DCP were fed to broilers during a period of 42 days. The results show that diets containing enhanced concentrations of (210)Pb and (210)Po lead to larger specific accumulation in broiler tissues compared to the blank diet. Radionuclides do not accumulate homogeneously within the animal body: (210)Pb follows the calcium pathways to some extent and accumulates largely in bones, while (210)Po accumulates to a large extent in liver and kidneys. However, the total amount of radionuclide accumulation in tissues is small compared to the amounts excreted in feces. The single-compartment non-linear biokinetic model proposed here for (210)Pb and (210)Po in the whole animal takes into account the size evolution and is self-consistent in that no fitting parameterization of intake and excretions rates is required.

  10. A Web-Based Course of Lectures in Respiratory Physiology

    Science.gov (United States)

    West, John B.

    2011-01-01

    A complete course of respiratory physiology suitable for first-year medical and graduate students has been placed on the Web for our own students and for other educational institutions. There are several reasons for doing this. The first is that the modern-day student uses a variety of options for acquiring knowledge. These include attending…

  11. Towards a physiologically based diagnosis of anorexia nervosa and bulimia nervosa.

    Science.gov (United States)

    Hatch, Kent A; Spangler, Diane L; Backus, Elizabeth M; Balagna, Jonathan T; Burns, Keven S; Guzman, Brooke S; Hubbard, Matthew J; Lindblad, Stephanie L; Roeder, Beverly L; Ryther, Natalie E; Seawright, Max A; Tyau, Jaymie N; Williams, Dustin

    2007-11-01

    Diagnosis of anorexia nervosa (AN) and bulimia nervosa (BN), while including such physiological data as weight and the reproductive status of the individual, are primarily based on questionnaires and interviews that rely on self-report of both body-related concerns and eating-related behaviors. While some key components of eating disorders are psychological and thus introspective in nature, reliance on self-report for the assessment of eating-related behaviors and nutritional status lacks the objectivity that a physiologically based measure could provide. The development of a more physiologically informed diagnosis for AN and BN would provide a more objective means of diagnosing these disorders, provide a sound physiological basis for diagnosing subclinical disorders and could also aid in monitoring the effectiveness of treatments for these disorders. Empirically supported, physiologically based methods for diagnosing AN and BN are reviewed herein as well as promising physiological measures that may potentially be used in the diagnosis of AN and BN.

  12. Controlling intake of uranium in the workplace: Applications of biokinetic modeling and occupational monitoring data

    Energy Technology Data Exchange (ETDEWEB)

    Leggett, Richard Wayne [ORNL; Eckerman, Keith F [ORNL; McGinn, Wilson [ORNL; Meck, Dr. Robert A. [U.S. Nuclear Regulatory Commission

    2012-01-01

    This report provides methods for interpreting and applying occupational uranium monitoring data. The methods are based on current international radiation protection guidance, current information on the chemical toxicity of uranium, and best available biokinetic models for uranium. Emphasis is on air monitoring data and three types of bioassay data: the concentration of uranium in urine; the concentration of uranium in feces; and the externally measured content of uranium in the chest. Primary Reference guidance levels for prevention of chemical effects and limitation of radiation effects are selected based on a review of current scientific data and regulatory principles for setting standards. Generic investigation levels and immediate action levels are then defined in terms of these primary guidance levels. The generic investigation and immediate actions levels are stated in terms of radiation dose and concentration of uranium in the kidneys. These are not directly measurable quantities, but models can be used to relate the generic levels to the concentration of uranium in air, urine, or feces, or the total uranium activity in the chest. Default investigation and immediate action levels for uranium in air, urine, feces, and chest are recommended for situations in which there is little information on the form of uranium taken into the body. Methods are prescribed also for deriving case-specific investigation and immediate action levels for uranium in air, urine, feces, and chest when there is sufficient information on the form of uranium to narrow the range of predictions of accumulation of uranium in the main target organs for uranium: kidneys for chemical effects and lungs for radiological effects. In addition, methods for using the information herein for alternative guidance levels, different from the ones selected for this report, are described.

  13. Performance analysis of numeric solutions applied to biokinetics of radionuclides; Analise de desempenho de solucoes numericas aplicadas a biocinetica de radionuclideos

    Energy Technology Data Exchange (ETDEWEB)

    Mingatos, Danielle dos Santos; Bevilacqua, Joyce da Silva, E-mail: dani@ime.usp.br, E-mail: joyce@ime.usp.br [Universidade de Sao Paulo (IME/USP), SP (Brazil). Instituto de Matematica e Estatistica; Todo, Alberto Saburo; Rodrigues Junior, Orlando, E-mail: astodo@ipen.br, E-mail: rodrijr@ipen.br [Instituto de Pesquisas Energeticas Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2013-07-01

    Biokinetics models for radionuclides applied to dosimetry problems are constantly reviewed by ICRP. The radionuclide trajectory could be represented by compartmental models, assuming constant transfer rates between compartments. A better understanding of physiological or biochemical phenomena, improve the comprehension of radionuclide behavior in the human body and, in general, more complex compartmental models are proposed, increasing the difficulty of obtaining the analytical solution for the system of first order differential equations. Even with constant transfer rates numerical solutions must be carefully implemented because of almost singular characteristic of the matrix of coefficients. In this work we compare numerical methods with different strategies for ICRP-78 models for Thorium-228 and Uranium-234. The impact of uncertainty in the parameters of the equations is also estimated for local and global truncation errors. (author)

  14. Biokinetic and dosimetric modelling in the estimation of radiation risks from internal emitters.

    Science.gov (United States)

    Harrison, John

    2009-06-01

    The International Commission on Radiological Protection (ICRP) has developed biokinetic and dosimetric models that enable the calculation of organ and tissue doses for a wide range of radionuclides. These are used to calculate equivalent and effective dose coefficients (dose in Sv Bq(-1) intake), considering occupational and environmental exposures. Dose coefficients have also been given for a range of radiopharmaceuticals used in diagnostic medicine. Using equivalent and effective dose, exposures from external sources and from different radionuclides can be summed for comparison with dose limits, constraints and reference levels that relate to risks from whole-body radiation exposure. Risk estimates are derived largely from follow-up studies of the survivors of the atomic bombings at Hiroshima and Nagasaki in 1945. New dose coefficients will be required following the publication in 2007 of new ICRP recommendations. ICRP biokinetic and dosimetric models are subject to continuing review and improvement, although it is arguable that the degree of sophistication of some of the most recent models is greater than required for the calculation of effective dose to a reference person for the purposes of regulatory control. However, the models are also used in the calculation of best estimates of doses and risks to individuals, in epidemiological studies and to determine probability of cancer causation. Models are then adjusted to best fit the characteristics of the individuals and population under consideration. For example, doses resulting from massive discharges of strontium-90 and other radionuclides to the Techa River from the Russian Mayak plutonium plant in the early years of its operation are being estimated using models adapted to take account of measurements on local residents and other population-specific data. Best estimates of doses to haemopoietic bone marrow, in utero and postnatally, are being used in epidemiological studies of radiation-induced leukaemia

  15. Quantitative biokinetics of titanium dioxide nanoparticles after oral application in rats: Part 2.

    Science.gov (United States)

    Kreyling, Wolfgang G; Holzwarth, Uwe; Schleh, Carsten; Kozempel, Ján; Wenk, Alexander; Haberl, Nadine; Hirn, Stephanie; Schäffler, Martin; Lipka, Jens; Semmler-Behnke, Manuela; Gibson, Neil

    2017-05-01

    The biokinetics of a size-selected fraction (70 nm median size) of commercially available and (48)V-radiolabeled [(48)V]TiO2 nanoparticles has been investigated in female Wistar-Kyoto rats at retention timepoints 1 h, 4 h, 24 h and 7 days after oral application of a single dose of an aqueous [(48)V]TiO2-nanoparticle suspension by intra-esophageal instillation. A completely balanced quantitative body clearance and biokinetics in all organs and tissues was obtained by applying typical [(48)V]TiO2-nanoparticle doses in the range of 30-80 μg•kg(-1) bodyweight, making use of the high sensitivity of the radiotracer technique. The [(48)V]TiO2-nanoparticle content was corrected for nanoparticles in the residual blood retained in organs and tissue after exsanguination and for (48)V-ions not bound to TiO2-nanoparticles. Beyond predominant fecal excretion about 0.6% of the administered dose passed the gastro-intestinal-barrier after one hour and about 0.05% were still distributed in the body after 7 days, with quantifiable [(48)V]TiO2-nanoparticle organ concentrations present in liver (0.09 ng•g(-1)), lungs (0.10 ng•g(-1)), kidneys (0.29 ng•g(-1)), brain (0.36 ng•g(-1)), spleen (0.45 ng•g(-1)), uterus (0.55 ng•g(-1)) and skeleton (0.98 ng•g(-1)). Since chronic, oral uptake of TiO2 particles (including a nano-fraction) by consumers has continuously increased in the past decades, the possibility of chronic accumulation of such biopersistent nanoparticles in secondary organs and the skeleton raises questions about the responsiveness of their defense capacities, and whether these could be leading to adverse health effects in the population at large. After normalizing the fractions of retained [(48)V]TiO2-nanoparticles to the fraction that passed the gastro-intestinal-barrier and reached systemic circulation, the biokinetics was compared to the biokinetics determined after IV-injection (Part 1). Since the biokinetics patterns differ

  16. Nanoparticle-based capillary electroseparation of proteins in polymer capillaries under physiological conditions

    DEFF Research Database (Denmark)

    Nilsson, C.; Harwigsson, I.; Becker, K.

    2010-01-01

    Totally porous lipid-based liquid crystalline nanoparticles were used as pseudostationary phase for capillary electroseparation with LIF detection of proteins at physiological conditions using unmodified cyclic olefin copolymer capillaries (Topas (R), 6.7 cm effective length). In the absence...... at protein friendly conditions. The developed capillary-based method facilitates future electrochromatography of proteins on polymer-based microchips under physiological conditions and enables the initial optimization of separation conditions in parallel to the chip development....

  17. Mechanism of cisplatin proximal tubule toxicity revealed by integrating transcriptomics, proteomics, metabolomics and biokinetics.

    Science.gov (United States)

    Wilmes, Anja; Bielow, Chris; Ranninger, Christina; Bellwon, Patricia; Aschauer, Lydia; Limonciel, Alice; Chassaigne, Hubert; Kristl, Theresa; Aiche, Stephan; Huber, Christian G; Guillou, Claude; Hewitt, Philipp; Leonard, Martin O; Dekant, Wolfgang; Bois, Frederic; Jennings, Paul

    2015-12-25

    Cisplatin is one of the most widely used chemotherapeutic agents for the treatment of solid tumours. The major dose-limiting factor is nephrotoxicity, in particular in the proximal tubule. Here, we use an integrated omics approach, including transcriptomics, proteomics and metabolomics coupled to biokinetics to identify cell stress response pathways induced by cisplatin. The human renal proximal tubular cell line RPTEC/TERT1 was treated with sub-cytotoxic concentrations of cisplatin (0.5 and 2 μM) in a daily repeat dose treating regime for up to 14 days. Biokinetic analysis showed that cisplatin was taken up from the basolateral compartment, transported to the apical compartment, and accumulated in cells over time. This is in line with basolateral uptake of cisplatin via organic cation transporter 2 and bioactivation via gamma-glutamyl transpeptidase located on the apical side of proximal tubular cells. Cisplatin affected several pathways including, p53 signalling, Nrf2 mediated oxidative stress response, mitochondrial processes, mTOR and AMPK signalling. In addition, we identified novel pathways changed by cisplatin, including eIF2 signalling, actin nucleation via the ARP/WASP complex and regulation of cell polarization. In conclusion, using an integrated omic approach together with biokinetics we have identified both novel and established mechanisms of cisplatin toxicity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. A physiologically based in silico kinetic model predicting plasma cholesterol concentrations in humans

    NARCIS (Netherlands)

    Pas, van de N.C.A.; Woutersen, R.A.; Ommen, van B.; Rietjens, I.M.C.M.; Graaf, de A.A.

    2012-01-01

    Increased plasma cholesterol concentration is associated with increased risk of cardiovascular disease. This study describes the development, validation, and analysis of a physiologically based kinetic (PBK) model for the prediction of plasma cholesterol concentrations in humans. This model was dire

  19. A physiologically based in silico kinetic model predicting plasma cholesterol concentrations in humans

    NARCIS (Netherlands)

    Pas, N.C.A. van de; Woutersen, R.A.; Ommen, B. van; Rietjens, I.M.C.M.; Graaf, A.A. de

    2012-01-01

    Increased plasma cholesterol concentration is associated with increased risk of cardiovascular disease. This study describes the development, validation, and analysis of a physiologically based kinetic (PBK) model for the prediction of plasma cholesterol concentrations in humans. This model was

  20. A Cusum-based multilevel alerting method for physiological monitoring.

    Science.gov (United States)

    Yang, Ping; Dumont, Guy; Ansermino, J Mark

    2010-07-01

    Alerting systems used by current physiological monitors are designed to detect changes in the levels of vital signs, but they tend to be very sensitive to artifacts. This paper proposes a method to detect changes in the direction of trend and generate multilevel alerts according to the statistical significance of the detection. One-point-ahead signal predictions are calculated by averaging the historical data with the weights decreasing in the past. The two-sided cumulative sums (Cusum) of the prediction errors are tested against multiple thresholds to detect change points with two levels of certainty. The temporal shapes of the detected changes are analyzed using heuristics to determine whether to trigger an alert. The method was tested offline using 20 cases collected during surgery at a local hospital. The detection results were evaluated by two experienced anesthesiologists. The direction of trend was correctly detected in 90.2% of the annotated changes for end-tidal carbon dioxide, 89.4% for expiratory minute volume, 91.8% for peak airway pressure, and 95.4% for noninvasive blood pressure. The certainty levels of the true-positive alerts estimated by the algorithm have a high ratio of agreement with the anesthesiologists' evaluations.

  1. Physiologically based toxicokinetic modeling of secondary acute myelolytic leukemia.

    Science.gov (United States)

    Mukhopadhyay, Manas Kumar; Nath, Debjani

    2014-01-01

    Benzene, designated as environmental and occupational carcinogen and hematotoxin, has been associated with secondary leukemia. To develop a toxicokinetic model of AML, benzene can be used as leukemogenic agent. The aim of the present study was to optimize the dose, period and time of cumulative benzene exposure of Swiss Albino mice and to analyze survival rate; alteration in cell cycle regulation and other clinical manifestations in mice exposed to benzene vapour at a dose 300 ppm × 6 h/day × 5 days/week for 2 weeks, i.e., 9000(a)ppm cumulative dose. Analyzing physiological parameters like plasma enzyme profile, complete hematology (Hb %, RBC indices and WBC differentials), hematopoietic cells morphology, expression of cell cycle regulatory proteins, tissue histology and analysis of DNA fragmentation, optimum conditions were established. Down regulation of p53 and p21 and up regulation of CDK2, CDK4, CDK6, cyclin D1 and E in this exposed group were marked as the optimum conditions of cellular deregulation for the development of secondary AML. Elevated level of Plasma AST/ALT with corresponding changes in liver histology showing extended sinusoids within the hepatocytic cell cords in optimally exposed animals also confirmed the toxicokinetic relation of benzene with leukemia. It can be concluded from the above observations that the 9000(a)ppm exposed animals can serve as the induced laboratory model of secondary acute myeloid leukemia.

  2. Anatomy and physiology for nursing students: is problem-based learning effective?

    Science.gov (United States)

    Mayner, Lidia; Gillham, David; Sansoni, Julita

    2013-01-01

    This study investigated whether problem-based learning (PBL) was an effective strategy for nursing students learning anatomy and physiology. Anatomy and physiology are subject areas that have posed long standing difficulty for nursing students. Since anatomy and physiology underpin clinical decision making it is important that nursing students are able to understand and retain this knowledge and apply it to practice. Problem-based learning offers potential advantages for teaching anatomy and physiology as clinical cases can provide the impetus for student problem solving. This project trialled a simple PBL scenario and investigated students' response to the task of problem solving in a laboratory setting adapted to simulate a hospital ward. The study found students learn better, retain the knowledge and merge theory with simulated practice when a PBL teaching mode is used. While PBL was effective, blended, web based and hybrid PBL models warrant investigation.

  3. Gestation-Specific Changes in the Anatomy and Physiology of Healthy Pregnant Women: An Extended Repository of Model Parameters for Physiologically Based Pharmacokinetic Modeling in Pregnancy.

    Science.gov (United States)

    Dallmann, André; Ince, Ibrahim; Meyer, Michaela; Willmann, Stefan; Eissing, Thomas; Hempel, Georg

    2017-04-11

    In the past years, several repositories for anatomical and physiological parameters required for physiologically based pharmacokinetic modeling in pregnant women have been published. While providing a good basis, some important aspects can be further detailed. For example, they did not account for the variability associated with parameters or were lacking key parameters necessary for developing more detailed mechanistic pregnancy physiologically based pharmacokinetic models, such as the composition of pregnancy-specific tissues. The aim of this meta-analysis was to provide an updated and extended database of anatomical and physiological parameters in healthy pregnant women that also accounts for changes in the variability of a parameter throughout gestation and for the composition of pregnancy-specific tissues. A systematic literature search was carried out to collect study data on pregnancy-related changes of anatomical and physiological parameters. For each parameter, a set of mathematical functions was fitted to the data and to the standard deviation observed among the data. The best performing functions were selected based on numerical and visual diagnostics as well as based on physiological plausibility. The literature search yielded 473 studies, 302 of which met the criteria to be further analyzed and compiled in a database. In total, the database encompassed 7729 data. Although the availability of quantitative data for some parameters remained limited, mathematical functions could be generated for many important parameters. Gaps were filled based on qualitative knowledge and based on physiologically plausible assumptions. The presented results facilitate the integration of pregnancy-dependent changes in anatomy and physiology into mechanistic population physiologically based pharmacokinetic models. Such models can ultimately provide a valuable tool to investigate the pharmacokinetics during pregnancy in silico and support informed decision making regarding

  4. Physiological acoustic sensing based on accelerometers: a survey for mobile healthcare.

    Science.gov (United States)

    Hu, Yating; Kim, Eric Guorui; Cao, Gang; Liu, Sheng; Xu, Yong

    2014-11-01

    This paper reviews the applications of accelerometers on the detection of physiological acoustic signals such as heart sounds, respiratory sounds, and gastrointestinal sounds. These acoustic signals contain a rich reservoir of vital physiological and pathological information. Accelerometer-based systems enable continuous, mobile, low-cost, and unobtrusive monitoring of physiological acoustic signals and thus can play significant roles in the emerging mobile healthcare. In this review, we first briefly explain the operation principle of accelerometers and specifications that are important for mobile healthcare. Applications of accelerometer-based monitoring systems are then presented. Next, we review a variety of accelerometers which have been reported in literatures for physiological acoustic sensing, including both commercial products and research prototypes. Finally, we discuss some challenges and our vision for future development.

  5. Exercise in Inquiry: Critical Thinking in an Inquiry-Based Exercise Physiology Laboratory Course.

    Science.gov (United States)

    DiPasquale, Dana M.; Mason, Cheryl L.; Kolkhorst, Fred W.

    2003-01-01

    Describes an inquiry-based teaching method implemented in an undergraduate exercise physiology laboratory course. Indicates students' strong, positive feelings about the inquiry-based teaching method and shows that inquiry-based learning results in a higher order of learning not typically observed in traditional style classes. This teaching method…

  6. Distinctive microbial ecology and biokinetics of autotrophic ammonia and nitrite oxidation in a partial nitrification bioreactor.

    Science.gov (United States)

    Ahn, Joon Ho; Yu, Ran; Chandran, Kartik

    2008-08-15

    Biological nitrogen removal (BNR) based on partial nitrification and denitrification via nitrite is a cost-effective alternate to conventional nitrification and denitrification (via nitrate). The goal of this study was to investigate the microbial ecology, biokinetics, and stability of partial nitrification. Stable long-term partial nitrification resulting in 82.1 +/- 17.2% ammonia oxidation, primarily to nitrite (77.3 +/- 19.5% of the ammonia oxidized) was achieved in a lab-scale bioreactor by operation at a pH, dissolved oxygen and solids retention time of 7.5 +/- 0.1, 1.54 +/- 0.87 mg O(2)/L, and 3.0 days, respectively. Bioreactor ammonia oxidizing bacteria (AOB) and nitrite oxidizing bacteria (NOB) populations were most closely related to Nitrosomonas europaea and Nitrobacter spp., respectively. The AOB population fraction varied in the range 61 +/- 45% and was much higher than the NOB fraction, 0.71 +/- 1.1%. Using direct measures of bacterial concentrations in conjunction with independent activity measures and mass balances, the maximum specific growth rate (micro(max)), specific decay (b) and observed biomass yield coefficients (Y(obs)) for AOB were 1.08 +/- 1.03 day(-1), 0.32 +/- 0.34 day(-1), and 0.15 +/- 0.06 mg biomass COD/mg N oxidized, respectively. Corresponding micro(max), b, and Y(obs) values for NOB were 2.6 +/- 2.05 day(-1), 1.7 +/- 1.9 day(-1), and 0.04 +/- 0.02 mg biomass COD/mg N oxidized, respectively. The results of this study demonstrate that the highly selective partial nitrification operating conditions enriched for a narrow diversity of rapidly growing AOB and NOB populations unlike conventional BNR reactors, which host a broader diversity of nitrifying bacteria. Further, direct measures of microbial abundance enabled not only elucidation of mixed community microbial ecology but also estimation of key engineering parameters describing bioreactor systems supporting these communities. 2008 Wiley Periodicals, Inc.

  7. A comprehensive physiologically based pharmacokinetic knowledgebase and web-based interface for rapid model ranking and querying

    Science.gov (United States)

    Published physiologically based pharmacokinetic (PBPK) models from peer-reviewed articles are often well-parameterized, thoroughly-vetted, and can be utilized as excellent resources for the construction of models pertaining to related chemicals. Specifically, chemical-specific pa...

  8. Implementation of iodine biokinetic model for interpreting I-131 contamination in breast milk after the Fukushima nuclear disaster

    Science.gov (United States)

    Tani, Kotaro; Kurihara, Osamu; Kim, Eunjoo; Yoshida, Satoshi; Sakai, Kazuo; Akashi, Makoto

    2015-07-01

    After the accident at the Fukushima Daiichi Nuclear Power Plant run by Tokyo Electric Power Company in 2011, breast milk samples obtained from volunteers living in Fukushima and neighboring prefectures were examined and small amounts of I-131 (2.2-36.3 Bq/kg) were detected in some samples. In this work, the I-131 concentrations in breast milk from nursing mothers in Ibaraki prefecture were calculated based on the iodine biokinetic model during lactation together with time-variable intake scenarios by inhalation of ambient air and ingestion of tap water, using the authors’ code. The calculated I-131 concentrations in breast milk generally agreed with those measured for the volunteers. Based on the results, thyroid equivalent doses to breast-fed infants were estimated for each place of residence of the volunteers on the assumption that these infants consumed 800 ml of breast milk every day, resulting in 10-11 mSv for Mito and Kasama cities and 1.1-1.8 mSv for Tsukuba and Moriya cities. It was suggested that breast milk consumption could be a major contributor to internal dose of breast-fed infants in areas with mild I-131 pollution; however, further studies considering personal behavior surveys would be necessary to estimate individual doses.

  9. Proposal of a new biokinetic model for niobium; Proposta de um novo modelo biocinetico para o niobio

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Roges

    2006-07-01

    There are two niobium isotopes generated in nuclear power plants: 95 Nb and 94 Nb. Workers and members of the public are subjects to intake these radionuclides in accident situation. For dose calculation purpose, it is very important to develop a model that describes in a more realistic way the kinetics of niobium inside of the human body. Presently the model adopted by ICRP (ICRP, 1989) is based on animal studies and describes the behavior of niobium in human being in a simple manner. The new model proposal describes the kinetics of the niobium from the intake into the blood until the excretion, doing this in a more realistic form and considering not only data from animals but data from human beings as well. For this objective, a workers group of a niobium extraction and processing industry exposed to stable niobium (93 Nb) in oxide insoluble form with associated uranium, was monitored for uranium and niobium determination in urinary and fecal excretion, by mass spectrometry. Based in the ratios of the niobium concentration in urinary and faecal excretion of this workers and animal data study, a new biokinetic model for niobium was proposed, with the followings modifications relative to ICRP model: a new compartment that represents muscular tissue; the fractions which are deposited into the compartment are modified; a third component in the retention equation of the bone tissue; introduction of recirculation between organs and blood. The new model was applied for a case of accidental intake and described adequately the experimental data.

  10. A physiologically based pharmacokinetic (PB-PK) model for ethylene dibromide; relevance of extrahepatic metabolism

    NARCIS (Netherlands)

    Hissink, A.M.; Wormhoudt, L.W.; Sherratt, P.J.; Hayes, J.D.; Commandeur, J.N.M.; Vermeulen, N.P.E.; Bladeren, van P.J.

    2000-01-01

    A physiologically-based pharmacokinetic (PB-PK) model was developed for ethylene dibromide (1,2-dibromoethane, EDB) for rats and humans, partly based on previously published in vitro data (Ploemen et al., 1997). In the present study, this PB-PK model has been validated for the rat. In addition, new

  11. Predicting individual responses to pravastatin using a physiologically based kinetic model for plasma cholesterol concentrations

    NARCIS (Netherlands)

    Pas, N.C.A. van de; Rullmann, J.A.C.; Woutersen, R.A.; Ommen, B. van; Rietjens, I.M.C.M.; Graaf, A.A. de

    2014-01-01

    We used a previously developed physiologically based kinetic (PBK) model to analyze the effect of individual variations in metabolism and transport of cholesterol on pravastatin response. The PBK model is based on kinetic expressions for 21 reactions that interconnect eight different body

  12. 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

  13. Challenges of Teaching Physiology in an Integrated System-Based Curriculum

    OpenAIRE

    Hasan, Zuheir; Sequeira, Reginald

    2012-01-01

    The transformation of a traditional discipline-based medical curriculum into a system-based integrated curriculum often poses dilemmas to faculty involved in teaching basic medical sciences. This paper examines the challenges of teaching physiology to medical students in a system-based curriculum. Some of these challenges include: defining the core curriculum, curriculum links, sequencing curriculum content, interdisciplinary integration, and student assessment. A number of relevant issues in...

  14. Biokinetics and biotransformation of DDTs in the marine green mussels Perna viridis.

    Science.gov (United States)

    Kwong, Raymond W M; Yu, Peter K N; Lam, Paul K S; Wang, Wen-Xiong

    2009-07-26

    The biokinetics of p,p'-dichlorodiphenyltrichloroethane (DDT) and its metabolites, p,p'-dichlorodiphenydichloroethylene (DDE) and p,p'-dichlorodiphenyldichloroethane (DDD), in the green-lipped mussel Perna viridis were characterized in this study. We exposed the mussels to DDT in aqueous or dietary sources and then compared and evaluated the absorption, accumulation, distribution and elimination of DDT and its metabolites (DDD and DDE) in the mussels. In addition, a dynamic model was employed to quantify the depuration kinetics of each DDT compound in various organs of the mussels. The potential biotransformation pathway in the mussels after dietary exposure to DDT was also analyzed. Differing accumulation and elimination patterns of each DDT compound (DDT, DDD and DDE) in various organs were observed. Most of the DDT was confined to the hepatopancreas following either aqueous or dietary exposure, although the biological fate and biokinetics of DDT were differed significantly between routes of exposure. In addition, the elimination of dietary DDT was markedly slower than that following aqueous uptake. The biotransformation of DDT to DDE was rare in the mussels, suggesting that any DDE in the mussels came primarily from the ambient environment instead of through biotransformation process. Nevertheless, DDE may be retained in the mussels because of its exceptionally low elimination rate. In contrast, DDT was biotransformed to DDD in the mussels following dietary uptake, and this biotransformation may facilitate DDT elimination from the mussels.

  15. Uranium: biokinetics and toxicity; Biocinetique et toxicite de l'uranium

    Energy Technology Data Exchange (ETDEWEB)

    Menetrier, F.; Renaud-Salis, V.; Flury-Herard, A

    2000-07-01

    This report was achieved as a part of a collaboration with the Fuel Cycle Direction. Its aim was to give the state of the art about: the behaviour of uranium in the human organism (biokinetics) after ingestion, its toxicity (mainly renal) and the current regulation about its incorporation. Both in the upstream and in the downstream of the fuel cycle, uranium remains, quantitatively, the first element in the cycle which is, at the present time, temporarily disposed or recycled. Such a considerable quantity of uranium sets the problem of its risk on the health. In the long term, the biosphere may be affected and consequently the public may ingest water or food contaminated with uranium. In this way, radiological and chemical toxicity risk may be activated. This report emphasizes: the necessity of confirming some experimental and epidemiological biokinetic data used or not in the ICRP models. Unsolved questions remain about the gastrointestinal absorption according to chemical form (valency state, mixtures...), mass and individual variations (age, disease) further a chronic ingestion of uranium. It is well established that uranium is mainly deposited in the skeleton and the kidney. But the skeleton kinetics following a chronic ingestion and especially in some diseases has to be more elucidated; the necessity of taking into account uranium at first as a chemical toxic, essentially in the kidney and determining the threshold of functional lesion. In this way, it is important to look for some specific markers; the problem of not considering chemical toxicity of uranium in the texts regulating its incorporation.

  16. Physiologically Based Modelling of Dioxins. I. Validation of a rodent toxicokinetic model

    NARCIS (Netherlands)

    Zeilmaker MJ; Slob W

    1993-01-01

    In this report a rodent Physiologically Based PharmacoKinetic (PBPK) model for 2,3,7,8-tetrachlorodibenzodioxin is described. Validation studies, in which model simulations of TCDD disposition were compared with in vivo TCDD disposition in rodents exposed to TCDD, showed that the model adequately p

  17. DEVELOPMENT OF A PHYSIOLOGICALLY BASED PHARMACOKINETIC MODEL FOR DELTAMETHRIN IN DEVELOPING SPRAGUE-DAWLEY RATS

    Science.gov (United States)

    This work describes the development of a physiologically based pharmacokinetic (PBPK) model of deltamethrin, a type II pyrethroid, in the developing male Sprague-Dawley rat. Generalized Michaelis-Menten equations were used to calculate metabolic rate constants and organ weights ...

  18. Interactive Computer-Assisted Instruction in Acid-Base Physiology for Mobile Computer Platforms

    Science.gov (United States)

    Longmuir, Kenneth J.

    2014-01-01

    In this project, the traditional lecture hall presentation of acid-base physiology in the first-year medical school curriculum was replaced by interactive, computer-assisted instruction designed primarily for the iPad and other mobile computer platforms. Three learning modules were developed, each with ~20 screens of information, on the subjects…

  19. Effectiveness of Inquiry-Based Learning in an Undergraduate Exercise Physiology Course

    Science.gov (United States)

    Nybo, Lars; May, Michael

    2015-01-01

    The present study was conducted to investigate the effects of changing a laboratory physiology course for undergraduate students from a traditional step-by-step guided structure to an inquiry-based approach. With this aim in mind, quantitative and qualitative evaluations of learning outcomes (individual subject-specific tests and group interviews)…

  20. Predicting dopamine D2 receptor occupancy in humans using a physiology-based approach

    NARCIS (Netherlands)

    Johnson, Martin; Kozielska, Magdalena; Pilla Reddy, Venkatesh; Vermeulen, An; Barton, Hugh A.; Grimwood, Sarah; de Greef, Rik; Groothuis, Genoveva; Danhof, Meindert; Proost, Johannes

    2011-01-01

    Objectives: A hybrid physiology-based pharmacokinetic and pharmacodynamic model (PBPKPD) was used to predict the time course of dopamine receptor occupancy (D2RO) in human striatum following the administration of antipsychotic (AP) drugs, using in vitro and in silico information. Methods: A hybrid P

  1. A physiological foundation for the nutrition-based efficiency wage model

    DEFF Research Database (Denmark)

    Dalgaard, Carl-Johan Lars; Strulik, Holger

    2011-01-01

    . By extending the model with respect to heterogeneity in worker body size and a physiologically founded impact of body size on productivity, we demonstrate that the nutrition-based efficiency wage model is compatible with the empirical regularity that taller workers simultaneously earn higher wages and are less...

  2. Interactive Computer-Assisted Instruction in Acid-Base Physiology for Mobile Computer Platforms

    Science.gov (United States)

    Longmuir, Kenneth J.

    2014-01-01

    In this project, the traditional lecture hall presentation of acid-base physiology in the first-year medical school curriculum was replaced by interactive, computer-assisted instruction designed primarily for the iPad and other mobile computer platforms. Three learning modules were developed, each with ~20 screens of information, on the subjects…

  3. Assessing interactions among multiple physiological systems during walking outside a laboratory: An Android based gait monitor.

    Science.gov (United States)

    Sejdić, E; Millecamps, A; Teoli, J; Rothfuss, M A; Franconi, N G; Perera, S; Jones, A K; Brach, J S; Mickle, M H

    2015-12-01

    Gait function is traditionally assessed using well-lit, unobstructed walkways with minimal distractions. In patients with subclinical physiological abnormalities, these conditions may not provide enough stress on their ability to adapt to walking. The introduction of challenging walking conditions in gait can induce responses in physiological systems in addition to the locomotor system. There is a need for a device that is capable of monitoring multiple physiological systems in various walking conditions. To address this need, an Android-based gait-monitoring device was developed that enabled the recording of a patient's physiological systems during walking. The gait-monitoring device was tested during self-regulated overground walking sessions of fifteen healthy subjects that included 6 females and 9 males aged 18-35 years. The gait-monitoring device measures the patient's stride interval, acceleration, electrocardiogram, skin conductance and respiratory rate. The data is stored on an Android phone and is analyzed offline through the extraction of features in the time, frequency and time-frequency domains. The analysis of the data depicted multisystem physiological interactions during overground walking in healthy subjects. These interactions included locomotion-electrodermal, locomotion-respiratory and cardiolocomotion couplings. The current results depicting strong interactions between the locomotion system and the other considered systems (i.e., electrodermal, respiratory and cardiovascular systems) warrant further investigation into multisystem interactions during walking, particularly in challenging walking conditions with older adults.

  4. Physiological sensor signals classification for healthcare using sensor data fusion and case-based reasoning.

    Science.gov (United States)

    Begum, Shahina; Barua, Shaibal; Ahmed, Mobyen Uddin

    2014-07-03

    Today, clinicians often do diagnosis and classification of diseases based on information collected from several physiological sensor signals. However, sensor signal could easily be vulnerable to uncertain noises or interferences and due to large individual variations sensitivity to different physiological sensors could also vary. Therefore, multiple sensor signal fusion is valuable to provide more robust and reliable decision. This paper demonstrates a physiological sensor signal classification approach using sensor signal fusion and case-based reasoning. The proposed approach has been evaluated to classify Stressed or Relaxed individuals using sensor data fusion. Physiological sensor signals i.e., Heart Rate (HR), Finger Temperature (FT), Respiration Rate (RR), Carbon dioxide (CO2) and Oxygen Saturation (SpO2) are collected during the data collection phase. Here, sensor fusion has been done in two different ways: (i) decision-level fusion using features extracted through traditional approaches; and (ii) data-level fusion using features extracted by means of Multivariate Multiscale Entropy (MMSE). Case-Based Reasoning (CBR) is applied for the classification of the signals. The experimental result shows that the proposed system could classify Stressed or Relaxed individual 87.5% accurately compare to an expert in the domain. So, it shows promising result in the psychophysiological domain and could be possible to adapt this approach to other relevant healthcare systems.

  5. Physiological Sensor Signals Classification for Healthcare Using Sensor Data Fusion and Case-Based Reasoning

    Directory of Open Access Journals (Sweden)

    Shahina Begum

    2014-07-01

    Full Text Available Today, clinicians often do diagnosis and classification of diseases based on information collected from several physiological sensor signals. However, sensor signal could easily be vulnerable to uncertain noises or interferences and due to large individual variations sensitivity to different physiological sensors could also vary. Therefore, multiple sensor signal fusion is valuable to provide more robust and reliable decision. This paper demonstrates a physiological sensor signal classification approach using sensor signal fusion and case-based reasoning. The proposed approach has been evaluated to classify Stressed or Relaxed individuals using sensor data fusion. Physiological sensor signals i.e., Heart Rate (HR, Finger Temperature (FT, Respiration Rate (RR, Carbon dioxide (CO2 and Oxygen Saturation (SpO2 are collected during the data collection phase. Here, sensor fusion has been done in two different ways: (i decision-level fusion using features extracted through traditional approaches; and (ii data-level fusion using features extracted by means of Multivariate Multiscale Entropy (MMSE. Case-Based Reasoning (CBR is applied for the classification of the signals. The experimental result shows that the proposed system could classify Stressed or Relaxed individual 87.5% accurately compare to an expert in the domain. So, it shows promising result in the psychophysiological domain and could be possible to adapt this approach to other relevant healthcare systems.

  6. Challenges of Teaching Physiology in an Integrated System-Based Curriculum.

    Science.gov (United States)

    Hasan, Zuheir; Sequeira, Reginald

    2012-01-01

    The transformation of a traditional discipline-based medical curriculum into a system-based integrated curriculum often poses dilemmas to faculty involved in teaching basic medical sciences. This paper examines the challenges of teaching physiology to medical students in a system-based curriculum. Some of these challenges include: defining the core curriculum, curriculum links, sequencing curriculum content, interdisciplinary integration, and student assessment. A number of relevant issues including defining the core physiology content, faculty expertise, and coping and adapting to curriculum transitions are discussed from a personal perspective. For successful implementation of a system-based curriculum and to overcome the challenges, educational issues should be debated in regional and international forums.

  7. Clinical pharmacokinetic/pharmacodynamic and physiologically based pharmacokinetic modeling in new drug development: the capecitabine experience.

    Science.gov (United States)

    Blesch, Karen S; Gieschke, Ronald; Tsukamoto, Yuko; Reigner, Bruno G; Burger, Hans U; Steimer, Jean-Louis

    2003-05-01

    Preclinical studies, along with Phase I, II, and III clinical trials demonstrate the pharmacokinetics, pharmacodynamics, safety and efficacy of a new drug under well controlled circumstances in relatively homogeneous populations. However, these types of studies generally do not answer important questions about variability in specific factors that predict pharmacokinetic and pharmacodynamic (PKPD) activity, in turn affecting safety and efficacy. Semi-physiological and clinical PKPD modeling and simulation offer the possibility of utilizing data obtained in the laboratory and the clinic to make accurate characterizations and predictions of PKPD activity in the target population, based on variability in predictive factors. Capecitabine is an orally administered pro-drug of 5-fluorouracil (5-FU), designed to exploit tissue-specific differences in metabolic enzyme activities in order to enhance efficacy and safety. It undergoes extensive metabolism in multiple physiologic compartments, and presents particular challenges for predicting pharmacokinetic and pharmacodynamic activity in humans. Clinical and physiologically based pharmacokinetic (PBPK) and pharmacodynamic models were developed to characterize the activity of capecitabine and its metabolites, and the clinical consequences under varying physiological conditions such as creatinine clearance or activity of key metabolic enzymes. The results of the modeling investigations were consistent with capecitabine's rational design as a triple pro-drug of 5-FU. This paper reviews and discusses the PKPD and PBPK modeling approaches used in capecitabine development to provide a more thorough understanding of what the key predictors of its PBPK activity are, and how variability in these predictors may affect its PKPD, and ultimately, clinical outcomes.

  8. Development of a Physiologically-Based Pharmacokinetic Model for Preterm Neonates: Evaluation with In Vivo Data.

    Science.gov (United States)

    Claassen, Karina; Thelen, Kirstin; Coboeken, Katrin; Gaub, Thomas; Lippert, Jorg; Allegaert, Karel; Willmann, Stefan

    2015-01-01

    Among pediatric patients, preterm neonates and newborns are the most vulnerable subpopulation. Rapid developmental changes of physiological factors affecting the pharmacokinetics of drug substances in newborns require extreme care in dose and dose regimen decisions. These decisions could be supported by in silico methods such as physiologically-based pharmacokinetic (PBPK) modeling. In a comprehensive literature search, the physiological information of preterm neonates that is required to establish a PBPK model has been summarized and implemented into the database of a generic PBPK software. Physiological parameters include the organ weights and blood flow rates, tissue composition, as well as ontogeny information about metabolic and elimination processes in the liver and kidney. The aim of this work is to evaluate the model's accuracy in predicting the pharmacokinetics following intravenous administration of two model drugs with distinct physicochemical properties and elimination pathways based on earlier reported in vivo data. To this end, PBPK models of amikacin and paracetamol have been set up to predict their plasma levels in preterm neonates. Predicted plasma concentration-time profiles were compared to experimentally obtained in vivo data. For both drugs, plasma concentration time profiles following single and multiple dosing were appropriately predicted for a large range gestational and postnatal ages. In summary, PBPK simulations in preterm neonates appear feasible and might become a useful tool in the future to support dosing decisions in this special patient population.

  9. Biokinetics of plutonium-238 injected in non-human primates

    Science.gov (United States)

    Chelidze, Nino

    Seventeen intravenously injected monkey data were analyzed using PowerBasic and SAAM II softwares. The study was divided into three parts. In the first part SAAM II predictions were compared with those calculated by Birchall algorithm based on the ICRP 67 systemic model for plutonium. In the second part SAAM II simulations were performed and compared for two representations of systemic model for plutonium: the ICRP 67 model and the Leggett model. In the third part, optimization of transfer rates suggested by ICRP 67 and Leggett models were attempted by solving each monkey case independently. The Birchall algorithm and SAAM II predicted values coincide with each other for all data presented: blood, urine and feces. Unfortunately, these predictions do not coincide with the measurement values. Plutonium activity in liver is about 50% of the injected activity. The uptake of plutonium in liver in primates seems to be close to the assumption of equal distribution of 45% plutonium in liver and skeleton in humans. For longer sacrificed monkeys we have prolonged liver retention compared to plutonium liver retention in humans. Pu retention in urine and blood has been simulated based on the ICRP 67 and Leggett models respectively and plotted against the measured data points to acquire the understanding of the models with respect to reality. Pu activity was also evaluated in liver and skeleton at the time of the sacrifice for both models and compared with the autopsy measurements for individual cases. Optimization of transfer rates suggested in the ICRP 67 and Leggett models was attempted. Default transfer rates were varied to improve the fits to the data and predict activities in the liver and skeleton at the time of death has been carried out in SAAM II. Good fits for the individual cases were obtained successfully, however, consistency among parameters from case to case was not observed.

  10. Back to the future! Revisiting the physiological cost of negative work as a team-based activity for exercise physiology students.

    Science.gov (United States)

    Kilgas, Matthew A; Elmer, Steven J

    2017-03-01

    We implemented a team-based activity in our exercise physiology teaching laboratory that was inspired from Abbott et al.'s classic 1952 Journal of Physiology paper titled "The physiological cost of negative work." Abbott et al. connected two bicycles via one chain. One person cycled forward (muscle shortening contractions, positive work) while the other resisted the reverse moving pedals (muscle lengthening contractions, negative work), and the cost of work was compared. This study was the first to link human whole body energetics with isolated muscle force-velocity characteristics. The laboratory activity for our students (n = 35) was designed to reenact Abbott et al.'s experiment, integrate previously learned techniques, and illustrate differences in physiological responses to muscle shortening and lengthening contractions. Students (11-12 students/laboratory section) were split into two teams (positive work vs. negative work). One student from each team volunteered to cycle against the other for ~10 min. The remaining students in each team were tasked with measuring: 1) O2 consumption, 2) heart rate, 3) blood lactate, and 4) perceived exertion. Students discovered that O2 consumption during negative work was about one-half that of positive work and all other physiological parameters were also substantially lower. Muscle lengthening contractions were discussed and applied to rehabilitation and sport training. The majority of students (>90%) agreed or strongly agreed that they stayed engaged during the activity and it improved their understanding of exercise physiology. All students recommended the activity be performed again. This activity was engaging, emphasized teamwork, yielded clear results, was well received, and preserved the history of classic physiological experiments.

  11. A physiologically based, multi-scale model of skeletal muscle structure and function

    Directory of Open Access Journals (Sweden)

    Oliver eRöhrle

    2012-09-01

    Full Text Available Models of skeletal muscle can be classified as phenomenological or biophysical. Phenomenological models predict the muscle's response to a specified input based on experimental measurements. Prominent phenomenological models are the Hill-type muscle models, which have been incorporated into rigid-body modelling frameworks, and three-dimensional continuum-mechanical models. Biophysically based models attempt to predict the muscle's response as emerging from the underlying physiology of the system. In this contribution, the conventional biophysically based modelling methodology is extended to include several structural and functional characteristics of skeletal muscle. The result is a physiologically based, multi-scale skeletal muscle finite element model that is capable of representing detailed, geometrical descriptions of skeletal muscle fibres and their grouping. Together with a well-established model of motor unit recruitment, the electro-physiological behaviour of single muscle fibres within motor units is computed and linked to a continuum-mechanical constitutive law. The bridging between the cellular level and the organ level has been achieved via a multi-scale constitutive law and homogenisation. The effect of homogenisation has been investigated by varying the number of embedded skeletal muscle fibres and/or motor units and computing the resulting exerted muscle forces while applying the same excitatory input. All simulations were conducted using an anatomically realistic finite element model of the Tibialis Anterior muscle. Given the fact that the underlying electro-physiological cellular muscle model is capable of modelling metabolic fatigue effects such as potassium accumulation in the T-tubular space and inorganic phosphate build-up, the proposed framework provides a novel simulation-based way to investigate muscle behaviour ranging from motor unit recruitment to force generation and fatigue.

  12. Ultrasound-based lectures on cardiovascular physiology and reflexes for medical students.

    Science.gov (United States)

    Paganini, M; Rubini, A

    2016-06-01

    Ultrasound has become a widely used diagnostic technique. While its role in patient evaluation is well known, its utility during preclinical courses such as anatomy and physiology is becoming increasingly recognized. The aim of the present study was to assess the feasibility/utility of integrating ultrasound-based sessions into conventional undergraduate medical school programs of physiology of the cardiovascular system and cardiovascular reflexes and to evaluate student perceptions of an ultrasound-based didactic session. Second-year medical students enrolled in the University of Padova attended a didactic session during which basic concepts regarding ultrasound instrumentation, image production, and spatial orientation were presented. Five anatomic sectors (the heart, aorta, neck vessels, inferior vena cava, and femoral veins) were then examined on a volunteer. Student perceptions of the images that were projected, the usefulness of the presentation, and the reproducibility of the experience were assessed at the end of the lecture with an anonymous questionnaire consisting of positive and negative items that were rated using a 5-point Likert scale and with two questions. One hundred eleven students attended the lecture; 99% of them found it very interesting, and none considered it boring or a waste of time. More than 96% thought it helped them to gain a better comprehension of the subject and would recommend it to a colleague. In conclusion, as ultrasound has been found to be a valuable resource for the teaching of physiology of the cardiovascular system and cardiovascular reflexes, efforts should be made to integrate ultrasound sessions into the traditional human physiology curriculum. Copyright © 2016 The American Physiological Society.

  13. Cluster-based analysis for personalized stress evaluation using physiological signals.

    Science.gov (United States)

    Xu, Qianli; Nwe, Tin Lay; Guan, Cuntai

    2015-01-01

    Technology development in wearable sensors and biosignal processing has made it possible to detect human stress from the physiological features. However, the intersubject difference in stress responses presents a major challenge for reliable and accurate stress estimation. This research proposes a novel cluster-based analysis method to measure perceived stress using physiological signals, which accounts for the intersubject differences. The physiological data are collected when human subjects undergo a series of task-rest cycles, incurring varying levels of stress that is indicated by an index of the State Trait Anxiety Inventory. Next, a quantitative measurement of stress is developed by analyzing the physiological features in two steps: 1) a k -means clustering process to divide subjects into different categories (clusters), and 2) cluster-wise stress evaluation using the general regression neural network. Experimental results show a significant improvement in evaluation accuracy as compared to traditional methods without clustering. The proposed method is useful in developing intelligent, personalized products for human stress management.

  14. A review of non-contact, low-cost physiological information measurement based on photoplethysmographic imaging.

    Science.gov (United States)

    Liu, He; Wang, Yadong; Wang, Lei

    2012-01-01

    In recent decades, there has been increasing interest in low-cost, non-contact and pervasive methods for measuring physiological information, such as heart rate (HR), respiratory rate, heart rate variability (HRV) and oxyhemoglobin saturation. The conventional methods including wet adhesive Ag/AgCl electrodes for HR and HRV, the capnograph device for respiratory status and pulse oximetry for oxyhemoglobin saturation provide excellent signals but are expensive, troublesome and inconvenient. A method to monitor physiological information based on photoplethysmographic imaging offers a new means for health monitoring. Blood volume can be indirectly assessed in terms of blood velocity, blood flow rate and blood pressure, which, in turn, can reflect changes in physiological parameters. Changes in blood volume can be determined from the spectra of light reflected from or transmitted through body tissues. Images of an area of the skin surface are consecutively captured with the color camera of a computer or smartphone and, by processing and analyzing the light signals, physiological information such as HR, respiratory rate, HRV and oxyhemoglobin saturation can be acquired. In this paper, we review the latest developments in using photoplethysmographic imaging for non-contact health monitoring and discuss the challenges and future directions for this field.

  15. [Exercise is medicine: development and evidence-based practice in clinical exercise physiology].

    Science.gov (United States)

    Zhou, Shi

    2014-08-01

    It has been well established that appropriate physical activity and exercise play an important role in promotion of health and fitness, prevention of disease and treatment and rehabilitation of health conditions. However, practice based on scientific evidence, in respect of the role and effectiveness of exercise interventions in prevention and treatment of diseases, has only been promoted and implemented in the fields of clinical exercise physiology, public health and medicine in recent years. This brief review provides an introduction of the concept of "Exercise is Medicine", the development and evidence-based practice in Clinical Exercise Physiology, and the role and training of Clinical Exercise Physiologist in the health care system of some other countries.

  16. Matching/Mismatching in Web-Based Learning: A Perspective Based on Cognitive Styles and Physiological Factors

    Science.gov (United States)

    Huang, Yueh-Min; Hwang, Jan-Pan; Chen, Sherry Y.

    2016-01-01

    Cognitive styles have been regarded as a crucial factor that affects the effectiveness of web-based learning (WBL). Previous research indicated that educational settings that match with students' cognitive styles can enhance students' learning performance, which is, however, linked to their emotion. Various physiological signals can be applied to…

  17. Physiologically Based Pharmacokinetic Modeling for 1-Bromopropane in F344 Rats Using Gas Uptake Inhalation Experiments

    OpenAIRE

    2015-01-01

    1-Bromopropane (1-BP) was introduced into the workplace as an alternative to ozone-depleting solvents and increasingly used in manufacturing industry. The potential exposure to 1-BP and the current reports of adverse effects associated with occupational exposure to high levels of 1-BP have increased the need to understand the mechanism of 1-BP toxicity in animal models as a mean of understanding risk in workers. Physiologically based pharmacokinetic (PBPK) model for 1-BP has been developed to...

  18. Fluorescent naphthalene-based benzene tripod for selective recognition of fluoride in physiological condition

    Indian Academy of Sciences (India)

    Barun kumar Datta; Chirantan Kar; Gopal Das

    2015-02-01

    Aluminium complex of a naphthalene-based benzene tripod ligand system has been reported for the selective recognition of fluoride in aqueous medium in physiological condition. The ligand can selectively recognize Al3+ through enhancement in the fluorescence intensity and this in situ formed aluminium complex recognizes fluoride through quenching of fluorescence. The receptor system detects fluoride in nanomolar range. The sensing property was extended for practical utility to sense fluoride in tap water, pond water and river water.

  19. Evaluation of a Physiologically Based Pharmacokinetic (PBPK) Model Used to Develop Health Protective Levels for Trichloroethylene

    Science.gov (United States)

    2017-02-28

    AFRL-RH-WP-TR-2017-0014 EVALUATION OF A PHYSIOLOGICALLY-BASED PHARMACOKINETIC (PBPK) MODEL USED TO DEVELOP HEALTH PROTECTIVE LEVELS FOR...Pharmacokinetic (PBPK) Model Used to Develop Health Protective Levels for Trichloroethylene 5a. CONTRACT NUMBER FA8650-15-2-6608 5b. GRANT...Anita Meyer, Army Corps of Engineers (CEHNC-EMS) and Shannon S. Garcia, AFCEC/CZTE for their efforts to obtain the required funding. The authors also

  20. Physiologically based pharmacokinetic modeling in drug discovery and development: a pharmaceutical industry perspective.

    Science.gov (United States)

    Jones, H M; Chen, Y; Gibson, C; Heimbach, T; Parrott, N; Peters, S A; Snoeys, J; Upreti, V V; Zheng, M; Hall, S D

    2015-03-01

    The application of physiologically based pharmacokinetic (PBPK) modeling has developed rapidly within the pharmaceutical industry and is becoming an integral part of drug discovery and development. In this study, we provide a cross pharmaceutical industry position on "how PBPK modeling can be applied in industry" focusing on the strategies for application of PBPK at different stages, an associated perspective on the confidence and challenges, as well as guidance on interacting with regulatory agencies and internal best practices.

  1. Fluorescence intensity and lifetime-based cyanide sensitive probes for physiological safeguard

    Energy Technology Data Exchange (ETDEWEB)

    Badugu, Ramachandram [Center for Fluorescence Spectroscopy, Department of Biochemistry and Molecular Biology, Medical Biotechnology Center, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD 21201 (United States); Lakowicz, Joseph R. [Center for Fluorescence Spectroscopy, Department of Biochemistry and Molecular Biology, Medical Biotechnology Center, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD 21201 (United States)]. E-mail: lakowicz@cfs.umbi.umd.edu; Geddes, Chris D. [Center for Fluorescence Spectroscopy, Department of Biochemistry and Molecular Biology, Medical Biotechnology Center, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD 21201 (United States) and Institute of Fluorescence and Center for Fluorescence Spectroscopy, Medical Biotechnology Center, University of Maryland Biotechnology Institute, 725 West Lombard Street, Baltimore, MD 21201 (United States)]. E-mail: chris@cfs.umbi.umd.edu

    2004-09-20

    We characterize six new fluorescent probes that show both intensity and lifetime changes in the presence of free uncomplexed aqueous cyanide, allowing for fluorescence based cyanide sensing up to physiological safeguard levels, i.e. <30 {mu}M. One of the probes, m-BMQBA, shows a {approx}15-fold reduction in intensity and a {approx}10% change in mean lifetime at this level. The response of the new probes is based on their ability to bind the cyanide anion through a boronic acid functional group, changing from the neutral form of the boronic acid group R-B(OH){sub 2} to the anionic R-B{sup -}(CN){sub 3} form, a new cyanide binding mechanism which we have recently reported. The presence of an electron deficient quaternary heterocyclic nitrogen nucleus, and the electron rich cyanide bound form, provides for the intensity changes observed. We have determined the disassociation constants of the probes to be in the range {approx}15-84 {mu}M{sup 3}. In addition we have synthesized control compounds which do not contain the boronic acid moiety, allowing for a rationale of the cyanide responses between the probe isomers to be made. The lifetime of the cyanide bound probes are significantly shorter than the free R-B(OH){sub 2} probe forms, providing for the opportunity of lifetime based cyanide sensing up to physiologically lethal levels. Finally, while fluorescent probes containing the boronic acid moiety have earned a well-deserved reputation for monosaccharide sensing, we show that strong bases such as CN{sup -} and OH{sup -} preferentially bind as compared to glucose, enabling the potential use of these probes for cyanide safeguard and determination in physiological fluids, especially given that physiologies do not experience any notable changes in pH.

  2. [Proposal for a physiologic concept of thought based on the results of stereotaxic psychosurgery].

    Science.gov (United States)

    Nádvorník, P; Pogády, J; Bernadic, M

    2003-05-01

    Authors have fifty years long experience with psychostereotactic surgery. On the bases of 209 operations of different types of mentally ill patients, authors built their own physiological conception of the central nervous system function. The new conception is described using block operators of thinking at the level of hypothalamus, limbic system, and neocortex in the hierarchic order. The basic physiological hypothalamic block contains two operators: stimulus evaluation and decision to act. Both operators together form reasonable, objective substantiation of thinking, which is transformed into psychological, subjective description at higher cerebral levels. New operator is added to the block diagram at the level of the limbic system: the choice of response base on experience stored in the high capacity memory. Vast neocortical memory creates a model of the individual world and it enables a new operator to be involved: prediction of the future events. Thinking, originally based on concrete images, is using abstract terms, subjected to the principles of grammar. Physiological basis of thinking enables the convergence of subjective and objective.

  3. Carotenoid maintenance handicap and the physiology of carotenoid-based signalisation of health

    Science.gov (United States)

    Vinkler, Michal; Albrecht, Tomáš

    2010-01-01

    Despite a reasonable scientific interest in sexual selection, the general principles of health signalisation via ornamental traits remain still unresolved in many aspects. This is also true for the mechanism preserving honesty of carotenoid-based signals. Although it is widely accepted that this type of ornamentation reflects an allocation trade-off between the physiological utilisation of carotenoids (mainly in antioxidative processes) and their deposition in ornaments, some recent evidence suggests more complex interactions. Here, we further develop the models currently proposed to explain the honesty of carotenoid-based signalisation of heath status by adding the handicap principle concept regulated by testosterone. We propose that under certain circumstances carotenoids may be dangerous for the organism because they easily transform into toxic cleavage products. When reserves of other protective antioxidants are insufficient, physiological trade-offs may exist between maintenance of carotenoids for ornament expression and their removal from the body. Furthermore, we suggest that testosterone which enhances ornamentation by increasing carotenoid bioavailability may also promote oxidative stress and hence lower antioxidant reserves. The presence of high levels of carotenoids required for high-quality ornament expression may therefore represent a handicap and only individuals in prime health could afford to produce elaborate colourful ornaments. Although further testing is needed, this ‘carotenoid maintenance handicap’ hypothesis may offer a new insight into the physiological aspects of the relationship between carotenoid function, immunity and ornamentation.

  4. Towards a physiological signal-based access solution for a non-verbal adolescent with severe and multiple disabilities.

    Science.gov (United States)

    Memarian, Negar; Blain-Moraes, Stefanie; Chau, Tom

    2014-08-01

    To find physiologically arousing stimuli and labile physiological channels in a non-verbal adolescent with severe and multiple congenital disabilities, who did not have a reliable means of communication. The client was repeatedly presented with visual and audiovisual stimuli, representing variations of six contextual factors over three sessions in a one month period. For each stimulus, reactions were detected in the client's four peripheral autonomic nervous system signals using a rule-based classification algorithm. During the presentation of audiovisual stimuli, the number of physiological reactions significantly differed from that observed in baseline (χ(2) = 3.93, p = 0.0476). Aural stimuli articulated in an unfamiliar voice, and aural stimuli containing anticipatory patterns were also physiologically arousing. Fingertip temperature was the client's most labile physiological signal. The results of this case study suggest that physiological data may complement caregiver acumen in deciphering the reactions of non-verbal clients with severe and multiple disabilities.

  5. Physiologically based pharmacokinetic modeling of PLGA nanoparticles with varied mPEG content

    Directory of Open Access Journals (Sweden)

    Avgoustakis K

    2012-03-01

    Full Text Available Mingguang Li1, Zoi Panagi2, Konstantinos Avgoustakis2, Joshua Reineke11Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA; 2Pharmaceutical Technology Laboratory, Department of Pharmacy, University of Patras, Rion, Patras, GreeceAbstract: Biodistribution of nanoparticles is dependent on their physicochemical properties (such as size, surface charge, and surface hydrophilicity. Clear and systematic understanding of nanoparticle properties' effects on their in vivo performance is of fundamental significance in nanoparticle design, development and optimization for medical applications, and toxicity evaluation. In the present study, a physiologically based pharmacokinetic model was utilized to interpret the effects of nanoparticle properties on previously published biodistribution data. Biodistribution data for five poly(lactic-co-glycolic acid (PLGA nanoparticle formulations prepared with varied content of monomethoxypoly (ethyleneglycol (mPEG (PLGA, PLGA-mPEG256, PLGA-mPEG153, PLGA-mPEG51, PLGA-mPEG34 were collected in mice after intravenous injection. A physiologically based pharmacokinetic model was developed and evaluated to simulate the mass-time profiles of nanoparticle distribution in tissues. In anticipation that the biodistribution of new nanoparticle formulations could be predicted from the physiologically based pharmacokinetic model, multivariate regression analysis was performed to build the relationship between nanoparticle properties (size, zeta potential, and number of PEG molecules per unit surface area and biodistribution parameters. Based on these relationships, characterized physicochemical properties of PLGA-mPEG495 nanoparticles (a sixth formulation were used to calculate (predict biodistribution profiles. For all five initial formulations, the developed model adequately simulates the experimental data indicating that the model is suitable for

  6. PPDB: A Tool for Investigation of Plants Physiology Based on Gene Ontology.

    Science.gov (United States)

    Sharma, Ajay Shiv; Gupta, Hari Om; Prasad, Rajendra

    2015-09-01

    Representing the way forward, from functional genomics and its ontology to functional understanding and physiological model, in a computationally tractable fashion is one of the ongoing challenges faced by computational biology. To tackle the standpoint, we herein feature the applications of contemporary database management to the development of PPDB, a searching and browsing tool for the Plants Physiology Database that is based upon the mining of a large amount of gene ontology data currently available. The working principles and search options associated with the PPDB are publicly available and freely accessible online ( http://www.iitr.ac.in/ajayshiv/ ) through a user-friendly environment generated by means of Drupal-6.24. By knowing that genes are expressed in temporally and spatially characteristic patterns and that their functionally distinct products often reside in specific cellular compartments and may be part of one or more multicomponent complexes, this sort of work is intended to be relevant for investigating the functional relationships of gene products at a system level and, thus, helps us approach to the full physiology.

  7. Physiologically-based pharmacokinetic modeling of renally excreted antiretroviral drugs in pregnant women.

    Science.gov (United States)

    De Sousa Mendes, Maïlys; Hirt, Deborah; Urien, Saik; Valade, Elodie; Bouazza, Naïm; Foissac, Frantz; Blanche, Stephane; Treluyer, Jean-Marc; Benaboud, Sihem

    2015-11-01

    Physiological changes during pregnancy can affect drug disposition. Anticipating these changes will help to maximize drug efficacy and safety in pregnant women. Our objective was to determine if physiologically-based pharmacokinetics (PBPK) can accurately predict changes in the disposition of renally excreted antiretroviral drugs during pregnancy. Whole body PBPK models were developed for three renally excreted antiretroviral drugs, tenofovir (TFV), emtricitabine (FTC) and lamivudine (3TC). To assess the impact of pregnancy on PK, time-varying pregnancy-related physiological parameters available within the p-PBPK Simcyp software package were used. Renal clearance during pregnancy followed glomerular filtration changes with or without alterations in secretion. PK profiles were simulated and compared with observed data, i.e. area under the curves (AUC), peak plasma concentrations (Cmax ) and oral clearances (CL/F). PBPK models successfully predicted TFV, FTC and 3TC disposition for non-pregnant and pregnant populations. Both renal secretion and filtration changed during pregnancy. Changes in renal clearance secretion were related to changes in renal plasma flow. The maximum clearance increases were approximately 30% (TFV 33%, FTC 31%, 3TC 29%). Pregnancy PBPK models are useful tools to quantify a priori the drug exposure changes during pregnancy for renally excreted drugs. These models can be applied to evaluate alternative dosing regimens to optimize drug therapy during pregnancy. © 2015 The British Pharmacological Society.

  8. Calibration of hydrodynamic behavior and biokinetics for TOC removal modeling in biofilm reactors under different hydraulic conditions.

    Science.gov (United States)

    Zeng, Ming; Soric, Audrey; Roche, Nicolas

    2013-09-01

    In this study, total organic carbon (TOC) biodegradation was simulated by GPS-X software in biofilm reactors with carriers of plastic rings and glass beads under different hydraulic conditions. Hydrodynamic model by retention time distribution and biokinetic measurement by in-situ batch test served as two significant parts of model calibration. Experimental results showed that TOC removal efficiency was stable in both media due to the enough height of column, although the actual hydraulic volume changed during the variation of hydraulic condition. Simulated TOC removal efficiencies were close to experimental ones with low theil inequality coefficient values (below 0.15). Compared with glass beads, more TOC was removed in the filter with plastic rings due to the larger actual hydraulic volume and lower half saturation coefficient in spite of its lower maximum specific growth rate of biofilm, which highlighted the importance of calibrating hydrodynamic behavior and biokinetics.

  9. Development of Physiologically Based Pharmacokinetic/Pharmacodynamic Model for Indomethacin Disposition in Pregnancy.

    Directory of Open Access Journals (Sweden)

    Saeed Alqahtani

    Full Text Available Findings of a recent clinical study showed indomethacin has lower plasma levels and higher steady-state apparent clearance in pregnant subjects when compared to those in non-pregnant subjects reported in separate studies. Thus, in the current work we developed a pregnancy physiological based pharmacokinetic/pharmacodynamic (PBPK/PD model for indomethacin to explain the differences in indomethacin pharmacokinetics between pregnancy and non-pregnancy. A whole-body PBPK model with key pregnancy-related physiological changes was developed to characterize indomethacin PK in pregnant women and compare these parameters to those in non-pregnant subjects. Data related to maternal physiological and biological changes were obtained from literature and incorporated into the structural PBPK model that describes non-pregnant PK data. Changes in indomethacin area under the curve (AUC, maximum concentration (Cmax and average steady-state concentration (Cave in pregnant women were predicted. Model-simulated PK profiles were in agreement with observed data. The predicted mean ratio (non-pregnant:second trimester (T2 of indomethacin Cave was 1.6 compared to the observed value of 1.59. In addition, the predicted steady-state apparent clearance (CL/Fss ratio was almost similar to the observed value (0.46 vs. 0.42. Sensitivity analysis suggested changes in CYP2C9 activity, and to a lesser extent UGT2B7, as the primary factor contributing to differences in indomethacin disposition between pregnancy and non-pregnancy. The developed PBPK model which integrates prior physiological knowledge, in vitro and in vivo data, allowed the successful prediction of indomethacin disposition during T2. Our PBPK/PD model suggested a higher indomethacin dosing requirement during pregnancy.

  10. A Bio-Inspired Glucose Controller Based on Pancreatic β-Cell Physiology

    Science.gov (United States)

    Herrero, Pau; Georgiou, Pantelis; Oliver, Nick; Johnston, Desmond G; Toumazou, Christofer

    2012-01-01

    Introduction Control algorithms for closed-loop insulin delivery in type 1 diabetes have been mainly based on control engineering or artificial intelligence techniques. These, however, are not based on the physiology of the pancreas but seek to implement engineering solutions to biology. Developments in mathematical models of the β-cell physiology of the pancreas have described the glucose-induced insulin release from pancreatic β cells at a molecular level. This has facilitated development of a new class of bio-inspired glucose control algorithms that replicate the functionality of the biological pancreas. However, technologies for sensing glucose levels and delivering insulin use the subcutaneous route, which is nonphysiological and introduces some challenges. In this article, a novel glucose controller is presented as part of a bio-inspired artificial pancreas. Methods A mathematical model of β-cell physiology was used as the core of the proposed controller. In order to deal with delays and lack of accuracy introduced by the subcutaneous route, insulin feedback and a gain scheduling strategy were employed. A United States Food and Drug Administration-accepted type 1 diabetes mellitus virtual population was used to validate the presented controller. Results Premeal and postmeal mean ± standard deviation blood glucose levels for the adult and adolescent populations were well within the target range set for the controller [(70, 180) mg/dl], with a percent time in range of 92.8 ± 7.3% for the adults and 83.5 ± 14% for the adolescents. Conclusions This article shows for the first time very good glucose control in a virtual population with type 1 diabetes mellitus using a controller based on a subcellular β-cell model. PMID:22768892

  11. Development of a physiologically based pharmacokinetic model for flunixin in cattle (Bos taurus).

    Science.gov (United States)

    Leavens, Teresa L; Tell, Lisa A; Kissell, Lindsey W; Smith, Geoffrey W; Smith, David J; Wagner, Sarah A; Shelver, Weilin L; Wu, Huali; Baynes, Ronald E; Riviere, Jim E

    2014-01-01

    Frequent violation of flunixin residues in tissues from cattle has been attributed to non-compliance with the USFDA-approved route of administration and withdrawal time. However, the effect of administration route and physiological differences among animals on tissue depletion has not been determined. The objective of this work was to develop a physiologically based pharmacokinetic (PBPK) model to predict plasma, liver and milk concentrations of flunixin in cattle following intravenous (i.v.), intramuscular (i.m.) or subcutaneous (s.c.) administration for use as a tool to determine factors that may affect the withdrawal time. The PBPK model included blood flow-limited distribution in all tissues and elimination in the liver, kidney and milk. Regeneration of parent flunixin due to enterohepatic recirculation and hydrolysis of conjugated metabolites was incorporated in the liver compartment. Values for physiological parameters were obtained from the literature, and partition coefficients for all tissues but liver and kidney were derived empirically. Liver and kidney partition coefficients and elimination parameters were estimated for 14 pharmacokinetic studies (including five crossover studies) from the literature or government sources in which flunixin was administered i.v., i.m. or s.c. Model simulations compared well with data for the matrices following all routes of administration. Influential model parameters included those that may be age or disease-dependent, such as clearance and rate of milk production. Based on the model, route of administration would not affect the estimated days to reach the tolerance concentration (0.125 mg kg(-1)) in the liver of treated cattle. The majority of USDA-reported violative residues in liver were below the upper uncertainty predictions based on estimated parameters, which suggests the need to consider variability due to disease and age in establishing withdrawal intervals for drugs used in food animals. The model predicted

  12. [Development of physiological monitors based on the Zigbee technology for hyperbaric oxygen chambers].

    Science.gov (United States)

    Zheng, Jin-Nuan; Wu, Bao-Ming; Lin, Jin-Zhao; Wang, Qiang

    2008-05-01

    This paper introduces a monitor that can monitor five physiological parameters (ECG, blood pressure, spo2, respiration and temperature) based on Wireless Sensor Networks. The monitor will be applied to hyperbaric oxygen chambers. After acquisition, the signal will be displayed on the LCD screen of the monitor terminal in the cabin. At the same time, the Zigbee RF module will send the signal to the extravehicular guardianship PC terminals. This monitor equipment can realize synchronous real-time monitoring both inside and outside. What's more? A host can also display monitoring data the three monitor terminals collected. Preliminary clinical tests show that the monitors are safe and the monitoring results are satisfactory.

  13. Proposal of fifteen new species of Parasynechococcus based on genomic, physiological and ecological features.

    Science.gov (United States)

    Coutinho, F H; Dutilh, B E; Thompson, C C; Thompson, F L

    2016-12-01

    Members of the recently proposed genus Parasynechococcus (Cyanobacteria) are extremely abundant throughout the global ocean and contribute significantly to global primary productivity. However, the taxonomy of these organisms remains poorly characterized. The aim of this study was to propose a new taxonomic framework for Parasynechococcus based on a genomic taxonomy approach that incorporates genomic, physiological and ecological data. Through in silico DNA-DNA hybridization, average amino acid identity, dinucleotide signatures and phylogenetic reconstruction, a total of 15 species of Parasynechococcus could be delineated. Each species was then described on the basis of their gene content, light and nutrient utilization strategies, geographical distribution patterns throughout the oceans and response to environmental parameters.

  14. A Physiologically-Based Flow Network Model for Hepatic Drug Elimination I: Regular Lattice Lobule Model

    CERN Document Server

    Rezania, Vahid; Coombe, Dennis; Tuszynski, Jack A

    2011-01-01

    We develop a physiologically-based lattice model for the transport and metabolism of drugs in the functional unit of the liver, called the lobule. In contrast to earlier studies, we have emphasized the dominant role of convection in well-vascularized tissue with a given structure. Estimates of convective, diffusive and reaction contributions are given. We have compared drug concentration levels observed exiting the lobule with their predicted detailed distribution inside the lobule, assuming that most often the former is accessible information while the latter is not.

  15. Threshold Research on Highway Length under Typical Landscape Patterns Based on Drivers’ Physiological Performance

    Directory of Open Access Journals (Sweden)

    Xia Zhao

    2015-01-01

    Full Text Available The appropriately landscaped highway scenes may not only help improve road safety and comfort but also help protect ecological environment. Yet there is very little research data on highway length threshold with consideration of distinctive landscape patterns. Against this backdrop, the paper aims to quantitatively analyze highway landscape’s effect on driving behavior based on drivers’ physiological performance and quantify highway length thresholds under three typical landscape patterns, namely, “open,” “semiopen,” and “vertical” ones. The statistical analysis was based on data collected in a driving simulator and electrocardiograph. Specifically, vehicle-related data, ECG data, and supplemental subjective stress perception were collected. The study extracted two characteristic indices, lane deviation and LF/HF, and extrapolated the drivers’ U-shaped physiological response to landscape patterns. Models on highway length were built based on LF/HF’s variation trend with highway length. The results revealed that the theoretical highway length threshold tended to increase when the landscape pattern was switched to open, semiopen, and vertical ones. And the reliability and accuracy of the results were validated by questionnaires and field operational tests. Findings from this research will assist practitioners in taking active environmental countermeasures pertaining to different roadside landscape patterns.

  16. Effectiveness of inquiry-based learning in an undergraduate exercise physiology course

    DEFF Research Database (Denmark)

    Nybo, Lars; May, Michael

    2015-01-01

    The present study was conducted to investigate the effects of changing a laboratory physiology course for undergraduate students from a traditional step-by-step guided structure to an inquiry-based approach. With this aim in mind, quantitative and qualitative evaluations of learning outcomes......). The I-based course was a guided inquiry course where students had to design the experimental protocol and conduct their own study on the basis of certain predefined criteria (i.e., they should evaluate respiratory responses to submaximal and maximal exercise and provide indirect and direct measures...... of aerobic exercise capacity). The results indicated that the overall time spent on the experimental course as well as self-evaluated learning outcomes were similar across groups. However, students in the I-based course used more time in preparation (102 ± 5 min) than students in the traditional course (42...

  17. PHYSIOLOGICAL INFORMATION FOR PAVEMENT HEALTH MONITORING BASED ON SURFACE RIDE QUALITY

    Science.gov (United States)

    Tomiyama, Kazuya; Kawamura, Akira; Takahashi, Kiyoshi; Ishida, Tateki

    Pavement ride quality testing has traditionally been based on subjective questionnaire ratings. The questionnaire survey has ability to directly measure the sense of road users' ride quality. However, it is difficult to quantify the evaluation results based on the questionnaire due to its lack of objectivity. This study examines pavement health monitoring method using physiological information such as heart rate variability (HRV) for detecting mental stress of road users toward pavement ride quality. First, a results of a driving simulator experiment shows that potential mental stress caused by road roughness can be observed in high-frequency oscillations in 0.15-0.4Hz of HRV processed by continuous wavelet transform. Then, the high-frequency oscillations of HRV is summarized as an index related to the mental stress that makes objective ride quality evaluation possible. Finally, this study indicates that the index contributes to improve the accuracy of pavement health monitoring based on surface ride quality.

  18. A generalized physiologically-based toxicokinetic modeling system for chemical mixtures containing metals

    Directory of Open Access Journals (Sweden)

    Isukapalli Sastry S

    2010-06-01

    Full Text Available Abstract Background Humans are routinely and concurrently exposed to multiple toxic chemicals, including various metals and organics, often at levels that can cause adverse and potentially synergistic effects. However, toxicokinetic modeling studies of exposures to these chemicals are typically performed on a single chemical basis. Furthermore, the attributes of available models for individual chemicals are commonly estimated specifically for the compound studied. As a result, the available models usually have parameters and even structures that are not consistent or compatible across the range of chemicals of concern. This fact precludes the systematic consideration of synergistic effects, and may also lead to inconsistencies in calculations of co-occurring exposures and corresponding risks. There is a need, therefore, for a consistent modeling framework that would allow the systematic study of cumulative risks from complex mixtures of contaminants. Methods A Generalized Toxicokinetic Modeling system for Mixtures (GTMM was developed and evaluated with case studies. The GTMM is physiologically-based and uses a consistent, chemical-independent physiological description for integrating widely varying toxicokinetic models. It is modular and can be directly "mapped" to individual toxicokinetic models, while maintaining physiological consistency across different chemicals. Interaction effects of complex mixtures can be directly incorporated into the GTMM. Conclusions The application of GTMM to different individual metals and metal compounds showed that it explains available observational data as well as replicates the results from models that have been optimized for individual chemicals. The GTMM also made it feasible to model toxicokinetics of complex, interacting mixtures of multiple metals and nonmetals in humans, based on available literature information. The GTMM provides a central component in the development of a "source

  19. Making physiology learning memorable: a mobile phone-assisted case-based instructional strategy.

    Science.gov (United States)

    Kukolja Taradi, S; Taradi, M

    2016-09-01

    The goal of the present study was to determine whether an active learning/teaching strategy facilitated with mobile technologies can improve students' levels of memory retention of key physiological concepts. We used a quasiexperimental pretest/posttest nonequivalent group design to compare the test performances of second-year medical students (n = 311) taught by conventional didactic methods (traditional group) with those involved in a case-based problem-solving learning approach facilitated with mobile phones as web-based "clickers" (experimental group). Using their cell phones, students answered the same questions about the key physiological concepts three times. A pretest to determine their baseline knowledge was followed by two followup tests after 1 wk and 2 mo, respectively. The experimental group scored a mean of 93.2% correct items after 1 wk and 84.8% correct items after 2 mo [95% confidence intervals: (89.4, 97.0) and (79.4, 90.3), respectively]. Compared with their colleagues in the traditional group who scored 33.3% [95% confidence interval: (18.9, 47.8)] and 38.5% [95% confidence interval: (23.6, 53.4)] correct items, respectively, this was a significant increase of ∼50% (P < 0.0001). Furthermore, for the experimental group, Cohen's effect size (d) values of d = 1.67 (1-wk posttest) and d = 1.38 (2-mo posttest) suggested a very high practical significance. In contrast, in the traditional group, Cohen's d values of d = 0.04 (1-wk posttest) and d = 0.15 (2-mo posttest) assumed a very low practical significance. Copyright © 2016 The American Physiological Society.

  20. Biokinetics of {sup 99m}Tc-UBI 29-41 in humans

    Energy Technology Data Exchange (ETDEWEB)

    Melendez-Alafort, Laura; Rodriguez-Cortes, Jeannette; Ferro-Flores, Guillermina E-mail: gff@nuclear.inin.mx; Arteaga De Murphy, Consuelo; Herrera-Rodriguez, Ruth; Mitsoura, Eleni; Martinez-Duncker, Carlos

    2004-04-01

    Antimicrobial peptides have been proposed as new agents to distinguish between bacterial infections and sterile inflammatory processes. {sup 99m}Tc-UBI labeled by a direct method has shown high in vitro and in vivo stability, specific uptake at the site of infection, rapid background clearance, minimal accumulation in non-target tissues and rapid detection of infection sites in mice. The aim of this study was to establish a {sup 99m}Tc-UBI biokinetic model and evaluate its feasibility as an infection imaging agent in humans. Whole-body images from 6 children with suspected bone infection were acquired at 1, 30, 120, 240 min and 24 h after {sup 99m}Tc-UBI administration. Regions of interest (ROIs) were drawn around source organs (heart, liver, kidneys and bladder) on each time frame. The same set of ROIs was used for all 6 scans and the cpm of each ROI were converted to activity using the conjugate view counting method. Counts were corrected by physical decay and by the background correction factor derived from preclinical phantom studies. The image sequence was used to extrapolate {sup 99m}Tc-UBI time-activity curves in each organ and calculate the cumulated activity (A-tilde). Urine samples were used to obtain the cumulative percent of injected activity (% I.A.) versus time renal elimination. The absorbed dose in organs was evaluated according to the general equation described in the MIRD formalism. In addition, {sup 67}Ga-citrate images were obtained from all the patients and used as a control. Biokinetic data showed a fast blood clearance with a mean residence time of 0.52 h. Approximately 85% of the injected activity was eliminated by renal clearance 24 h after {sup 99m}Tc-UBI administration. Images showed minimal accumulation in non-target tissues with an average target/non-target ratio of 2.18 {+-} 0.74 in positive lesions at 2 h. All infection positive{sup 99m}Tc-UBI images were in agreement with those obtained with {sup 67}Ga-citrate. The mean radiation

  1. Quantitative biokinetics of titanium dioxide nanoparticles after intratracheal instillation in rats: Part 3.

    Science.gov (United States)

    Kreyling, Wolfgang G; Holzwarth, Uwe; Haberl, Nadine; Kozempel, Ján; Wenk, Alexander; Hirn, Stephanie; Schleh, Carsten; Schäffler, Martin; Lipka, Jens; Semmler-Behnke, Manuela; Gibson, Neil

    2017-05-01

    The biokinetics of a size-selected fraction (70 nm median size) of commercially available and (48)V-radiolabeled [(48)V]TiO2 nanoparticles has been investigated in healthy adult female Wistar-Kyoto rats at retention time-points of 1 h, 4 h, 24 h, 7 d and 28 d after intratracheal instillation of a single dose of an aqueous [(48)V]TiO2-nanoparticle suspension. A completely balanced quantitative biodistribution in all organs and tissues was obtained by applying typical [(48)V]TiO2-nanoparticle doses in the range of 40-240 μg·kg(-1) bodyweight and making use of the high sensitivity of the radiotracer technique. The [(48)V]TiO2-nanoparticle content was corrected for residual blood retained in organs and tissues after exsanguination and for (48)V-ions not bound to TiO2-nanoparticles. About 4% of the initial peripheral lung dose passed through the air-blood-barrier after 1 h and were retained mainly in the carcass (4%); 0.3% after 28 d. Highest organ fractions of [(48)V]TiO2-nanoparticles present in liver and kidneys remained constant (0.03%). [(48)V]TiO2-nanoparticles which entered across the gut epithelium following fast and long-term clearance from the lungs via larynx increased from 5 to 20% of all translocated/absorbed [(48)V]TiO2-nanoparticles. This contribution may account for 1/5 of the nanoparticle retention in some organs. After normalizing the fractions of retained [(48)V]TiO2-nanoparticles to the fraction that reached systemic circulation, the biodistribution was compared with the biodistributions determined after IV-injection (Part 1) and gavage (GAV) (Part 2). The biokinetics patterns after IT-instillation and GAV were similar but both were distinctly different from the pattern after intravenous injection disproving the latter to be a suitable surrogate of the former applications. Considering that chronic occupational inhalation of relatively biopersistent TiO2-particles (including nanoparticles) and accumulation in secondary organs may

  2. Biokinetics and dosimetry of target-specific radiopharmaceuticals for molecular imaging and therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ferro F, G.; Torres G, E. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico); Gonzalez V, A. [UAEM, Facultad de Medicina, Toluca (Mexico); Murphy, C.A. de [INCMNSZ, Mexico D.F. (Mexico)

    2006-07-01

    Molecular imaging techniques directly or indirectly monitor and record the spatiotemporal distribution of molecular or cellular processes for biochemical, biologic, diagnostic or therapeutic applications. {sup 99m}Tc-HYNlC-TOC has shown high in vitro and in vivo stability, rapid background clearance and rapid detection of somatostatin receptor-positive tumors. Therapies using radiolabeled anti-CD20 have demonstrated their efficacy in patients with B-cell non Hodgkin's Iymphoma (NHL). The aim of this study was to establish biokinetic models for {sup 99m}Tc-HYNlC-TOC and {sup 188}Re-anti-CD20 prepared from Iyophilized kits, and to evaluate their dosimetry as target-specific radiopharmaceuticals. Whole-body images were acquired at different times after {sup 99m}Tc-HYNlC-TOC or {sup 188}Re-anti-CD20 administration obtained from instant freeze-dried kit formulations with radiochemical purities > 95 %. Regions of interest (ROls) were drawn around source organs on each time frame. The cpm of each ROI was converted to activity using the conjugate view counting method. The image sequence was used to extrapolate time-activity curves in each organ, to adjust the biokinetic model using the SAAM software, and to calculate the total number of disintegrations (N) that occurred in the source regions. N data were the input for the OLINDA/EXM code to calculate internal radiation dose estimates. {sup 99m}Tc-HYNlC-TOC images showed an average tumor/blood (heart) ratio of 4.3 {+-} 0.7 in receptor-positive tumors at 1 h and the mean radiation absorbed dose calculated for a study using 740 MBq was 24, 21.5, 5.5 and 1.0 mSv for spleen, kidneys, liver and bone marrow respectively and the effective dose was 4.4 mSv. Results showed that after administration of 7 GBq of {sup 188}Re-anti-CD20 the absorbed dose to whole body would be 0.7 Gy (0.1 mGy/MBq) which is the indicated dose for non Hodgkin's Iymphome therapies. (Author)

  3. Biokinetics of (13)C in the human body after oral administration of (13)C-labeled glucose as an index for the biokinetics of (14)C.

    Science.gov (United States)

    Masuda, Tsuyoshi; Tako, Yasuhiro; Matsushita, Kensaku; Takeda, Hiroshi; Endo, Masahiro; Nakamura, Yuji; Hisamatsu, Shun'ichi

    2016-09-01

    The retention of (13)C in the human body after oral administration of (13)C-labeled glucose was studied in three healthy volunteer subjects to estimate the 50 year cumulative body burden for (13)C as an index of the committed dose of the radioisotope (14)C. After administration of (13)C-labeled glucose, the volunteers ingested controlled diets with a fixed number of calories for 112 d. Samples of breath and urine were collected up to 112 d after administration. Samples of feces were collected up to 14 d after administration. Hair samples were obtained at 119 d after administration and analyzed as a representative index of the rate of excretion of organic (13)C via pathways such as skin cell exfoliation and mucus secretion. All samples were analyzed for (13)C/(12)C atomic ratio to determine the rate of excretion via each pathway. We then constructed a metabolic model with a total of four pathways (breath, urine, feces, and other) comprising seven compartments. We determined the values of the biokinetic parameters in the model by using the obtained excretion data. From 74% to 94% of the (13)C administered was excreted in breath, whereas    0.1). In addition, the dataset for one of the three subjects was markedly different from those of the other two. When we estimated the 50 year cumulative body burden for (13)C by using our model and we included non-statistically significant parameters, a considerable cumulative body burden was found in the compartments excreting to the other pathway. Although our results on the cumulative body burden of (13)C from orally administered carbon as glucose were inconclusive, we found that the compartments excreting to the other pathway had a markedly long residence time and therefore should be studied further to clarify the fate of carbon in the human body. In addition to excreta, data for serum and blood cell samples were also collected from the subjects to examine the metabolism of (13)C in human body.

  4. Setting safe acute exposure limits for halon replacement chemicals using physiologically based pharmacokinetic modeling.

    Science.gov (United States)

    Vinegar, A; Jepson, G W; Cisneros, M; Rubenstein, R; Brock, W J

    2000-08-01

    Most proposed replacements for Halon 1301 as a fire suppressant are halogenated hydrocarbons. The acute toxic endpoint of concern for these agents is cardiac sensitization. An approach is described that links the cardiac endpoint as assessed in dogs to a target arterial concentration in humans. Linkage was made using a physiologically based pharmacokinetic (PBPK) model. Monte Carlo simulations, which account for population variability, were used to establish safe exposure times at different exposure concentrations for Halon 1301 (bromotrifluoromethane), CF(3)I (trifluoroiodomethane), HFC-125 (pentafluoroethane), HFC-227ea (1,1,1,2,3,3,3-heptafluoropropane), and HFC-236fa (1,1,1,3,3,3-hexafluoropropane). Application of the modeling technique described here not only makes use of the conservative cardiac sensitization endpoint, but also uses an understanding of the pharmacokinetics of the chemical agents to better establish standards for safe exposure. The combined application of cardiac sensitization data and physiologically based modeling provides a quantitative approach, which can facilitate the selection and effective use of halon replacement candidates.

  5. Physiologically Based Pharmacokinetic (PBPK model for biodistribution of radiolabeled peptides in patients with neuroendocrine tumours

    Directory of Open Access Journals (Sweden)

    Viktor Popov

    2016-07-01

    Full Text Available Objective(s: The objectives of this work was to assess the benefits of the application of Physiologically Based Pharmacokinetic (PBPK models in patients with different neuroendocrine tumours (NET who were treatedwith Lu-177 DOTATATE. The model utilises clinical data on biodistribution of radiolabeled peptides (RLPs obtained by whole body scintigraphy (WBS of the patients.Methods: The blood flow restricted (perfusion rate limited type of the PBPK model for biodistribution of radiolabeled peptides (RLPs in individual human organs is based on the multi-compartment approach, which takes into account the main physiological processes in the organism: absorption, distribution, metabolism and excretion (ADME. The approachcalibrates the PBPK model for each patient in order to increase the accuracy of the dose estimation. Datasets obtained using WBS in four patients have been used to obtain the unknown model parameters. The scintigraphic data were acquired using a double head gamma camera in patients with different neuroendocrine tumours who were treated with Lu-177 DOTATATE. The activity administered to each patient was 7400MBq.Results: Satisfactory agreement of the model predictions with the data obtained from the WBS for each patient has been achieved. Conclusion: The study indicates that the PBPK model can be used for more accurate calculation of biodistribution and absorbed doses in patients. This approach is the first attempt of utilizing scintigraphic data in PBPK models, which was obtained during Lu-177 peptide therapy of patients with NET.

  6. Quantitative acid-base physiology using the Stewart model. Does it improve our understanding of what is really wrong?

    NARCIS (Netherlands)

    Derksen, R.; Scheffer, G.J.; Hoeven, J.G. van der

    2006-01-01

    Traditional theories of acid-base balance are based on the Henderson-Hasselbalch equation to calculate proton concentration. The recent revival of quantitative acid-base physiology using the Stewart model has increased our understanding of complicated acid-base disorders, but has also led to several

  7. The influence of physical and physiological cues on atomic force microscopy-based cell stiffness assessment.

    Directory of Open Access Journals (Sweden)

    Yu-Wei Chiou

    Full Text Available Atomic force microscopy provides a novel technique for differentiating the mechanical properties of various cell types. Cell elasticity is abundantly used to represent the structural strength of cells in different conditions. In this study, we are interested in whether physical or physiological cues affect cell elasticity in Atomic force microscopy (AFM-based assessments. The physical cues include the geometry of the AFM tips, the indenting force and the operating temperature of the AFM. All of these cues show a significant influence on the cell elasticity assessment. Sharp AFM tips create a two-fold increase in the value of the effective Young's modulus (E(eff relative to that of the blunt tips. Higher indenting force at the same loading rate generates higher estimated cell elasticity. Increasing the operation temperature of the AFM leads to decreases in the cell stiffness because the structure of actin filaments becomes disorganized. The physiological cues include the presence of fetal bovine serum or extracellular matrix-coated surfaces, the culture passage number, and the culture density. Both fetal bovine serum and the extracellular matrix are critical for cells to maintain the integrity of actin filaments and consequently exhibit higher elasticity. Unlike primary cells, mouse kidney progenitor cells can be passaged and maintain their morphology and elasticity for a very long period without a senescence phenotype. Finally, cell elasticity increases with increasing culture density only in MDCK epithelial cells. In summary, for researchers who use AFM to assess cell elasticity, our results provide basic and significant information about the suitable selection of physical and physiological cues.

  8. Development of Physiologically Based Pharmacokinetic Model (PBPK) of BMP2 in Mice.

    Science.gov (United States)

    Utturkar, Aditya; Paul, Bikram; Akkiraju, Hemanth; Bonor, Jeremy; Dhurjati, Prasad; Nohe, Anja

    2013-01-01

    Bone Morphogenetic protein 2 holds great promise for potential applications in the clinic. It is a potent growth factor for the use in the cervical spine surgery (FDA approved 2002) and has been marketed as "Infuse" for treating open tibial shaft fractures (FDA approved 2004). However, its use is limited by several significant side effects that maybe due to its potency and effect on different stem cell populations in the spine. BMP2 is expressed throughout the human body in several tissues and at a very high concentration in the blood. BMP receptors, especially BMP receptor type Ia, is ubiquitously expressed in most tissues. Currently, it is difficult to determine how BMP2 is physiologically distributed in mice or humans and no quantitative models are available. A Physiologically-Based Pharmaco-Kinetic (PBPK) model has been developed to determine steady-state distribution of BMP2 in mice. The multi-compartmental PBPK model represents relevant organ/tissues with physiological accuracy. The organs/tissue compartments chosen were brain, lung, heart, liver, pancreas, kidney, uterus, bone and fat. A blood compartment maintained connectivity among the various organs. Four processes characterized the change in the concentration of the protein in every compartment: blood flow in, blood flow out, protein turnover and receptor binding in the organ. The unique aspects of the model are the determination of elimination using receptor kinetics and generation using protein turnover. The model also predicts steady state concentrations of BMP2 in tissues in mice and may be used for possible scale-up of dosage regimens in humans.

  9. Excretion of radionuclides in human breast milk after nuclear medicine examinations. Biokinetic and dosimetric data and recommendations on breastfeeding interruption

    Energy Technology Data Exchange (ETDEWEB)

    Leide-Svegborn, Sigrid; Ahlgren, Lars; Mattsson, Soeren [Lund University, Department of Medical Radiation Physics, Skaane University Hospital, Malmoe (Sweden); Johansson, Lennart [Umeaa University, Department of Radiation Sciences, Umeaa (Sweden)

    2016-05-15

    To review early recommendations and propose guidelines for breastfeeding interruption after administration of radiopharmaceuticals, based on additional biokinetic and dosimetric data. Activity concentrations in breast milk from 53 breastfeeding patients were determined. The milk was collected at various times after administration of 16 different radiopharmaceuticals. The fraction of the activity administered to the mother excreted in the breast milk, the absorbed doses to various organs and tissues and the effective dose to the infant were estimated. The fraction of the administered activity excreted per millilitre of milk varied widely from 10{sup -10} to 10{sup -3} MBq/MBq administered. For {sup 99m}Tc-labelled radiopharmaceuticals, the total fraction of the administered activity excreted in the milk varied from 0.0057 % for {sup 99m}Tc-labelled red blood cells (RBC) to 19 % for {sup 99m}Tc-pertechnetate. The effective dose to an infant per unit activity administered to the mother ranged from 6.7 x 10{sup -6} mSv/MBq for {sup 99m}Tc-labelled RBC to 3.6 x 10{sup -2} mSv/MBq for {sup 99m}Tc-pertechnetate. For the other radiopharmaceuticals, the total fraction of administered activity excreted in the milk varied from 0.018 % ({sup 51}Cr-EDTA) to 48 % ({sup 131}I-NaI). The effective dose ranged from 5.6 x 10{sup -5} mSv{sub infant}/MBq{sub mother} ({sup 51}Cr-EDTA) to 106 mSv{sub infant}/MBq{sub mother} ({sup 131}I-NaI). Based on an effective dose limit of 1 mSv to the infant and a typical administered activity, we recommend cessation of breastfeeding for {sup 131}I-NaI and interruption of feeding for 12 h for {sup 125}I-iodohippurate, {sup 131}I-iodohippurate, {sup 99m}Tc-pertechnetate and {sup 99m}Tc-MAA. During this 12-h period all breast milk should be expressed at least three times and discarded. For the other radiopharmaceuticals included in this study, no interruption of breastfeeding is necessary. (orig.)

  10. Bayesian Analysis of a Lipid-Based Physiologically Based Toxicokinetic Model for a Mixture of PCBs in Rats

    Directory of Open Access Journals (Sweden)

    Alan F. Sasso

    2012-01-01

    Full Text Available A lipid-based physiologically based toxicokinetic (PBTK model has been developed for a mixture of six polychlorinated biphenyls (PCBs in rats. The aim of this study was to apply population Bayesian analysis to a lipid PBTK model, while incorporating an internal exposure-response model linking enzyme induction and metabolic rate. Lipid-based physiologically based toxicokinetic models are a subset of PBTK models that can simulate concentrations of highly lipophilic compounds in tissue lipids, without the need for partition coefficients. A hierarchical treatment of population metabolic parameters and a CYP450 induction model were incorporated into the lipid-based PBTK framework, and Markov-Chain Monte Carlo was applied to in vivo data. A mass balance of CYP1A and CYP2B in the liver was necessary to model PCB metabolism at high doses. The linked PBTK/induction model remained on a lipid basis and was capable of modeling PCB concentrations in multiple tissues for all dose levels and dose profiles.

  11. Biokinetic model for nitrogen removal in free water surface constructed wetlands.

    Science.gov (United States)

    Gargallo, S; Martín, M; Oliver, N; Hernández-Crespo, C

    2017-06-01

    In this article, a mechanistic biokinetic model for nitrogen removal in free water surface constructed wetlands treating eutrophic water was developed, including organic matter performance due to its importance in nitrogen removal by denitrification. Ten components and fourteen processes were introduced in order to simulate the forms of nitrogen and organic matter, the mechanisms of autotrophic and heterotrophic microorganisms in both aerobic and anoxic conditions, as well as macrophytes nitrogen uptake and release. Dissolved oxygen was introduced as an input variable with a time step of 0.5days for mimicking eutrophic environments: aerobic conditions were assigned during daylight hours and anoxic conditions during the night. The sensitivity analysis showed that the most influential parameters were those related to the growth of heterotrophic and autotrophic microorganisms. The model was properly calibrated and validated in two full scale systems working in real conditions for treating eutrophic water from Lake L'Albufera (València). In the studied systems, ammonium was mainly removed by the growth of autotrophic microorganisms (nitrification) whereas nitrate was removed by the anoxic growth of heterotrophic microorganisms (denitrification). Macrophyte uptake removed between 9 and 19% of the ammonium entering to the systems, although degradation of dead standing macrophytes returned a significant part to water column.

  12. Decoupling of cadmium biokinetics and metallothionein turnover in a marine polychaete after metal exposure

    Energy Technology Data Exchange (ETDEWEB)

    Ng, Tania Y.-T. [Department of Biology, Hong Kong University of Science and Technology (HKUST), Clear Water Bay, Kowloon, Hong Kong (China); Rainbow, Philip S. [Department of Zoology, Natural History Museum, Cromwell Road, London SW7 5BD (United Kingdom); Amiard-Triquet, Claude; Amiard, Jean-Claude [Universite de Nantes, Faculte de Pharmacie, MMS EA2160, Service d' ecotoxicologie, F-44000 Nantes (France); Wang Wenxiong [Department of Biology, Hong Kong University of Science and Technology (HKUST), Clear Water Bay, Kowloon, Hong Kong (China)], E-mail: wwang@ust.hk

    2008-08-11

    This study investigated the kinetics of Cd bioaccumulation, detoxification, subcellular distribution, and efflux in the nereid polychaete Perinereis aibuhitensis after Cd pre-exposure. Cd pre-exposure increased the Cd body burden in the worms, but did not affect the overall Cd uptake and efflux rates and metallothionein-like protein (MTLP) concentrations. During short-term exposure to dissolved Cd, Cd in the cytosolic fraction increased after Cd pre-exposure, and this fraction also increased during the Cd efflux period, indicating that the insoluble fraction of Cd was presumably lost at a faster rate than the loss of cytosolic Cd. Even though the MTLP concentration remained comparable after Cd pre-exposure, both the MTLP synthesis rate and the degradation rate increased, thus leading to a high MTLP turnover in the Cd-exposed worms. However, Cd uptake and efflux into different protein size fractions did not follow the patterns of MTLP synthesis and degradation, strongly suggesting that Cd kinetics is decoupled from the MTLP kinetics in the worms. Our study adds to an increasing body of evidence on the complicated relationship between metal biokinetics and MTLP kinetics in different groups of marine invertebrates which have strong contrasts in their metal handling strategies.

  13. Assessment of salinity tolerance in rice using seedling based morpho-physiological indices

    Directory of Open Access Journals (Sweden)

    Syed Adeel Zafar

    2015-08-01

    Full Text Available Background: Salinity is among the most damaging abiotic stresses for rice production which limits its growing area. The present research was conducted to evaluate five rice varieties for salinity tolerance at seedling stage. Methods: Experiment was conducted in triplicate and in two sets. One set was grown as a control (non-stress and other as salt stressed. Salt stress of 15 dS/m was applied to one set of rice seedlings under controlled conditions. Data for different growth related morpho-physiological traits, i.e. germination percentage, root and shoot length, seedling fresh and dry weight, Na+ and K+ uptake were recorded after 15 days of seedling emergence under control as well as salinity condition. Results: Significant differences were observed among the genotypes under both the treatments and interaction of the evaluated traits suggested a significant variability among the rice genotypes under salt stress. NIAB-IRRI-9, Basmati-198 and KSK-133 were proved to be relatively salt tolerant varieties as they showed good performance for the recorded parameters. However, Basmati-385 was observed a salt sensitive variety due to highest reduction in seedling fresh and dry weight along with the maximum Na+ uptake. Conclusion: Based on obtained results, it was concluded that the evaluated morpho-physiological traits were useful to screen rice cultivars for salinity stress. In addition, NIAB-IRRI-9, Basmati-198 and KSK-133 can be used in breeding programs as tolerant check and Basmati-385 can be used as sensitive check.

  14. Development of a Physiologically-Based Pharmacokinetic Model of the Rat Central Nervous System

    Directory of Open Access Journals (Sweden)

    Raj K. Singh Badhan

    2014-03-01

    Full Text Available Central nervous system (CNS drug disposition is dictated by a drug’s physicochemical properties and its ability to permeate physiological barriers. The blood–brain barrier (BBB, blood-cerebrospinal fluid barrier and centrally located drug transporter proteins influence drug disposition within the central nervous system. Attainment of adequate brain-to-plasma and cerebrospinal fluid-to-plasma partitioning is important in determining the efficacy of centrally acting therapeutics. We have developed a physiologically-based pharmacokinetic model of the rat CNS which incorporates brain interstitial fluid (ISF, choroidal epithelial and total cerebrospinal fluid (CSF compartments and accurately predicts CNS pharmacokinetics. The model yielded reasonable predictions of unbound brain-to-plasma partition ratio (Kpuu,brain and CSF:plasma ratio (CSF:Plasmau using a series of in vitro permeability and unbound fraction parameters. When using in vitro permeability data obtained from L-mdr1a cells to estimate rat in vivo permeability, the model successfully predicted, to within 4-fold, Kpuu,brain and CSF:Plasmau for 81.5% of compounds simulated. The model presented allows for simultaneous simulation and analysis of both brain biophase and CSF to accurately predict CNS pharmacokinetics from preclinical drug parameters routinely available during discovery and development pathways.

  15. Why Fish Oil Fails: A Comprehensive 21st Century Lipids-Based Physiologic Analysis

    Directory of Open Access Journals (Sweden)

    B. S. Peskin

    2014-01-01

    Full Text Available The medical community suffered three significant fish oil failures/setbacks in 2013. Claims that fish oil’s EPA/DHA would stop the progression of heart disease were crushed when The Risk and Prevention Study Collaborative Group (Italy released a conclusive negative finding regarding fish oil for those patients with high risk factors but no previous myocardial infarction. Fish oil failed in all measures of CVD prevention—both primary and secondary. Another major 2013 setback occurred when fish oil’s DHA was shown to significantly increase prostate cancer in men, in particular, high-grade prostate cancer, in the Selenium and Vitamin E Cancer Prevention Trial (SELECT analysis by Brasky et al. Another monumental failure occurred in 2013 whereby fish oil’s EPA/DHA failed to improve macular degeneration. In 2010, fish oil’s EPA/DHA failed to help Alzheimer’s victims, even those with low DHA levels. These are by no means isolated failures. The promise of fish oil and its so-called active ingredients EPA / DHA fails time and time again in clinical trials. This lipids-based physiologic review will explain precisely why there should have never been expectation for success. This review will focus on underpublicized lipid science with a focus on physiology.

  16. A physiologically based pharmacokinetic model for quinoxaline-2-carboxylic acid in rats, extrapolation to pigs.

    Science.gov (United States)

    Yang, X; Zhou, Y-F; Yu, Y; Zhao, D-H; Shi, W; Fang, B-H; Liu, Y-H

    2015-02-01

    A multi-compartment physiologically based pharmacokinetic (PBPK) model to describe the disposition of cyadox (CYX) and its metabolite quinoxaline-2-carboxylic acid (QCA) after a single oral administration was developed in rats (200 mg/kg b.w. of CYX). Considering interspecies differences in physiology and physiochemistry, the model efficiency was validated by pharmacokinetic data set in swine. The model included six compartments that were blood, muscle, liver, kidney, adipose, and a combined compartment for the rest of tissues. The model was parameterized using rat plasma and tissue concentration data that were generated from this study. Model simulations were achieved using a commercially available software program (ACSLXL ibero version 3.0.2.1). Results supported the validity of the model with simulated tissue concentrations within the range of the observations. The correlation coefficients of the predicted and experimentally determined values for plasma, liver, kidney, adipose, and muscles in rats were 0.98, 0.98, 0.98, 0.99, and 0.95, respectively. The rat model parameters were then extrapolated to pigs to estimate QCA disposition in tissues and validated by tissue concentration of QCA in swine. The correlation coefficients between the predicted and observed values were over 0.90. This model could provide a foundation for developing more reliable pig models once more data are available.

  17. Treating chronic worry: Psychological and physiological effects of a training programme based on mindfulness.

    Science.gov (United States)

    Delgado, Luis Carlos; Guerra, Pedro; Perakakis, Pandelis; Vera, María Nieves; Reyes del Paso, Gustavo; Vila, Jaime

    2010-09-01

    The present study examines psychological and physiological indices of emotional regulation in non-clinical high worriers after a mindfulness-based training programme aimed at reducing worry. Thirty-six female university students with high Penn State Worry Questionnaire scores were split into two equal intervention groups: (a) mindfulness, and (b) progressive muscle relaxation plus self-instruction to postpone worrying to a specific time of the day. Assessment included clinical questionnaires, daily self-report of number/duration of worry episodes and indices of emotional meta-cognition. A set of somatic and autonomic measures was recorded (a) during resting, mindfulness/relaxation and worrying periods, and (b) during cued and non-cued affective modulation of defence reactions (cardiac defence and eye-blink startle). Both groups showed equal post-treatment improvement in the clinical and daily self-report measures. However, mindfulness participants reported better emotional meta-cognition (emotional comprehension) and showed improved indices of somatic and autonomic regulation (reduced breathing pattern and increased vagal reactivity during evocation of cardiac defense). These findings suggest that mindfulness reduces chronic worry by promoting emotional and physiological regulatory mechanisms contrary to those maintaining chronic worry. 2010 Elsevier Ltd. All rights reserved.

  18. MRI-based three-dimensional thermal physiological characterization of thyroid gland of human body.

    Science.gov (United States)

    Jin, Chao; He, Zhi Zhu; Yang, Yang; Liu, Jing

    2014-01-01

    This article is dedicated to present a MRI (magnetic resonance imaging) based three-dimensional finite element modeling on the thermal manifestations relating to the pathophysiology of thyroid gland. An efficient approach for identifying the metabolic dysfunctions of thyroid has also been demonstrated through tracking the localized non-uniform thermal distribution or enhanced dynamic imaging. The temperature features over the skin surface and thyroid domain have been characterized using the numerical simulation and experimental measurement which will help better interpret the thermal physiological mechanisms of the thyroid under steady-state or water-cooling condition. Further, parametric simulations on the hypermetabolism symptoms of hyperthyroidism and thermal effects within thyroid domain caused by varying breathing airflow in the trachea and blood-flow in artery and vein were performed. It was disclosed that among all the parameters, the airflow volume has the largest effect on the total heat flux of thyroid surface. However, thermal contributions caused by varying the breathing frequency and blood-flow velocity are negligibly small. The present study suggests a generalized way for simulating the close to reality physiological behavior or process of human thyroid, which is of significance for disease diagnosis and treatment planning.

  19. Distinctive identification of Cladosporium sphaerospermum and Cladosporium halotolerans based on physiological methods

    Institute of Scientific and Technical Information of China (English)

    Naoki KOBAYASHI; Maiko WATANABE; Yukiko HARA-KUDO

    2012-01-01

    We aimed to detect physiological characteristics that clearly varied among the closely-related Cladosporium sphaerospermum-like species.We isolated the fungi identified as C.sphaerospermum s.l.based on traditional morphological criteria from various locations and substrata,and redefined this initial identification by the molecular phylogenetic methods.The isolates were identified as only C.sphaerospermum and C.halotolerans.We analyzed the substrate-utilization of 95 carbon sources using the Biolog system and made statistical comparisons of isolates by their abilities to grow at different osmolarities.The substrate-utilization patterns separated the isolates into two groups corresponding to the molecular data,and the osmotolerance was different between the species.We first showed that C.sphaerospermum and C.halotolerans were diverse not only at the molecular level but also at the ecological and the physiological levels,by analyzing substrate-utilization patterns and osmotolerance.Furthermore,we showed the potential utility of the Biolog system for discriminating among closely-related fugal species.

  20. Computing network-based features from physiological time series: application to sepsis detection.

    Science.gov (United States)

    Santaniello, Sabato; Granite, Stephen J; Sarma, Sridevi V; Winslow, Raimond L

    2014-01-01

    Sepsis is a systemic deleterious host response to infection. It is a major healthcare problem that affects millions of patients every year in the intensive care units (ICUs) worldwide. Despite the fact that ICU patients are heavily instrumented with physiological sensors, early sepsis detection remains challenging, perhaps because clinicians identify sepsis by using static scores derived from bed-side measurements individually, i.e., without systematically accounting for potential interactions between these signals and their dynamics. In this study, we apply network-based data analysis to take into account interactions between bed-side physiological time series (PTS) data collected in ICU patients, and we investigate features to distinguish between sepsis and non-sepsis conditions. We treated each PTS source as a node on a graph and we retrieved the graph connectivity matrix over time by tracking the correlation between each pair of sources' signals over consecutive time windows. Then, for each connectivity matrix, we computed the eigenvalue decomposition. We found that, even though raw PTS measurements may have indistinguishable distributions in non-sepsis and early sepsis states, the median /I of the eigenvalues computed from the same data is statistically different (p sepsis detection.

  1. Characterizing the Effects of Race/Ethnicity on Acetaminophen Pharmacokinetics Using Physiologically Based Pharmacokinetic Modeling.

    Science.gov (United States)

    Zurlinden, Todd J; Reisfeld, Brad

    2017-02-01

    Acetaminophen (APAP, paracetamol) is currently the principal cause of acute liver failure in both the USA and the UK. However, relatively little is known about the influence of genes and race/ethnicity on the disposition of APAP and the extent to which genetic variation and ethnicity may predispose individuals to a higher risk of APAP-induced hepatotoxicity. The objective of this research was to develop subpopulation-specific physiologically based pharmacokinetic (PBPK) models for two genetically different groups (Western Europeans and East Asians) and then use the models to quantify the difference in absorption, distribution, metabolism, and excretion (ADME) of APAP between these groups. A comprehensive set of human pharmacokinetic data mined from the literature was divided into two groups based on ethnicity as an indicator of the expected abundance of phenol-metabolizing alleles. Using these datasets and a Bayesian hierarchical framework, subpopulation-specific physiologically based pharmacokinetic models for APAP were developed and tested for the two groups. Model simulations were in good agreement with experimental data for both time-dependent parent and metabolite concentrations and summary pharmacokinetic parameters. In addition, simulations were conducted to characterize the difference between ADME in these groups with regard to urinary excretion and APAP area under the curve (AUC) in the liver. Although not dramatic at therapeutic dosing levels, these results demonstrated the divergence in the liver-specific APAP concentrations and AUC between the two groups and suggested that differences in glucuronidation capacity may play a role in this disparity. Overall, the models developed in this study, and others created using this type of hierarchical methodology, are expected to be useful in quantifying ADME in a subpopulation-specific manner and reducing prediction uncertainty compared to that from generalized PBPK modeling approaches.

  2. The Routing Algorithm Based on Fuzzy Logic Applied to the Individual Physiological Monitoring Wearable Wireless Sensor Network

    OpenAIRE

    Jie Jiang; Yun Liu; Fuxing Song; Ronghao Du; Mengsen Huang

    2015-01-01

    In recent years, the research of individual wearable physiological monitoring wireless sensor network is in the primary stage. The monitor of physiology and geographical position used in wearable wireless sensor network requires performances such as real time, reliability, and energy balance. According to these requirements, this paper introduces a design of individual wearable wireless sensor network monitoring system; what is more important, based on this background, this paper improves the...

  3. Fluorene-based boronic acids as fluorescent chemosensor for monosaccharides at physiological pH.

    Science.gov (United States)

    Hosseinzadeh, Rahman; Mohadjerani, Maryam; Pooryousef, Mona

    2015-08-01

    Two fluorene-based boronic acids, 9,9-dimethyl-9H-fluoren-2-yl-2-boronic acid (1) and 9,9-dimethyl-9H-fluoren-2,7-diyl-2,7-diboronic acid (2), were synthesized and their sensing abilities for detection of D-monosaccharides were investigated by fluorescence at physiological pH. It was found that both boronic acids 1 and 2 have high selectivity and sensitivity for D-fructose with stability constant of 47.2 and 412.9, respectively. The sensor 2 showed a linear response toward D-fructose in the concentration range from 5 × 10(-5) to 10(-1) mol L(-1) with the detection limit of 2 × 10(-5) mol L(-1). Copyright © 2014 John Wiley & Sons, Ltd.

  4. A new boronic acid fluorescent sensor based on fluorene for monosaccharides at physiological pH

    Science.gov (United States)

    Hosseinzadeh, Rahman; Mohadjerani, Maryam; Pooryousef, Mona; Eslami, Abbas; Emami, Saeed

    2015-06-01

    Fluorescent boronic acids are very useful fluorescent sensor for detection of biologically important saccharides. Herein we synthesized a new fluorene-based fluorescent boronic acid that shows significant fluorescence changes upon addition of saccharides at physiological pH. Upon addition of fructose, sorbitol, glucose, galactose, ribose, and maltose at different concentration to the solution of 7-(dimethylamino)-9,9-dimethyl-9H-fluoren-2-yl-2-boronic acid (7-DMAFBA, 1), significant decreases in fluorescent intensity were observed. It was found that this boronic acid has high affinity (Ka = 3582.88 M-1) and selectivity for fructose over glucose at pH = 7.4. The sensor 1 showed a linear response toward D-fructose in the concentrations ranging from 2.5 × 10-5 to 4 × 10-4 mol L-1 with the detection limit of 1.3 × 10-5 mol L-1.

  5. Development of a Human Physiologically Based Pharmacokinetic (PBPK Toolkit for Environmental Pollutants

    Directory of Open Access Journals (Sweden)

    Patricia Ruiz

    2011-10-01

    Full Text Available Physiologically Based Pharmacokinetic (PBPK models can be used to determine the internal dose and strengthen exposure assessment. Many PBPK models are available, but they are not easily accessible for field use. The Agency for Toxic Substances and Disease Registry (ATSDR has conducted translational research to develop a human PBPK model toolkit by recoding published PBPK models. This toolkit, when fully developed, will provide a platform that consists of a series of priority PBPK models of environmental pollutants. Presented here is work on recoded PBPK models for volatile organic compounds (VOCs and metals. Good agreement was generally obtained between the original and the recoded models. This toolkit will be available for ATSDR scientists and public health assessors to perform simulations of exposures from contaminated environmental media at sites of concern and to help interpret biomonitoring data. It can be used as screening tools that can provide useful information for the protection of the public.

  6. Interactive computer-assisted instruction in acid-base physiology for mobile computer platforms.

    Science.gov (United States)

    Longmuir, Kenneth J

    2014-03-01

    In this project, the traditional lecture hall presentation of acid-base physiology in the first-year medical school curriculum was replaced by interactive, computer-assisted instruction designed primarily for the iPad and other mobile computer platforms. Three learning modules were developed, each with ∼20 screens of information, on the subjects of the CO2-bicarbonate buffer system, other body buffer systems, and acid-base disorders. Five clinical case modules were also developed. For the learning modules, the interactive, active learning activities were primarily step-by-step learner control of explanations of complex physiological concepts, usually presented graphically. For the clinical cases, the active learning activities were primarily question-and-answer exercises that related clinical findings to the relevant basic science concepts. The student response was remarkably positive, with the interactive, active learning aspect of the instruction cited as the most important feature. Also, students cited the self-paced instruction, extensive use of interactive graphics, and side-by-side presentation of text and graphics as positive features. Most students reported that it took less time to study the subject matter with this online instruction compared with subject matter presented in the lecture hall. However, the approach to learning was highly examination driven, with most students delaying the study of the subject matter until a few days before the scheduled examination. Wider implementation of active learning computer-assisted instruction will require that instructors present subject matter interactively, that students fully embrace the responsibilities of independent learning, and that institutional administrations measure instructional effort by criteria other than scheduled hours of instruction.

  7. A physiologically based pharmacokinetic model for lactational transfer of Na-131I

    Science.gov (United States)

    Turner, Anita Loretta

    The excretion of radionuclides in human breast milk after administration of radiopharmaceuticals is a concern as a radiation risk to nursing infants. It is not uncommon to administer radiopharmaceuticals to lactating patients due to emergency nuclear medicine investigations such as thyroid complications, kidney failure, and pulmonary embolism. There is a need to quantify the amount of radioactivity translocated into breast milk in cases of ingestion by a breast-fed infant. A physiologically based pharmacokinetic model (PBPK) and a modified International Commission on Radiological Protection (ICRP) model have been developed to predict iodine concentrations in breast milk after ingestion of radioiodine by the mother. In the PBPK model, all compartments are interconnected by blood flow and represent real anatomic tissue regions in the body. All parameters involved are measurable values with physiological or physiochemical meaning such as tissue masses, blood flow rates, partition coefficients and cardiac output. However, some of the parameters such as the partition coefficients and metabolic constants are not available for iodine and had to be inferred from other information. The structure of the PBPK model for the mother consists of the following tissue compartments: gastrointestinal tract, blood, kidney, thyroid, milk, and other tissues. With the exception of the milk compartment, the model for the nursing infant is structured similarly to the mother. The ICRP model describing iodine metabolism in a standard 70-kg man was modified to represent iodine metabolism in a lactating woman and nursing infant. The parameters involved in this model are transfer rates and biological half-lives which are based on experimental observations. The results of the PBPK model and the modified ICRP model describing the lactational transfer of iodine were compared. When administering 1 mCi of Na131I to the lactating mother, the concentration reaches a maximum of 0.1 mCi/liter in 24

  8. Effectiveness of Mindfulness-based interventions on physiological and psychological complications in adults with diabetes: A systematic review.

    Science.gov (United States)

    Noordali, Farhan; Cumming, Jennifer; Thompson, Janice L

    2015-12-30

    This systematic review aimed to examine the effectiveness of Mindfulness-based interventions in reducing diabetes-related physiological and psychological symptoms in adults with types 1 and 2 diabetes. Five databases were systematically searched. A total of 11 studies satisfied the inclusion criteria. Mindfulness-based intervention effectiveness for physiological outcomes (glycaemic control and blood pressure) was mixed. Mindfulness-based interventions appear to have psychological benefits reducing depression, anxiety and distress symptoms across several studies. Studies' short-term follow-up periods may not allow sufficient time to observe physiological changes or illustrate Mindfulness-based interventions' potential long-term efficacy. More long-term studies that include a consistent, standardised set of outcome measures are required.

  9. Physiological Signals based Day-Dependence Analysis with Metric Multidimensional Scaling for Sentiment Classification in Wearable Sensors

    Directory of Open Access Journals (Sweden)

    Wei Wang

    2015-01-01

    Full Text Available The interaction of the affective has emerged in implicit human-computer interaction. Given the physiological signals in the recognition process of the affective, the different positions by which the physiological signal sensors are installed in the body, along with the daily habits and moods of human beings, influence the affective physiological signals. The scalar product matrix was calculated in this study based on metric multidimensional scaling with dissimilarity matrix. Subsequently, the matrix of individual attribute reconstructs was obtained using the principal component factor. The method proposed in this study eliminates day dependence, reduces the effect of time in the physiological signals of the affective, and improves the accuracy of affection classification.

  10. [Construction and analysis of a monitoring system with remote real-time multiple physiological parameters based on cloud computing].

    Science.gov (United States)

    Zhu, Lingyun; Li, Lianjie; Meng, Chunyan

    2014-12-01

    There have been problems in the existing multiple physiological parameter real-time monitoring system, such as insufficient server capacity for physiological data storage and analysis so that data consistency can not be guaranteed, poor performance in real-time, and other issues caused by the growing scale of data. We therefore pro posed a new solution which was with multiple physiological parameters and could calculate clustered background data storage and processing based on cloud computing. Through our studies, a batch processing for longitudinal analysis of patients' historical data was introduced. The process included the resource virtualization of IaaS layer for cloud platform, the construction of real-time computing platform of PaaS layer, the reception and analysis of data stream of SaaS layer, and the bottleneck problem of multi-parameter data transmission, etc. The results were to achieve in real-time physiological information transmission, storage and analysis of a large amount of data. The simulation test results showed that the remote multiple physiological parameter monitoring system based on cloud platform had obvious advantages in processing time and load balancing over the traditional server model. This architecture solved the problems including long turnaround time, poor performance of real-time analysis, lack of extensibility and other issues, which exist in the traditional remote medical services. Technical support was provided in order to facilitate a "wearable wireless sensor plus mobile wireless transmission plus cloud computing service" mode moving towards home health monitoring for multiple physiological parameter wireless monitoring.

  11. Human-on-a-chip design strategies and principles for physiologically based pharmacokinetics/pharmacodynamics modeling.

    Science.gov (United States)

    Abaci, Hasan Erbil; Shuler, Michael L

    2015-04-01

    Advances in maintaining multiple human tissues on microfluidic platforms has led to a growing interest in the development of microphysiological systems for drug development studies. Determination of the proper design principles and scaling rules for body-on-a-chip systems is critical for their strategic incorporation into physiologically based pharmacokinetic (PBPK)/pharmacodynamic (PD) model-aided drug development. While the need for a functional design considering organ-organ interactions has been considered, robust design criteria and steps to build such systems have not yet been defined mathematically. In this paper, we first discuss strategies for incorporating body-on-a-chip technology into the current PBPK modeling-based drug discovery to provide a conceptual model. We propose two types of platforms that can be involved in the different stages of PBPK modeling and drug development; these are μOrgans-on-a-chip and μHuman-on-a-chip. Then we establish the design principles for both types of systems and develop parametric design equations that can be used to determine dimensions and operating conditions. In addition, we discuss the availability of the critical parameters required to satisfy the design criteria, consider possible limitations for estimating such parameter values and propose strategies to address such limitations. This paper is intended to be a useful guide to the researchers focused on the design of microphysiological platforms for PBPK/PD based drug discovery.

  12. Estimating marbofloxacin withdrawal time in broiler chickens using a population physiologically based pharmacokinetics model.

    Science.gov (United States)

    Yang, F; Yang, Y R; Wang, L; Huang, X H; Qiao, G; Zeng, Z L

    2014-12-01

    Residue depletion of marbofloxacin in broiler chicken after oral administration at 5 mg/kg/day for three consecutive days was studied in this study. The areas under the concentration-time curve from 0 h to ∞ (AUC0-∞ s) of marbofloxacin in tissues and plasma were used to calculate tissue/plasma partition coefficients (PX s). Based on PX s and the other parameters derived from published studies, a flow-limited physiologically based pharmacokinetics (PBPK) model was developed to predict marbofloxacin concentrations, which were then compared with those derived from the residue depletion study so as to validate this model. Considering individual difference in drug disposition, a Monte Carlo simulation included 1000 iterations was further incorporated into the validated model to generate a population PBPK model and to estimate the marbofloxacin residue withdrawal times in edible tissues. The withdrawal periods were compared to those derived from linear regression analysis. The PBPK model presented here successfully predicted the measured concentrations in all tissues. The withdrawal times in all edible tissues derived from the population PBPK model were longer than those from linear regression analysis, and based on the residues in kidney, a withdrawal time of 4 days was estimated for marbofloxacin after oral administration at 5 mg/kg/day for three consecutive days. It was shown that population PBPK model could be used to accurately predict marbofloxacin residue withdrawal time in edible tissues in broiler chickens.

  13. Acid-base physiology, neurobiology and behaviour in relation to CO2-induced ocean acidification.

    Science.gov (United States)

    Tresguerres, Martin; Hamilton, Trevor J

    2017-06-15

    Experimental exposure to ocean and freshwater acidification affects the behaviour of multiple aquatic organisms in laboratory tests. One proposed cause involves an imbalance in plasma chloride and bicarbonate ion concentrations as a result of acid-base regulation, causing the reversal of ionic fluxes through GABAA receptors, which leads to altered neuronal function. This model is exclusively based on differential effects of the GABAA receptor antagonist gabazine on control animals and those exposed to elevated CO2 However, direct measurements of actual chloride and bicarbonate concentrations in neurons and their extracellular fluids and of GABAA receptor properties in aquatic organisms are largely lacking. Similarly, very little is known about potential compensatory mechanisms, and about alternative mechanisms that might lead to ocean acidification-induced behavioural changes. This article reviews the current knowledge on acid-base physiology, neurobiology, pharmacology and behaviour in relation to marine CO2-induced acidification, and identifies important topics for future research that will help us to understand the potential effects of predicted levels of aquatic acidification on organisms. © 2017. Published by The Company of Biologists Ltd.

  14. Blending problem-based learning with Web technology positively impacts student learning outcomes in acid-base physiology.

    Science.gov (United States)

    Taradi, Suncana Kukolja; Taradi, Milan; Radic, Kresimir; Pokrajac, Niksa

    2005-03-01

    World Wide Web (Web)-based learning (WBL), problem-based learning (PBL), and collaborative learning are at present the most powerful educational options in higher education. A blended (hybrid) course combines traditional face-to-face and WBL approaches in an educational environment that is nonspecific as to time and place. To provide educational services for an undergraduate second-year elective course in acid-base physiology, a rich, student-centered educational Web-environment designed to support PBL was created by using Web Course Tools courseware. The course is designed to require students to work in small collaborative groups using problem solving activities to develop topic understanding. The aim of the study was to identify the impact of the blended WBL-PBL-collaborative learning environment on student learning outcomes. Student test scores and satisfaction survey results from a blended WBL-PBL-based test group (n = 37) were compared with a control group whose instructional opportunities were from a traditional in-class PBL model (n = 84). WBL students scored significantly (t = 3.3952; P = 0.0009) better on the final acid-base physiology examination and expressed a positive attitude to the new learning environment in the satisfaction survey. Expressed in terms of a difference effect, the mean of the treated group (WBL) is at the 76th percentile of the untreated (face-to-face) group, which stands for a "medium" effect size. Thus student progress in the blended WBL-PBL collaborative environment was positively affected by the use of technology.

  15. Physiologically-based toxicokinetic modeling of zearalenone and its metabolites: application to the Jersey girl study.

    Directory of Open Access Journals (Sweden)

    Dwaipayan Mukherjee

    Full Text Available Zearalenone (ZEA, a fungal mycotoxin, and its metabolite zeranol (ZAL are known estrogen agonists in mammals, and are found as contaminants in food. Zeranol, which is more potent than ZEA and comparable in potency to estradiol, is also added as a growth additive in beef in the US and Canada. This article presents the development and application of a Physiologically-Based Toxicokinetic (PBTK model for ZEA and ZAL and their primary metabolites, zearalenol, zearalanone, and their conjugated glucuronides, for rats and for human subjects. The PBTK modeling study explicitly simulates critical metabolic pathways in the gastrointestinal and hepatic systems. Metabolic events such as dehydrogenation and glucuronidation of the chemicals, which have direct effects on the accumulation and elimination of the toxic compounds, have been quantified. The PBTK model considers urinary and fecal excretion and biliary recirculation and compares the predicted biomarkers of blood, urinary and fecal concentrations with published in vivo measurements in rats and human subjects. Additionally, the toxicokinetic model has been coupled with a novel probabilistic dietary exposure model and applied to the Jersey Girl Study (JGS, which involved measurement of mycoestrogens as urinary biomarkers, in a cohort of young girls in New Jersey, USA. A probabilistic exposure characterization for the study population has been conducted and the predicted urinary concentrations have been compared to measurements considering inter-individual physiological and dietary variability. The in vivo measurements from the JGS fall within the high and low predicted distributions of biomarker values corresponding to dietary exposure estimates calculated by the probabilistic modeling system. The work described here is the first of its kind to present a comprehensive framework developing estimates of potential exposures to mycotoxins and linking them with biologically relevant doses and biomarker

  16. Physiologically based pharmacokinetic modeling using microsoft excel and visual basic for applications.

    Science.gov (United States)

    Marino, Dale J

    2005-01-01

    Abstract Physiologically based pharmacokinetic (PBPK) models are mathematical descriptions depicting the relationship between external exposure and internal dose. These models have found great utility for interspecies extrapolation. However, specialized computer software packages, which are not widely distributed, have typically been used for model development and utilization. A few physiological models have been reported using more widely available software packages (e.g., Microsoft Excel), but these tend to include less complex processes and dose metrics. To ascertain the capability of Microsoft Excel and Visual Basis for Applications (VBA) for PBPK modeling, models for styrene, vinyl chloride, and methylene chloride were coded in Advanced Continuous Simulation Language (ACSL), Excel, and VBA, and simulation results were compared. For styrene, differences between ACSL and Excel or VBA compartment concentrations and rates of change were less than +/-7.5E-10 using the same numerical integration technique and time step. Differences using VBA fixed step or ACSL Gear's methods were generally <1.00E-03, although larger differences involving very small values were noted after exposure transitions. For vinyl chloride and methylene chloride, Excel and VBA PBPK model dose metrics differed by no more than -0.013% or -0.23%, respectively, from ACSL results. These differences are likely attributable to different step sizes rather than different numerical integration techniques. These results indicate that Microsoft Excel and VBA can be useful tools for utilizing PBPK models, and given the availability of these software programs, it is hoped that this effort will help facilitate the use and investigation of PBPK modeling.

  17. Physiologically-Based Toxicokinetic Modeling of Zearalenone and Its Metabolites: Application to the Jersey Girl Study

    Science.gov (United States)

    Mukherjee, Dwaipayan; Royce, Steven G.; Alexander, Jocelyn A.; Buckley, Brian; Isukapalli, Sastry S.; Bandera, Elisa V.; Zarbl, Helmut; Georgopoulos, Panos G.

    2014-01-01

    Zearalenone (ZEA), a fungal mycotoxin, and its metabolite zeranol (ZAL) are known estrogen agonists in mammals, and are found as contaminants in food. Zeranol, which is more potent than ZEA and comparable in potency to estradiol, is also added as a growth additive in beef in the US and Canada. This article presents the development and application of a Physiologically-Based Toxicokinetic (PBTK) model for ZEA and ZAL and their primary metabolites, zearalenol, zearalanone, and their conjugated glucuronides, for rats and for human subjects. The PBTK modeling study explicitly simulates critical metabolic pathways in the gastrointestinal and hepatic systems. Metabolic events such as dehydrogenation and glucuronidation of the chemicals, which have direct effects on the accumulation and elimination of the toxic compounds, have been quantified. The PBTK model considers urinary and fecal excretion and biliary recirculation and compares the predicted biomarkers of blood, urinary and fecal concentrations with published in vivo measurements in rats and human subjects. Additionally, the toxicokinetic model has been coupled with a novel probabilistic dietary exposure model and applied to the Jersey Girl Study (JGS), which involved measurement of mycoestrogens as urinary biomarkers, in a cohort of young girls in New Jersey, USA. A probabilistic exposure characterization for the study population has been conducted and the predicted urinary concentrations have been compared to measurements considering inter-individual physiological and dietary variability. The in vivo measurements from the JGS fall within the high and low predicted distributions of biomarker values corresponding to dietary exposure estimates calculated by the probabilistic modeling system. The work described here is the first of its kind to present a comprehensive framework developing estimates of potential exposures to mycotoxins and linking them with biologically relevant doses and biomarker measurements

  18. PKQuest_Java: free, interactive physiologically based pharmacokinetic software package and tutorial

    Directory of Open Access Journals (Sweden)

    Levitt David G

    2009-08-01

    Full Text Available Abstract Background Physiologically based pharmacokinetics (PBPK uses a realistic organ model to describe drug kinetics. The blood-tissue exchange of each organ is characterized by its volume, perfusion, metabolism, capillary permeability and blood/tissue partition coefficient. PBPK applications require both sophisticated mathematical modeling software and a reliable complete set of physiological parameters. Currently there are no software packages available that combine ease of use with the versatility that is required of a general PBPK program. Findings The program is written in Java and is available for free download at http://www.pkquest.com/. Included in the download is a detailed tutorial that discusses the pharmacokinetics of 6 solutes (D2O, amoxicillin, desflurane, propofol, ethanol and thiopental illustrated using experimental human pharmacokinetic data. The complete PBPK description for each solute is stored in Excel spreadsheets that are included in the download. The main features of the program are: 1 Intuitive and versatile interactive interface; 2 Absolute and semi-logarithmic graphical output; 3 Pre-programmed optimized human parameter data set (but, arbitrary values can be input; 4 Time dependent changes in the PBPK parameters; 5 Non-linear parameter optimization; 6 Unique approach to determine the oral "first pass metabolism" of non-linear solutes (e.g. ethanol; 7 Pulmonary perfusion/ventilation heterogeneity for volatile solutes; 8 Input and output of Excel spreadsheet data; 9 Antecubital vein sampling. Conclusion PKQuest_Java is a free, easy to use, interactive PBPK software routine. The user can either directly use the pre-programmed optimized human or rat data set, or enter an arbitrary data set. It is designed so that drugs that are classified as "extracellular" or "highly fat soluble" do not require information about tissue/blood partition coefficients and can be modeled by a minimum of user input parameters. PKQuest

  19. PKQuest_Java: free, interactive physiologically based pharmacokinetic software package and tutorial.

    Science.gov (United States)

    Levitt, David G

    2009-08-05

    Physiologically based pharmacokinetics (PBPK) uses a realistic organ model to describe drug kinetics. The blood-tissue exchange of each organ is characterized by its volume, perfusion, metabolism, capillary permeability and blood/tissue partition coefficient. PBPK applications require both sophisticated mathematical modeling software and a reliable complete set of physiological parameters. Currently there are no software packages available that combine ease of use with the versatility that is required of a general PBPK program. The program is written in Java and is available for free download at http://www.pkquest.com/. Included in the download is a detailed tutorial that discusses the pharmacokinetics of 6 solutes (D2O, amoxicillin, desflurane, propofol, ethanol and thiopental) illustrated using experimental human pharmacokinetic data. The complete PBPK description for each solute is stored in Excel spreadsheets that are included in the download. The main features of the program are: 1) Intuitive and versatile interactive interface; 2) Absolute and semi-logarithmic graphical output; 3) Pre-programmed optimized human parameter data set (but, arbitrary values can be input); 4) Time dependent changes in the PBPK parameters; 5) Non-linear parameter optimization; 6) Unique approach to determine the oral "first pass metabolism" of non-linear solutes (e.g. ethanol); 7) Pulmonary perfusion/ventilation heterogeneity for volatile solutes; 8) Input and output of Excel spreadsheet data; 9) Antecubital vein sampling. PKQuest_Java is a free, easy to use, interactive PBPK software routine. The user can either directly use the pre-programmed optimized human or rat data set, or enter an arbitrary data set. It is designed so that drugs that are classified as "extracellular" or "highly fat soluble" do not require information about tissue/blood partition coefficients and can be modeled by a minimum of user input parameters. PKQuest_Java, along with the included tutorial, could be

  20. Physiologically based kinetic modeling of bioactivation and detoxification of the alkenylbenzene methyleugenol in human as compared with rat

    NARCIS (Netherlands)

    Al-Subeihi, A.A.; Spenkelink, A.; Punt, A.; Boersma, M.G.; Bladeren, van P.J.; Rietjens, I.

    2012-01-01

    This study defines a physiologically based kinetic (PBK) model for methyleugenol (ME) in human based on in vitro and in silico derived parameters. With the model obtained, bioactivation and detoxification of methyleugenol (ME) at different doses levels could be investigated. The outcomes of the curr

  1. Physiologically based kinetic models for the alkenylbenzene elemicin in rat and human and possible implications for risk assessment.

    NARCIS (Netherlands)

    Berg, van den S.J.; Punt, A.; Soffers, A.E.M.F.; Vervoort, J.J.M.; Ngeleja, S.; Spenkelink, B.; Rietjens, I.M.C.M.

    2012-01-01

    The present study describes physiologically based kinetic (PBK) models for the alkenylbenzene elemicin (3,4,5-trimethoxyallylbenzene) in rat and human, based on the PBK models previously developed for the structurally related alkenylbenzenes estragole, methyleugenol, and safrole. Using the newly dev

  2. Development of Multi-Route Physiologically-based Pharmacokinetic Models for Ethanol in the Adult, Pregnant, and Neonatal Rat

    Science.gov (United States)

    Biofuel blends of 10% ethanol (EtOH) and gasoline are common in the United States, and higher EtOH concentrations are being considered (15-85%). Currently, no physiologically-based pharmacokinetic (PBPK) models are available to describe the kinetics of EtOH-based biofuels. PBPK...

  3. The use of in vitro metabolic parameters and physiologically based pharmacokinetic (PBPK) modeling to explore the risk assessment of trichloroethylene

    NARCIS (Netherlands)

    Hissink, E.M.; Bogaards, J.J.P.; Freidig, A.P.; Commandeur, J.N.M.; Vermeulen, N.P.E.; Bladeren, P.J. van

    2002-01-01

    A physiologically based pharmacokinetic (PBPK) model has been developed for trichloroethylene (1,1,2-trichloroethene, TRI) for rat and humans, based on in vitro metabolic parameters. These were obtained using individual cytochrome P450 and glutathione S-transferase enzymes. The main enzymes involved

  4. A novel bench-scale column assay to investigate site-specific nitrification biokinetics in biological rapid sand filters

    DEFF Research Database (Denmark)

    Tatari, Karolina; Smets, Barth F.; Albrechtsen, Hans-Jørgen

    2013-01-01

    A bench-scale assay was developed to obtain site-specific nitrification biokinetic information from biological rapid sand filters employed in groundwater treatment. The experimental set-up uses granular material subsampled from a full-scale filter, packed in a column, and operated with controlled....../h could easily be determined at 7.5 g NH4+–N/m3 packed sand/h. This assay, with conditions reflecting full-scale observations, and where the biological activity is subject to minimal physical disturbance, provides a simple and fast, yet powerful tool to gain insight in nitrification kinetics in rapid sand...

  5. Biokinetics and imaging with the somatostatin receptor PET radioligand {sup 68}Ga-DOTATOC: preliminary data

    Energy Technology Data Exchange (ETDEWEB)

    Hofmann, M.; Boerner, A.R.; Weckesser, E.; Oei, M.L.; Meyer, G.J.; Knapp, W.H. [Dept. of Nuclear Medicine, Hannover University Medical School (Germany); Maecke, H.; Heppeler, A. [Dept. of Radiology, Kantonspittal, Basel (Switzerland); Schoeffski, P. [Dept. of Haematology and Oncology, Hannover University Medical School (Germany); Schumacher, J.; Henze, M. [German Cancer Research Centre, Heidelberg (Germany)

    2001-12-01

    Somatostatin (SMS) scintigraphy is widely used for the detection and staging of neuroendocrine tumours. Because of its superior imaging properties, there is growing interest in the use of positron emission tomography (PET) technology for SMS scintigraphy. This study addressed the production of gallium-68 DOTATOC, its biokinetics and its clinical performance in detecting SMS-positive tumours and metastases. A preparation protocol was developed, yielding 40% overall incorporation of {sup 68}Ga into the peptide (DOTATOC). After column filtration, the radiochemical purity exceeded 98%. Eight patients with histologically verified carcinoid tumours were injected with 80-250 MBq of this tracer. PET acquisition was initiated immediately after administration and carried out until 3 h post injection. Images were quantitated using standardised uptake values and target to non-target ratios. Prior to {sup 68}Ga-DOTATOC PET, all patients underwent indium-111 octreotide planar and single-photon emission tomographic (SPET) imaging. Arterial activity elimination was bi-exponential, with half-lives of 2.0 ({+-}0.3) min and 48 ({+-}7) min. No radioactive metabolites were detected within 4 h in serum. Maximal tumour activity accumulation was reached 70{+-}20 min post injection. Kidney uptake averaged <50% compared with spleen uptake. Of 40 lesions predefined by computed tomography and/or magnetic resonance imaging, {sup 68}Ga-DOTATOC PET identified 100%, whereas {sup 111}In-octreotide planar and SPET imaging identified only 85%. Tumour to non-tumour ratios ranged from >3:1 for liver ({sup 111}In-octreotide: 1.5:1) to 100:1 for CNS ({sup 111}In-octreotide: 10:1). With {sup 68}Ga-DOTATOC >30% additional lesions were detected. It is concluded that PET using {sup 68}Ga-DOTATOC results in high tumour to non-tumour contrast and low kidney accumulation and yields higher detection rates as compared with {sup 111}In-octreotide scintigraphy. (orig.)

  6. Biokinetics and imaging with the somatostatin receptor PET radioligand (68)Ga-DOTATOC: preliminary data.

    Science.gov (United States)

    Hofmann, M; Maecke, H; Börner, R; Weckesser, E; Schöffski, P; Oei, L; Schumacher, J; Henze, M; Heppeler, A; Meyer, J; Knapp, H

    2001-12-01

    Somatostatin (SMS) scintigraphy is widely used for the detection and staging of neuroendocrine tumours. Because of its superior imaging properties, there is growing interest in the use of positron emission tomography (PET) technology for SMS scintigraphy. This study addressed the production of gallium-68 DOTATOC, its biokinetics and its clinical performance in detecting SMS-positive tumours and metastases. A preparation protocol was developed, yielding 40% overall incorporation of (68)Ga into the peptide (DOTATOC). After column filtration, the radiochemical purity exceeded 98%. Eight patients with histologically verified carcinoid tumours were injected with 80-250 MBq of this tracer. PET acquisition was initiated immediately after administration and carried out until 3 h post injection. Images were quantitated using standardised uptake values and target to non-target ratios. Prior to (68)Ga-DOTATOC PET, all patients underwent indium-111 octreotide planar and single-photon emission tomographic (SPET) imaging. Arterial activity elimination was bi-exponential, with half-lives of 2.0 (+/-0.3) min and 48 (+/-7) min. No radioactive metabolites were detected within 4 h in serum. Maximal tumour activity accumulation was reached 70+/-20 min post injection. Kidney uptake averaged 68)Ga-DOTATOC PET identified 100%, whereas (111)In-octreotide planar and SPET imaging identified only 85%. Tumour to non-tumour ratios ranged from >3:1 for liver ((111)In-octreotide: 1.5:1) to 100:1 for CNS ((111)In-octreotide: 10:1). With (68)Ga-DOTATOC >30% additional lesions were detected. It is concluded that PET using (68)Ga-DOTATOC results in high tumour to non-tumour contrast and low kidney accumulation and yields higher detection rates as compared with (111)In-octreotide scintigraphy.

  7. Can Computer-Based Visual-Spatial Aids Lead to Increased Student Performance in Anatomy & Physiology?

    Science.gov (United States)

    Kesner, Michael H.; Linzey, Alicia V.

    2005-01-01

    InterActive Physiology (IAP) is one of a new generation of anatomy and physiology learning aids with a broader range of sensory inputs than is possible from a static textbook or moderately dynamic lecture. This best-selling software has modules covering the muscular, respiratory, urinary, cardiovascular, and nervous systems plus a module on fluids…

  8. Smartwatch-based driver alertness monitoring with wearable motion and physiological sensor.

    Science.gov (United States)

    Lee, Boon-Giin; Lee, Boon-Leng; Chung, Wan-Young

    2015-01-01

    Studies have shown that a high precision driver alertness monitoring system is an essential and a monetary countermeasure to reduce the road accidents. This paper presents a novel approach to measure the driver alertness, evaluated by a smartwatch device based on fusion of direct and indirect method. The driver chronic physiological state is monitor by adopting a photoplethysmography sensor on the driver finger that is connected to a wrist-type wearable device. A Bluetooth Low Energy module connected to the wearable device transmits the PPG data to the smartwatch in real-time. Meanwhile, the indirect method, driver steering wheel movement can be derived by utilizing the motion sensors integrated in the smartwatch which include a tri-axis accelerometer and a gyroscope sensors. The respiration signals can be derived from the PPG time- and frequency-domains attributes. The data obtained from both methods aforementioned are subsequently decomposed into relevant features in time, spectral context and phase space domain, and thus computes the alertness index. Here, the correlations between the extracted features and the subjective Koralinska Sleepiness Scale are studied as well along with the recorded experimental videos. This study reveals that the alertness index prediction accuracy can be reached up to 96.3% based on the descriptive extracted features.

  9. Physiologically based pharmacokinetic modeling for 1-bromopropane in F344 rats using gas uptake inhalation experiments.

    Science.gov (United States)

    Garner, C Edwin; Liang, Shenxuan; Yin, Lei; Yu, Xiaozhong

    2015-05-01

    1-Bromopropane (1-BP) was introduced into the workplace as an alternative to ozone-depleting solvents and increasingly used in manufacturing industry. The potential exposure to 1-BP and the current reports of adverse effects associated with occupational exposure to high levels of 1-BP have increased the need to understand the mechanism of 1-BP toxicity in animal models as a mean of understanding risk in workers. Physiologically based pharmacokinetic (PBPK) model for 1-BP has been developed to examine 2 metabolic pathway assumptions for gas-uptake inhalation study. Based on previous gas-uptake experiments in the Fischer 344 rat, the PBPK model was developed by simulating the 1-BP concentration in a closed chamber. In the model, we tested the hypothesis that metabolism responsibilities were shared by the p450 CYP2E1 and glutathione (GSH) conjugation. The results showed that 2 metabolic pathways adequately simulated 1-BP closed chamber concentration. Furthermore, the above model was tested by simulating the gas-uptake data of the female rats pretreated with 1-aminobenzotrizole, a general P450 suicide inhibitor, or d,l-buthionine (S,R)-sulfoximine, an inhibitor of GSH synthesis, prior to exposure to 800 ppm 1-BP. The comparative investigation on the metabolic pathway of 1-BP through the PBPK modeling in both sexes provides critical information for understanding the role of p450 and GSH in the metabolism of 1-BP and eventually helps to quantitatively extrapolate current animal studies to human.

  10. Wearable carbon nanotube-based fabric sensors for monitoring human physiological performance

    Science.gov (United States)

    Wang, Long; Loh, Kenneth J.

    2017-05-01

    A target application of wearable sensors is to detect human motion and to monitor physical activity for improving athletic performance and for delivering better physical therapy. In addition, measuring human vital signals (e.g., respiration rate and body temperature) provides rich information that can be used to assess a subject’s physiological or psychological condition. This study aims to design a multifunctional, wearable, fabric-based sensing system. First, carbon nanotube (CNT)-based thin films were fabricated by spraying. Second, the thin films were integrated with stretchable fabrics to form the fabric sensors. Third, the strain and temperature sensing properties of sensors fabricated using different CNT concentrations were characterized. Furthermore, the sensors were demonstrated to detect human finger bending motions, so as to validate their practical strain sensing performance. Finally, to monitor human respiration, the fabric sensors were integrated with a chest band, which was directly worn by a human subject. Quantification of respiration rates were successfully achieved. Overall, the fabric sensors were characterized by advantages such as flexibility, ease of fabrication, lightweight, low-cost, noninvasiveness, and user comfort.

  11. Physiologically based Pharmacokinetic Modeling of 1,4-Dioxane in Rats, Mice, and Humans

    Energy Technology Data Exchange (ETDEWEB)

    Sweeney, Lisa M.; Thrall, Karla D.; Poet, Torka S.; Corley, Rick; Weber, Thomas J.; Locey, B. J.; Clarkson, Jacquelyn; Sager, S.; Gargas, M. L.

    2008-01-01

    ABSTRACT 1,4-Dioxane (CAS No. 123-91-1) is used primarily as a solvent or as a solvent stabilizer. It can cause lung, liver and kidney damage at sufficiently high exposure levels. Two physiologically-based pharmacokinetic (PBPK) models of 1,4-dioxane and its major metabolite, hydroxyethoxyacetic acid (HEAA), were published in 1990. These models have uncertainties and deficiencies that could be addressed and the model strengthened for use in a contemporary cancer risk assessment for 1,4-dioxane. Studies were performed to fill data gaps and reduce uncertainties pertaining to the pharmacokinetics of 1,4-dioxane and HEAA in rats, mice, and humans. Three types of studies were performed:partition coefficient measurements, blood time course in mice, and in vitro pharmacokinetics using rat, mouse, and human hepatocytes. Updated PBPK models were developed based on these new data and previously available data. The optimized rate of metabolism for the mouse was significantly higher than the value previously estimated. The optimized rat kinetic parameters were similar to those in the 1990 models. Only two human studies were identified. Model predictions were consistent with one study, but did not fit the second as well. In addition, a rat nasal exposure was completed. The results confirmed water directly contacts rat nasal tissues during drinking water under bioassays. Consistent with previous PBPK models, nasal tissues were not specifically included in the model. Use of these models will reduce the uncertainty in future 1,4-dioxane risk assessments.

  12. Physiologically based pharmacokinetic modeling of 1,4-Dioxane in rats, mice, and humans.

    Science.gov (United States)

    Sweeney, Lisa M; Thrall, Karla D; Poet, Torka S; Corley, Richard A; Weber, Thomas J; Locey, Betty J; Clarkson, Jacquelyn; Sager, Shawn; Gargas, Michael L

    2008-01-01

    1,4-Dioxane (CAS No. 123-91-1) is used primarily as a solvent or as a solvent stabilizer. It can cause lung, liver, and kidney damage at sufficiently high exposure levels. Two physiologically based pharmacokinetic (PBPK) models of 1,4-dioxane and its major metabolite, hydroxyethoxyacetic acid (HEAA), were published in 1990. These models have uncertainties and deficiencies that could be addressed and the model strengthened for use in a contemporary cancer risk assessment for 1,4-dioxane. Studies were performed to fill data gaps and reduce uncertainties pertaining to the pharmacokinetics of 1,4-dioxane and HEAA in rats, mice, and humans. Three types of studies were performed: partition coefficient measurements, blood time course in mice, and in vitro pharmacokinetics using rat, mouse, and human hepatocytes. Updated PBPK models were developed based on these new data and previously available data. The optimized rate of metabolism for the mouse was significantly higher than the value previously estimated. The optimized rat kinetic parameters were similar to those in the 1990 models. Only two human studies were identified. Model predictions were consistent with one study, but did not fit the second as well. In addition, a rat nasal exposure was completed. The results confirmed water directly contacts rat nasal tissues during drinking water under bioassay conditions. Consistent with previous PBPK models, nasal tissues were not specifically included in the model. Use of these models will reduce the uncertainty in future 1,4-dioxane risk assessments.

  13. Adaptation of task difficulty in rehabilitation exercises based on the user's motor performance and physiological responses.

    Science.gov (United States)

    Shirzad, Navid; Van der Loos, H F Machiel

    2013-06-01

    Although robot-assisted rehabilitation regimens are as effective, functionally, as conventional therapies, they still lack features to increase patients' engagement in the regimen. Providing rehabilitation tasks at a "desirable difficulty" is one of the ways to address this issue and increase the motivation of a patient to continue with the therapy program. Then the problem is to design a system that is capable of estimating the user's desirable difficulty, and ultimately, modifying the task based on this prediction. In this paper we compared the performance of three machine learning algorithms in predicting a user's desirable difficulty during a typical reaching motion rehabilitation task. Different levels of error amplification were used as different levels of task difficulty. We explored the usefulness of using participants' motor performance and physiological signals during the reaching task in prediction of their desirable difficulties. Results showed that a Neural Network approach gives higher prediction accuracy in comparison with models based on k-Nearest Neighbor and Discriminant Analysis methods.

  14. Physiological levels of HBB transgene expression from S/MAR element-based replicating episomal vectors.

    Science.gov (United States)

    Sgourou, Argyro; Routledge, Samantha; Spathas, Dionysios; Athanassiadou, Aglaia; Antoniou, Michael N

    2009-08-20

    Replicating episomal vectors (REV) are in principle able to provide long-term transgene expression in the absence of integration into the target cell genome. The scaffold/matrix attachment region (S/MAR) located 5' of the human beta-interferon gene (IFNB1) has been shown to confer a stable episomal replication and retention function within plasmid vectors when stably transfected and selected in mammalian cells. The minimal requirement for the IFNB1 S/MAR to function in DNA replication and episomal retention is transcription through this element. We used the erythroid beta-globin locus control region-beta-globin gene (betaLCR-HBB) microlocus cassette as a model to assess tissue-specific expression from within an IFNB1 S/MAR-based plasmid REV. The betaLCR-HBB plus S/MAR combination constructs provided either high or low levels of transcription through the S/MAR element. Our results show that the betaLCR-HBB microlocus is able to reproducibly and stably express at full physiological levels on an episome copy number basis. In addition, our data show that even low levels of transcription from betaLCR-HBB through the S/MAR element are sufficient to allow efficient episomal replication and retention. These data provide the principles upon which generic and flexible expression cassette-S/MAR-based REVs can be designed for a wide range of applications.

  15. Specificity improvement for network distributed physiologic alarms based on a simple deterministic reactive intelligent agent in the critical care environment.

    Science.gov (United States)

    Blum, James M; Kruger, Grant H; Sanders, Kathryn L; Gutierrez, Jorge; Rosenberg, Andrew L

    2009-02-01

    Automated physiologic alarms are available in most commercial physiologic monitors. However, due to the variability of data coming from the physiologic sensors describing the state of patients, false positive alarms frequently occur. Each alarm requires review and documentation, which consumes clinicians' time, may reduce patient safety through 'alert fatigue' and makes automated physician paging infeasible. To address these issues a computerized architecture based on simple reactive intelligent agent technology has been developed and implemented in a live critical care unit to facilitate the investigation of deterministic algorithms for the improvement of the sensitivity and specificity of physiologic alarms. The initial proposed algorithm uses a combination of median filters and production rules to make decisions about what alarms to generate. The alarms are used to classify the state of patients and alerts can be easily viewed and distributed using standard network, SQL database and Internet technologies. To evaluate the proposed algorithm, a 28 day study was conducted in the University of Michigan Medical Center's 14 bed Cardiothoracic Intensive Care Unit. Alarms generated by patient monitors, the intelligent agent and alerts documented on patient flow sheets were compared. Significant improvements in the specificity of the physiologic alarms based on systolic and mean blood pressure was found on average to be 99% and 88% respectively. Even through significant improvements were noted based on this algorithm much work still needs to be done to ensure the sensitivity of alarms and methods to handle spurious sensor data due to patient or sensor movement and other influences.

  16. A physiologically based pharmacokinetic model for ionic silver and silver nanoparticles

    Directory of Open Access Journals (Sweden)

    Bachler G

    2013-09-01

    Full Text Available Gerald Bachler, Natalie von Goetz, Konrad Hungerbühler ETH Zurich, Institute for Chemical and Bioengineering, Zurich, Switzerland Abstract: Silver is a strong antibiotic that is increasingly incorporated into consumer products as a bulk, salt, or nanosilver, thus potentially causing side-effects related to human exposure. However, the fate and behavior of (nanosilver in the human body is presently not well understood. In order to aggregate the existing experimental information, a physiologically based pharmacokinetic model (PBPK was developed in this study for ionic silver and nanosilver. The structure of the model was established on the basis of toxicokinetic data from intravenous studies. The number of calibrated parameters was minimized in order to enhance the predictive capability of the model. We validated the model structure for both silver forms by reproducing exposure conditions (dermal, oral, and inhalation of in vivo experiments and comparing simulated and experimentally assessed organ concentrations. Therefore, the percutaneous, intestinal, or pulmonary absorption fraction was estimated based on the blood silver concentration of the respective experimental data set. In all of the cases examined, the model could successfully predict the biodistribution of ionic silver and 15–150 nm silver nanoparticles, which were not coated with substances designed to prolong the circulatory time (eg, polyethylene glycol. Furthermore, the results of our model indicate that: (1 within the application domain of our model, the particle size and coating had a minor influence on the biodistribution; (2 in vivo, it is more likely that silver nanoparticles are directly stored as insoluble salt particles than dissolve into Ag+; and (3 compartments of the mononuclear phagocytic system play a minor role in exposure levels that are relevant for human consumers. We also give an example of how the model can be used in exposure and risk assessments based on five

  17. A physiologically based pharmacokinetic model for ionic silver and silver nanoparticles

    Science.gov (United States)

    Bachler, Gerald; von Goetz, Natalie; Hungerbühler, Konrad

    2013-01-01

    Silver is a strong antibiotic that is increasingly incorporated into consumer products as a bulk, salt, or nanosilver, thus potentially causing side-effects related to human exposure. However, the fate and behavior of (nano)silver in the human body is presently not well understood. In order to aggregate the existing experimental information, a physiologically based pharmacokinetic model (PBPK) was developed in this study for ionic silver and nanosilver. The structure of the model was established on the basis of toxicokinetic data from intravenous studies. The number of calibrated parameters was minimized in order to enhance the predictive capability of the model. We validated the model structure for both silver forms by reproducing exposure conditions (dermal, oral, and inhalation) of in vivo experiments and comparing simulated and experimentally assessed organ concentrations. Therefore, the percutaneous, intestinal, or pulmonary absorption fraction was estimated based on the blood silver concentration of the respective experimental data set. In all of the cases examined, the model could successfully predict the biodistribution of ionic silver and 15–150 nm silver nanoparticles, which were not coated with substances designed to prolong the circulatory time (eg, polyethylene glycol). Furthermore, the results of our model indicate that: (1) within the application domain of our model, the particle size and coating had a minor influence on the biodistribution; (2) in vivo, it is more likely that silver nanoparticles are directly stored as insoluble salt particles than dissolve into Ag+; and (3) compartments of the mononuclear phagocytic system play a minor role in exposure levels that are relevant for human consumers. We also give an example of how the model can be used in exposure and risk assessments based on five different exposure scenarios, namely dietary intake, use of three separate consumer products, and occupational exposure. PMID:24039420

  18. A physiologically based toxicokinetic model for methylmercury in female American kestrels

    Science.gov (United States)

    Nichols, J.W.; Bennett, R.S.; Rossmann, R.; French, J.B.; Sappington, K.G.

    2010-01-01

    A physiologically based toxicokinetic (PBTK) model was developed to describe the uptake, distribution, and elimination of methylmercury (CH 3Hg) in female American kestrels. The model consists of six tissue compartments corresponding to the brain, liver, kidney, gut, red blood cells, and remaining carcass. Additional compartments describe the elimination of CH3Hg to eggs and growing feathers. Dietary uptake of CH 3Hg was modeled as a diffusion-limited process, and the distribution of CH3Hg among compartments was assumed to be mediated by the flow of blood plasma. To the extent possible, model parameters were developed using information from American kestrels. Additional parameters were based on measured values for closely related species and allometric relationships for birds. The model was calibrated using data from dietary dosing studies with American kestrels. Good agreement between model simulations and measured CH3Hg concentrations in blood and tissues during the loading phase of these studies was obtained by fitting model parameters that control dietary uptake of CH 3Hg and possible hepatic demethylation. Modeled results tended to underestimate the observed effect of egg production on circulating levels of CH3Hg. In general, however, simulations were consistent with observed patterns of CH3Hg uptake and elimination in birds, including the dominant role of feather molt. This model could be used to extrapolate CH 3Hg kinetics from American kestrels to other bird species by appropriate reassignment of parameter values. Alternatively, when combined with a bioenergetics-based description, the model could be used to simulate CH 3Hg kinetics in a long-term environmental exposure. ?? 2010 SETAC.

  19. Learning style-based teaching harvests a superior comprehension of respiratory physiology.

    Science.gov (United States)

    Anbarasi, M; Rajkumar, G; Krishnakumar, S; Rajendran, P; Venkatesan, R; Dinesh, T; Mohan, J; Venkidusamy, S

    2015-09-01

    Students entering medical college generally show vast diversity in their school education. It becomes the responsibility of teachers to motivate students and meet the needs of all diversities. One such measure is teaching students in their own preferred learning style. The present study was aimed to incorporate a learning style-based teaching-learning program for medical students and to reveal its significance and utility. Learning styles of students were assessed online using the visual-auditory-kinesthetic (VAK) learning style self-assessment questionnaire. When respiratory physiology was taught, students were divided into three groups, namely, visual (n = 34), auditory (n = 44), and kinesthetic (n = 28), based on their learning style. A fourth group (the traditional group; n = 40) was formed by choosing students randomly from the above three groups. Visual, auditory, and kinesthetic groups were taught following the appropriate teaching-learning strategies. The traditional group was taught via the routine didactic lecture method. The effectiveness of this intervention was evaluated by a pretest and two posttests, posttest 1 immediately after the intervention and posttest 2 after a month. In posttest 1, one-way ANOVA showed a significant statistical difference (P=0.005). Post hoc analysis showed significance between the kinesthetic group and traditional group (P=0.002). One-way ANOVA showed a significant difference in posttest 2 scores (P < 0.0001). Post hoc analysis showed significance between the three learning style-based groups compared with the traditional group [visual vs. traditional groups (p=0.002), auditory vs. traditional groups (p=0.03), and Kinesthetic vs. traditional groups (p=0.001)]. This study emphasizes that teaching methods tailored to students' style of learning definitely improve their understanding, performance, and retrieval of the subject.

  20. Research on Healthy Anomaly Detection Model Based on Deep Learning from Multiple Time-Series Physiological Signals

    Directory of Open Access Journals (Sweden)

    Kai Wang

    2016-01-01

    Full Text Available Health is vital to every human being. To further improve its already respectable medical technology, the medical community is transitioning towards a proactive approach which anticipates and mitigates risks before getting ill. This approach requires measuring the physiological signals of human and analyzes these data at regular intervals. In this paper, we present a novel approach to apply deep learning in physiological signals analysis that allows doctor to identify latent risks. However, extracting high level information from physiological time-series data is a hard problem faced by the machine learning communities. Therefore, in this approach, we apply model based on convolutional neural network that can automatically learn features from raw physiological signals in an unsupervised manner and then based on the learned features use multivariate Gauss distribution anomaly detection method to detect anomaly data. Our experiment is shown to have a significant performance in physiological signals anomaly detection. So it is a promising tool for doctor to identify early signs of illness even if the criteria are unknown a priori.

  1. Lipid rafts-mediated endocytosis and physiology-based cell membrane traffic models of doxorubicin liposomes.

    Science.gov (United States)

    Li, Yinghuan; Gao, Lei; Tan, Xi; Li, Feiyang; Zhao, Ming; Peng, Shiqi

    2016-08-01

    The clathrin-mediated endocytosis is likely a major mechanism of liposomes' internalization. A kinetic approach was used to assess the internalization mechanism of doxorubicin (Dox) loaded cationic liposomes and to establish physiology-based cell membrane traffic mathematic models. Lipid rafts-mediated endocytosis, including dynamin-dependent or -independent endocytosis of noncaveolar structure, was a dominant process. The mathematic models divided Dox loaded liposomes binding lipid rafts (B) into saturable binding (SB) and nonsaturable binding (NSB) followed by energy-driven endocytosis. The intracellular trafficking demonstrated early endosome-late endosome-lysosome or early/late endosome-cytoplasm-nucleus pathways. The three properties of liposome structures, i.e., cationic lipid, fusogenic lipid, and pegylation, were investigated to compare their contributions to cell membrane and intracellular traffic. The results revealed great contribution of cationic lipid DOTAP and fusogenic lipid DOPE to cell membrane binding and internalization. The valid Dox in the nuclei of HepG2 and A375 cells treated with cationic liposomes containing 40mol% of DOPE were 1.2-fold and 1.5-fold higher than that in the nuclei of HepG2 and A375 cells treated with liposomes containing 20mol% of DOPE, respectively, suggesting the dependence of cell type. This tendency was proportional to the increase of cell-associated total liposomal Dox. The mathematic models would be useful to predict intracellular trafficking of liposomal Dox.

  2. Filter-based multiscale entropy analysis of complex physiological time series.

    Science.gov (United States)

    Xu, Yuesheng; Zhao, Liang

    2013-08-01

    Multiscale entropy (MSE) has been widely and successfully used in analyzing the complexity of physiological time series. We reinterpret the averaging process in MSE as filtering a time series by a filter of a piecewise constant type. From this viewpoint, we introduce filter-based multiscale entropy (FME), which filters a time series to generate multiple frequency components, and then we compute the blockwise entropy of the resulting components. By choosing filters adapted to the feature of a given time series, FME is able to better capture its multiscale information and to provide more flexibility for studying its complexity. Motivated by the heart rate turbulence theory, which suggests that the human heartbeat interval time series can be described in piecewise linear patterns, we propose piecewise linear filter multiscale entropy (PLFME) for the complexity analysis of the time series. Numerical results from PLFME are more robust to data of various lengths than those from MSE. The numerical performance of the adaptive piecewise constant filter multiscale entropy without prior information is comparable to that of PLFME, whose design takes prior information into account.

  3. Problem-based writing with peer review improves academic performance in physiology.

    Science.gov (United States)

    Pelaez, Nancy J

    2002-12-01

    The aim of this study was to determine whether problem-based writing with peer review (PW-PR) improves undergraduate student performance on physiology exams. Didactic lectures were replaced with assignments to give students practice explaining their reasoning while solving qualitative problems, thus transferring the responsibility for abstraction and generalization to the students. Performance on exam items about concepts taught using PW-PR was compared with performance on concepts taught using didactic lectures followed by group work. Calibrated Peer Review, a Web-delivered program, was used to collect student essays and to manage anonymous peer review after students "passed" three calibration peer reviews. Results show that the students had difficulty relating concepts. Relationship errors were categorized as (1) problems recognizing levels of organization, (2) problems with cause/effect, and (3) overgeneralizations. For example, some described cells as molecules; others thought that vesicles transport materials through the extracellular fluid. With PW-PR, class discussion was used to confront and resolve such difficulties. Both multiple-choice and essay exam results were better with PW-PR instead of lecture.

  4. Indoor Air Quality Assessment Based on Human Physiology - Part 1. New Criteria Proposal

    Directory of Open Access Journals (Sweden)

    M. V. Jokl

    2003-01-01

    Full Text Available Human physiology research makes evident that the Weber-Fechner law applies not only to noise perception but also to the perception of other environmental components. Based on this fact, new decibel units for dor component representing indoor air quality in majority locations have been proposed: decicarbdiox dCd (for carbon dioxide CO2 and decitvoc dTv (for total volatile organic compound TVOC. Equations of these new units have been proved by application of a experimental relationships between odor intensity (representing odor perception by the human body and odor concentrations of CO2 and TVOC, b individually  measured CO2 and TVOC levels (concentrations – from these new decibel units can be calculated and their values compared with decibel units of noise measured in the same locations. The undoubted benefit of using the decibel scale is that it gives much better approximation to human perception of odor intensity compared to the CO2 and TVOC concentration scales.

  5. Physiologically Based Pharmacokinetic Modeling Framework for Quantitative Prediction of an Herb–Drug Interaction

    Science.gov (United States)

    Brantley, S J; Gufford, B T; Dua, R; Fediuk, D J; Graf, T N; Scarlett, Y V; Frederick, K S; Fisher, M B; Oberlies, N H; Paine, M F

    2014-01-01

    Herb–drug interaction predictions remain challenging. Physiologically based pharmacokinetic (PBPK) modeling was used to improve prediction accuracy of potential herb–drug interactions using the semipurified milk thistle preparation, silibinin, as an exemplar herbal product. Interactions between silibinin constituents and the probe substrates warfarin (CYP2C9) and midazolam (CYP3A) were simulated. A low silibinin dose (160 mg/day × 14 days) was predicted to increase midazolam area under the curve (AUC) by 1%, which was corroborated with external data; a higher dose (1,650 mg/day × 7 days) was predicted to increase midazolam and (S)-warfarin AUC by 5% and 4%, respectively. A proof-of-concept clinical study confirmed minimal interaction between high-dose silibinin and both midazolam and (S)-warfarin (9 and 13% increase in AUC, respectively). Unexpectedly, (R)-warfarin AUC decreased (by 15%), but this is unlikely to be clinically important. Application of this PBPK modeling framework to other herb–drug interactions could facilitate development of guidelines for quantitative prediction of clinically relevant interactions. PMID:24670388

  6. Design of a telemetry system based on wireless power transmission for physiological parameter monitoring

    Energy Technology Data Exchange (ETDEWEB)

    Jia, Zhiwei, E-mail: jiayege@hotmail.com [College of Electrical and Information Engineering, Changsha University of Science and Technology, Changsha (China); Yan, Guozheng; Zhu, Bingquan [820 Institute, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai (China)

    2015-04-15

    An implanted telemetry system for experimental animals with or without anaesthesia can be used to continuously monitor physiological parameters. This system is significant not only in the study of organisms but also in the evaluation of drug efficacy, artificial organs, and auxiliary devices. The system is composed of a miniature electronic capsule, a wireless power transmission module, a data-recording device, and a processing module. An electrocardiograph, a temperature sensor, and a pressure sensor are integrated in the miniature electronic capsule, in which the signals are transmitted in vitro by wireless communication after filtering, amplification, and A/D sampling. To overcome the power shortage of batteries, a wireless power transmission module based on electromagnetic induction was designed. The transmitting coil of a rectangular-section solenoid and a 3D receiving coil are proposed according to stability and safety constraints. Experiments show that at least 150 mW of power could pick up on the load in a volume of Φ10.5 mm × 11 mm, with a transmission efficiency of 2.56%. Vivisection experiments verified the feasibility of the integrated radio-telemetry system.

  7. Elucidating the Plasma and Liver Pharmacokinetics of Simeprevir in Special Populations Using Physiologically Based Pharmacokinetic Modelling.

    Science.gov (United States)

    Snoeys, Jan; Beumont, Maria; Monshouwer, Mario; Ouwerkerk-Mahadevan, Sivi

    2016-11-29

    The disposition of simeprevir (SMV) in humans is characterised by cytochrome P450 3A4 metabolism and hepatic uptake by organic anion transporting polypeptide 1B1/3 (OATP1B1/3). This study was designed to investigate SMV plasma and liver exposure upon oral administration in subjects infected with hepatitis C virus (HCV), in subjects of Japanese or Chinese origin, subjects with organ impairment and subjects with OATP genetic polymorphisms, using physiologically based pharmacokinetic modelling. Simulations showed that compared with healthy Caucasian subjects, SMV plasma exposure was 2.4-, 1.7-, 2.2- and 2.0-fold higher, respectively, in HCV-infected Caucasian subjects, in healthy Japanese, healthy Chinese and subjects with severe renal impairment. Further simulations showed that compared with HCV-infected Caucasian subjects, SMV plasma exposure was 1.6-fold higher in HCV-infected Japanese subjects. In subjects with OATP1B1 genetic polymorphisms, no noteworthy changes in SMV pharmacokinetics were observed. Simulations suggested that liver concentrations in Caucasians with HCV are 18 times higher than plasma concentrations.

  8. Metabolism and physiologically based pharmacokinetic modeling of flumioxazin in pregnant animals

    Energy Technology Data Exchange (ETDEWEB)

    Takaku, Tomoyuki, E-mail: takakut@sc.sumitomo-chem.co.jp; Nagahori, Hirohisa; Sogame, Yoshihisa

    2014-06-15

    A physiologically based pharmacokinetic (PBPK) model was developed to predict the concentration of flumioxazin, in the blood and fetus of pregnant humans during a theoretical accidental intake (1000 mg/kg). The data on flumioxazin concentration in pregnant rats (30 mg/kg po) was used to develop the PBPK model in pregnant rats using physiological parameters and chemical specific parameters. The rat PBPK model developed was extrapolated to a human model. Liver microsomes of female rats and a mixed gender of humans were used for the in vitro metabolism study. To determine the % of flumioxazin absorbed after administration at a dose of 1000 mg/kg assuming maximum accidental intake, the biliary excretion study of [phenyl-U-{sup 14}C]flumioxazin was conducted in bile duct-cannulated female rats (Crl:CD (SD)) to collect and analyze the bile, urine, feces, gastrointestinal tract, and residual carcass. The % of flumioxazin absorbed at a dose of 1000 mg/kg in rats was low (12.3%) by summing up {sup 14}C of the urine, bile, and residual carcass. The pregnant human model that was developed demonstrated that the maximum flumioxazin concentration in the blood and fetus of a pregnant human at a dose of 1000 mg/kg po was 0.86 μg/mL and 0.68 μg/mL, respectively, which is much lower than K{sub m} (202.4 μg/mL). Because the metabolism was not saturated and the absorption rate was low at a dose of 1000 mg/kg, the calculated flumioxazin concentration in pregnant humans was thought to be relatively low, considering the flumioxazin concentration in pregnant rats at a dose of 30 mg/kg. For the safety assessment of flumioxazin, these results would be useful for further in vitro toxicology experiments. - Highlights: • A PBPK model of flumioxazin in pregnant humans was developed. • Simulated flumioxazin concentration in pregnant humans was relatively low. • The results would be useful for further in vitro toxicology experiments.

  9. A physiologically based pharmacokinetic (PB/PK) model for multiple exposure routes for soman in multiple species

    NARCIS (Netherlands)

    Sweeney, R.E.; Langenberg, J.P.; Maxwell, D.M.

    2006-01-01

    A physiologically based pharmacokinetic (PB/PK) model has been developed in advanced computer simulation language (ACSL) to describe blood and tissue concentration-time profiles of the C(±)P(-) stereoisomers of soman after inhalation, subcutaneous and intravenous exposures at low (0.8-1.0 × LD50), m

  10. The calculation of human toxicity thresholds of 2,3,7,8-TCDD; A Physiologically Based Pharmacokinetic modeling approach

    NARCIS (Netherlands)

    Zeilmaker MJ; van Eijkeren JCH; LBO

    1998-01-01

    Dit rapport beschrijft de toepassing van een 'Physiologically Based PharmacoKinetic' model (PBPK model) bij het berekenen van de verwachte 'No Adverse Effect Level' van 2,3,7,8-TetraChloroDibenzo-p-Dioxine (TCDD) bij de mens. Het model houdt rekening met variabiliteit en onzeker

  11. DEVELOPMENT OF A PHYSIOLOGICALLY BASED PHARMACOKINETIC MODEL FOR DELTAMETHRIN IN ADULT AND DEVELOPING SPRAGUE-DAWLEY RATS

    Science.gov (United States)

    This work describes the development of a physiologically based pharmacokinetic (PBPK) model of deltamethrin, a type II pyrethroid, in the developing male Sprague-Dawley rat. Generalized Michaelis-Menten equations were used to calculate metabolic rate constants and organ weights ...

  12. Collaborative Teaching Strategies Lead to Retention of Skills in Acid-Base Physiology: A 2-Yr Follow-Up Study

    Science.gov (United States)

    Hartmann, Jacob P.; Toksvang, Linea Natalie; Berg, Ronan M. G.

    2015-01-01

    A basic understanding of acid-base physiology is critical for the correct assessment of arterial blood gases in the clinical setting. In this context, collaborative teaching strategies in the undergraduate classroom setting may be useful, since it has been reported to enhance both transfer and retention of learned material in a time-efficient…

  13. DEVELOPMENT OF A PHYSIOLOGICALLY BASED PHARMACOKINETIC MODEL FOR DELTAMETHRIN IN THE ADULT MALE SPRAGUE-DAWLEY RAT

    Science.gov (United States)

    Deltamethrin (DLT) is a Type II pyrethroid insecticide widely used in agriculture and public health. DLT is a potent neurotoxin that is primarily cleared from the body by metabolism. To better understand the dosimetry of DLT in the central nervous system, a physiologically based ...

  14. Report from the EMA workshop on qualification and reporting of physiologically based pharmacokinetic (PBPK) modeling and simulation

    Science.gov (United States)

    2017-01-01

    On Nov 21, 2016, the European Medicines Agency (EMA) hosted a workshop to discuss its draft guideline on qualification and reporting of physiologically based pharmacokinetic (PBPK) analysis.1 Published on July 21, 2016, the draft PBPK guideline is currently under the period of public comments. PMID:28035755

  15. Teaching Baroreflex Physiology to Medical Students: A Comparison of Quiz-Based and Conventional Teaching Strategies in a Laboratory Exercise

    Science.gov (United States)

    Berg, Ronan M. G.; Plovsing, Ronni R.; Damgaard, Morten

    2012-01-01

    Quiz-based and collaborative teaching strategies have previously been found to be efficient for the improving meaningful learning of physiology during lectures. These approaches have, however, not been investigated during laboratory exercises. In the present study, we compared the impact of solving quizzes individually and in groups with…

  16. Collaborative Teaching Strategies Lead to Retention of Skills in Acid-Base Physiology: A 2-Yr Follow-Up Study

    Science.gov (United States)

    Hartmann, Jacob P.; Toksvang, Linea Natalie; Berg, Ronan M. G.

    2015-01-01

    A basic understanding of acid-base physiology is critical for the correct assessment of arterial blood gases in the clinical setting. In this context, collaborative teaching strategies in the undergraduate classroom setting may be useful, since it has been reported to enhance both transfer and retention of learned material in a time-efficient…

  17. Network-based integration of molecular and physiological data elucidates regulatory mechanisms underlying adaptation to high-fat diet

    NARCIS (Netherlands)

    Derous, D.; Kelder, T.; Schothorst, E.M. van; Erk, M. van; Voigt, A.; Klaus, S.; Keijer, J.; Radonjic, M.

    2015-01-01

    Health is influenced by interplay of molecular, physiological and environmental factors. To effectively maintain health and prevent disease, health-relevant relations need to be understood at multiple levels of biological complexity. Network-based methods provide a powerful platform for integration

  18. Physiologically based kinetic modeling of hesperidin metabolism and its use to predict in vivo effective doses in humans

    NARCIS (Netherlands)

    Boonpawa, Rungnapa; Spenkelink, Bert; Punt, Ans; Rietjens, Ivonne

    2017-01-01

    Scope: To develop a physiologically based kinetic (PBK) model that describes the absorption, distribution, metabolism, and excretion of hesperidin in humans, enabling the translation of in vitro concentration-response curves to in vivo dose-response curves. Methods and results: The PBK model for

  19. Network-based integration of molecular and physiological data elucidates regulatory mechanisms underlying adaptation to high-fat diet

    NARCIS (Netherlands)

    Derous, D.; Kelder, T.; Schothorst, E.M. van; Erk, M. van; Voigt, A.; Klaus, S.; Keijer, J.; Radonjic, M.

    2015-01-01

    Health is influenced by interplay of molecular, physiological and environmental factors. To effectively maintain health and prevent disease, health-relevant relations need to be understood at multiple levels of biological complexity. Network-based methods provide a powerful platform for integration

  20. A physiologically-inspired model of numerical classification based on graded stimulus coding

    Directory of Open Access Journals (Sweden)

    John Pearson

    2010-01-01

    Full Text Available In most natural decision contexts, the process of selecting among competing actions takes place in the presence of informative, but potentially ambiguous, stimuli. Decisions about magnitudes—quantities like time, length, and brightness that are linearly ordered—constitute an important subclass of such decisions. It has long been known that perceptual judgments about such quantities obey Weber’s Law, wherein the just-noticeable difference in a magnitude is proportional to the magnitude itself. Current physiologically inspired models of numerical classification assume discriminations are made via a labeled line code of neurons selectively tuned for numerosity, a pattern observed in the firing rates of neurons in the ventral intraparietal area (VIP of the macaque. By contrast, neurons in the contiguous lateral intraparietal area (LIP signal numerosity in a graded fashion, suggesting the possibility that numerical classification could be achieved in the absence of neurons tuned for number. Here, we consider the performance of a decision model based on this analog coding scheme in a paradigmatic discrimination task—numerosity bisection. We demonstrate that a basic two-neuron classifier model, derived from experimentally measured monotonic responses of LIP neurons, is sufficient to reproduce the numerosity bisection behavior of monkeys, and that the threshold of the classifier can be set by reward maximization via a simple learning rule. In addition, our model predicts deviations from Weber Law scaling of choice behavior at high numerosity. Together, these results suggest both a generic neuronal framework for magnitude-based decisions and a role for reward contingency in the classification of such stimuli.

  1. Predicting lung dosimetry of inhaled particleborne benzo[a]pyrene using physiologically based pharmacokinetic modeling

    Science.gov (United States)

    Campbell, Jerry; Franzen, Allison; Van Landingham, Cynthia; Lumpkin, Michael; Crowell, Susan; Meredith, Clive; Loccisano, Anne; Gentry, Robinan; Clewell, Harvey

    2016-01-01

    Abstract Benzo[a]pyrene (BaP) is a by-product of incomplete combustion of fossil fuels and plant/wood products, including tobacco. A physiologically based pharmacokinetic (PBPK) model for BaP for the rat was extended to simulate inhalation exposures to BaP in rats and humans including particle deposition and dissolution of absorbed BaP and renal elimination of 3-hydroxy benzo[a]pyrene (3-OH BaP) in humans. The clearance of particle-associated BaP from lung based on existing data in rats and dogs suggest that the process is bi-phasic. An initial rapid clearance was represented by BaP released from particles followed by a slower first-order clearance that follows particle kinetics. Parameter values for BaP-particle dissociation were estimated using inhalation data from isolated/ventilated/perfused rat lungs and optimized in the extended inhalation model using available rat data. Simulations of acute inhalation exposures in rats identified specific data needs including systemic elimination of BaP metabolites, diffusion-limited transfer rates of BaP from lung tissue to blood and the quantitative role of macrophage-mediated and ciliated clearance mechanisms. The updated BaP model provides very good prediction of the urinary 3-OH BaP concentrations and the relative difference between measured 3-OH BaP in nonsmokers versus smokers. This PBPK model for inhaled BaP is a preliminary tool for quantifying lung BaP dosimetry in rat and humans and was used to prioritize data needs that would provide significant model refinement and robust internal dosimetry capabilities. PMID:27569524

  2. A Human Life-Stage Physiologically Based Pharmacokinetic and Pharmacodynamic Model for Chlorpyrifos: Development and Validation

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Jordan N.; Hinderliter, Paul M.; Timchalk, Charles; Bartels, M. J.; Poet, Torka S.

    2014-08-01

    Sensitivity to chemicals in animals and humans are known to vary with age. Age-related changes in sensitivity to chlorpyrifos have been reported in animal models. A life-stage physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model was developed to computationally predict disposition of CPF and its metabolites, chlorpyrifos-oxon (the ultimate toxicant) and 3,5,6-trichloro-2-pyridinol (TCPy), as well as B-esterase inhibition by chlorpyrifos-oxon in humans. In this model, age-dependent body weight was calculated from a generalized Gompertz function, and compartments (liver, brain, fat, blood, diaphragm, rapid, and slow) were scaled based on body weight from polynomial functions on a fractional body weight basis. Blood flows among compartments were calculated as a constant flow per compartment volume. The life-stage PBPK/PD model was calibrated and tested against controlled adult human exposure studies. Model simulations suggest age-dependent pharmacokinetics and response may exist. At oral doses ≥ 0.55 mg/kg of chlorpyrifos (significantly higher than environmental exposure levels), 6 mo old children are predicted to have higher levels of chlorpyrifos-oxon in blood and higher levels of red blood cell cholinesterase inhibition compared to adults from equivalent oral doses of chlorpyrifos. At lower doses that are more relevant to environmental exposures, the model predicts that adults will have slightly higher levels of chlorpyrifos-oxon in blood and greater cholinesterase inhibition. This model provides a computational framework for age-comparative simulations that can be utilized to predict CPF disposition and biological response over various postnatal life-stages.

  3. Validation of human physiologically based pharmacokinetic model for vinyl acetate against human nasal dosimetry data.

    Science.gov (United States)

    Hinderliter, P M; Thrall, K D; Corley, R A; Bloemen, L J; Bogdanffy, M S

    2005-05-01

    Vinyl acetate has been shown to induce nasal lesions in rodents in inhalation bioassays. A physiologically based pharmacokinetic (PBPK) model for vinyl acetate has been used in human risk assessment, but previous in vivo validation was conducted only in rats. Controlled human exposures to vinyl acetate were conducted to provide validation data for the application of the model in humans. Five volunteers were exposed to 1, 5, and 10 ppm 13C1,13C2 vinyl acetate via inhalation. A probe inserted into the nasopharyngeal region sampled both 13C1,13C2 vinyl acetate and the major metabolite 13C1,13C2 acetaldehyde during rest and light exercise. Nasopharyngeal air concentrations were analyzed in real time by ion trap mass spectrometry (MS/MS). Experimental concentrations of both vinyl acetate and acetaldehyde were then compared to predicted concentrations calculated from the previously published human model. Model predictions of vinyl acetate nasal extraction compared favorably with measured values of vinyl acetate, as did predictions of nasopharyngeal acetaldehyde when compared to measured acetaldehyde. The results showed that the current PBPK model structure and parameterization are appropriate for vinyl acetate. These analyses were conducted from 1 to 10 ppm vinyl acetate, a range relevant to workplace exposure standards but which would not be expected to saturate vinyl acetate metabolism. Risk assessment based on this model further concluded that 24 h per day exposures up to 1 ppm do not present concern regarding cancer or non-cancer toxicity. Validation of the vinyl acetate human PBPK model provides support for these conclusions.

  4. Physiologically based pharmacokinetic modeling of zinc oxide nanoparticles and zinc nitrate in mice

    Directory of Open Access Journals (Sweden)

    Chen WY

    2015-10-01

    Full Text Available Wei-Yu Chen,1 Yi-Hsien Cheng,2 Nan-Hung Hsieh,3 Bo-Chun Wu,2 Wei-Chun Chou,4 Chia-Chi Ho,4 Jen-Kun Chen,5 Chung-Min Liao,2,* Pinpin Lin4,* 1Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, 2Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei, 3Institute of Labor, Occupational Safety and Health, Ministry of Labor, New Taipei City, 4National Institute of Environmental Health Sciences, 5Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan, Taiwan *These authors contributed equally to this work Abstract: Zinc oxide nanoparticles (ZnO NPs have been widely used in consumer products, therapeutic agents, and drug delivery systems. However, the fate and behavior of ZnO NPs in living organisms are not well described. The purpose of this study was to develop a physiologically based pharmacokinetic model to describe the dynamic interactions of 65ZnO NPs in mice. We estimated key physicochemical parameters of partition coefficients and excretion or elimination rates, based on our previously published data quantifying the biodistributions of 10 nm and 71 nm 65ZnO NPs and zinc nitrate (65Zn(NO32 in various mice tissues. The time-dependent partition coefficients and excretion or elimination rates were used to construct our physiologically based pharmacokinetic model. In general, tissue partition coefficients of 65ZnO NPs were greater than those of 65Zn(NO32, particularly the lung partition coefficient of 10 nm 65ZnO NPs. Sensitivity analysis revealed that 71 nm 65ZnO NPs and 65Zn(NO32 were sensitive to excretion and elimination rates in the liver and gastrointestinal tract. Although the partition coefficient of the brain was relative low, it increased time-dependently for 65ZnO NPs and 65Zn(NO32. The simulation of 65Zn(NO32 was well fitted with the experimental data. However, replacing partition coefficients of 65ZnO NPs with

  5. Biokinetics and dosimetry of depleted uranium (DU) in rats implanted with DU fragments.

    Energy Technology Data Exchange (ETDEWEB)

    Guilmette, Ray A.; Hahn, Fletcher F.; Durbin, P. W.

    2004-01-01

    A number of U. S. veterans of the Persian Gulf War were wounded with depleted uranium (DU) metal fragments as a result of 'friendly fire' incidents, in which Abrams tanks and Bradley fighting vehicles were struck by DU anti-armor munitions. Some of the crew members who survived were left with multiple small fragments of DU in their muscles and soft tissues. The number, size and location of the fragments made them inoperable in general, and therefore subject to long-term retention. Because there was inadequate data to predict the potential carcinogenicity of DU fragments in soft tissues, Hahn et al. (2003) conducted a lifespan cancer study in rats. As part of that study, a number of rats were maintained to study the biokinetics and dosimetry of DU implanted intramuscularly in male Wistar rats. Typically, four metal fragments, either as cylindrical pellets or square wafers were implanted into the biceps femoris muscles of the rats. Urine samples were collected periodically during their lifespans, and DU was analyzed in kidneys and eviscerated carcass (minus the implant sites) at death. The daily DU urinary excretion rate increased steeply during the first 30 d after implantation peaking at about 90 d at 3-10 x 10{sup -3}%/d. During the first 150 d, the average excretion rate was 2.4 x 10{sup -3}%/d, decreasing thereafter to about 1 x 10{sup -3}%/d. Serial radiographs were made of the wound sites to monitor gross morphologic changes in the DU implant and the surrounding tissue. As early as 1 w after implantation, radiographs showed the presence of surface corrosion and small, dense bodies near the original implant, presumably DU. This corrosion from the surface of the implant continued with time, but did not result in an increasing amount of DU reaching the blood and urine after the first 3 mo. During this 3-mo period, connective tissue capsules formed around the implants, and are hypothesized to have reduced the access of DU to tissue fluids by limiting the

  6. Compared biokinetic and biological studies of chronic and acute inhalations of uranium compounds in the rat; Etudes biocinetique et biologique comparees d'inhalations chroniques et aigues de composes uraniferes chez le rat

    Energy Technology Data Exchange (ETDEWEB)

    Monleau, M

    2005-12-15

    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

  7. Study of the influence of radionuclide biokinetics on in vivo counting using voxel phantoms; Etude de l'influence de la biocinetique des radionucleides sur la mesure anthroporadiametrique a l'aide de fantomes numeriques voxelises

    Energy Technology Data Exchange (ETDEWEB)

    Lamart, St.

    2008-10-15

    The in vivo measurement is an efficient method to estimate the retention of activity in case of internal contamination. However, it is currently limited by the use of physical phantoms for the calibration, not enabling to reproduce neither the morphology of the measured person nor the actual distribution of the contamination. The current method of calibration therefore leads to significant systematic uncertainties on the quantification of the contamination. To improve the in vivo measurement, the Laboratory of Internal Dose Assessment (LEDI, IRSN) has developed an original numerical calibration method with the OEDIPE software. It is based on voxel phantoms created from the medical images of persons, and associated with the MCNPX Monte Carlo code of particle transport. The first version of this software enabled to model simple homogeneous sources and to better estimate the systematic uncertainties in the lung counting of actinides due to the detector position and to the heterogeneous distribution of activity inside the lungs. However, it was not possible to take into account the dynamic feature, and often heterogeneous distribution between body organs and tissues of the activity. Still, the efficiency of the detection system depends on the distribution of the source of activity. The main purpose of the thesis work is to answer to the question: what is the influence of the biokinetics of the radionuclides on the in vivo counting? To answer it, it was necessary to deeply modify OEDIPE. This new development enabled to model the source of activity more realistically from the reference biokinetic models defined by the ICRP. The first part of the work consisted in developing the numerical tools needed to integrate the biokinetics in OEDIPE. Then, a methodology was developed to quantify its influence on the in vivo counting from the results of simulations. This method was carried out and validated on the model of the in vivo counting system of the LEDI. Finally, the

  8. Physiologically-based toxicokinetic models help identifying the key factors affecting contaminant uptake during flood events

    Energy Technology Data Exchange (ETDEWEB)

    Brinkmann, Markus; Eichbaum, Kathrin [Department of Ecosystem Analysis, Institute for Environmental Research,ABBt – Aachen Biology and Biotechnology, RWTH Aachen University, Worringerweg 1, 52074 Aachen (Germany); Kammann, Ulrike [Thünen-Institute of Fisheries Ecology, Palmaille 9, 22767 Hamburg (Germany); Hudjetz, Sebastian [Department of Ecosystem Analysis, Institute for Environmental Research,ABBt – Aachen Biology and Biotechnology, RWTH Aachen University, Worringerweg 1, 52074 Aachen (Germany); Institute of Hydraulic Engineering and Water Resources Management, RWTH Aachen University, Mies-van-der-Rohe-Straße 1, 52056 Aachen (Germany); Cofalla, Catrina [Institute of Hydraulic Engineering and Water Resources Management, RWTH Aachen University, Mies-van-der-Rohe-Straße 1, 52056 Aachen (Germany); Buchinger, Sebastian; Reifferscheid, Georg [Federal Institute of Hydrology (BFG), Department G3: Biochemistry, Ecotoxicology, Am Mainzer Tor 1, 56068 Koblenz (Germany); Schüttrumpf, Holger [Institute of Hydraulic Engineering and Water Resources Management, RWTH Aachen University, Mies-van-der-Rohe-Straße 1, 52056 Aachen (Germany); Preuss, Thomas [Department of Environmental Biology and Chemodynamics, Institute for Environmental Research,ABBt- Aachen Biology and Biotechnology, RWTH Aachen University, Worringerweg 1, 52074 Aachen (Germany); and others

    2014-07-01

    Highlights: • A PBTK model for trout was coupled with a sediment equilibrium partitioning model. • The influence of physical exercise on pollutant uptake was studies using the model. • Physical exercise during flood events can increase the level of biliary metabolites. • Cardiac output and effective respiratory volume were identified as relevant factors. • These confounding factors need to be considered also for bioconcentration studies. - Abstract: As a consequence of global climate change, we will be likely facing an increasing frequency and intensity of flood events. Thus, the ecotoxicological relevance of sediment re-suspension is of growing concern. It is vital to understand contaminant uptake from suspended sediments and relate it to effects in aquatic biota. Here we report on a computational study that utilizes a physiologically based toxicokinetic model to predict uptake, metabolism and excretion of sediment-borne pyrene in rainbow trout (Oncorhynchus mykiss). To this end, data from two experimental studies were compared with the model predictions: (a) batch re-suspension experiments with constant concentration of suspended particulate matter at two different temperatures (12 and 24 °C), and (b) simulated flood events in an annular flume. The model predicted both the final concentrations and the kinetics of 1-hydroxypyrene secretion into the gall bladder of exposed rainbow trout well. We were able to show that exhaustive exercise during exposure in simulated flood events can lead to increased levels of biliary metabolites and identified cardiac output and effective respiratory volume as the two most important factors for contaminant uptake. The results of our study clearly demonstrate the relevance and the necessity to investigate uptake of contaminants from suspended sediments under realistic exposure scenarios.

  9. Physiological Differences and Similarities in Asthma and COPD—Based on Respiratory Function Testing—

    Directory of Open Access Journals (Sweden)

    Michiaki Mishima

    2009-01-01

    Full Text Available Physiological differences and similarities in asthma and COPD are documented based on respiratory function testing. (1 The airflow reversibility is usually important for the diagnosis of asthma. However, patients with long disease histories may have poor reversibility. The reversibility test in COPD is useful for predicting the treatment response. (2 In some of the stable asthmatic patients without attack, the concave downslope of flow- volume curve is present. In severe COPD, the flow in the second half of the curve is smaller than that of rest- breathing. (3 Inspiratory capacity (IC is a good estimator of air trapping and of predicting the exercise capacity in COPD or persistent asthma. (4 Peak expiratory flow (PEF can be an important aid in both diagnosis and monitoring of asthma. PEF is not used in COPD because the main disorder is in the peripheral airway. (5 Measurements of airway responsiveness may help to a diagnosis of asthma. However, many COPD cases also have it. (6 Impulse oscillation system (IOS revealed that the predominant airway disorders in asthma and COPD are central and peripheral respiratory resistance, respectively. However, some asthma patients have larger values of peripheral component. (7 Dlco reflects the extent of pathological emphysema and it is useful for the follow-up of COPD, whereas Dlco is not decreased in asthma. (8 The patient with widened A-aDO2 and alveolar hypoventilation may lead to the life threatening hypoxia in severe asthma attack or severe COPD. When PaCO2 overcomes PaO2, the patient should immediately be treated by mechanical ventilation.

  10. Adaptation to shift work: physiologically based modeling of the effects of lighting and shifts' start time.

    Science.gov (United States)

    Postnova, Svetlana; Robinson, Peter A; Postnov, Dmitry D

    2013-01-01

    Shift work has become an integral part of our life with almost 20% of the population being involved in different shift schedules in developed countries. However, the atypical work times, especially the night shifts, are associated with reduced quality and quantity of sleep that leads to increase of sleepiness often culminating in accidents. It has been demonstrated that shift workers' sleepiness can be improved by a proper scheduling of light exposure and optimizing shifts timing. Here, an integrated physiologically-based model of sleep-wake cycles is used to predict adaptation to shift work in different light conditions and for different shift start times for a schedule of four consecutive days of work. The integrated model combines a model of the ascending arousal system in the brain that controls the sleep-wake switch and a human circadian pacemaker model. To validate the application of the integrated model and demonstrate its utility, its dynamics are adjusted to achieve a fit to published experimental results showing adaptation of night shift workers (n = 8) in conditions of either bright or regular lighting. Further, the model is used to predict the shift workers' adaptation to the same shift schedule, but for conditions not considered in the experiment. The model demonstrates that the intensity of shift light can be reduced fourfold from that used in the experiment and still produce good adaptation to night work. The model predicts that sleepiness of the workers during night shifts on a protocol with either bright or regular lighting can be significantly improved by starting the shift earlier in the night, e.g.; at 21:00 instead of 00:00. Finally, the study predicts that people of the same chronotype, i.e. with identical sleep times in normal conditions, can have drastically different responses to shift work depending on their intrinsic circadian and homeostatic parameters.

  11. Use of partition coefficients in flow-limited physiologically-based pharmacokinetic modeling.

    Science.gov (United States)

    Thompson, Matthew D; Beard, Daniel A; Wu, Fan

    2012-08-01

    Permeability-limited two-subcompartment and flow-limited, well-stirred tank tissue compartment models are routinely used in physiologically-based pharmacokinetic modeling. Here, the permeability-limited two-subcompartment model is used to derive a general flow-limited case of a two-subcompartment model with the well-stirred tank being a specific case where tissue fractional blood volume approaches zero. The general flow-limited two-subcompartment model provides a clear distinction between two partition coefficients typically used in PBPK: a biophysical partition coefficient and a well-stirred partition coefficient. Case studies using diazepam and cotinine demonstrate that, when the well-stirred tank is used with a priori predicted biophysical partition coefficients, simulations overestimate or underestimate total organ drug concentration relative to flow-limited two-subcompartment model behavior in tissues with higher fractional blood volumes. However, whole-body simulations show predicted drug concentrations in plasma and lower fractional blood volume tissues are relatively unaffected. These findings point to the importance of accurately determining tissue fractional blood volume for flow-limited PBPK modeling. Simulations using biophysical and well-stirred partition coefficients optimized with flow-limited two-subcompartment and well-stirred models, respectively, lead to nearly identical fits to tissue drug distribution data. Therefore, results of whole-body PBPK modeling with diazepam and cotinine indicate both flow-limited models are appropriate PBPK tissue models as long as the correct partition coefficient is used: the biophysical partition coefficient is for use with two-subcompartment models and the well-stirred partition coefficient is for use with the well-stirred tank model.

  12. [Spectacle lenses in sports: optimization of the imaging properties based on physiological aspects].

    Science.gov (United States)

    Becken, Wolfgang; Seidemann, Anne; Altheimer, Helmut; Esser, Gregor; Uttenweiler, Dietmar

    2007-01-01

    The goal of correction spectacles is to create a sharp image on the retina by the combined optical system of the eye and the spectacle lens for a given ametropia. As a matter of principle, in this optical system an aberration free correction can be achieved in the optical centre of the spectacle lens, but not over the entire range of gaze angles. In spectacle optics large angles play an important role, different from paraxial optics where only rays close to the axis with small angles of incidence are relevant. This generates additional aberrations, the so-called oblique astigmatism, which can only be compensated at the expense of the spherical power. Therefore, every spectacle lens represents apart from the main visual point-, a more or less good compromise. For sports lenses in the currently used curved frames, an additional challenge arises from the fact that their orientation in front of the eye is generally not perpendicular to the principal gaze direction but tilted. In this article the imaging properties of such tilted sports lenses are discussed, and it is described why this results in a minor quality without a specific consideration of the obliqueness. The fact that tilted sports spectacles are also able to possess an improved correction behaviour for all gaze angles is due to individual mathematical optimization methods. The aim of the present article is, based on the underlying physical and physiological effects, to point out the advantages of individually optimized sports spectacle lenses in comparison to tilted lenses generated without applying this sophisticated computational method.

  13. OLED-based physiologically-friendly very low-color temperature illumination for night

    Science.gov (United States)

    Jou, Jwo-Huei; Shen, Shih-Ming; Tang, Ming-Chun; Chen, Pin-Chu; Chen, Szu-Hao; Wang, Yi-Shan; Chen, Chien-Chih; Wang, Ching-Chun; Hsieh, Chun-Yu; Lin, Chin-Chiao; Chen, Chien-Tien

    2012-09-01

    Numerous medical research studies reveal intense white or blue light to drastically suppress at night the secretion of melatonin (MLT), a protective oncostatic hormone. Lighting devices with lower color-temperature (CT) possess lesser MLT suppression effect based on the same luminance, explaining why physicians have long been calling for the development of lighting sources with low CT or free from blue emission for use at night to safeguard human health. We will demonstrate in the presentation the fabrication of OLED devices with very-low CT, especially those with CT much lower than that of incandescent bulbs (2500K) or even candles (2000K). Without any light extraction method, OLEDs with an around 1800K CT are easily obtainable with an efficacy of 30 lm/W at 1,000 nits. To also ensure high color-rendering to provide visual comfort, low CT OLEDs composing long wavelength dominant 5-spectrum emission have been fabricated. While keeping the color-rendering index as high as 85 and CT as low as 2100K, the resulting efficacy can also be much greater than that of incandescent bulbs (15 lm/W), proving these low CT OLED devices to be also capable of being energy-saving and high quality. The color-temperature can be further decreased to 1700K or lower upon removing the undesired short wavelength emission but on the cost of losing some color rendering index. It is hoped that the devised energy-saving, high quality low CT OLED could properly echo the call for a physiologically-friendly illumination for night, and more attention could be drawn to the development of MLT suppression-less non-white light.

  14. Adaptation to shift work: physiologically based modeling of the effects of lighting and shifts' start time.

    Directory of Open Access Journals (Sweden)

    Svetlana Postnova

    Full Text Available Shift work has become an integral part of our life with almost 20% of the population being involved in different shift schedules in developed countries. However, the atypical work times, especially the night shifts, are associated with reduced quality and quantity of sleep that leads to increase of sleepiness often culminating in accidents. It has been demonstrated that shift workers' sleepiness can be improved by a proper scheduling of light exposure and optimizing shifts timing. Here, an integrated physiologically-based model of sleep-wake cycles is used to predict adaptation to shift work in different light conditions and for different shift start times for a schedule of four consecutive days of work. The integrated model combines a model of the ascending arousal system in the brain that controls the sleep-wake switch and a human circadian pacemaker model. To validate the application of the integrated model and demonstrate its utility, its dynamics are adjusted to achieve a fit to published experimental results showing adaptation of night shift workers (n = 8 in conditions of either bright or regular lighting. Further, the model is used to predict the shift workers' adaptation to the same shift schedule, but for conditions not considered in the experiment. The model demonstrates that the intensity of shift light can be reduced fourfold from that used in the experiment and still produce good adaptation to night work. The model predicts that sleepiness of the workers during night shifts on a protocol with either bright or regular lighting can be significantly improved by starting the shift earlier in the night, e.g.; at 21:00 instead of 00:00. Finally, the study predicts that people of the same chronotype, i.e. with identical sleep times in normal conditions, can have drastically different responses to shift work depending on their intrinsic circadian and homeostatic parameters.

  15. Kinetics of drug action in disease states: towards physiology-based pharmacodynamic (PBPD) models.

    Science.gov (United States)

    Danhof, Meindert

    2015-10-01

    Gerhard Levy started his investigations on the "Kinetics of Drug Action in Disease States" in the fall of 1980. The objective of his research was to study inter-individual variation in pharmacodynamics. To this end, theoretical concepts and experimental approaches were introduced, which enabled assessment of the changes in pharmacodynamics per se, while excluding or accounting for the cofounding effects of concomitant changes in pharmacokinetics. These concepts were applied in several studies. The results, which were published in 45 papers in the years 1984-1994, showed considerable variation in pharmacodynamics. These initial studies on kinetics of drug action in disease states triggered further experimental research on the relations between pharmacokinetics and pharmacodynamics. Together with the concepts in Levy's earlier publications "Kinetics of Pharmacologic Effects" (Clin Pharmacol Ther 7(3): 362-372, 1966) and "Kinetics of pharmacologic effects in man: the anticoagulant action of warfarin" (Clin Pharmacol Ther 10(1): 22-35, 1969), they form a significant impulse to the development of physiology-based pharmacodynamic (PBPD) modeling as novel discipline in the pharmaceutical sciences. This paper reviews Levy's research on the "Kinetics of Drug Action in Disease States". Next it addresses the significance of his research for the evolution of PBPD modeling as a scientific discipline. PBPD models contain specific expressions to characterize in a strictly quantitative manner processes on the causal path between exposure (in terms of concentration at the target site) and the drug effect (in terms of the change in biological function). Pertinent processes on the causal path are: (1) target site distribution, (2) target binding and activation and (3) transduction and homeostatic feedback.

  16. Tennis for physical health: acute age- and gender-based physiological responses to cardio tennis.

    Science.gov (United States)

    Murphy, Alistair P; Duffield, Rob; Reid, Machar

    2014-11-01

    This study described physiological and perceptual responses to Cardio tennis for "younger" and "older" adult populations of both sexes for health-related outcomes. Thirty-one active participants, each with prior recreational tennis experience (∼2 years) (8 younger and 8 older males, and 7 younger and 8 older females) performed preliminary testing and a 50-minute instructor-led Cardio tennis session. Cardio tennis is a conditioning-based tennis program comprised of warm-up movements, drill-based exercises (set movement and hitting games), and competitive play scenarios. Participants performed the 20-m shuttle run test to determine maximal heart rate (HR) during preliminary testing. Before, after, and 30-minute post Cardio tennis session, HR, blood pressure (BP), rate pressure product (RPP), and capillary blood lactate and glucose were determined. Furthermore, HR and pedometer-derived step counts were measured throughout, while the session was filmed and coded for technical skill. After the session, ratings of perceived exertion, enjoyment, and challenge were obtained. Heart rate, systolic BP, and RPP were significantly increased by Cardio tennis (p ≤ 0.05), though returned to pre-exercise levels after 30 minutes (p > 0.05). Heart rate and BP did not differ between groups pre- or 30-minute postexercise (p > 0.05); however, these were lower in younger males during and higher in younger females postsession (p ≤ 0.05). Lactate and glucose concentrations were increased in all groups (p ≤ 0.05), with lactate being highest in male groups (p ≤ 0.05), without differences in glucose between groups (p > 0.05). Stroke and step counts were not different between groups (p > 0.05). Ratings of perceived exertion and perceived challenge were lowest in the younger male group compared with all other groups (p ≤ 0.05). Cardio tennis presents as an effective stimulus to invoke sufficient cardiovascular and metabolic load to benefit health and fitness, though age- and sex-based

  17. Optimizing the Clinical Use of Carvedilol in Liver Cirrhosis Using a Physiologically Based Pharmacokinetic Modeling Approach.

    Science.gov (United States)

    Rasool, Muhammad Fawad; Khalil, Feras; Läer, Stephanie

    2017-06-01

    Liver cirrhosis is a complex pathophysiological condition that can affect the pharmacokinetics (PK) and hereby dosing of administered drugs. The physiologically based pharmacokinetic (PBPK) models are a valuable tool to explore PK of drugs in cirrhosis patients. The objective of this study was to develop and evaluate a PBPK-carvedilol-cirrhosis model with the available clinical data in liver cirrhosis patients and to recommend model-based drug dosing after exploring the underlying differences in unbound and total (bound and unbound) systemic carvedilol concentrations with the different disease stages. A whole body PBPK model was developed using the population-based PBPK simulator, Simcyp(®). After model development and evaluation in healthy adults, system parameters were modified according to the pathophysiological changes that occur in liver cirrhosis, and predictions were compared to available experimental data from liver cirrhosis Child-Pugh [CP]-C patients. A two-fold error range for the observed/predicted ratios (ratioObs/Pred) of the pharmacokinetic parameters was used for model evaluation. Simulations were then extended to cirrhosis CP-A and CP-B populations were no experimental data that are available to explore changes in drug disposition in these patients. Finally, drug unbound and total (bound and unbound) exposure were predicted in cirrhotic patients of different disease severity, and the results were compared to those of healthy adults. The developed model has successfully described carvedilol PK in healthy and cirrhosis CP-C patients. The model predictions showed that, there was an ~13-fold increase in unbound and ~7-fold increase in total (bound and unbound) systemic exposure of carvedilol between healthy and CP-C populations. To have comparable predicted unbound drug exposure in cirrhosis CP-A, CP-B, and CP-C populations as in healthy subjects receiving a dose of 25 mg, reductions of administered doses to 9.375 mg in CP-A, 4.68 mg in CP-B, and 2

  18. Biomechanical Analysis of a Novel Prosthesis Based on the Physiological Curvature of Endplate for Cervical Disc Replacement.

    Directory of Open Access Journals (Sweden)

    Cheng-Cheng Yu

    Full Text Available Biomechanical analysis of a novel prosthesis based on the physiological curvature of endplate was performed.To compare the biomechanical differences between a novel prosthesis based on the physiological curvature of the endplate and the Prestige LP prosthesis after cervical disc replacement (CDR.Artificial disc prostheses have been widely used to preserve the physiological function of treated and adjacent motion segments in CDR, while most of those present a flat surface instead of an arcuate surface which approximately similar to anatomic structures in vivo. We first reported a well-designed artificial disc prosthesis based on the physiological curvature of the endplate.Three motion segments of 24 ovine cervical spines (C2-5 were evaluated in a robotic spine system with axial compressive loads of 50N. Testing conditions were as follows: 1 intact, 2 C3-4 CDR with artificial disc prosthesis based on the physiological curvature of the endplate, and 3 C3-4 CDR with the Prestige LP prosthesis. The range of motion (ROM and the pressures on the inferior surface of the two prostheses were recorded and analyzed.As compared to the intact state, the ROM of all three segments had no significant difference in the replacement group. Additionally, there was no significant difference in ROM between the two prostheses. The mean pressure on the novel prosthesis was significantly less than the Prestige LP prosthesis.ROM in 3 groups (intact group, CDR group with novel prosthesis and CDR group with Prestige LP showed no significant difference. The mean pressure on the inferior surface of the novel prosthesis was significantly lower than the Prestige LP prosthesis. Therefore, the novel artificial disc prosthesis is feasible and effective, and can reduce the implant-bone interface pressure on the endplate, which may be one possible reason of prosthesis subsidence.

  19. Doppler radar physiological sensing

    CERN Document Server

    Lubecke, Victor M; Droitcour, Amy D; Park, Byung-Kwon; Singh, Aditya

    2016-01-01

    Presents a comprehensive description of the theory and practical implementation of Doppler radar-based physiological monitoring. This book includes an overview of current physiological monitoring techniques and explains the fundamental technology used in remote non-contact monitoring methods. Basic radio wave propagation and radar principles are introduced along with the fundamentals of physiological motion and measurement. Specific design and implementation considerations for physiological monitoring radar systems are then discussed in detail. The authors address current research and commercial development of Doppler radar based physiological monitoring for healthcare and other applications.

  20. Improvement in DTPA efficacy for plutonium decorporation: biokinetic and dosimetric approaches

    Energy Technology Data Exchange (ETDEWEB)

    Serandour, A.L.; Grillon, G.; Taulelle, C.; Frechou, M.; Ben Salah, M.; Fritsch, P.; Le Gall, B.; Poncy, J.L. [CEA Bruyeres-le-Chatel (DSV/DRR), Lab. Radiotoxicologie, 91 (France); Gervelas, C.; Tsapis, N.; Fatal, E. [Paris-11 Univ., UMR CNRS 8612, Physico-chimie-Pharmacotechnie-Biopharmacie, 92 - Chatenay-Malabry (France); Phan, G.; Benech, H. [CEA Saclay (DSV/DRM), Service de Pharmacologie et d' Immunologie, 91 - Gif-sur-Yvette (France); Deverre, J.R. [Service Hospitalier Frederic Joliot (CEA/DSV/DRM), 91 - Gif-sur-Yvette (France)

    2006-07-01

    DTPA for pulmonary administration. DTPA has already been formulated as a micronized dry powder for inhalation and delivered to humans with a Spinhaler TM inhalator device. Both the powder and the inhalator device were far from being optimized since only 3% of the powder actually deposits in the lungs [3]. We have formulated DTPA into porous particles with optimised physical properties for major deposition in the deep lung [4]. Aerodynamic evaluation of our powder show that up to 60% of the initial dose deposits in the lungs with about 30% in the alveolar region. The ability of the DTPA powder to de-corporate Pu was evaluated in rats after contamination by inhalation with industrial Pu oxide. Six days after the exposure, the treatment was performed by a single insufflation of the dry DTPA powder [5]. After 24 hours, results showed a significant decrease of the alpha activity in the liver and in the bone, associated with an increase of actinide urinary excretion as compared to untreated rats. These results suggested that the novel DTPA formulation, which may be rapidly administered at the workplace, allows a fast systemic delivery of DTPA. Studies are in progress to compare the Pu decorporation efficacy of such DTPA powder with free DTPA intravenous injection in rats after contamination with more soluble Pu forms. To complete the biokinetic approach, modeling of DTPA decorporation from biological data reported after accidental contamination of workers is in progress [6]. Our aim is to estimate the reduction of dose associated with chelate treatment. The first case analyzed corresponds to a Pu wound which has been treated by repeated perfusions of DTPA during several months. The hypothesis that a 90 Pu decorporation involves only blood and interstitial fluids (STO) was initially applied. The first results show that the systemic model of ICRP 67 was not suitable to fit a theoretic curve to the amount of Pu excreted in urines. This was mainly due to an underestimate of the

  1. Indoor thermal comfort studies based on physiological parameter measurement and questionnaire investigation

    Institute of Scientific and Technical Information of China (English)

    ZHENG Jie; CHEN Liang; LI Bai-zhan; CHEN Lu

    2006-01-01

    Physiological parameters of people and enact assessment standard of indoor thermal environment that are appropriate to our national conditions were explored from the perspective of physiology. From December 2005 to January 2006, nerve conduction velocities and skin temperatures of 20 healthy students were tested with questionnaire investigation. The results show that the nerve conduction velocities as well as skin temperatures present an obvious decline trend in a continuous draught, and that the nerve conduction velocities and skin temperatures have a definite linear relationship. Draught velocity is an important factor in winter that affects body comfort, and the subjects are sensitive to air velocity.

  2. Application for internal dosimetry using biokinetic distribution of photons based on nuclear medicine images.

    Science.gov (United States)

    Leal Neto, Viriato; Vieira, José Wilson; Lima, Fernando Roberto de Andrade

    2014-01-01

    This article presents a way to obtain estimates of dose in patients submitted to radiotherapy with basis on the analysis of regions of interest on nuclear medicine images. A software called DoRadIo (Dosimetria das Radiações Ionizantes [Ionizing Radiation Dosimetry]) was developed to receive information about source organs and target organs, generating graphical and numerical results. The nuclear medicine images utilized in the present study were obtained from catalogs provided by medical physicists. The simulations were performed with computational exposure models consisting of voxel phantoms coupled with the Monte Carlo EGSnrc code. The software was developed with the Microsoft Visual Studio 2010 Service Pack and the project template Windows Presentation Foundation for C# programming language. With the mentioned tools, the authors obtained the file for optimization of Monte Carlo simulations using the EGSnrc; organization and compaction of dosimetry results with all radioactive sources; selection of regions of interest; evaluation of grayscale intensity in regions of interest; the file of weighted sources; and, finally, all the charts and numerical results. The user interface may be adapted for use in clinical nuclear medicine as a computer-aided tool to estimate the administered activity.

  3. Application for internal dosimetry using biokinetic distribution of photons based on nuclear medicine images

    Energy Technology Data Exchange (ETDEWEB)

    Leal Neto, Viriato, E-mail: viriatoleal@yahoo.com.br [Instituto Federal de Educacao, Ciencia e Tecnologia de Pernambuco (IFPE), Recife, PE (Brazil); Vieira, Jose Wilson [Universidade Federal de Pernambuco (UPE), Recife, PE (Brazil); Lima, Fernando Roberto de Andrade [Centro Regional de Ciencias Nucleares (CRCN-NE/CNEN-PE), Recife, PE (Brazil)

    2014-09-15

    Objective: this article presents a way to obtain estimates of dose in patients submitted to radiotherapy with basis on the analysis of regions of interest on nuclear medicine images. Materials and methods: a software called DoRadIo (Dosimetria das Radiacoes Ionizantes [Ionizing Radiation Dosimetry]) was developed to receive information about source organs and target organs, generating graphical and numerical results. The nuclear medicine images utilized in the present study were obtained from catalogs provided by medical physicists. The simulations were performed with computational exposure models consisting of voxel phantoms coupled with the Monte Carlo EGSnrc code. The software was developed with the Microsoft Visual Studio 2010 Service Pack and the project template Windows Presentation Foundation for C ⧣ programming language. Results: with the mentioned tools, the authors obtained the file for optimization of Monte Carlo simulations using the EGSnrc; organization and compaction of dosimetry results with all radioactive sources; selection of regions of interest; evaluation of grayscale intensity in regions of interest; the file of weighted sources; and, finally, all the charts and numerical results. Conclusion: the user interface may be adapted for use in clinical nuclear medicine as a computer-aided tool to estimate the administered activity. (author)

  4. Physiologically-based pharmacokinetic model for Fentanyl in support of the development of Provisional Advisory Levels

    Energy Technology Data Exchange (ETDEWEB)

    Shankaran, Harish, E-mail: harish.shankaran@pnnl.gov [Computational Biology and Bioinformatics Group, Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Adeshina, Femi [National Homeland Security Research Center, United States Environmental Protection Agency, Washington, DC 20460 (United States); Teeguarden, Justin G. [Systems Toxicology Group, Pacific Northwest National Laboratory, Richland, WA 99352 (United States)

    2013-12-15

    Provisional Advisory Levels (PALs) are tiered exposure limits for toxic chemicals in air and drinking water that are developed to assist in emergency responses. Physiologically-based pharmacokinetic (PBPK) modeling can support this process by enabling extrapolations across doses, and exposure routes, thereby addressing gaps in the available toxicity data. Here, we describe the development of a PBPK model for Fentanyl – a synthetic opioid used clinically for pain management – to support the establishment of PALs. Starting from an existing model for intravenous Fentanyl, we first optimized distribution and clearance parameters using several additional IV datasets. We then calibrated the model using pharmacokinetic data for various formulations, and determined the absorbed fraction, F, and time taken for the absorbed amount to reach 90% of its final value, t90. For aerosolized pulmonary Fentanyl, F = 1 and t90 < 1 min indicating complete and rapid absorption. The F value ranged from 0.35 to 0.74 for oral and various transmucosal routes. Oral Fentanyl was absorbed the slowest (t90 ∼ 300 min); the absorption of intranasal Fentanyl was relatively rapid (t90 ∼ 20–40 min); and the various oral transmucosal routes had intermediate absorption rates (t90 ∼ 160–300 min). Based on these results, for inhalation exposures, we assumed that all of the Fentanyl inhaled from the air during each breath directly, and instantaneously enters the arterial circulation. We present model predictions of Fentanyl blood concentrations in oral and inhalation scenarios relevant for PAL development, and provide an analytical expression that can be used to extrapolate between oral and inhalation routes for the derivation of PALs. - Highlights: • We develop a Fentanyl PBPK model for relating external dose to internal levels. • We calibrate the model to oral and inhalation exposures using > 50 human datasets. • Model predictions are in good agreement with the available

  5. Occupational physiology

    CERN Document Server

    Toomingas, Allan; Tornqvist, Ewa Wigaeus

    2011-01-01

    In a clear and accessible presentation, Occupational Physiology focuses on important issues in the modern working world. Exploring major public health problems-such as musculoskeletal disorders and stress-this book explains connections between work, well-being, and health based on up-to-date research in the field. It provides useful methods for risk assessment and guidelines on arranging a good working life from the perspective of the working individual, the company, and society as a whole.The book focuses on common, stressful situations in different professions. Reviewing bodily demands and r

  6. Cadmium bioavailability to Hyalella azteca from a periphyton diet compared to an artificial diet and application of a biokinetic model

    Energy Technology Data Exchange (ETDEWEB)

    Golding, Lisa A., E-mail: lisa.golding@csiro.au [Department of Biology, University of Waterloo, Waterloo, Ontario N2L 3G1 (Canada); Borgmann, Uwe [Environment Canada, 867 Lakeshore Road, Burlington, Ontario L7R 4A6 (Canada); George Dixon, D. [Department of Biology, University of Waterloo, Waterloo, Ontario N2L 3G1 (Canada)

    2013-01-15

    Differences between the bioavailability of cadmium in a periphyton diet and an artificial laboratory diet (TetraMin{sup Registered-Sign }) have important consequences for predicting bioaccumulation and toxicity in the freshwater amphipod Hyalella azteca. The assimilation efficiency (AE) of Cd was compared between periphyton and TetraMin{sup Registered-Sign} at low (1510 and 358 nmol/g ash-free dry mass respectively) and chronically lethal (31,200 and 2890 nmol/g ash-free dry mass respectively) Cd concentrations and in fresh and dry forms using a {sup 109}Cd radiotracer pulse-chase feeding technique. Assimilation efficiency of Cd from periphyton (AE = 3-14%) was lower than that for TetraMin{sup Registered-Sign} (AE = 44-86%) regardless of Cd concentration or food form. Ingestion rate (IR) was lower for dry than fresh forms of periphyton (0.042 and 0.16 g AFDM/g H. azteca/day respectively) and TetraMin{sup Registered-Sign} (0.19 and 0.87 AFDM/g H. azteca/day respectively) and depuration rate (k{sub e}) did not differ statistically with food type, form or Cd concentration (0.032-0.094 d{sup -1}). Biokinetic models with parameters of AE, IR and k{sub e} were used to estimate bioaccumulation from the separate food types. These estimates were compared to those from an independent chronic Cd saturation bioaccumulation model. While the model estimates did not concur, a sensitivity analysis indicated that AE and IR were the most influential biokinetic model parameters for Cd in periphyton and TetraMin{sup Registered-Sign} respectively. It was hypothesized that AE was underestimated for Cd in periphyton due to a non-adapted gut enzyme system and IR was overestimated for Cd in TetraMin{sup Registered-Sign} due to an initial rapid ingestion phase in H. azteca's feeding habits. This research demonstrated the importance of using ecologically relevant food types in laboratory experiments and verifying acute biokinetic model predictions of dietary metal contribution with

  7. Cadmium bioavailability to Hyalella azteca from a periphyton diet compared to an artificial diet and application of a biokinetic model.

    Science.gov (United States)

    Golding, Lisa A; Borgmann, Uwe; George Dixon, D

    2013-01-15

    Differences between the bioavailability of cadmium in a periphyton diet and an artificial laboratory diet (TetraMin(®)) have important consequences for predicting bioaccumulation and toxicity in the freshwater amphipod Hyalella azteca. The assimilation efficiency (AE) of Cd was compared between periphyton and TetraMin(®) at low (1510 and 358 nmol/g ash-free dry mass respectively) and chronically lethal (31,200 and 2890 nmol/g ash-free dry mass respectively) Cd concentrations and in fresh and dry forms using a (109)Cd radiotracer pulse-chase feeding technique. Assimilation efficiency of Cd from periphyton (AE=3-14%) was lower than that for TetraMin(®) (AE=44-86%) regardless of Cd concentration or food form. Ingestion rate (IR) was lower for dry than fresh forms of periphyton (0.042 and 0.16 g AFDM/g H. azteca/day respectively) and TetraMin(®) (0.19 and 0.87 AFDM/g H. azteca/day respectively) and depuration rate (k(e)) did not differ statistically with food type, form or Cd concentration (0.032-0.094 d(-1)). Biokinetic models with parameters of AE, IR and k(e) were used to estimate bioaccumulation from the separate food types. These estimates were compared to those from an independent chronic Cd saturation bioaccumulation model. While the model estimates did not concur, a sensitivity analysis indicated that AE and IR were the most influential biokinetic model parameters for Cd in periphyton and TetraMin(®) respectively. It was hypothesized that AE was underestimated for Cd in periphyton due to a non-adapted gut enzyme system and IR was overestimated for Cd in TetraMin(®) due to an initial rapid ingestion phase in H. azteca's feeding habits. This research demonstrated the importance of using ecologically relevant food types in laboratory experiments and verifying acute biokinetic model predictions of dietary metal contribution with those derived from a chronic exposure which is more representative of a field exposure scenario.

  8. Mode of action based risk assessment of the botanical food-borne alkenylbenzene apiol from parsley using physiologically based kinetic (PBK) modelling and read-across from safrole

    NARCIS (Netherlands)

    Alajlouni, A.M.; Al-Malahmeh, A.J.; Kiwamoto, Reiko; Wesseling, Sebastiaan; Soffers, A.E.M.F.; Al-Subeihi, A.A.A.; Vervoort, Jacques; Rietjens, I.M.C.M.

    2016-01-01

    The present study developed physiologically-based kinetic (PBK) models for the alkenylbenzene apiol in order to facilitate risk assessment based on read-across from the related alkenylbenzene safrole. Model predictions indicate that in rat liver the formation of the 1'-sulfoxy metabolite is about

  9. Predicting keeping quality of batches of numbers of cucumber fruit based on a physiological mechanism

    NARCIS (Netherlands)

    Schouten, R.E.; Tijskens, L.M.M.; Kooten, van O.

    2002-01-01

    The keeping quality for a cucumber, defined as the time the colour remains acceptable to the consumer, depends on the state of the chlorophyll metabolism. By building a physiological model of the chlorophyll metabolism for cucumbers and using colour data from cucumbers stored at 12, 20 and 28 °C,

  10. Research on human physiological parameters intelligent clothing based on distributed Fiber Bragg Grating

    Science.gov (United States)

    Miao, Changyun; Shi, Boya; Li, Hongqiang

    2008-12-01

    A human physiological parameters intelligent clothing is researched with FBG sensor technology. In this paper, the principles and methods of measuring human physiological parameters including body temperature and heart rate in intelligent clothing with distributed FBG are studied, the mathematical models of human physiological parameters measurement are built; the processing method of body temperature and heart rate detection signals is presented; human physiological parameters detection module is designed, the interference signals are filtered out, and the measurement accuracy is improved; the integration of the intelligent clothing is given. The intelligent clothing can implement real-time measurement, processing, storage and output of body temperature and heart rate. It has accurate measurement, portability, low cost, real-time monitoring, and other advantages. The intelligent clothing can realize the non-contact monitoring between doctors and patients, timely find the diseases such as cancer and infectious diseases, and make patients get timely treatment. It has great significance and value for ensuring the health of the elders and the children with language dysfunction.

  11. Improvement in the physiological function and standing stability based on kinect multimedia for older people.

    Science.gov (United States)

    Chen, Chih-Chen

    2016-04-01

    [Purpose] The increase in the Taiwanese older population is associated with age-related inconveniences. Finding adequate and simple physical activities to help the older people maintaining their physiological function and preventing them from falls has become an urgent social issue. [Subjects and Methods] This study aimed to design a virtual exercise training game suitable for Taiwanese older people. This system will allow for the maintenance of the physiological function and standing stability through physical exercise, while using a virtual reality game. The participants can easily exercise in a carefree, interactive environment. This study will use Kinect for Windows for physical movement detection and Unity software for virtual world development. [Results] Group A and B subjects were involved in the exercise training method of Kinect interactive multimedia for 12 weeks. The results showed that the functional reach test and the unipedal stance test improved significantly. [Conclusion] The physiological function and standing stability of the group A subjects were examined at six weeks post training. The results showed that these parameters remained constant. This proved that the proposed system provide substantial support toward the preservation of the Taiwanese older people' physiological function and standing stability.

  12. Predicting keeping quality of batches of numbers of cucumber fruit based on a physiological mechanism

    NARCIS (Netherlands)

    Schouten, R.E.; Tijskens, L.M.M.; Kooten, van O.

    2002-01-01

    The keeping quality for a cucumber, defined as the time the colour remains acceptable to the consumer, depends on the state of the chlorophyll metabolism. By building a physiological model of the chlorophyll metabolism for cucumbers and using colour data from cucumbers stored at 12, 20 and 28 °C, th

  13. A Physiologic-Based Approach to the Treatment of Acute Hyperkalemia

    OpenAIRE

    Shingarev, Roman; Allon, Michael

    2010-01-01

    Hyperkalemia is a common and potentially lethal disorder. Given its variable presentation clinicians should have a high index of suspicion, especially in patients with chronic kidney disease. The present case highlights key physiological mechanisms in the development of hyperkalemia and provides an outline for emergent treatment. In this context, we discuss specific mechanisms of action of available treatments of hyperkalemia.

  14. The learning continuum based on student's level of competence and specific pedagogical learning material on physiological aspects from teachers's opinions

    Science.gov (United States)

    Hadi, Ria Fitriyani; Subali, Bambang

    2017-08-01

    The scope of learning continuum at the conceptual knowledge is formulated based on the student's level of competence and specific pedagogical learning material. The purpose of this study is to develop a learning continuum of specific pedagogical material aspects of physiology targeted for students in primary and secondary education. This research was conducted in Province of Yogyakarta Special Region from October 2016 to January 2017. The method used in this study was survey method. The data were collected using questionnaire that had been validated from the aspects of construct validity and experts judgements. Respondents in this study consist of 281 Science/Biology teachers at Public Junior and Senior High Schools in the Province of Yogyakarta Special Region which spread in Yogyakarta city and 4 regencies namely Sleman, Bantul, Kulonprogo, and Gunungkidul. The data were taken using a census. Data were analyzed using a descriptive analysis technique. The results show the learning continuum of physiology based on teachers's opinion from grade VII, VIII, and IX are taught in grade VII, VIII, IX and X on level of C2 (understanding) and the learning continuum of physiology based on teachers's opinion from grade X, XI and XII are taught in grade X and XI on level of C2 (understanding), C3 (applying), and C4 (analyzing) based on teachers's opinions. The conclusion is that many teachers refer to the existing curriculum rather than their own original idea for developing learning continuum.

  15. A Generic Integrated Physiologically based Whole-body Model of the Glucose-Insulin-Glucagon Regulatory System

    Science.gov (United States)

    Schaller, S; Willmann, S; Lippert, J; Schaupp, L; Pieber, T R; Schuppert, A; Eissing, T

    2013-01-01

    Models of glucose metabolism are a valuable tool for fundamental and applied medical research in diabetes. Use cases range from pharmaceutical target selection to automatic blood glucose control. Standard compartmental models represent little biological detail, which hampers the integration of multiscale data and confines predictive capabilities. We developed a detailed, generic physiologically based whole-body model of the glucose-insulin-glucagon regulatory system, reflecting detailed physiological properties of healthy populations and type 1 diabetes individuals expressed in the respective parameterizations. The model features a detailed representation of absorption models for oral glucose, subcutaneous insulin and glucagon, and an insulin receptor model relating pharmacokinetic properties to pharmacodynamic effects. Model development and validation is based on literature data. The quality of predictions is high and captures relevant observed inter- and intra-individual variability. In the generic form, the model can be applied to the development and validation of novel diabetes treatment strategies. PMID:23945606

  16. The Routing Algorithm Based on Fuzzy Logic Applied to the Individual Physiological Monitoring Wearable Wireless Sensor Network

    Directory of Open Access Journals (Sweden)

    Jie Jiang

    2015-01-01

    Full Text Available In recent years, the research of individual wearable physiological monitoring wireless sensor network is in the primary stage. The monitor of physiology and geographical position used in wearable wireless sensor network requires performances such as real time, reliability, and energy balance. According to these requirements, this paper introduces a design of individual wearable wireless sensor network monitoring system; what is more important, based on this background, this paper improves the classical Collection Tree Protocol and puts forward the improved routing protocol F-CTP based on the fuzzy logic routing algorithm. Simulation results illustrate that, with the F-CTP protocol, the sensor node can transmit data to the sink node in real time with higher reliability and the energy of the nodes consumes balance. The sensor node can make full use of network resources reasonably and prolong the network life.

  17. Biokinetic and dosimetric studies of {sup 188}Re-hyaluronic acid: a new radiopharmaceutical for treatment of hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Melendez-Alafort, Laura [Dipartimento di Scienze Farmaceutiche, Universita degli Studi di Padova, 35131 Padua (Italy)], E-mail: laura.melendez@unipd.it; Nadali, Anna; Zangoni, Elena [Dipartimento di Scienze Farmaceutiche, Universita degli Studi di Padova, 35131 Padua (Italy); Banzato, Alessandra; Rondina, Maria [Dipartimento di Scienze Oncologiche e Chirurgiche, Universita degli Studi di Padova, Padua (Italy); Rosato, Antonio [Dipartimento di Scienze Oncologiche e Chirurgiche, Universita degli Studi di Padova, Padua (Italy); Istituto Oncologico Veneto, IOV, Padova, Padua (Italy); Mazzi, Ulderico [Dipartimento di Scienze Farmaceutiche, Universita degli Studi di Padova, 35131 Padua (Italy)

    2009-08-15

    Hepatocellular carcinoma (HCC) is the most common primary liver cancer and has very limited therapeutic options. Recently, it has been found that hyaluronic acid (HA) shows selective binding to CD44 receptors expressed in most cancer histotypes. Since the trend in cancer treatment is the use of targeted radionuclide therapy, the aim of this research was to label HA with rhenium-188 and to evaluate its potential use as a hepatocarcinoma therapeutic radiopharmaceutical. Methods: {sup 188}Re-HA was prepared by a direct labelling method to produce a ReO(O-COO){sub 2}-type coordination complex. {sup 188}Re-HA protein binding and its stability in saline, phosphate buffer, human serum and cysteine solutions were determined. Biokinetic and dosimetric data were estimated in healthy mice (n=60) using the Medical Internal Radiation Dose methodology and mouse model beta-absorbed fractions. To evaluate liver toxicity, alanine aminotranferase (AST) and aspartate aminotranferase (ALT) levels in mice were assessed and the liver maximum tolerated dose (MTD) of {sup 188}Re-HA was determined. Results: A stable complex of {sup 188}Re-HA was obtained with high radiochemical purity (>90%) and low serum protein binding (2%). Biokinetic studies showed a rapid blood clearance (T{sub 1/2}{alpha}=21 min). Four hours after administration, {sup 188}Re-HA was almost totally removed from the blood by the liver due to the selective uptake via HA-specific receptors (73.47{+-}5.11% of the injected dose). The liver MTD in mice was {approx}40 Gy after 7.4 MBq of {sup 188}Re-HA injection. Conclusions: {sup 188}Re-HA complex showed good stability, pharmacokinetic and dosimetric characteristics that confirm its potential as a new agent for HCC radiation therapy.

  18. Social Adversity in Adolescence Increases the Physiological Vulnerability to Job Strain in Adulthood : A Prospective Population-Based Study

    OpenAIRE

    Hugo Westerlund; Gustafsson, Per E.; Töres Theorell; Urban Janlert; Anne Hammarström

    2012-01-01

    Background: It has been argued that the association between job strain and health could be confounded by early life exposures, and studies have shown early adversity to increase individual vulnerability to later stress. We therefore investigated if early life exposure to adversity increases the individual's physiological vulnerability job strain in adulthood. Methodology/Principal Findings: In a population-based cohort (343 women and 330 men, 83% of the eligible participants), we examined the...

  19. Bluetooth-based sensor networks for remotely monitoring the physiological signals of a patient.

    Science.gov (United States)

    Zhang, Ying; Xiao, Hannan

    2009-11-01

    Integrating intelligent medical microsensors into a wireless communication network makes it possible to remotely collect physiological signals of a patient, release the patient from being tethered to monitoring medical instrumentations, and facilitate the patient's early hospital discharge. This can further improve life quality by providing continuous observation without the need of disrupting the patient's normal life, thus reducing the risk of infection significantly, and decreasing the cost of the hospital and the patient. This paper discusses the implementation issues, and describes the overall system architecture of our developed Bluetooth sensor network for patient monitoring and the corresponding heart activity sensors. It also presents our approach to developing the intelligent physiological sensor nodes involving integration of Bluetooth radio technology, hardware and software organization, and our solutions for onboard signal processing.

  20. Physiologically based pharmacokinetic modeling of a homologous series of barbiturates in the rat: a sensitivity analysis.

    Science.gov (United States)

    Nestorov, I A; Aarons, L J; Rowland, M

    1997-08-01

    Sensitivity analysis studies the effects of the inherent variability and uncertainty in model parameters on the model outputs and may be a useful tool at all stages of the pharmacokinetic modeling process. The present study examined the sensitivity of a whole-body physiologically based pharmacokinetic (PBPK) model for the distribution kinetics of nine 5-n-alkyl-5-ethyl barbituric acids in arterial blood and 14 tissues (lung, liver, kidney, stomach, pancreas, spleen, gut, muscle, adipose, skin, bone, heart, brain, testes) after i.v. bolus administration to rats. The aims were to obtain new insights into the model used, to rank the model parameters involved according to their impact on the model outputs and to study the changes in the sensitivity induced by the increase in the lipophilicity of the homologues on ascending the series. Two approaches for sensitivity analysis have been implemented. The first, based on the Matrix Perturbation Theory, uses a sensitivity index defined as the normalized sensitivity of the 2-norm of the model compartmental matrix to perturbations in its entries. The second approach uses the traditional definition of the normalized sensitivity function as the relative change in a model state (a tissue concentration) corresponding to a relative change in a model parameter. Autosensitivity has been defined as sensitivity of a state to any of its parameters; cross-sensitivity as the sensitivity of a state to any other states' parameters. Using the two approaches, the sensitivity of representative tissue concentrations (lung, liver, kidney, stomach, gut, adipose, heart, and brain) to the following model parameters: tissue-to-unbound plasma partition coefficients, tissue blood flows, unbound renal and intrinsic hepatic clearance, permeability surface area product of the brain, have been analyzed. Both the tissues and the parameters were ranked according to their sensitivity and impact. The following general conclusions were drawn: (i) the overall

  1. A generic organ based ontology system, applied to vertebrate heart anatomy, development and physiology.

    Science.gov (United States)

    Bertens, Laura M F; Slob, Joris; Verbeek, Fons J

    2011-09-08

    We present a novel approach to modelling biological information using ontologies. The system interlinks three ontologies, comprising anatomical, developmental and taxonomical information, and includes instances of structures for different species. The framework is constructed for comparative analyses in the field of evolutionary development. We have applied the approach to the vertebrate heart and present four case studies of the functionality of the system, focusing on cross-species comparisons, developmental studies, physiological studies and 3D visualisation.

  2. Genetic and physiological bases for phenological responses to current and predicted climates

    OpenAIRE

    Wilczek, A. M.; Burghardt, L. T.; Cobb, A. R.; Cooper, M D; Welch, S. M.; Schmitt, J

    2010-01-01

    We are now reaching the stage at which specific genetic factors with known physiological effects can be tied directly and quantitatively to variation in phenology. With such a mechanistic understanding, scientists can better predict phenological responses to novel seasonal climates. Using the widespread model species Arabidopsis thaliana, we explore how variation in different genetic pathways can be linked to phenology and life-history variation across geographical regions and seasons. We sho...

  3. Breath-based meditation: A mechanism to restore the physiological and cognitive reserves for optimal human performance.

    Science.gov (United States)

    Carter, Kirtigandha Salwe; Carter, Robert

    2016-04-16

    Stress can be associated with many physiological changes resulting in significant decrements in human performance. Due to growing interests in alternative and complementary medicine by Westerners, many of the traditions and holistic yogic breathing practices today are being utilized as a measure for healthier lifestyles. These state-of-the-art practices can have a significant impact on common mental health conditions such as depression and generalized anxiety disorder. However, the potential of yogic breathing on optimizing human performance and overall well-being is not well known. Breathing techniques such as alternate nostril, Sudarshan Kriya and bhastrika utilizes rhythmic breathing to guide practitioners into a deep meditative state of relaxation and promote self-awareness. Furthermore, yogic breathing is physiologically stimulating and can be described as a natural "technological" solution to optimize human performance which can be categorized into: (1) cognitive function (i.e., mind, vigilance); and (2) physical performance (i.e., cardiorespiratory, metabolism, exercise, whole body). Based on previous studies, we postulate that daily practice of breathing meditation techniques play a significant role in preserving the compensatory mechanisms available to sustain physiological function. This preservation of physiological function may help to offset the time associated with reaching a threshold for clinical expression of chronic state (i.e., hypertension, depression, dementia) or acute state (i.e., massive hemorrhage, panic attic) of medical conditions. However, additional rigorous biomedical research is needed to evaluate the physiological mechanisms of various forms of meditation (i.e., breath-based, mantra, mindfulness) on human performance. These efforts will help to define how compensatory reserve mechanisms of cardiovascular and immune systems are modulated by breath-based meditation. While it has been suggested that breath-based meditation is easier for

  4. Physiologically Based Pharmacokinetic Modeling: Methodology, Applications, and Limitations with a Focus on Its Role in Pediatric Drug Development

    Directory of Open Access Journals (Sweden)

    Feras Khalil

    2011-01-01

    Full Text Available The concept of physiologically based pharmacokinetic (PBPK modeling was introduced years ago, but it has not been practiced significantly. However, interest in and implementation of this modeling technique have grown, as evidenced by the increased number of publications in this field. This paper demonstrates briefly the methodology, applications, and limitations of PBPK modeling with special attention given to discuss the use of PBPK models in pediatric drug development and some examples described in detail. Although PBPK models do have some limitations, the potential benefit from PBPK modeling technique is huge. PBPK models can be applied to investigate drug pharmacokinetics under different physiological and pathological conditions or in different age groups, to support decision-making during drug discovery, to provide, perhaps most important, data that can save time and resources, especially in early drug development phases and in pediatric clinical trials, and potentially to help clinical trials become more “confirmatory” rather than “exploratory”.

  5. Biochemical and physiological bases for utilization of dietary amino acids by young Pigs.

    Science.gov (United States)

    Rezaei, Reza; Wang, Weiwei; Wu, Zhenlong; Dai, Zhaolai; Wang, Junjun; Wu, Guoyao

    2013-02-27

    Protein is quantitatively the most expensive nutrient in swine diets. Hence it is imperative to understand the physiological roles played by amino acids in growth, development, lactation, reproduction, and health of pigs to improve their protein nutrition and reduce the costs of pork production. Due to incomplete knowledge of amino acid biochemistry and nutrition, it was traditionally assumed that neonatal, post-weaning, growing-finishing, and gestating pigs could synthesize sufficient amounts of all "nutritionally nonessential amino acids" (NEAA) to support maximum production performance. Therefore, over the past 50 years, much emphasis has been placed on dietary requirements of nutritionally essential amino acids as building blocks for tissue proteins. However, a large body of literature shows that NEAA, particularly glutamine, glutamate, arginine and proline regulate physiological functions via cell signaling pathways, such as mammalian target of rapamycin, AMP-activated protein kinase, extracellular signal-related kinase, Jun kinase, mitogen-activated protein kinase, and NEAA-derived gaseous molecules (e.g., nitric oxide, carbon monoxide, and hydrogen sulfide). Available evidence shows that under current feeding programs, only 70% and 55% of dietary amino acids are deposited as tissue proteins in 14-day-old sow-reared piglets and in 30-day-old pigs weaned at 21 days of age, respectively. Therefore, there is an urgent need to understand the roles and dietary requirements of NEAA in swine nutrition. This review highlights the basic biochemistry and physiology of absorption and utilization of amino acids in young pigs to enhance the efficacy of utilization of dietary protein and to minimize excretion of nitrogenous wastes from the body.

  6. Effects of model-based physiological noise correction on default mode network anti-correlations and correlations.

    Science.gov (United States)

    Chang, Catie; Glover, Gary H

    2009-10-01

    Previous studies have reported that the spontaneous, resting-state time course of the default-mode network is negatively correlated with that of the "task-positive network", a collection of regions commonly recruited in demanding cognitive tasks. However, all studies of negative correlations between the default-mode and task-positive networks have employed some form of normalization or regression of the whole-brain average signal ("global signal"); these processing steps alter the time series of voxels in an uninterpretable manner as well as introduce spurious negative correlations. Thus, the extent of negative correlations with the default mode network without global signal removal has not been well characterized, and it is has recently been hypothesized that the apparent negative correlations in many of the task-positive regions could be artifactually induced by global signal pre-processing. The present study aimed to examine negative and positive correlations with the default-mode network when model-based corrections for respiratory and cardiac noise are applied in lieu of global signal removal. Physiological noise correction consisted of (1) removal of time-locked cardiac and respiratory artifacts using RETROICOR (Glover, G.H., Li, T.Q., Ress, D., 2000. Image-based method for retrospective correction of physiological motion effects in fMRI: RETROICOR. Magn. Reson. Med. 44, 162-167), and (2) removal of low-frequency respiratory and heart rate variations by convolving these waveforms with pre-determined transfer functions (Birn et al., 2008; Chang et al., 2009) and projecting the resulting two signals out of the data. It is demonstrated that negative correlations between the default-mode network and regions of the task-positive network are present in the majority of individual subjects both with and without physiological noise correction. Physiological noise correction increased the spatial extent and magnitude of negative correlations, yielding negative

  7. Classification of 2-pore domain potassium channels based on rectification under quasi-physiological ionic conditions.

    Science.gov (United States)

    Chen, Haijun; Zuo, Dongchuan; Zhang, Jianing; Zhou, Min; Ma, Liqun

    2014-01-01

    It is generally expected that 2-pore domain K(+) (K2P) channels are open or outward rectifiers in asymmetric physiological K(+) gradients, following the Goldman-Hodgkin-Katz (GHK) current equation. Although cloned K2P channels have been extensively studied, their current-voltage (I-V) relationships are not precisely characterized and previous definitions are contradictory. Here we study all the functional channels from 6 mammalian K2P subfamilies in transfected Chinese hamster ovary cells with patch-clamp technique, and examine whether their I-V relationships are described by the GHK current equation. K2P channels display 2 distinct types of I-V curves in asymmetric physiological K(+) gradients. Two K2P isoforms in the TWIK subfamily conduct large inward K(+) currents and have a nearly linear I-V curve. Ten isoforms from 5 other K2P subfamilies conduct small inward K(+) currents and exhibit open rectification, but fits with the GHK current equation cannot precisely reveal the differences in rectification among K2P channels. The Rectification Index, a ratio of limiting I-V slopes for outward and inward currents, is used to quantitatively describe open rectification of each K2P isoform, which is previously qualitatively defined as strong or weak open rectification. These results systematically and precisely classify K2P channels and suggest that TWIK K(+) channels have a unique feature in regulating cellular function.

  8. Calibration and validation of a physiologically based model for soman intoxication in the rat, marmoset, guinea pig and pig.

    Science.gov (United States)

    Chen, Kaizhen; Seng, Kok-Yong

    2012-09-01

    A physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model has been developed for low, medium and high levels of soman intoxication in the rat, marmoset, guinea pig and pig. The primary objective of this model was to describe the pharmacokinetics of soman after intravenous, intramuscular and subcutaneous administration in the rat, marmoset, guinea pig, and pig as well as its subsequent pharmacodynamic effects on blood acetylcholinesterase (AChE) levels, relating dosimetry to physiological response. The reactions modelled in each physiologically realistic compartment are: (1) partitioning of C(±)P(±) soman from the blood into the tissue; (2) inhibition of AChE and carboxylesterase (CaE) by soman; (3) elimination of soman by enzymatic hydrolysis; (4) de novo synthesis and degradation of AChE and CaE; and (5) aging of AChE-soman and CaE-soman complexes. The model was first calibrated for the rat, then extrapolated for validation in the marmoset, guinea pig and pig. Adequate fits to experimental data on the time course of soman pharmacokinetics and AChE inhibition were achieved in the mammalian models. In conclusion, the present model adequately predicts the dose-response relationship resulting from soman intoxication and can potentially be applied to predict soman pharmacokinetics and pharmacodynamics in other species, including human.

  9. Diversity evaluation based on morphological, physiological and isozyme variation in genetic resources of garlic (Allium sativum L.) collected worldwide.

    Science.gov (United States)

    Hirata, Sho; Abdelrahman, Mostafa; Yamauchi, Naoki; Shigyo, Masayoshi

    2016-11-26

    The aim of this study was to obtain primary information about the global diversity of garlic (Allium sativum L.) by evaluating morphological, physiological and isozyme variation. A total of 107 garlic accessions collected worldwide were grown in Yamaguchi, Japan. Five morphological traits (bulb weight, bulb diameter, number of cloves per bulb, number of bulbils and scape length) and one physiological trait (bolting period) of the collected garlic showed wide variation. Meanwhile, a total of 140 garlic accessions, including the 107 mentioned above, were characterized by leucine aminopeptidase (LAP) and phosphoglucoisomerase (PGI) isozyme analyses; they clearly showed polymorphisms in putative isozyme loci (Lap-1, Lap-2 and Pgi-1). Allelic frequencies were estimated in each group of accessions categorized by their geographical origin, and the observed (Ho) and expected (He) heterozygosities were calculated. The allelic frequencies differed between groups. A principal component analysis based on morpho-physiological data indicated a grouping of the garlic accessions into Central Asian and Northern Mediterranean groups as well as others. We discuss the roles of artificial and natural selection that may have caused differentiation in these traits, on the assumption that ancestral domesticated garlic populations have adapted in various regions using standing variation or mutations that accumulated during expansion, and have evolved along with human-preferred traits over a long history of cultivation.

  10. Development and application of an antibody-based protein microarray to assess physiological stress in grizzly bears (Ursus arctos).

    Science.gov (United States)

    Carlson, Ruth I; Cattet, Marc R L; Sarauer, Bryan L; Nielsen, Scott E; Boulanger, John; Stenhouse, Gordon B; Janz, David M

    2016-01-01

    A novel antibody-based protein microarray was developed that simultaneously determines expression of 31 stress-associated proteins in skin samples collected from free-ranging grizzly bears (Ursus arctos) in Alberta, Canada. The microarray determines proteins belonging to four broad functional categories associated with stress physiology: hypothalamic-pituitary-adrenal axis proteins, apoptosis/cell cycle proteins, cellular stress/proteotoxicity proteins and oxidative stress/inflammation proteins. Small skin samples (50-100 mg) were collected from captured bears using biopsy punches. Proteins were isolated and labelled with fluorescent dyes, with labelled protein homogenates loaded onto microarrays to hybridize with antibodies. Relative protein expression was determined by comparison with a pooled standard skin sample. The assay was sensitive, requiring 80 µg of protein per sample to be run in triplicate on the microarray. Intra-array and inter-array coefficients of variation for individual proteins were generally bears. This suggests that remotely delivered biopsy darts could be used in future sampling. Using generalized linear mixed models, certain proteins within each functional category demonstrated altered expression with respect to differences in year, season, geographical sampling location within Alberta and bear biological parameters, suggesting that these general variables may influence expression of specific proteins in the microarray. Our goal is to apply the protein microarray as a conservation physiology tool that can detect, evaluate and monitor physiological stress in grizzly bears and other species at risk over time in response to environmental change.

  11. Genetic influences on the neural and physiological bases of acute threat: A research domain criteria (RDoC) perspective.

    Science.gov (United States)

    Sumner, Jennifer A; Powers, Abigail; Jovanovic, Tanja; Koenen, Karestan C

    2016-01-01

    The NIMH Research Domain Criteria (RDoC) initiative aims to describe key dimensional constructs underlying mental function across multiple units of analysis-from genes to observable behaviors-in order to better understand psychopathology. The acute threat ("fear") construct of the RDoC Negative Valence System has been studied extensively from a translational perspective, and is highly pertinent to numerous psychiatric conditions, including anxiety and trauma-related disorders. We examined genetic contributions to the construct of acute threat at two units of analysis within the RDoC framework: (1) neural circuits and (2) physiology. Specifically, we focused on genetic influences on activation patterns of frontolimbic neural circuitry and on startle, skin conductance, and heart rate responses. Research on the heritability of activation in threat-related frontolimbic neural circuitry is lacking, but physiological indicators of acute threat have been found to be moderately heritable (35-50%). Genetic studies of the neural circuitry and physiology of acute threat have almost exclusively relied on the candidate gene method and, as in the broader psychiatric genetics literature, most findings have failed to replicate. The most robust support has been demonstrated for associations between variation in the serotonin transporter (SLC6A4) and catechol-O-methyltransferase (COMT) genes with threat-related neural activation and physiological responses. However, unbiased genome-wide approaches using very large samples are needed for gene discovery, and these can be accomplished with collaborative consortium-based research efforts, such as those of the Psychiatric Genomics Consortium (PGC) and Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium.

  12. Heartbeat detection in multimodal physiological signals using signal quality assessment based on sample entropy.

    Science.gov (United States)

    Singh, Omkar; Sunkaria, Ramesh Kumar

    2017-09-08

    This paper presents a novel technique to identify heartbeats in multimodal data using electrocardiogram (ECG) and arterial blood pressure (ABP) signals. Multiple physiological signals such as ECG, ABP, and Respiration are often recorded in parallel from the activity of heart. These signals generally possess related information as they are generated by the same physical system. The ECG and ABP correspond to the same phenomenon of contraction and relaxation activity of heart. Multiple signals acquired from various sensors are generally processed independently, thus discarding the information from other measurements. In the estimation of heart rate and heart rate variability, the R peaks are generally identified from ECG signal. Efficient detection of R-peaks in electrocardiogram (ECG) is a key component in the estimation of clinically relevant parameters from ECG. However, when the signal is severely affected by undesired artifacts, this becomes a challenging task. Sometimes in clinical environment, other physiological signals reflecting the cardiac activity such as ABP signal are also acquired simultaneously. Under the availability of such multimodal signals, the accuracy of R peak detection methods can be improved using sensor-fusion techniques. In the proposed method, the sample entropy (SampEn) is used as a metric for assessing the noise content in the physiological signal and the R peaks in ECG and the systolic peaks in ABP signals are fused together to enhance the efficiency of heartbeat detection. The proposed method was evaluated on the 100 records from the computing in cardiology challenge 2014 training data set. The performance parameters are: sensitivity (Se) and positive predictivity (PPV). The unimodal R peaks detector achieved: Se gross = 99.40%, PPV gross = 99.29%, Se average = 99.37%, PPV average = 99.29%. Similarly unimodal BP delineator achieved Se gross = 99.93%, PPV gross = 99.99%, Se average = 99.93%, PPV average = 99.99% whereas, the proposed

  13. Nanoparticle-Based and Bioengineered Probes and Sensors to Detect Physiological and Pathological Biomarkers in Neural Cells.

    Science.gov (United States)

    Maysinger, Dusica; Ji, Jeff; Hutter, Eliza; Cooper, Elis

    2015-01-01

    Nanotechnology, a rapidly evolving field, provides simple and practical tools to investigate the nervous system in health and disease. Among these tools are nanoparticle-based probes and sensors that detect biochemical and physiological properties of neurons and glia, and generate signals proportionate to physical, chemical, and/or electrical changes in these cells. In this context, quantum dots (QDs), carbon-based structures (C-dots, grapheme, and nanodiamonds) and gold nanoparticles are the most commonly used nanostructures. They can detect and measure enzymatic activities of proteases (metalloproteinases, caspases), ions, metabolites, and other biomolecules under physiological or pathological conditions in neural cells. Here, we provide some examples of nanoparticle-based and genetically engineered probes and sensors that are used to reveal changes in protease activities and calcium ion concentrations. Although significant progress in developing these tools has been made for probing neural cells, several challenges remain. We review many common hurdles in sensor development, while highlighting certain advances. In the end, we propose some future directions and ideas for developing practical tools for neural cell investigations, based on the maxim "Measure what is measurable, and make measurable what is not so" (Galileo Galilei).

  14. Nanoparticle-based and bioengineered probes and sensors to detect physiological and pathological biomarkers in neural cells

    Directory of Open Access Journals (Sweden)

    Dusica eMaysinger

    2015-12-01

    Full Text Available Nanotechnology, a rapidly evolving field, provides simple and practical tools to investigate the nervous system in health and disease. Among these tools are nanoparticle-based probes and sensors that detect biochemical and physiological properties of neurons and glia, and generate signals proportionate to physical, chemical, and/or electrical changes in these cells. In this context, quantum dots (QDs, carbon-based structures (C-dots, graphene and nanodiamonds and gold nanoparticles are the most commonly used nanostructures. They can detect and measure enzymatic activities of proteases (metalloproteinases, caspases, ions, metabolites, and other biomolecules under physiological or pathological conditions in neural cells. Here, we provide some examples of nanoparticle-based and genetically engineered probes and sensors that are used to reveal changes in protease activities and calcium ion concentrations. Although significant progress in developing these tools has been made for probing neural cells, several challenges remain. We review many common hurdles in sensor development, while highlighting certain advances. In the end, we propose some future directions and ideas for developing practical tools for neural cell investigations, based on the maxim Measure what is measurable, and make measurable what is not so (Galileo Galilei.

  15. Biokinetics of radiolabeled Iodophenylpentadecanoic acid (I-123-IPPA) and thallium-201 in a rabbit model of chronic myocardial infarction measured using a series of thermoluminescent dosimeters

    Science.gov (United States)

    Medich, David Christopher

    1997-09-01

    The biokinetics of Iodophenylpentadecanoic acid (123I-IPPA) during a chronic period of myocardial infarction were determined and compared to 201Tl. IPPA was assessed as a perfusion and metabolic tracer in the scintigraphic diagnosis of coronary artery disease. The myocardial clearance kinetics were measured by placing a series of thermoluminescent dosimeters (TLDs) on normal and infarcted tissue to measure the local myocardial activity content over time. The arterial blood pool activity was fit to a bi-exponential function for 201Tl and a tri-exponential function for 123I-IPPA to estimate the left ventricle contribution to TLD response. At equilibrium, the blood pool contribution was estimated experimentally to be less than 5% of the total TLD response. The method was unable to resolve the initial uptake of the imaging agent due in part to the 2 minute TLD response integration time and in part to the 30 second lag time for the first TLD placement. A noticeable disparity was observed between the tracer concentrations of IPPA in normal and ischemic tissue of approximately 2:1. The fitting parameters (representing the biokinetic eigenvalue rate constants) were related to the fundamental rate constants of a recycling biokinetic model. The myocardial IPPA content within normal tissue was elevated after approximately 130 minutes post injection. This phenomenon was observed in all but one (950215) of the IPPA TLD kinetics curves.

  16. Anatomic and Physiological Bases of Social Blushing: Speculations from Neurology and Psychology

    Directory of Open Access Journals (Sweden)

    W. D. Cutlip II

    1993-01-01

    Full Text Available Although a common and occasionally troubling reaction, social blushing has received little systematic attention from either medical or behavioral researchers. This article reviews what is known of the physiological and psychological processes that mediate social blushing, and speculates regarding the role of central mechanisms in the phenomenon. Blushing is characterized by the unusual combination of cutaneous vasodilatation of the face, neck, and ears, accompanied by activation of the sympathetic nervous system. Psychologically, blushing appears to occur when people receive undesired social attention from others and may be analogous to the appeasement displays observed in non-human primates. Although poorly understood, the central mechanisms that mediate blushing obviously involve both involuntary autonomic effector systems and higher areas that involve self-reflective thought. Questions for future research are suggested.

  17. Development of an Educational Application to Support Learning the Molecular Bases of Endocrine Physiology

    Directory of Open Access Journals (Sweden)

    A.A. Brasil

    2009-05-01

    Full Text Available Studies point to a difficulty for students to visualize and understand the molecular structures that compose living organisms, certainly due to the fact that they are invisible and abstract. Thus, the construction of concepts, both biological and chemical, is closely related to the visual form in which students have contact during their learning. The benefits of using interactive applications in education have been discussed for a long time and have demonstrated that they can increase the cognitive capacity as well as facilitate fixation of information. In this work is presented an application to support learning the molecular basis of endocrine physiology. The application was developed in HTML and JAVA and made available online on the website http://www.biomol.net/aulas/endocrinomol/. The application presents  a theoretical introductory section on the basic concepts of endocrine physiology and another of interaction with three-dimensional hormone molecules. The three-dimensional models are accompanied by questions to be answered by students. The application was  used in classes of Biomedicine of Universidade Severino Sombra (USS and was evaluated by the students through spontaneous comments and Likert five-point questionnaire with questions covering usability, structure of the application and its use as a learning tool. In the results from the evaluation, the application was approved with regards to its usability and structure, and it was shown that facilitated the understanding by students of the molecular structures of hormones and their interactions.

  18. Dry period cooling ameliorates physiological variables and blood acid base balance, improving milk production in murrah buffaloes

    Science.gov (United States)

    Aarif, Ovais; Aggarwal, Anjali

    2016-03-01

    This study aimed to evaluate the impact of evaporative cooling during late gestation on physiological responses, blood gas and acid base balance and subsequent milk production of Murrah buffaloes. To investigate this study sixteen healthy pregnant dry Murrah buffaloes (second to fourth parity) at sixty days prepartum were selected in the months of May to June and divided into two groups of eight animals each. One group of buffaloes (Cooled/CL) was managed under fan and mist cooling system during dry period. Group second buffaloes (Noncooled/NCL) remained as control without provision of cooling during dry period. The physiological responses viz. Rectal temperature (RT), Respiratory rate (RR) and Pulse rate were significantly ( P < 0.05) lower in group 2, with the provision of cooling. Skin surface temperature at thorax was significantly lower in cooled group relative to noncooled group. Blood pH and pO2 were significantly ( P < 0.05) higher in heat stressed group as compared to the cooled group. pCO2, TCO2, HCO3, SBC, base excess in extracellular fluid (BEecf), base excess in blood (BEb), PCV and Hb were significantly ( P < 0.05) higher in cooled group as compared to noncooled group. DMI was significantly ( P < 0.05) higher in cooled relative to noncooled animals. Milk yield, FCM, fat yield, lactose yield and total solid yield was significantly higher ( P < 0.05) in cooled group of Murrah buffaloes.

  19. Dry period cooling ameliorates physiological variables and blood acid base balance, improving milk production in murrah buffaloes.

    Science.gov (United States)

    Aarif, Ovais; Aggarwal, Anjali

    2016-03-01

    This study aimed to evaluate the impact of evaporative cooling during late gestation on physiological responses, blood gas and acid base balance and subsequent milk production of Murrah buffaloes. To investigate this study sixteen healthy pregnant dry Murrah buffaloes (second to fourth parity) at sixty days prepartum were selected in the months of May to June and divided into two groups of eight animals each. One group of buffaloes (Cooled/CL) was managed under fan and mist cooling system during dry period. Group second buffaloes (Noncooled/NCL) remained as control without provision of cooling during dry period. The physiological responses viz. Rectal temperature (RT), Respiratory rate (RR) and Pulse rate were significantly (P base excess in extracellular fluid (BEecf), base excess in blood (BEb), PCV and Hb were significantly (P < 0.05) higher in cooled group as compared to noncooled group. DMI was significantly (P < 0.05) higher in cooled relative to noncooled animals. Milk yield, FCM, fat yield, lactose yield and total solid yield was significantly higher (P < 0.05) in cooled group of Murrah buffaloes.

  20. Animal laboratory, interactive and computer based learning, in enhancing basic concepts in physiology: an outlook of 481 undergraduate medical students.

    Science.gov (United States)

    Shore, Najla; Khawar, Shireen; Qutab, Miraa; Ayub, Muhammad

    2013-01-01

    Laboratory exercises are intended to illustrate concepts and add an active learning component to courses. Since 1980s, there has been a decline in animal laboratories in medical physiology courses. Other cost-effective non-aninmal alternatives are being sought. The present study was designed to find out the students' opinion regarding the animal versus computer lab and whether innovative teaching methodologies helped students achieve their goals. Opinions of 481 female in medical students of 2nd and 3rd year MBBS were included in the study. A questionnaire based on animal/computer based experiments and new teaching methodologies in physiology was voluntarily filled in by the students. Majority of students immensely benefited from both the animal lab and other teaching methodologies. Although computer based learning is considered effective in helping students acquire basic concepts, there is evidence that some students acquire a more thorough understanding of the material through more advanced and challenging experience of an animal laboratory. The fact that such labs as well various teaching methods offer distinct educational advantages should be taken into account when courses are designed.

  1. Physiological Networks: towards systems physiology

    Science.gov (United States)

    Bartsch, Ronny P.; Bashan, Amir; Kantelhardt, Jan W.; Havlin, Shlomo; Ivanov, Plamen Ch.

    2012-02-01

    The human organism is an integrated network where complex physiologic systems, each with its own regulatory mechanisms, continuously interact, and where failure of one system can trigger a breakdown of the entire network. Identifying and quantifying dynamical networks of diverse systems with different types of interactions is a challenge. Here, we develop a framework to probe interactions among diverse systems, and we identify a physiologic network. We find that each physiologic state is characterized by a specific network structure, demonstrating a robust interplay between network topology and function. Across physiologic states the network undergoes topological transitions associated with fast reorganization of physiologic interactions on time scales of a few minutes, indicating high network flexibility in response to perturbations. The proposed system-wide integrative approach may facilitate new dimensions to the field of systems physiology.

  2. In vitro and in vivo interactions of selected nanoparticles with rodent serum proteins and their consequences in biokinetics

    Directory of Open Access Journals (Sweden)

    Wolfgang G. Kreyling

    2014-10-01

    Full Text Available When particles incorporated within a mammalian organism come into contact with body fluids they will bind to soluble proteins or those within cellular membranes forming what is called a protein corona. This binding process is very complex and highly dynamic due to the plethora of proteins with different affinities and fractions in different body fluids and the large variation of compounds and structures of the particle surface. Interestingly, in the case of nanoparticles (NP this protein corona is well suited to provide a guiding vehicle of translocation within body fluids and across membranes. This NP translocation may subsequently lead to accumulation in various organs and tissues and their respective cell types that are not expected to accumulate such tiny foreign bodies. Because of this unprecedented NP accumulation, potentially adverse biological responses in tissues and cells cannot be neglected a priori but require thorough investigations. Therefore, we studied the interactions and protein binding kinetics of blood serum proteins with a number of engineered NP as a function of their physicochemical properties. Here we show by in vitro incubation tests that the binding capacity of different engineered NP (polystyrene, elemental carbon for selected serum proteins depends strongly on the NP size and the properties of engineered surface modifications. In the following attempt, we studied systematically the effect of the size (5, 15, 80 nm of gold spheres (AuNP, surface-modified with the same ionic ligand; as well as 5 nm AuNP with five different surface modifications on the binding to serum proteins by using proteomics analyses. We found that the binding of numerous serum proteins depended strongly on the physicochemical properties of the AuNP. These in vitro results helped us substantially in the interpretation of our numerous in vivo biokinetics studies performed in rodents using the same NP. These had shown that not only the

  3. Biokinetics and radiation doses for carbon-14 urea in adults and children undergoing the Helicobacter pylori breath test

    Energy Technology Data Exchange (ETDEWEB)

    Leide-Svegborn, S.; Olofsson, M.; Mattsson, S.; Nosslin, B.; Pau, K. [Department of Radiation Physics, Lund University, Malmoe University Hospital, Malmoe (Sweden); Stenstroem, K.; Erlandsson, B.; Hellborg, R. [Department of Nuclear Physics, Lund University, Lund (Sweden); Nilsson, L. [Department of Clinical Physiology, Lund University, Malmoe University Hospital, Malmoe (Sweden); Johansson, L. [Department of Radiation Physics, Umeaa University, Umeaa University Hospital, Umeaa (Sweden); Skog, G. [Radiocarbon Dating Laboratory, Department of Quaternary Geology, Lund University, Lund (Sweden)

    1999-06-01

    The long-term biokinetics and dosimetry of carbon-14 were studied in nine adults and eight children undergoing carbon-14 urea breath test for Helicobacter pylori (HP) infection. The elimination of {sup 14}C via exhaled air and urine was measured with the liquid scintillation counting technique and with accelerator mass spectrometry. After the subjects had been given 110 kBq {sup 14}C-urea (children: 55 kBq) orally, samples of exhaled air were taken up to 180 days after administration and samples of urine were collected up to 40 days. Sixteen of the subjects were found to be HP-negative. In these subjects a total of 91.1%{+-}3.9% (mean of adults and children {+-} standard error of the mean) of the administered {sup 14}C activity was recovered. The majority of the administered activity, 88.3%{+-}6.2% in adults and 87.7%{+-}5.0% in children, was excreted via the urine within 72 h after administration. A smaller fraction was exhaled. In adults 4.6%{+-}0.6% of the activity was exhaled within 20 days and in children 2.6%{+-}0.3%. Uncertainties in the biokinetic results are mainly due to assumptions concerning endogenous CO{sub 2} production and urinary excretion rate and are estimated to be less than 30%. The absorbed dose to various organs and the effective dose were calculated using the ICRP model for urea and CO{sub 2}. The urinary bladder received the highest absorbed dose: in adults, 0.15{+-}0.01 mGy/MBq and in children of various ages (7-14 years), 0.14-0.36 mGy/MBq. The findings indicate that an investigation with {sup 14}C-urea gives an effective dose to adults of 2.1{+-}0.1 {mu}Sv (for 110 kBq) and to children of 0.9-2.5 {mu}Sv (for 55 kBq). From a radiation protection point of view, there is thus no reason for restrictions on even repeated screening investigations with {sup 14}C-urea in whole families, including children. (orig.) With 5 figs., 4 tabs., 32 refs.

  4. Enhancing learning through optimal sequencing of web-based and manikin simulators to teach shock physiology in the medical curriculum.

    Science.gov (United States)

    Cendan, Juan C; Johnson, Teresa R

    2011-12-01

    The Association of American Medical Colleges has encouraged educators to investigate proper linkage of simulation experiences with medical curricula. The authors aimed to determine if student knowledge and satisfaction differ between participation in web-based and manikin simulations for learning shock physiology and treatment and to determine if a specific training sequencing had a differential effect on learning. All 40 second-year medical students participated in a randomized, counterbalanced study with two interventions: group 1 (n = 20) participated in a web-based simulation followed by a manikin simulation and group 2 (n = 20) participated in reverse order. Knowledge and attitudes were documented. Mixed-model ANOVA indicated a significant main effect of time (F(1,38) = 18.6, P learning when web-based simulation precedes manikin use. This finding warrants further study.

  5. [Good Practice of Clinical Physiology Examination for Patient Safety with a Team-Based Approach: Quality Practice in Ultrasonographic Examination].

    Science.gov (United States)

    Asai, Satomi; Miyachi, Hayato

    2015-07-01

    For the safety of patient care, a team-based approach has been advocated as an effective measure. In clinical physiology examination, we have been making efforts to promote good practice for patient safety based on such an approach in Tokai University Hospital, as represented by quality practice in ultrasonographic examination. The entire process of ultrasonographic examination can be divided into three parts: pre-examination, examination, and post-examination processes. In each process of the examination, specific quality issues must be considered, eventually ensuring the quality and safety of patient care. A laboratory physician is responsible for not only quality assurance of examination, diagnosis, and reporting, but also patient safety. A laboratory physician can play a key role in all aspects of patient safety related to each process of the examination by taking a leadership role in the team-based approach.

  6. Development of a Physiologically Based Computational Kidney Model to Describe the Renal Excretion of Hydrophilic Agents in Rats

    Science.gov (United States)

    Niederalt, Christoph; Wendl, Thomas; Kuepfer, Lars; Claassen, Karina; Loosen, Roland; Willmann, Stefan; Lippert, Joerg; Schultze-Mosgau, Marcus; Winkler, Julia; Burghaus, Rolf; Bräutigam, Matthias; Pietsch, Hubertus; Lengsfeld, Philipp

    2013-01-01

    A physiologically based kidney model was developed to analyze the renal excretion and kidney exposure of hydrophilic agents, in particular contrast media, in rats. In order to study the influence of osmolality and viscosity changes, the model mechanistically represents urine concentration by water reabsorption in different segments of kidney tubules and viscosity dependent tubular fluid flow. The model was established using experimental data on the physiological steady state without administration of any contrast media or drugs. These data included the sodium and urea concentration gradient along the cortico-medullary axis, water reabsorption, urine flow, and sodium as well as urea urine concentrations for a normal hydration state. The model was evaluated by predicting the effects of mannitol and contrast media administration and comparing to experimental data on cortico-medullary concentration gradients, urine flow, urine viscosity, hydrostatic tubular pressures and single nephron glomerular filtration rate. Finally the model was used to analyze and compare typical examples of ionic and non-ionic monomeric as well as non-ionic dimeric contrast media with respect to their osmolality and viscosity. With the computational kidney model, urine flow depended mainly on osmolality, while osmolality and viscosity were important determinants for tubular hydrostatic pressure and kidney exposure. The low diuretic effect of dimeric contrast media in combination with their high intrinsic viscosity resulted in a high viscosity within the tubular fluid. In comparison to monomeric contrast media, this led to a higher increase in tubular pressure, to a reduction in glomerular filtration rate and tubular flow and to an increase in kidney exposure. The presented kidney model can be implemented into whole body physiologically based pharmacokinetic models and extended in order to simulate the renal excretion of lipophilic drugs which may also undergo active secretion and reabsorption

  7. An Internet-based program for depression using activity and physiological sensors: efficacy, expectations, satisfaction, and ease of use

    Science.gov (United States)

    Botella, Cristina; Mira, Adriana; Moragrega, Inés; García-Palacios, Azucena; Bretón-López, Juana; Castilla, Diana; Riera López del Amo, Antonio; Soler, Carla; Molinari, Guadalupe; Quero, Soledad; Guillén-Botella, Verónica; Miralles, Ignacio; Nebot, Sara; Serrano, Berenice; Majoe, Dennis; Alcañiz, Mariano; Baños, Rosa María

    2016-01-01

    Purpose Computerized cognitive behavioral therapy (CCBT) has been shown to be efficacious. Moreover, CCBT can be enhanced by using physiological and activity sensors, but there is no evidence about the acceptability of all these tools. The objective of this study is to examine the efficacy, expectations, satisfaction, and ease of use of an Internet-based CCBT program for preventing depression, with and without sensors (electroencephalography, electrocardiograhpy ECG, and actigraphy), in a high-risk population (unemployed men). Patients and methods Sixty participants at risk of depression (unemployed men) were randomly assigned to three experimental conditions: 1) intervention program (N=22), 2) intervention program plus sensors (N=19), and 3) control group (N=19). Participants completed depression, anxiety, positive and negative affect, and perceived stress measures. Furthermore, they also completed the measures for expectation, satisfaction, and the ease of use of the program. Results Results showed that the two intervention groups improved significantly more than the control group on the clinical variables, and the improvements were greater in the group that used sensors than in the group that did not use them. Furthermore, participants in both intervention groups scored high on expectations and satisfaction with the CCBT program (with and without sensors). The mean score for usability was 88 out of 100 (standard deviation =12.32). No significant differences were found between groups on any of these variables. Conclusion This is the first study to analyze the efficacy, expectations, satisfaction, and ease of use of an Internet-based program using physiological and activity sensors. These results suggest that an Internet program for depression with or without physiological and activity sensors is effective, satisfactory, and easy to use. PMID:27042067

  8. Prediction of Ketoconazole absorption using an updated in vitro transfer model coupled to physiologically based pharmacokinetic modelling.

    Science.gov (United States)

    Ruff, Aaron; Fiolka, Tom; Kostewicz, Edmund S

    2017-03-30

    The aim of this study was to optimize the in vitro transfer model and to increase its biorelevance to more accurately mimic the in vivo supersaturation and precipitation behaviour of weak basic drugs. Therefore, disintegration of the formulation, volumes of the stomach and intestinal compartments, transfer rate, bile salt concentration, pH range and paddle speed were varied over a physiological relevant range. The supersaturation and precipitation data from these experiments for Ketoconazole (KTZ) were coupled to physiologically based pharmacokinetic (PBPK) model using Stella® software, which also incorporated the disposition kinetics of KTZ taken from the literature, in order to simulate the oral absorption and plasma profile in humans. As expected for a poorly soluble weak base, KTZ demonstrated supersaturation followed by precipitation under various in vitro conditions simulating the proximal small intestine with the results influenced by transfer rate, hydrodynamics, volume, bile salt concentration and pH values. When the in vitro data representing the "average" GI conditions was coupled to the PBPK model, the simulated profiles came closest to the observed mean plasma profiles for KTZ. In line with the high permeability of KTZ, the simulated profiles were highly influenced by supersaturation whilst precipitation was not predicted to occur in vivo. A physiological relevant in vitro "standard" transfer model setup to investigate supersaturation and precipitation was established. For translating the in vitro data to the in vivo setting, it is important that permeability is considered which can be achieved by coupling the in vitro data to PBPK modelling. Copyright © 2016. Published by Elsevier B.V.

  9. Sensing human physiological response using wearable carbon nanotube-based fabrics

    Science.gov (United States)

    Wang, Long; Loh, Kenneth J.; Koo, Helen S.

    2016-04-01

    Flexible and wearable sensors for human monitoring have received increased attention. Besides detecting motion and physical activity, measuring human vital signals (e.g., respiration rate and body temperature) provide rich data for assessing subjects' physiological or psychological condition. Instead of using conventional, bulky, sensing transducers, the objective of this study was to design and test a wearable, fabric-like sensing system. In particular, multi-walled carbon nanotube (MWCNT)-latex thin films of different MWCNT concentrations were first fabricated using spray coating. Freestanding MWCNT-latex films were then sandwiched between two layers of flexible fabric using iron-on adhesive to form the wearable sensor. Second, to characterize its strain sensing properties, the fabric sensors were subjected to uniaxial and cyclic tensile load tests, and they exhibited relatively stable electromechanical responses. Finally, the wearable sensors were placed on a human subject for monitoring simple motions and for validating their practical strain sensing performance. Overall, the wearable fabric sensor design exhibited advances such as flexibility, ease of fabrication, light weight, low cost, noninvasiveness, and user comfort.

  10. The Endocrine Regulation of Stem Cells: Physiological Importance and Pharmacological Potentials for Cell-Based Therapy.

    Science.gov (United States)

    Ghorbani, Ahmad; Naderi-Meshkin, Hojjat

    2016-01-01

    Throughout life, different types of stem cells participate in tissue generation, maintenance, plasticity, and repair. Their abilities to secrete growth factors, to proliferate and differentiate into several cell lineages, and to migrate and home into the damaged tissues have made them attractive candidates for cell therapy and tissue engineering applications. Normal stem cell function is tied to the cell-intrinsic mechanisms and extrinsic signals derived from the surrounding microenvironment or circulation. Understanding the regulatory signals that govern stem cell functions is essential in order to have full knowledge about organogenesis, tissue maintenance and tissue plasticity in the physiological condition. It is also important for optimizing tissue engineering and improving the therapeutic efficiency of stem cells in regenerative medicine. A growing body of evidence indicates that hormonal signals can critically influence stem cell functions in fetal, postnatal, and adult tissues. This review focuses on recent studies revealing how growth hormone, insulin, thyroid hormone, parathormone, adrenocorticotropin, glucocorticoids, erythropoietin, and gastrointestinal hormones control stem cell behavior through influencing survival, proliferation, migration, homing, and differentiation of these cells. Moreover, how environmental factors such as exercise, hypoxia, and nutrition might affect stem cell functions through influencing the endocrine system is discussed. Some of the current limitations of cell therapy and how hormones can help overcoming these limitations are briefly outlined.

  11. Physiological bases of genetic differences in cannibalism behavior of the confused flour beetle Tribolium confusum.

    Science.gov (United States)

    Giray, T; Luyten, Y A; MacPherson, M; Stevens, L

    2001-04-01

    Physiological causes of genetic differences in cannibalism were examined to gain a better understanding of constraints on behavior evolution. Cannibalism has complex population level consequences in Tribolium confusum, including dramatic effects on population size. Laboratory strains with low and high cannibalism rates, obtained through inbreeding, have maintained distinct levels of cannibalism for over two decades even in the absence of artificial selection to maintain the differences. Why strains differ in their cannibalism rates was examined by measuring: (1) the nutritional benefit from cannibalism in both nutritionally good and poor environments, and (2) the possibility that eggs are an important source of water. How strains achieve differences in cannibalism was examined by testing for differences between strains in their ability to find eggs and in their tendency to eat eggs. Beetles from both strains survive equally well in a nutritionally good environment, but they accomplish this in different ways. The low cannibalism strain has high survivorship with and without cannibalism. The high cannibalism strain has low survivorship when not fed eggs and survivorship equivalent to the low cannibalism strain when fed eggs, suggesting it compensates for poor nutritional adaptation by eating eggs. The strains also differ in feeding behavior; beetles from the high cannibalism strain have a higher appetite for eggs. Beetles from the two strains did not differ in locomotor activity, search efficiency, or need for water. The observed behavioral and nutritional differences may contribute to the maintenance of different levels of cannibalism.

  12. A physiologically based hypothesis for learning proprioception and in approximating inverse kinematics.

    Science.gov (United States)

    Simkins, Matt

    2016-05-01

    A long-standing problem in muscle control is the "curse of dimensionality". In part, this problem relates to the fact that coordinated movement is only achieved through the simultaneous contraction and extension of multitude muscles to specific lengths. Couched in robotics terms, the problem includes the determination of forward and inverse kinematics. Of the many neurophysiological discoveries in cortex is the existence of position gradients. Geometrically, position gradients are described by planes in Euclidean space whereby neuronal activity increases as the hand approaches locations that lie in a plane. This work demonstrates that position gradients, when coupled with known physiology in the spinal cord, allows for a way to approximate proprioception (forward kinematics) and to specify muscle lengths for goal-directed postures (inverse kinematics). Moreover, position gradients provide a means to learn and adjust kinematics as animals learn to move and grow. This hypothesis is demonstrated using computer simulation of a human arm. Finally, experimental predictions are described that might confirm or falsify the hypothesis.

  13. Cognitive behavior evaluation based on physiological parameters among young healthy subjects with yoga as intervention.

    Science.gov (United States)

    Nagendra, H; Kumar, Vinod; Mukherjee, S

    2015-01-01

    To investigate the effect of yoga practice on cognitive skills, autonomic nervous system, and heart rate variability by analyzing physiological parameters. The study was conducted on 30 normal young healthy engineering students. They were randomly selected into two groups: yoga group and control group. The yoga group practiced yoga one and half hour per day for six days in a week, for a period of five months. The yoga practising group showed increased α, β, and δ EEG band powers and significant reduction in θ and γ band powers. The increased α and β power can represent enhanced cognitive functions such as memory and concentration, and that of δ signifies synchronization of brain activity. The heart rate index θ/α decreased, neural activity β/θ increased, attention resource index β/(α + θ) increased, executive load index (δ + θ)/α decreased, and the ratio (δ + θ)/(α + β) decreased. The yoga practice group showed improvement in heart rate variability, increased SDNN/RMSSD, and reduction in LF/HF ratio. Yoga practising group showed significant improvement in various cognitive functions, such as performance enhancement, neural activity, attention, and executive function. It also resulted in increase in the heart rate variability, parasympathetic nervous system activity, and balanced autonomic nervous system reactivity.

  14. Cognitive Behavior Evaluation Based on Physiological Parameters among Young Healthy Subjects with Yoga as Intervention

    Directory of Open Access Journals (Sweden)

    H. Nagendra

    2015-01-01

    Full Text Available Objective. To investigate the effect of yoga practice on cognitive skills, autonomic nervous system, and heart rate variability by analyzing physiological parameters. Methods. The study was conducted on 30 normal young healthy engineering students. They were randomly selected into two groups: yoga group and control group. The yoga group practiced yoga one and half hour per day for six days in a week, for a period of five months. Results. The yoga practising group showed increased α, β, and δ EEG band powers and significant reduction in θ and γ band powers. The increased α and β power can represent enhanced cognitive functions such as memory and concentration, and that of δ signifies synchronization of brain activity. The heart rate index θ/α decreased, neural activity β/θ increased, attention resource index β/(α+θ increased, executive load index (δ+θ/α decreased, and the ratio (δ+θ/(α+β decreased. The yoga practice group showed improvement in heart rate variability, increased SDNN/RMSSD, and reduction in LF/HF ratio. Conclusion. Yoga practising group showed significant improvement in various cognitive functions, such as performance enhancement, neural activity, attention, and executive function. It also resulted in increase in the heart rate variability, parasympathetic nervous system activity, and balanced autonomic nervous system reactivity.

  15. FPGA-Based Smart Sensor for Drought Stress Detection in Tomato Plants Using Novel Physiological Variables and Discrete Wavelet Transform

    Directory of Open Access Journals (Sweden)

    Carlos Duarte-Galvan

    2014-10-01

    Full Text Available Soil drought represents one of the most dangerous stresses for plants. It impacts the yield and quality of crops, and if it remains undetected for a long time, the entire crop could be lost. However, for some plants a certain amount of drought stress improves specific characteristics. In such cases, a device capable of detecting and quantifying the impact of drought stress in plants is desirable. This article focuses on testing if the monitoring of physiological process through a gas exchange methodology provides enough information to detect drought stress conditions in plants. The experiment consists of using a set of smart sensors based on Field Programmable Gate Arrays (FPGAs to monitor a group of plants under controlled drought conditions. The main objective was to use different digital signal processing techniques such as the Discrete Wavelet Transform (DWT to explore the response of plant physiological processes to drought. Also, an index-based methodology was utilized to compensate the spatial variation inside the greenhouse. As a result, differences between treatments were determined to be independent of climate variations inside the greenhouse. Finally, after using the DWT as digital filter, results demonstrated that the proposed system is capable to reject high frequency noise and to detect drought conditions.

  16. FPGA-based smart sensor for drought stress detection in tomato plants using novel physiological variables and discrete wavelet transform.

    Science.gov (United States)

    Duarte-Galvan, Carlos; Romero-Troncoso, Rene de J; Torres-Pacheco, Irineo; Guevara-Gonzalez, Ramon G; Fernandez-Jaramillo, Arturo A; Contreras-Medina, Luis M; Carrillo-Serrano, Roberto V; Millan-Almaraz, Jesus R

    2014-10-09

    Soil drought represents one of the most dangerous stresses for plants. It impacts the yield and quality of crops, and if it remains undetected for a long time, the entire crop could be lost. However, for some plants a certain amount of drought stress improves specific characteristics. In such cases, a device capable of detecting and quantifying the impact of drought stress in plants is desirable. This article focuses on testing if the monitoring of physiological process through a gas exchange methodology provides enough information to detect drought stress conditions in plants. The experiment consists of using a set of smart sensors based on Field Programmable Gate Arrays (FPGAs) to monitor a group of plants under controlled drought conditions. The main objective was to use different digital signal processing techniques such as the Discrete Wavelet Transform (DWT) to explore the response of plant physiological processes to drought. Also, an index-based methodology was utilized to compensate the spatial variation inside the greenhouse. As a result, differences between treatments were determined to be independent of climate variations inside the greenhouse. Finally, after using the DWT as digital filter, results demonstrated that the proposed system is capable to reject high frequency noise and to detect drought conditions.

  17. A Novel Method for Assessing Drug Degradation Product Safety Using Physiologically-Based Pharmacokinetic Models and Stochastic Risk Assessment.

    Science.gov (United States)

    Nguyen, Hoa Q; Stamatis, Stephen D; Kirsch, Lee E

    2015-09-01

    Patient safety risk due to toxic degradation products is a potentially critical quality issue for a small group of useful drug substances. Although the pharmacokinetics of toxic drug degradation products may impact product safety, these data are frequently unavailable. The objective of this study is to incorporate the prediction capability of physiologically based pharmacokinetic (PBPK) models into a rational drug degradation product risk assessment procedure using a series of model drug degradants (substituted anilines). The PBPK models were parameterized using a combination of experimental and literature data and computational methods. The impact of model parameter uncertainty was incorporated into stochastic risk assessment procedure for estimating human safe exposure levels based on the novel use of a statistical metric called "PROB" for comparing probability that a human toxicity-target tissue exposure exceeds the rat exposure level at a critical no-observed-adverse-effect level. When compared with traditional risk assessment calculations, this novel PBPK approach appeared to provide a rational basis for drug instability risk assessment by focusing on target tissue exposure and leveraging physiological, biochemical, biophysical knowledge of compounds and species.

  18. Community-based behavioral weight-loss treatment: long-term maintenance of weight loss, physiological, and psychological outcomes.

    Science.gov (United States)

    Latner, Janet D; Ciao, Anna C; Wendicke, Annemarie U; Murakami, Jessica M; Durso, Laura E

    2013-08-01

    Obesity is a significant public health problem, and sustainable long-term treatments are needed. This study examined a community-based model of weight-loss treatment. Ninety participants were recruited from eight community organizations (mean age: 49.65 years, mean body mass index: 35.80 kg/m(2); 64% female). Treatment groups were randomly assigned to two maintenance conditions: 1) self-help continuing care, or 2) assessment-only. Both received the same initial 20-session group behavioral treatment. Those randomized to continuing care were additionally instructed to meet as self-sustaining groups for 18 months post-treatment. Weight, physiological, behavioral, and psychological outcomes were assessed at baseline, post-treatment, and at six-month and 18-month follow-up. Eighty-seven percent of participants completed treatment. Participant treatment satisfaction and therapist adherence to treatment protocol were high. No group differences or time by group interaction effects emerged. Participants achieved significant weight losses at post-treatment, with no significant weight regain at six-month or 18-month follow-up. Treatment produced sustained changes in waist circumference, cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, insulin, eating patterns, physical activity, quality of life, and body image. A community-based treatment program may be an effective form of behavioral-weight-loss treatment for overweight/obese adults. Weight losses, along with physiological and psychological benefits, were sustained over time. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Retracted: Physiologically based pharmacokinetic predictions of intestinal BCRP-mediated effect of telmisartan on the pharmacokinetics of rosuvastatin in humans.

    Science.gov (United States)

    Bae, Soo Hyeon; Park, Wan-Su; Han, Seunghoon; Park, Gab-Jin; Lee, Jongtae; Hong, Taegon; Jeon, Sangil; Yim, Dong-Seok

    2017-07-01

    'Physiologically based pharmacokinetic predictions of intestinal BCRP-mediated effect of telmisartan on the pharmacokinetics of rosuvastatin in humans' by Soo Hyeon Bae, Wan-Su Park, Seunghoon Han, Gab-jin Park, Jongtae Lee, Taegon Hong, Sangil Jeon and Dong-Seok Yim The above article, published online on 06 February 2017 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal Editor in Chief, K. Sandy Pang, and John Wiley & Sons, Ltd. The authors retracted the paper due to errors associated with use of log D vs. log P of telmisartan as inputs of the PBPK model. The authors concluded that there are too many changes in the article to be resolved by an Erratum, and had requested a retraction. Reference Bae, S. H., Park, W.-S., Han, S., Park, G., Lee, J., Hong, T., Jeon, S., and Yim, D.-S. (2016) Physiologically based pharmacokinetic predictions of intestinal BCRP-mediated effect of telmisartan on the pharmacokinetics of rosuvastatin in humans. Biopharm. Drug Dispos., doi: 10.1002/bdd.2060. Copyright © 2016 John Wiley & Sons, Ltd.

  20. Early physiological markers of cardiovascular risk in community based adolescents with a depressive disorder.

    Science.gov (United States)

    Waloszek, Joanna M; Byrne, Michelle L; Woods, Michael J; Nicholas, Christian L; Bei, Bei; Murray, Greg; Raniti, Monika; Allen, Nicholas B; Trinder, John

    2015-04-01

    Depression is recognised as an independent cardiovascular risk factor in adults. Identifying this relationship early on in life is potentially important for the prevention of cardiovascular disease (CVD). This study investigated whether clinical depression is associated with multiple physiological markers of CVD risk in adolescents from the general community. Participants aged 12-18 years were recruited from the general community and screened for depressive symptoms. Individuals with high and low depressive symptoms were administered a diagnostic interview. Fifty participants, 25 with a current depressive episode and 25 matched healthy controls, subsequently completed cardiovascular assessments. Variables assessed were automatic brachial and continuous beat-to-beat finger arterial blood pressure, heart rate, vascular functioning by pulse amplitude tonometry following reactive hyperaemia and pulse transit time (PTT) at rest. Blood samples were collected to measure cholesterol, glucose and glycohaemoglobin levels and an index of cumulative risk of traditional cardiovascular risk factors was calculated. Depressed adolescents had a significantly lower reactive hyperaemia index and shorter PTT, suggesting deterioration in vascular integrity and structure. Higher fasting glucose and triglyceride levels were also observed in the depressed group, who also had higher cumulative risk scores indicative of increased engagement in unhealthy behaviours and higher probability of advanced atherosclerotic lesions. The sample size and number of males who completed all cardiovascular measures was small. Clinically depressed adolescents had poorer vascular functioning and increased CVD risk compared to controls, highlighting the need for early identification and intervention for the prevention of CVD in depressed youth. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Fabric circuit board-based dry electrode and its characteristics for long-term physiological signal recording.

    Science.gov (United States)

    Yoo, Jerald; Yoo, Hoi-Jun

    2011-01-01

    This paper presents a dry fabric electrode and its characteristics. For long-term physiological signal monitoring, conventional wet type electrode such as an Ag/AgCl electrode may not be sufficient, because captured signal strength degrades over time as its electrolyte dehydrates. Moreover, the electrolyte may cause skin irritation over a period of time. As a complement, a dry electrode can be used. In this work, fabric-based dry electrodes are introduced. Planar-Fabric Circuit Board (P-FCB) technology enables low cost and uniform productions of such electrodes; electrical properties of the electrodes with various materials, sizes, and time are shown. Both the strengths and drawbacks of the fabric-based electrodes are also discussed.

  2. Teaching baroreflex physiology to medical students: a comparison of quiz-based and conventional teaching strategies in a laboratory exercise.

    Science.gov (United States)

    Berg, Ronan M G; Plovsing, Ronni R; Damgaard, Morten

    2012-06-01

    Quiz-based and collaborative teaching strategies have previously been found to be efficient for the improving meaningful learning of physiology during lectures. These approaches have, however, not been investigated during laboratory exercises. In the present study, we compared the impact of solving quizzes individually and in groups with conventional teaching on the immediate learning during a laboratory exercise. We implemented two quizzes in a mandatory 4-h laboratory exercise on baroreflex physiology. A total of 155 second-year medical students were randomized to solve quizzes individually (intervention group I, n = 57), in groups of three to four students (intervention group II, n = 56), or not to perform any quizzes (control; intervention group III, n = 42). After the laboratory exercise, all students completed an individual test, which encompassed two recall questions, two intermediate questions, and two integrated questions. The integrated questions were of moderate and advanced difficulty, respectively. Finally, students completed an evaluation form. Intervention group I reached the highest total test scores and proved best at answering the integrated question of advanced difficulty. Moreover, there was an overall difference between groups for student evaluations of the quality of the teaching, which was highest for intervention group II. In conclusion, solving quizzes individually during a laboratory exercise may enhance learning, whereas solving quizzes in groups is associated with higher student satisfaction.

  3. Physiologic and acid-base measures of gopher snakes during ketamine or halothane-nitrous oxide anesthesia.

    Science.gov (United States)

    Custer, R S; Bush, M

    1980-11-01

    Arterial acid-base and selected physiologic measures of gopher snakes (Pituophis melanoleucus catenifer) during ketamine or halothane-nitrous oxide anesthesia were compared with base-line values. During ketamine anesthesia, significant decreases in pH and HCO-3 concentrations indicated acid-base states of uncompensated metabolic acidosis. In contrast, halothane-nitrous oxide anesthesia induced acidosis of respiratory origin, through a significant depression in respiratory rate. In addition to the conventional measures, the OH-/H+ ratios and the alpha-imidazole (alpha IM) values were calculated to assess acid-base status during anesthesia. Values for both factors decreased significantly during both ketamine and halothane-nitrous oxide anesthesia. Where H+ concentrations nearly doubled, the decline in the OH-/H+ ratio exceeded 70% and the alpha IM decreased less than 20%. It was concluded that these 2 factors may be helpful in evaluation of the acid-base status of ectothermic animals when normal values for the conventional measures of pH and pCO2 are not available for comparison.

  4. Overview of Dioxin Kinetics and Application of Dioxin Physiologically Based Phannacokinetic (PBPK) Models to Risk Assessment

    Science.gov (United States)

    The available data on the pharmacokinetics of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in animals and humans have been thoroughly reviewed in literature. It is evident based on these reviews and other analyses that three distinctive features of TCDD play important roles in dete...

  5. Overview of Dioxin Kinetics and Application of Dioxin Physiologically Based Phannacokinetic (PBPK) Models to Risk Assessment

    Science.gov (United States)

    The available data on the pharmacokinetics of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in animals and humans have been thoroughly reviewed in literature. It is evident based on these reviews and other analyses that three distinctive features of TCDD play important roles in dete...

  6. Knowledge Acquisition in Biochemistry, Physiology and Anatomy within the Context of Problem-Based Learning

    Science.gov (United States)

    Hassan, S.

    2013-01-01

    The existing literature on Problem-based learning (PBL) mostly paints a positive picture. If there were more evidence of the limitations of PBL, more could be done to apply the appropriate interventions to optimize the experience of PBL for students. The purpose of this article is to discuss second year medical students' perceptions of the…

  7. [Design of multi-physiological parameters acquisition and storage system based on zigbee].

    Science.gov (United States)

    Wang, Guojing; Wang, Weidong; Ang, Qing; Sun, Congcong

    2012-03-01

    Based on CC2530 SoC and Micro-SD card, the system consists of three acquisition nodes and a coordinator node. The former three nodes implement data collection and wireless transmission by collecting the data of blood pressure, body temperature and ECG, while the last one fulfills the tasks of fast network organization, data reception and assorted storage.

  8. Mindfulness-based stress reduction and physiological activity during acute stress: a randomized controlled trial

    NARCIS (Netherlands)

    Nyklicek, I.; Mommersteeg, P.M.; Beugen, S. van; Ramakers, C.; Boxtel, G.J. Van

    2013-01-01

    OBJECTIVE: The aim was to examine the effects of a Mindfulness-Based Stress Reduction (MBSR) intervention on cardiovascular and cortisol activity during acute stress. METHOD: Eighty-eight healthy community-dwelling individuals reporting elevated stress levels were randomly assigned to the MBSR proto

  9. Impact of Case-Based Lectures on Students' Performance in Vascular Physiology Module

    Science.gov (United States)

    Latif, Rabia

    2014-01-01

    Lecture-Based Teaching (LBT) remains the predominant form of teaching in healthcare profession education. It is excellent in providing an overview of a particular topic to a large number of students. However, the concern, which has been highlighted time and again, is the monotony and passive nature of this form of information transmission, which…

  10. Impact of Case-Based Lectures on Students' Performance in Vascular Physiology Module

    Science.gov (United States)

    Latif, Rabia

    2014-01-01

    Lecture-Based Teaching (LBT) remains the predominant form of teaching in healthcare profession education. It is excellent in providing an overview of a particular topic to a large number of students. However, the concern, which has been highlighted time and again, is the monotony and passive nature of this form of information transmission, which…

  11. Application of physiologically based pharmacokinetic (PBPK) model of trichloroethylene in rats for estimation of internal dose

    Science.gov (United States)

    Potential human health risk from chemical exposure must often be assessed for conditions for which suitable human or animal data are not available, requiring extrapolation across duration and concentration. The default method for exposure-duration adjustment is based on Haber's r...

  12. Comparison of the use of a physiologically based pharmacokinetic model and a classical pharmacokinetic model for dioxin exposure assessments.

    Science.gov (United States)

    Emond, Claude; Michalek, Joel E; Birnbaum, Linda S; DeVito, Michael J

    2005-12-01

    In epidemiologic studies, exposure assessments of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) assume a fixed elimination rate. Recent data suggest a dose-dependent elimination rate for TCDD. A physiologically based pharmacokinetic (PBPK) model, which uses a body-burden-dependent elimination rate, was developed previously in rodents to describe the pharmacokinetics of TCDD and has been extrapolated to human exposure for this study. Optimizations were performed using data from a random selection of veterans from the Ranch Hand cohort and data from a human volunteer who was exposed to TCDD. Assessment of this PBPK model used additional data from the Ranch Hand cohort and a clinical report of two women exposed to TCDD. This PBPK model suggests that previous exposure assessments may have significantly underestimated peak blood concentrations, resulting in potential exposure misclassifications. Application of a PBPK model that incorporates an inducible elimination of TCDD may improve the exposure assessments in epidemiologic studies of TCDD.

  13. Reconstructing Organophosphorus Pesticide Doses Using the Reversed Dosimetry Approach in a Simple Physiologically-Based Pharmacokinetic Model

    Directory of Open Access Journals (Sweden)

    Chensheng Lu

    2012-01-01

    Full Text Available We illustrated the development of a simple pharmacokinetic (SPK model aiming to estimate the absorbed chlorpyrifos doses using urinary biomarker data, 3,5,6-trichlorpyridinol as the model input. The effectiveness of the SPK model in the pesticide risk assessment was evaluated by comparing dose estimates using different urinary composite data. The dose estimates resulting from the first morning voids appeared to be lower than but not significantly different to those using before bedtime, lunch or dinner voids. We found similar trend for dose estimates using three different urinary composite data. However, the dose estimates using the SPK model for individual children were significantly higher than those from the conventional physiologically based pharmacokinetic (PBPK modeling using aggregate environmental measurements of chlorpyrifos as the model inputs. The use of urinary data in the SPK model intuitively provided a plausible alternative to the conventional PBPK model in reconstructing the absorbed chlorpyrifos dose.

  14. A multi-scale biomechanical model based on the physiological structure and lignocellulose components of wheat straw.

    Science.gov (United States)

    Chen, Longjian; Li, Aiwei; He, Xueqin; Han, Lujia

    2015-11-20

    Biomechanical behavior is a fundamental property for the efficient utilization of wheat straw in such applications as fuel and renewable materials. Tensile experiments and lignocellulose analyses were performed on three types of wheat straw. A multi-scale finite element model composed of the microscopic model of the microfibril equivalent volume element and the macroscopic model of straw tissue was proposed based on the physiological structure and lignocellulose components of wheat straw. The tensile properties of wheat straw were simulated by ANSYS software. The predicted stress-strain data were compared with the observed data, and good correspondence was achieved for all three types of wheat straw. The validated multi-scale finite-element (FE) model was then used to investigate the effect of the lignocellulose components on the biomechanical properties of wheat straw. More than 80% of stress is carried by the cellulose fiber, whereas the strain is mainly carried by the amorphous cellulose.

  15. Biokinetics of a transuranic ({sup 238}PU) and a rare earth element ({sup 152}Eu) in the lobster (Homarus gammarus): transfer mechanisms (accumulation and detoxification) in organs and at the cellular level; Biocinetiques d'un element transuranien, le {sup 238}PU, et d'une terre rare, le {sup 152}EU, chez le homard homarus gammarus (organes et niveau cellulaire) modalites des transferts (accumulation et detoxication)

    Energy Technology Data Exchange (ETDEWEB)

    Tocquet, N

    1995-07-01

    The work presented here is an experimental investigation of the biokinetics of transfer of a transuranic and a rare earth element ({sup 238}Pu and {sup 152}Eu) in the lobster Homarus gammarus. The study of {sup 238}Pu biokinetics forms part of a wider framework of research concerning the transfer of transuranic elements in marine species, while the study of {sup 152}Eu is carried out with a view to supporting the analogy between the behaviour of transuranics and rare earths in living organisms. Exactly the same experimental protocol, based on techniques from various disciplines (biology, biochemistry and metrology), was used to Investigate the biokinetics of transfer of these two radionuclides. The Individual lobsters were radiolabelled by means of one-shot or chronic ingestion of spiked meals. As the first approach, the kinetics and transfer mechanisms were studied In whole animal samples and in different organs distinct series of pathways through the different organs were identified in the case of both radionuclides, being mainly linked to digestive processes induced by the meal as well as the transport function of hemo-lymph in this way, the Important role of the digestive gland was picked out, with two of four cellular types displaying a successive involvement In the fixation and then the retention of the studied radionuclides. As a corroborative approach, the digestive gland was subjected to a more detailed investigation with the aim of describing the mechanisms of Incorporation and elucidating transfer processes at the cellular and molecular levels. {sup 238}Pu is preferentially partitioned into the cytosol, where it is associated with various constituents such as ferritin (iron-storing protein). {sup 152}Eu is more diffusely distributed in the hepato-pancreatic cells, while the lysosomes appear to play a more important role during transfer. The results obtained in this study, both on the macroscopic scale (i.e. the whole animal and different organs) as well

  16. Nanomaterial translocation - the biokinetics, tissue accumulation, toxicity and fate of materials in secondary organs

    DEFF Research Database (Denmark)

    Kermanizadeh, Ali; Balharry, Dominique; Wallin, Håkan

    2015-01-01

    into the toxicity posed by the NMs in these secondary organs is expanding due to the realisation that some materials may reach and accumulate in these target sites. The translocation to secondary organs includes, but is not limited to, the hepatic, central nervous, cardiovascular and renal systems. Current data......Engineered nanomaterials (NMs) offer great technological advantages but their risks to human health are still not fully understood. An increasing body of evidence suggests that some NMs are capable of distributing from the site of exposure to a number of secondary organs. The research...... the gastrointestinal tract seems to follow the same pattern as inhalation translocation, whereas the dermal uptake of NMs is generally reported to be low. The toxicological effects in secondary organs include oxidative stress, inflammation, cytotoxicity and dysfunction of cellular and physiological processes...

  17. EMG-to-force estimation with full-scale physiology based muscle model

    OpenAIRE

    Hayashibe, Mitsuhiro; Guiraud, David; Poignet, Philippe

    2009-01-01

    International audience; EMG-to-force estimation for voluntary muscle contraction has many applications in human-machine interaction, motion analysis, and rehabilitation robotics for prosthetic limbs or exoskeletons. EMG-based model can account for a subject's individual activation patterns to estimate muscle force. For the estimation, so-called Hill-type model has been used in most of the cases. It already has shown its promising performance, but it is still known as a phenomenological model ...

  18. Design of a Physiology-Sensitive VR-Based Social Communication Platform for Children With Autism.

    Science.gov (United States)

    Kuriakose, Selvia; Lahiri, Uttama

    2017-08-01

    Individuals with autism are often characterized by impairments in communication, reciprocal social interaction and explicit expression of their affective states. In conventional techniques, a therapist adjusts the intervention paradigm by monitoring the affective state e.g., anxiety of these individuals for effective floor-time-therapy. Conventional techniques, though powerful, are observation-based and face resource limitations. Technology-assisted systems can provide a quantitative, individualized rehabilitation platform. Presently-available systems are designed primarily to chain learning via aspects of one's performance alone restricting individualization. Specifically, these systems are not sensitive to one's anxiety. Our presented work seeks to bridge this gap by developing a novel VR-based interactive system with Anxiety-Sensitive adaptive technology. Specifically, such a system is capable of objectively identifying and quantifying one's anxiety level from real-time biomarkers, along with performance metrics. In turn it can adaptively respond in an individualized manner to foster improved social communication skills. In our present research, we have used Virtual Reality (VR) to design a proof-of-concept application that exposes participants to social tasks of varying challenges. Results of a preliminary usability study indicate the potential of our VR-based Anxiety-Sensitive system to foster improved task performance, thereby serving as a potent complementary tool in the hands of therapist.

  19. Ubiquity: a framework for physiological/mechanism-based pharmacokinetic/pharmacodynamic model development and deployment.

    Science.gov (United States)

    Harrold, John M; Abraham, Anson K

    2014-04-01

    Practitioners of pharmacokinetic/pharmacodynamic modeling routinely employ various software packages that enable them to fit differential equation based mechanistic or empirical models to biological/pharmacological data. The availability and choice of different analytical tools, while enabling, can also pose a significant challenge in terms of both, implementation and transferability. A package has been developed that addresses these issues by creating a simple text-based format, which provides methods to reduce coding complexity and enables the modeler to describe the components of the model based on the underlying physiochemical processes. A Perl script builds the system for multiple formats (ADAPT, MATLAB, Berkeley Madonna, etc.), enabling analysis across several software packages and reducing the chance for transcription error. Workflows can then be built around this package, which can increase efficiency and model availability. As a proof of concept, tools are included that allow models constructed in this format to be run with MATLAB both at the scripting level and through a generic graphical application that can be compiled and run as a stand-alone application.

  20. Physiologically Based Pharmacokinetic Modeling to Predict Drug-Drug Interactions with Efavirenz Involving Simultaneous Inducing and Inhibitory Effects on Cytochromes.

    Science.gov (United States)

    Marzolini, Catia; Rajoli, Rajith; Battegay, Manuel; Elzi, Luigia; Back, David; Siccardi, Marco

    2017-04-01

    Antiretroviral drugs are among the therapeutic agents with the highest potential for drug-drug interactions (DDIs). In the absence of clinical data, DDIs are mainly predicted based on preclinical data and knowledge of the disposition of individual drugs. Predictions can be challenging, especially when antiretroviral drugs induce and inhibit multiple cytochrome P450 (CYP) isoenzymes simultaneously. This study predicted the magnitude of the DDI between efavirenz, an inducer of CYP3A4 and inhibitor of CYP2C8, and dual CYP3A4/CYP2C8 substrates (repaglinide, montelukast, pioglitazone, paclitaxel) using a physiologically based pharmacokinetic (PBPK) modeling approach integrating concurrent effects on CYPs. In vitro data describing the physicochemical properties, absorption, distribution, metabolism, and elimination of efavirenz and CYP3A4/CYP2C8 substrates as well as the CYP-inducing and -inhibitory potential of efavirenz were obtained from published literature. The data were integrated in a PBPK model developed using mathematical descriptions of molecular, physiological, and anatomical processes defining pharmacokinetics. Plasma drug-concentration profiles were simulated at steady state in virtual individuals for each drug given alone or in combination with efavirenz. The simulated pharmacokinetic parameters of drugs given alone were compared against existing clinical data. The effect of efavirenz on CYP was compared with published DDI data. The predictions indicate that the overall effect of efavirenz on dual CYP3A4/CYP2C8 substrates is induction of metabolism. The magnitude of induction tends to be less pronounced for dual CYP3A4/CYP2C8 substrates with predominant CYP2C8 metabolism. PBPK modeling constitutes a useful mechanistic approach for the quantitative prediction of DDI involving simultaneous inducing or inhibitory effects on multiple CYPs as often encountered with antiretroviral drugs.

  1. Physiologically Based Pharmacokinetic (PBPK) Modeling and Simulation Approaches: A Systematic Review of Published Models, Applications, and Model Verification.

    Science.gov (United States)

    Sager, Jennifer E; Yu, Jingjing; Ragueneau-Majlessi, Isabelle; Isoherranen, Nina

    2015-11-01

    Modeling and simulation of drug disposition has emerged as an important tool in drug development, clinical study design and regulatory review, and the number of physiologically based pharmacokinetic (PBPK) modeling related publications and regulatory submissions have risen dramatically in recent years. However, the extent of use of PBPK modeling by researchers, and the public availability of models has not been systematically evaluated. This review evaluates PBPK-related publications to 1) identify the common applications of PBPK modeling; 2) determine ways in which models are developed; 3) establish how model quality is assessed; and 4) provide a list of publically available PBPK models for sensitive P450 and transporter substrates as well as selective inhibitors and inducers. PubMed searches were conducted using the terms "PBPK" and "physiologically based pharmacokinetic model" to collect published models. Only papers on PBPK modeling of pharmaceutical agents in humans published in English between 2008 and May 2015 were reviewed. A total of 366 PBPK-related articles met the search criteria, with the number of articles published per year rising steadily. Published models were most commonly used for drug-drug interaction predictions (28%), followed by interindividual variability and general clinical pharmacokinetic predictions (23%), formulation or absorption modeling (12%), and predicting age-related changes in pharmacokinetics and disposition (10%). In total, 106 models of sensitive substrates, inhibitors, and inducers were identified. An in-depth analysis of the model development and verification revealed a lack of consistency in model development and quality assessment practices, demonstrating a need for development of best-practice guidelines.

  2. Scale-up of a physiologically-based pharmacokinetic model to predict the disposition of monoclonal antibodies in monkeys.

    Science.gov (United States)

    Glassman, Patrick M; Chen, Yang; Balthasar, Joseph P

    2015-10-01

    Preclinical assessment of monoclonal antibody (mAb) disposition during drug development often includes investigations in non-human primate models. In many cases, mAb exhibit non-linear disposition that relates to mAb-target binding [i.e., target-mediated disposition (TMD)]. The goal of this work was to develop a physiologically-based pharmacokinetic (PBPK) model to predict non-linear mAb disposition in plasma and in tissues in monkeys. Physiological parameters for monkeys were collected from several sources, and plasma data for several mAbs associated with linear pharmacokinetics were digitized from prior literature reports. The digitized data displayed great variability; therefore, parameters describing inter-antibody variability in the rates of pinocytosis and convection were estimated. For prediction of the disposition of individual antibodies, we incorporated tissue concentrations of target proteins, where concentrations were estimated based on categorical immunohistochemistry scores, and with assumed localization of target within the interstitial space of each organ. Kinetics of target-mAb binding and target turnover, in the presence or absence of mAb, were implemented. The model was then employed to predict concentration versus time data, via Monte Carlo simulation, for two mAb that have been shown to exhibit TMD (2F8 and tocilizumab). Model predictions, performed a priori with no parameter fitting, were found to provide good prediction of dose-dependencies in plasma clearance, the areas under plasma concentration versu time curves, and the time-course of plasma concentration data. This PBPK model may find utility in predicting plasma and tissue concentration versus time data and, potentially, the time-course of receptor occupancy (i.e., mAb-target binding) to support the design and interpretation of preclinical pharmacokinetic-pharmacodynamic investigations in non-human primates.

  3. A hierarchical model for structure learning based on the physiological characteristics of neurons

    Institute of Scientific and Technical Information of China (English)

    WEI Hui

    2007-01-01

    Almost all applications of Artificial Neural Networks (ANNs) depend mainly on their memory ability.The characteristics of typical ANN models are fixed connections,with evolved weights,globalized representations,and globalized optimizations,all based on a mathematical approach.This makes those models to be deficient in robustness,efficiency of learning,capacity,anti-jamming between training sets,and correlativity of samples,etc.In this paper,we attempt to address these problems by adopting the characteristics of biological neurons in morphology and signal processing.A hierarchical neural network was designed and realized to implement structure learning and representations based on connected structures.The basic characteristics of this model are localized and random connections,field limitations of neuron fan-in and fan-out,dynamic behavior of neurons,and samples represented through different sub-circuits of neurons specialized into different response patterns.At the end of this paper,some important aspects of error correction,capacity,learning efficiency,and soundness of structural representation are analyzed theoretically.This paper has demonstrated the feasibility and advantages of structure learning and representation.This model can serve as a fundamental element of cognitive systems such as perception and associative memory.Key-words structure learning,representation,associative memory,computational neuroscience

  4. Cell physiology of the biotechnological relevant bacterium Bacillus pumilus-an omics-based approach.

    Science.gov (United States)

    Handtke, Stefan; Volland, Sonja; Methling, Karen; Albrecht, Dirk; Becher, Dörte; Nehls, Jenny; Bongaerts, Johannes; Maurer, Karl-Heinz; Lalk, Michael; Liesegang, Heiko; Voigt, Birgit; Daniel, Rolf; Hecker, Michael

    2014-12-20

    Members of the species Bacillus pumilus get more and more in focus of the biotechnological industry as potential new production strains. Based on exoproteome analysis, B. pumilus strain Jo2, possessing a high secretion capability, was chosen for an omics-based investigation. The proteome and metabolome of B. pumilus cells growing either in minimal or complex medium was analyzed. In total, 1542 proteins were identified in growing B. pumilus cells, among them 1182 cytosolic proteins, 297 membrane and lipoproteins and 63 secreted proteins. This accounts for about 43% of the 3616 proteins encoded in the B. pumilus Jo2 genome sequence. By using GC-MS, IP-LC/MS and H NMR methods numerous metabolites were analyzed and assigned to reconstructed metabolic pathways. In the genome sequence a functional secretion system including the components of the Sec- and Tat-secretion machinery was found. Analysis of the exoproteome revealed secretion of about 70 proteins with predicted secretion signals. In addition, selected production-relevant genome features such as restriction modification systems and NRPS clusters of B. pumilus Jo2 are discussed.

  5. Rating of Perceived Exertion and Physiological Responses in Water-Based Exercise

    Directory of Open Access Journals (Sweden)

    Santana Pinto Stephanie

    2015-12-01

    Full Text Available The aim of the present study was to relate the overall rating of perceived exertion (RPE-overall with cardiorespiratory and neuromuscular variables during stationary running with the elbow flexion/extension performed with water-floating equipment. The sample consisted of eleven women that performed the water-based exercise at submaximal cadences. The heart rate, oxygen uptake, ventilation, and electromyographic signal (EMG from biceps brachii (%EMG BB, triceps brachii (%EMG TB, biceps femoris (%EMG BF and rectus femoris (%EMG RF muscles were measured during the exercise, and the overall RPE was measured immediately following its completion. The Pearson product-moment linear correlation was used to investigate associations between the variables analyzed in the present study. Significant relationships were observed between the RPE-overall and all the cardiorespiratory variables, with the r values ranging from 0.60 to 0.70 (p<0.05. In addition, the RPE-overall showed a significant (p<0.05 relationship with %EMG BB (r=0.55 and %EMG BF (r=0.50. These results suggest an association between the RPE-overall with all cardiorespiratory and two neuromuscular variables during the execution of a water-based aerobic exercise using water-floating equipment.

  6. Mathematical physiology

    CERN Document Server

    Sneyd, James

    2009-01-01

    There has been a long history of interaction between mathematics and physiology. This book looks in detail at a wide selection of mathematical models in physiology, showing how physiological problems can be formulated and studied mathematically, and how such models give rise to interesting and challenging mathematical questions. With its coverage of many recent models it gives an overview of the field, while many older models are also discussed, to put the modern work in context. In this second edition the coverage of basic principles has been expanded to include such topics as stochastic differential equations, Markov models and Gibbs free energy, and the selection of models has also been expanded to include some of the basic models of fluid transport, respiration/perfusion, blood diseases, molecular motors, smooth muscle, neuroendrocine cells, the baroreceptor loop, turboglomerular oscillations, blood clotting and the retina. Owing to this extensive coverage, the second edition is published in two volumes. ...

  7. Indoor Air Quality Assessment Based on Human Physiology - Part 2. Limits

    Directory of Open Access Journals (Sweden)

    M. V. Jokl

    2003-01-01

    Full Text Available In order to evaluate indoor air quality in practice it is necessary to establish limits, or more exactly, tolerable ranges for unadapted and adapted persons. The optimal value overwhelmingly corresponds to PD 20 %. A better value of PD 10 % could be prescribed for asthmatics and for persons with increased requirements, i.e. those allergic to the environment and operators in airport control towers and atomic power stations. A worse value PD 30 % could be accepted as an admissible value. These values differ for unadapted and adapted persons (as introduced by BSR/ASHRAE 62-1989 R. The long-term tolerable value is the end of SBS range (for CO2 it is based on USSR space research, for TVOC on Molhave. The short-term tolerable value is the beginning of the toxic range (for CO2 it is taken from British Guidance Note EH 40/90; for TVOC from Molhave.

  8. GPU technology as a platform for accelerating physiological systems modeling based on Laguerre-Volterra networks.

    Science.gov (United States)

    Papadopoulos, Agathoklis; Kostoglou, Kyriaki; Mitsis, Georgios D; Theocharides, Theocharis

    2015-01-01

    The use of a GPGPU programming paradigm (running CUDA-enabled algorithms on GPU cards) in biomedical engineering and biology-related applications have shown promising results. GPU acceleration can be used to speedup computation-intensive models, such as the mathematical modeling of biological systems, which often requires the use of nonlinear modeling approaches with a large number of free parameters. In this context, we developed a CUDA-enabled version of a model which implements a nonlinear identification approach that combines basis expansions and polynomial-type networks, termed Laguerre-Volterra networks and can be used in diverse biological applications. The proposed software implementation uses the GPGPU programming paradigm to take advantage of the inherent parallel characteristics of the aforementioned modeling approach to execute the calculations on the GPU card of the host computer system. The initial results of the GPU-based model presented in this work, show performance improvements over the original MATLAB model.

  9. The neurobiological bases of memory formation: from physiological conditions to psychopathology.

    Science.gov (United States)

    Bisaz, Reto; Travaglia, Alessio; Alberini, Cristina M

    2014-01-01

    The formation of long-term memories is a function necessary for an adaptive survival. In the last two decades, great progress has been made in the understanding of the biological bases of memory formation. The identification of mechanisms necessary for memory consolidation and reconsolidation, the processes by which the posttraining and postretrieval fragile memory traces become stronger and insensitive to disruption, has indicated new approaches for investigating and treating psychopathologies. In this review, we will discuss some key biological mechanisms found to be critical for memory consolidation and strengthening, the role/s and mechanisms of memory reconsolidation, and how the interference with consolidation and/or reconsolidation can modulate the retention and/or storage of memories that are linked to psychopathologies.

  10. Physiologic aspects of designing hidden information systems based on visible optical radiation

    Directory of Open Access Journals (Sweden)

    Brailovskii V. V.

    2015-02-01

    Full Text Available The paper presents the methodology and experimental results of the study of human eye sensitivity in central and peripheral vision field to the visible light pulses. The experimental results show that transmission systems based on visible rays can work in hidden mode. Conditions providing hidden transmission differ significantly for day and night light levels. At low light levels (at night the non-perceptive nature of the pulsed light which is applied in the information transfer process should be used. In this case an optical transmitter is perceived as «usual» illuminant. In daylight, light pulse can be invisible at certain values of duration and frequency of the light pulses for central and peripheral vision. For example, light pulses with the duration of 5•10–6 s in the range from 20 to 200 Hz are «invisible».

  11. Generating pedestrian trajectories consistent with the fundamental diagram based on physiological and psychological factors.

    Directory of Open Access Journals (Sweden)

    Sahil Narang

    Full Text Available Pedestrian crowds often have been modeled as many-particle system including microscopic multi-agent simulators. One of the key challenges is to unearth governing principles that can model pedestrian movement, and use them to reproduce paths and behaviors that are frequently observed in human crowds. To that effect, we present a novel crowd simulation algorithm that generates pedestrian trajectories that exhibit the speed-density relationships expressed by the Fundamental Diagram. Our approach is based on biomechanical principles and psychological factors. The overall formulation results in better utilization of free space by the pedestrians and can be easily combined with well-known multi-agent simulation techniques with little computational overhead. We are able to generate human-like dense crowd behaviors in large indoor and outdoor environments and validate the results with captured real-world crowd trajectories.

  12. Physiologically corrected coupled motion during gait analysis using a model-based approach.

    Science.gov (United States)

    Bonnechère, Bruno; Sholukha, Victor; Salvia, Patrick; Rooze, Marcel; Van Sint Jan, Serge

    2015-01-01

    Gait analysis is used in daily clinics for patients' evaluation and follow-up. Stereophotogrammetric devices are the most used tool to perform these analyses. Although these devices are accurate results must be analyzed carefully due to relatively poor reproducibility. One of the major issues is related to skin displacement artifacts. Motion representation is recognized reliable for the main plane of motion displacement, but secondary motions, or combined, are less reliable because of the above artifacts. Model-based approach (MBA) combining accurate joint kinematics and motion data was previously developed based on a double-step registration method. This study presents an extensive validation of this MBA method by comparing results with a conventional motion representation model. Thirty five healthy subjects participated to this study. Gait motion data were obtained from a stereophotogrammetric system. Plug-in Gait model (PiG) and MBA were applied to raw data, results were then compared. Range-of-motion, were computed for pelvis, hip, knee and ankle joints. Differences between PiG and MBA were then computed. Paired-sample t-tests were used to compare both methods. Normalized root-mean square errors were also computed. Shapes of the curves were compared using coefficient of multiple correlations. The MBA and PiG approaches shows similar results for the main plane of motion displacement but statistically significative discrepancies appear for the combined motions. MBA appear to be usable in applications (such as musculoskeletal modeling) requesting better approximations of the joints-of-interest thanks to the integration of validated joint mechanisms.

  13. Physiology of acid-base balance in bovines with diarrhea backgrounds from Monteria, Colombia

    Directory of Open Access Journals (Sweden)

    César Betancur H

    2015-05-01

    Full Text Available ABSTRACT Objective. Evaluate the acid-base balance (ABB in bovines with diarrheic backgrounds in four areas of Montería, Colombia. Materials and methods. From a total of 300 pregnant cows, 60 were selected with their newborns. A direct inspection was performed of vital signs on the calves and the ABB indicators were determined using a gasometric method. Data were processed by means of descriptive statistics and the Duncan test was used to differentiate between the averages. The degree of association was established between the ABB indicators in cows and calves by using the Pearson correlation and a comparison of proportions was performed on the indexes of the newborns. Results. Regarding the cows, the ABB indicators were found within the reference values; however, in the calves the pH, pCO2, HCO3 - , the anion gap (AG and the bases excess (BE varied. A correlation was found between AG, BE and metabolic hydrogen ions (M*H. The AG in cows and calves showed notable differences (p<0.05 among the farms in the study. According to the numeric classification system, the suction reflect indicated a greater percentage of calves in group one. Conclusions. The ABB analyte measurement in cows was similar to the consulted reference; however, in calves some analytes did not coincide. This suggests metabolic acidosis in newborn calves due to the increase of AG and the decrease of BE. Additionally, its correlation with M*H opens the possibility of new proposals to determine ABB in bovines.

  14. Team-Based Learning Enhances Long-Term Retention and Critical Thinking in an Undergraduate Microbial Physiology Course

    Directory of Open Access Journals (Sweden)

    L. Dee Fink

    2003-12-01

    Full Text Available We used team-based learning to improve comprehension and critical thinking of students in an undergraduate microbial metabolism-physiology course. The course used well-known bacterial pathways to highlight themes of energy conservation and biodegradation. Prior to the introduction of team-based learning, student recall of this information was poor and students had difficulty extrapolating information to new organisms. Initially, individual and group quizzes were added to promote problem-solving and critical-thinking skills. This significantly improved student attitudes about the amount of information they learned and whether the instructor promoted critical thinking. However, retention of the material as judged by final examination scores was still poor. In the next year, two challenging projects were added to the course to complement the above themes: (i postulating a pathway for the metabolism of a substrate by a bacterium, and (ii modifying the current model for anaerobic sulfate reduction by incorporating recent genetic information. The inclusion of the team projects significantly improved final examination scores compared to the previous year without team projects. Overall, team-based learning with challenging projects improved the students’ comprehension and retention of information, critical thinking, and attitudes about the course and focused student-instructor interactions on learning rather than grades.

  15. Study on inter-ethnic human differences in bioactivation and detoxification of estragole using physiologically based kinetic modeling.

    Science.gov (United States)

    Ning, Jia; Louisse, Jochem; Spenkelink, Bert; Wesseling, Sebastiaan; Rietjens, Ivonne M C M

    2017-03-29

    Considering the rapid developments in food safety in the past decade in China, it is of importance to obtain insight into what extent safety and risk assessments of chemicals performed for the Caucasian population apply to the Chinese population. The aim of the present study was to determine physiologically based kinetic (PBK) modeling-based predictions for differences between Chinese and Caucasians in terms of metabolic bioactivation and detoxification of the food-borne genotoxic carcinogen estragole. The PBK models were defined based on kinetic constants for hepatic metabolism derived from in vitro incubations using liver fractions of the two ethnic groups, and used to evaluate the inter-ethnic differences in metabolic activation and detoxification of estragole. The models predicted that at realistic dietary intake levels, only 0.02% of the dose was converted to the ultimate carcinogenic metabolite 1'-sulfooxyestragole in Chinese subjects, whereas this amounted to 0.09% of the dose in Caucasian subjects. Detoxification of 1'-hydroxyestragole, mainly via conversion to 1'-oxoestragole, was similar within the two ethnic groups. The 4.5-fold variation in formation of the ultimate carcinogenic metabolite of estragole accompanied by similar rates of detoxification may indicate a lower risk of estragole for the Chinese population at similar levels of exposure. The study provides a proof of principle for how PBK modeling can identify differences in ethnic sensitivity and provide a more refined risk assessment for a specific ethnic group for a compound of concern.

  16. Foundations of space biology and medicine. Volume 2, book 2: Ecological and physiological bases of space biology and medicine

    Science.gov (United States)

    Calvin, M. (Editor); Gazenko, O. G. (Editor)

    1975-01-01

    The influence on living organisms of radiant energy, the psychophysical problems of space flight, methods of physiological investigations in flight, and the transmission of information are considered.

  17. The ecological and physiological bases of variation in the phenology of gonad growth in an urban and desert songbird.

    Science.gov (United States)

    Davies, Scott; Lane, Samuel; Meddle, Simone L; Tsutsui, Kazuyoshi; Deviche, Pierre

    2016-05-01

    Birds often adjust to urban areas by advancing the timing (phenology) of vernal gonad growth. However, the ecological and physiological bases of this adjustment are unclear. We tested whether the habitat-related disparity in gonad growth phenology of male Abert's towhees, Melozone aberti, is due to greater food availability in urban areas of Phoenix, Arizona USA or, alternatively, a habitat-related difference in the phenology of key food types. To better understand the physiological mechanism underlying variation in gonad growth phenology, we compared the activity of the reproductive system at all levels of hypothalamo-pituitary-gonadal (HPG) axis. We found no habitat-associated difference in food availability (ground arthropod biomass), but, in contrast to the seasonal growth of leaves on desert trees, the leaf foliage of urban trees was already developed at the beginning of our study. Multiple estimates of energetic status did not significantly differ between the non-urban and urban towhees during three years that differed in the habitat-related disparity in gonad growth and winter precipitation levels. Thus, our results provide no support for the hypothesis that greater food abundance in urban areas of Phoenix drives the habitat-related disparity in gonad growth phenology in Abert's towhees. By contrast, they suggest that differences in the predictability and magnitude of change in food availability between urban and desert areas of Phoenix contribute to the observed habitat-related disparity in gonad growth. Endocrine responsiveness of the gonads may contribute to this phenomenon as desert - but not urban - towhees had a marked plasma testosterone response to GnRH challenge.

  18. A mobile phone based telemonitoring concept for the simultaneous acquisition of biosignals physiological parameters.

    Science.gov (United States)

    Kumpusch, Hannes; Hayn, Dieter; Kreiner, Karl; Falgenhauer, Markus; Mor, Jürgen; Schreier, Günter

    2010-01-01

    Congestive Heart Failure (CHF) is a common chronic heart disease with high socioeconomic impact. Conventional treatment of CHF is often ineffective and inefficient, since self-management is complex and patients are insufficiently involved in therapy management. With telemedical concepts, continuous monitoring of the health status can be ensured, and consequently therapy management can be adapted to the individual requirements of every individual patient. Therefore, a mobile phone based patient terminal for the concurrent acquisition of biosignals (e.g. ECG) and bioparameters (e.g. blood pressure) for patients with CHF has been developed and prototypically implemented. Usability and interoperability aspects were especially considered by using Bluetooth and Near Field Communication (NFC) technology for data acquisition and standardized data formats for transmission of the data to a central monitoring centre. Results indicated that even complicated measurements like the acquisition of ECG signals could be accomplished autonomously by the patients in an intuitive and easy-to-use way. Through the usage of IHE conform HL7 messages, self-measured data could easily be integrated into a higher-ranking eHealth infrastructure.

  19. On the stability and compressive nonlinearity of a physiologically based model of the cochlea

    Energy Technology Data Exchange (ETDEWEB)

    Nankali, Amir [Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan (United States); Grosh, Karl [Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan (United States); Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan (United States)

    2015-12-31

    Hearing relies on a series of coupled electrical, acoustical (fluidic) and mechanical interactions inside the cochlea that enable sound processing. A positive feedback mechanism within the cochlea, called the cochlear amplifier, provides amplitude and frequency selectivity in the mammalian auditory system. The cochlear amplifier and stability are studied using a nonlinear, micromechanical model of the Organ of Corti (OoC) coupled to the electrical potentials in the cochlear ducts. It is observed that the mechano-electrical transduction (MET) sensitivity and somatic motility of the outer hair cell (OHC), control the cochlear stability. Increasing MET sensitivity beyond a critical value, while electromechanical coupling coefficient is within a specific range, causes instability. We show that instability in this model is generated through a supercritical Hopf bifurcation. A reduced order model of the system is approximated and it is shown that the tectorial membrane (TM) transverse mode effect on the dynamics is significant while the radial mode can be simplified from the equations. The cochlear amplifier in this model exhibits good agreement with the experimental data. A comprehensive 3-dimensional model based on the cross sectional model is simulated and the results are compared. It is indicated that the global model qualitatively inherits some characteristics of the local model, but the longitudinal coupling along the cochlea shifts the stability boundary (i.e., Hopf bifurcation point) and enhances stability.

  20. Evaluation of bluetooth low power for physiological monitoring in a home based cardiac rehabilitation program.

    Science.gov (United States)

    Martin, Timothy; Ding, Hang; D'Souza, Matthew; Karunanithi, Mohan

    2012-01-01

    Cardiovascular disease (CVD) is the leading cause of mortality in Australia, and places large burdens on the healthcare system. To assist patients with CVDs in recovering from cardiac events and mediating cardiac risk factors, a home based cardiac rehabilitation program, known as the Care Assessment Platform (CAP), was developed. In the CAP program, patients are required to manually enter health information into their mobile phones on a daily basis. The manual operation is often subject to human errors and is inconvenient for some elderly patients. To improve this, an automated wireless solution has been desired. The objectives of this paper are to investigate the feasibility of implementing the newly released Bluetooth 4.0 (BT4.0) for the CAP program, and practically evaluate BT4.0 communications between a developed mobile application and some emulated healthcare devices. The study demonstrated that BT4.0 addresses usability, interoperability and security for healthcare applications, reduces the power consumption in wireless communication, and improves the flexibility of interface for software development. This evaluation study provides an essential mobile BT4.0 framework to incorporate a large range of healthcare devices for clinical assessment and intervention in the CAP program, and hence it is useful for similar development and research work of other mobile healthcare solutions.

  1. Experimental studies on the biokinetics of plutonium and americium in the cephalopod Octopus vulgaris

    Energy Technology Data Exchange (ETDEWEB)

    Guary, J.C.; Fowler, S.W.

    1982-03-05

    Radiotracer experiments using the photon-emitters /sup 237/Pu and /sup 241/Am were performed to examine uptake, tissue distribution and retention of plutonium and americium in the cephalopod Octopus vulgaris Cuvier. A 2 wk exposure in contaminated sea water resulted in twice as much /sup 237/Pu being taken up by whole octopus as /sup 241/Am. Immediately following uptake approximately 41% and 73% of the /sup 237/Pu and /sup 241/Am respectively were located in the branchial hearts. Depuration rates for both radionuclides were identical; approximately 46% of both radionuclides initially incorporated were associated with a long-lived compartment which turned over very slowly (Tbsub(1/2) = 1.5 yr). Longer exposures to /sup 241/Am resulted in an increase in the size of the slowly exchanging /sup 241/Am pool in the octopus. After 2 mo depuration, the majority of the residual activity of both radionuclides was in the branchial hearts. On average 33% of the /sup 241/Am ingested with food was assimilated into tissues, primarily the hepatopancreas. Different whole-body /sup 241/Am excretion rates were observed at different times following assimilation and were related to transfer processes taking place within internal tissues, most notably between hepatopancreas and the branchial hearts. Relationships between circulatory and excretory functions of these 2 organs are discussed and a physiological mechanism is proposed to explain the observed patterns of /sup 241/Am excretion in O. vulgaris.

  2. A PHYSIOLOGICALLY BASED PHARMACOKINETIC/PHARMACODYNAMIC (PBPK/PD) MODEL FOR ESTIMATION OF CUMULATIVE RISK FROM EXPOSURE TO THREE N-METHYL CARBAMATES: CARBARYL, ALDICARB, AND CARBOFURAN

    Science.gov (United States)

    A physiologically-based pharmacokinetic (PBPK) model for a mixture of N-methyl carbamate pesticides was developed based on single chemical models. The model was used to compare urinary metabolite concentrations to levels from National Health and Nutrition Examination Survey (NHA...

  3. Corti's organ physiology-based cochlear model: a microelectronic prosthetic implant

    Science.gov (United States)

    Rios, Francisco; Fernandez-Ramos, Raquel; Romero-Sanchez, Jorge; Martin, Jose Francisco

    2003-04-01

    Corti"s Organ is an Electro-Mechanical transducer that allows the energy coupling between acoustical stimuli and auditory nerve. Although the structure and funtionality of this organ are complex, state of the art models have been currently developed and tested. Cochlea model presented in this paper is based on the theories of Bekesy and others and concerns on the behaviour of auditory system on frequency-place domain and mechanisms of lateral inhibition. At the same time, present state of technology will permit us developing a microsystem that reproduce this phenomena applied to hearing aid prosthesis. Corti"s Organ is composed of more than 20.000 cilia excited by mean of travelling waves. These waves produce relative pressures distributed along the cochlea, exciting an specific number of cilia in a local way. Nonlinear mechanisms of local adaptation to the intensity (external cilia cells) and lateral inhibition (internal cilia cells) allow the selection of very few elements excited. These transmit a very precise intensity and frequency information. These signals are the only ones coupled to the auditory nerve. Distribution of pressure waves matches a quasilogaritmic law due to Cochlea morphology. Microsystem presented in this paper takes Bark"s law as an approximation to this behaviour consisting on grouped arbitrary elements composed of a set of selective coupled exciters (bank of filters according to Patterson"s model).These sets apply the intensity adaptation principles and lateral inhibition. Elements excited during the process generate a bioelectric signal in the same way than cilia cell. A microelectronic solution is presented for the development of an implantable prosthesis device.

  4. Reproductive physiology

    Science.gov (United States)

    Gee, G.F.; Russman, S.E.; Ellis, David H.; Gee, George F.; Mirande, Claire M.

    1996-01-01

    Conclusions: Although the general pattern of avian physiology applies to cranes, we have identified many physiological mechanisms (e.g., effects of disturbance) that need further study. Studies with cranes are expensive compared to those done with domestic fowl because of the crane's larger size, low reproductive rate, and delayed sexual maturity. To summarize, the crane reproductive system is composed of physiological and anatomical elements whose function is controlled by an integrated neural-endocrine system. Males generally produce semen at a younger age than when females lay eggs. Eggs are laid in clutches of two (1 to 3), and females will lay additional clutches if the preceding clutches are removed. Both sexes build nests and incubate the eggs. Molt begins during incubation and body molt may be completed annually in breeding pairs. However, remiges are replaced sequentially over 2 to 3 years, or abruptly every 2 to 3 years in other species. Most immature birds replace their juvenal remiges over a 2 to 3 year period. Stress interferes with reproduction in cranes by reducing egg production or terminating the reproductive effort. In other birds, stress elevates corticosterone levels and decreases LHRH release. We know little about the physiological response of cranes to stress.

  5. Exercise physiology

    DEFF Research Database (Denmark)

    Kiens, Bente; Richter, Erik; Wojtaszewski, Jørgen

    2014-01-01

    The passing of Professor Bengt Saltin on September 12, 2014 truly marks the end of an era. As editor of the Journal of Applied Physiology and one of Bengt’s many collaborators and colleagues, I wanted the Journal to celebrate his many seminal contributions by means of an Editorial. Professor Bent...

  6. Information Processing: Rate-Based Investigation of Cell Physiological Changes along Design Space Development.

    Science.gov (United States)

    Sagmeister, Patrick; Wechselberger, Patrick; Herwig, Christoph

    2012-01-01

    Recent initiatives summarized under the term quality by design (QbD) urge for science and risk-based pharmaceutical bioprocess development strategies. One of the most accepted concepts communicated by the regulatory authorities is the concept of design space-a multidimensional combination of critical process parameter (CPP) ranges where the quality acceptance criteria (critical quality attributes, CQAs) are fulfilled. Current design space development along QbD principles focuses on the investigation of statistical CPP/CQA interactions, while the biological mechanistic of this interaction is hardly considered. Furthermore, the plethora of available online and offline data gathered within design space development is typically not used for the demonstration of process understanding. Here we present a methodology about how typical recorded process data can be processed and used to gather mechanistic process knowledge within upstream design space development, without the need for further experiments or additional analytical procedures. Data derived from online and offline measurements (off gas quantification, air flows, substrate flows, biomass dry cell weight measurements) were processed into scale-independent information in the form of specific rates and yield coefficients (data processing). Subsequently, the obtained information was regressed with the investigated process parameters aiming at the investigation of mechanistic interactions (information processing). The power of the presented approach was demonstrated on a multivariate study involving two process parameters (induction phase temperature and induction phase feeding strategy) aiming at the production of recombinant product in an Escherichia coli K12 strain. The knowledge successfully extracted indicated a time dependency of the metabolic load posed on the system, a possible down regulation of the promoter at reduced temperatures, and reduced cell lysis at higher specific feeding regimes. The presented data

  7. Grandma's TUM-my Trouble: A Case Study in Renal Physiology and Acid-Base Balance

    Science.gov (United States)

    Massey, Ann T.

    2015-01-01

    This case study involves the role of the kidneys in regulating blood pH and electrolytes. The case was used near the end of a two-semester Human Anatomy and Physiology course sequence, during the time when renal physiology was under study. Groups of two to three students were given the case and associated information (lab values, etc.). Students…

  8. Physiological changes following a 12 week gym based stair-climbing, elliptical trainer and treadmill running program in females

    OpenAIRE

    EGANA, MIKEL

    2004-01-01

    PUBLISHED Despite the growing popularity of the elliptical trainer aerobic exercise modality the physiological changes induced following a training program using elliptical trainers remains unknown. Donne investigates the metabolic and cardiorespiratory improvements following a 12-week aerobic training program using elliptical trainer, treadmill or stair-climbing modalities. Findings reveal that in moderately active females similar physiological improvements were observed using stair-climb...

  9. Grandma's TUM-my Trouble: A Case Study in Renal Physiology and Acid-Base Balance

    Science.gov (United States)

    Massey, Ann T.

    2015-01-01

    This case study involves the role of the kidneys in regulating blood pH and electrolytes. The case was used near the end of a two-semester Human Anatomy and Physiology course sequence, during the time when renal physiology was under study. Groups of two to three students were given the case and associated information (lab values, etc.). Students…

  10. Exploring ethical considerations for the use of biological and physiological markers in population-based surveys in less developed countries

    Directory of Open Access Journals (Sweden)

    Hyder Adnan A

    2005-11-01

    Full Text Available Abstract Background The health information needs of developing countries increasingly include population-based estimates determined by biological and physiological measures. Collection of data on these biomarkers requires careful reassessment of ethical standards and procedures related to issues of safety, informed consent, reporting, and referral policies. This paper reviews the survey practices of health examination surveys that have been conducted in developed nations and discusses their application to similar types of surveys proposed for developing countries. Discussion The paper contends that a unitary set of ethical principles should be followed for surveys around the world that precludes the danger of creating double standards (and implicitly lowers standards for work done in developing countries. Global ethical standards must, however, be interpreted in the context of the unique historical and cultural context of the country in which the work is being done. Factors that influence ethical considerations, such as the relationship between investigators in developed and developing countries are also discussed. Summary The paper provides a set of conclusions reached through this discussion and recommendations for the ethical use of biomarkers in populations-based surveys in developing countries.

  11. Physiologically based kinetic models for the alkenylbenzene elemicin in rat and human and possible implications for risk assessment.

    Science.gov (United States)

    van den Berg, Suzanne J P L; Punt, Ans; Soffers, Ans E M F; Vervoort, Jacques; Ngeleja, Stephen; Spenkelink, Bert; Rietjens, Ivonne M C M

    2012-11-19

    The present study describes physiologically based kinetic (PBK) models for the alkenylbenzene elemicin (3,4,5-trimethoxyallylbenzene) in rat and human, based on the PBK models previously developed for the structurally related alkenylbenzenes estragole, methyleugenol, and safrole. Using the newly developed models, the level of metabolic activation of elemicin in rat and human was predicted to obtain insight in species differences in the bioactivation of elemicin and read across to the other methoxy allylbenzenes, estragole and methyleugenol. Results reveal that the differences between rat and human in the formation of the proximate carcinogenic metabolite 1'-hydroxyelemicin and the ultimate carcinogenic metabolite 1'-sulfoxyelemicin are limited (rat and human liver. The insights thus obtained were used to perform a risk assessment for elemicin using the margin of exposure (MOE) approach and read across to the other methoxy allylbenzene derivatives for which in vivo animal tumor data are available. This reveals that elemicin poses a lower priority for risk management as compared to its structurally related analogues estragole and methyleugenol. Altogether, the results obtained indicate that PBK modeling provides an important insight in the occurrence of species differences in the metabolic activation of elemicin. Moreover, they provide an example of how PBK modeling can facilitate a read across in risk assessment from compounds for which in vivo toxicity studies are available to a compound for which only limited toxicity data have been described, thus contributing to the development of alternatives for animal testing.

  12. Human plasma concentrations of cytochrome P450 probes extrapolated from pharmacokinetics in cynomolgus monkeys using physiologically based pharmacokinetic modeling.

    Science.gov (United States)

    Shida, Satomi; Utoh, Masahiro; Murayama, Norie; Shimizu, Makiko; Uno, Yasuhiro; Yamazaki, Hiroshi

    2015-01-01

    1. Cynomolgus monkeys are widely used in preclinical studies as non-human primate species. Pharmacokinetics of human cytochrome P450 probes determined in cynomolgus monkeys after single oral or intravenous administrations were extrapolated to give human plasma concentrations. 2. Plasma concentrations of slowly eliminated caffeine and R-/S-warfarin and rapidly eliminated omeprazole and midazolam previously observed in cynomolgus monkeys were scaled to human oral biomonitoring equivalents using known species allometric scaling factors and in vitro metabolic clearance data with a simple physiologically based pharmacokinetic (PBPK) model. Results of the simplified human PBPK models were consistent with reported experimental PK data in humans or with values simulated by a fully constructed population-based simulator (Simcyp). 3. Oral administrations of metoprolol and dextromethorphan (human P450 2D probes) in monkeys reportedly yielded plasma concentrations similar to their quantitative detection limits. Consequently, ratios of in vitro hepatic intrinsic clearances of metoprolol and dextromethorphan determined in monkeys and humans were used with simplified PBPK models to extrapolate intravenous PK in monkeys to oral PK in humans. 4. These results suggest that cynomolgus monkeys, despite their rapid clearance of some human P450 substrates, could be a suitable model for humans, especially when used in conjunction with simple PBPK models.

  13. An Internet-based program for depression using activity and physiological sensors: efficacy, expectations, satisfaction, and ease of use

    Directory of Open Access Journals (Sweden)

    Botella C

    2016-02-01

    Full Text Available Cristina Botella,1,2 Adriana Mira,1 Inés Moragrega,2,3 Azucena García-Palacios,1,2 Juana Bretón-López,1,2 Diana Castilla,1,2 Antonio Riera López del Amo,1 Carla Soler,1 Guadalupe Molinari,1 Soledad Quero,1,2 Verónica Guillén-Botella,2,3 Ignacio Miralles,1,2 Sara Nebot,1 Berenice Serrano,1,2 Dennis Majoe,4 Mariano Alcañiz,2,5 Rosa María Baños2,31Department of Basic, Clinical Psychology and Psychobiology, Universitat Jaume, Castellón, Spain; 2CIBER Physiopathology of Obesity and Nutrition, CIBERobn, Instituto de Salud Carlos III, Santiago de Compostela, Spain; 3Department of Personality, Evaluation and Psychological Treatment, Universidad de Valencia, Valencia, Spain; 4Native Systems Institute, ETH Zurich, Zurich, Switzerland; 5Human-Centered Technology Institute, Universidad Politécnica de Valencia, Valencia, Spain Purpose: Computerized cognitive behavioral therapy (CCBT has been shown to be efficacious. Moreover, CCBT can be enhanced by using physiological and activity sensors, but there is no evidence about the acceptability of all these tools. The objective of this study is to examine the efficacy, expectations, satisfaction, and ease of use of an Internet-based CCBT program for preventing depression, with and without sensors (electroencephalography, electrocardiograhpy ECG, and actigraphy, in a high-risk population (unemployed men.Patients and methods: Sixty participants at risk of depression (unemployed men were randomly assigned to three experimental conditions: 1 intervention program (N=22, 2 intervention program plus sensors (N=19, and 3 control group (N=19. Participants completed depression, anxiety, positive and negative affect, and perceived stress measures. Furthermore, they also completed the measures for expectation, satisfaction, and the ease of use of the program.Results: Results showed that the two intervention groups improved significantly more than the control group on the clinical variables, and the improvements

  14. Physiologically based pharmacokinetic toolkit to evaluate environmental exposures: Applications of the dioxin model to study real life exposures.

    Science.gov (United States)

    Emond, Claude; Ruiz, Patricia; Mumtaz, Moiz

    2017-01-15

    Chlorinated dibenzo-p-dioxins (CDDs) are a series of mono- to octa-chlorinated homologous chemicals commonly referred to as polychlorinated dioxins. One of the most potent, well-known, and persistent member of this family is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). As part of translational research to make computerized models accessible to health risk assessors, we present a Berkeley Madonna recoded version of the human physiologically based pharmacokinetic (PBPK) model used by the U.S. Environmental Protection Agency (EPA) in the recent dioxin assessment. This model incorporates CYP1A2 induction, which is an important metabolic vector that drives dioxin distribution in the human body, and it uses a variable elimination half-life that is body burden dependent. To evaluate the model accuracy, the recoded model predictions were compared with those of the original published model. The simulations performed with the recoded model matched well with those of the original model. The recoded model was then applied to available data sets of real life exposure studies. The recoded model can describe acute and chronic exposures and can be useful for interpreting human biomonitoring data as part of an overall dioxin and/or dioxin-like compounds risk assessment. Copyright © 2016. Published by Elsevier Inc.

  15. Physiologically Based Absorption Modeling to Impact Biopharmaceutics and Formulation Strategies in Drug Development-Industry Case Studies.

    Science.gov (United States)

    Kesisoglou, Filippos; Chung, John; van Asperen, Judith; Heimbach, Tycho

    2016-09-01

    In recent years, there has been a significant increase in use of physiologically based pharmacokinetic models in drug development and regulatory applications. Although most of the published examples have focused on aspects such as first-in-human (FIH) dose predictions or drug-drug interactions, several publications have highlighted the application of these models in the biopharmaceutics field and their use to inform formulation development. In this report, we present 5 case studies of use of such models in this biopharmaceutics/formulation space across different pharmaceutical companies. The case studies cover different aspects of biopharmaceutics or formulation questions including (1) prediction of absorption prior to FIH studies; (2) optimization of formulation and dissolution method post-FIH data; (3) early exploration of a modified-release formulation; (4) addressing bridging questions for late-stage formulation changes; and (5) prediction of pharmacokinetics in the fed state for a Biopharmaceutics Classification System class I drug with fasted state data. The discussion of the case studies focuses on how such models can facilitate decisions and biopharmaceutic understanding of drug candidates and the opportunities for increased use and acceptance of such models in drug development and regulatory interactions.

  16. The Interactions between L-Tyrosine Based Nanoparticles Decorated with Folic Acid and Cervical Cancer Cells Under Physiological Flow

    Science.gov (United States)

    Ditto, Andrew J.; Shah, Kush N.; Robishaw, Nikki K.; Panzner, Matthew J.; Youngs, Wiley J.; Yun, Yang H.

    2012-01-01

    Many anticancer drugs have been established clinically, but their efficacy can be compromised by nonspecific toxicity and an inability to reach the desired cancerous intracellular spaces. In order to address these issues, researchers have explored the use of folic acid as a targeted moiety to increase specificity of chemotherapeutic drugs. To expand upon such research, we have conjugated folic acid to functionalized poly(ethylene glycol) and subsequently decorated the surface of L-tyrosine polyphosphate (LTP) nanoparticles. These nanoparticles possess the appropriate size (100–500 nm) for internalization as shown by scanning electron microscopy and dynamic light scattering. Under simulated physiological flow, LTP nanoparticles decorated with folic acid (targeted nanoparticles) show a 10-fold greater attachment to HeLa, a cervical cancer cell line, compared to control nanoparticles and to human dermal fibroblasts. The attachment of these targeted nanoparticles progresses at a linear rate, and the strength of this nanoparticle attachment is shown to withstand shear stresses of 3.0 dynes/cm2. These interactions of the targeted nanoparticles to HeLa are likely a result of a receptor-ligand binding, as a competition study with free folic acid inhibits the nanoparticle attachment. Finally, the targeted nanoparticles encapsulated with a silver based drug show increased efficacy in comparison to non-decorated (plain) nanoparticles and drug alone against HeLa cells. Thus, targeted nanoparticles are a promising delivery platform for developing anticancer therapies that over-express the folate receptors (FRs). PMID:22957928

  17. Social adversity in adolescence increases the physiological vulnerability to job strain in adulthood: a prospective population-based study.

    Directory of Open Access Journals (Sweden)

    Hugo Westerlund

    Full Text Available BACKGROUND: It has been argued that the association between job strain and health could be confounded by early life exposures, and studies have shown early adversity to increase individual vulnerability to later stress. We therefore investigated if early life exposure to adversity increases the individual's physiological vulnerability job strain in adulthood. METHODOLOGY/PRINCIPAL FINDINGS: In a population-based cohort (343 women and 330 men, 83% of the eligible participants, we examined the association between on the one hand exposure to adversity in adolescence, measured at age 16, and job strain measured at age 43, and on the other hand allostatic load at age 43. Adversity was operationalised as an index comprising residential mobility and crowding, parental loss, parental unemployment, and parental physical and mental illness (including substance abuse. Allostatic load summarised body fat, blood pressure, inflammatory markers, glucose, blood lipids, and cortisol regulation. There was an interaction between adversity in adolescence and job strain (B = 0.09, 95% CI 0.02 to 0.16 after adjustment for socioeconomic status, particularly psychological demands, indicating that job strain was associated with increased allostatic load only among participants with adversity in adolescence. Job strain was associated with lower allostatic load in men (β = -0.20, 95% CI -0.35 to -0.06. CONCLUSIONS/SIGNIFICANCE: Exposure to adversity in adolescence was associated with increased levels of biological stress among those reporting job strain in mid-life, indicating increased vulnerability to environmental stressors.

  18. A simple, physiologically-based model of sea turtle remigration intervals and nesting population dynamics: Effects of temperature.

    Science.gov (United States)

    Neeman, Noga; Spotila, James R; O'Connor, Michael P

    2015-09-07

    Variation in the yearly number of sea turtles nesting at rookeries can interfere with population estimates and obscure real population dynamics. Previous theoretical models suggested that this variation in nesting numbers may be driven by changes in resources at the foraging grounds. We developed a physiologically-based model that uses temperatures at foraging sites to predict foraging conditions, resource accumulation, remigration probabilities, and, ultimately, nesting numbers for a stable population of sea turtles. We used this model to explore several scenarios of temperature variation at the foraging grounds, including one-year perturbations and cyclical temperature oscillations. We found that thermally driven resource variation can indeed synchronize nesting in groups of turtles, creating cohorts, but that these cohorts tend to break down over 5-10 years unless regenerated by environmental conditions. Cohorts were broken down faster at lower temperatures. One-year perturbations of low temperature had a synchronizing effect on nesting the following year, while high temperature perturbations tended to delay nesting in a less synchronized way. Cyclical temperatures lead to cyclical responses both in nesting numbers and remigration intervals, with the amplitude and lag of the response depending on the duration of the cycle. Overall, model behavior is consistent with observations at nesting beaches. Future work should focus on refining the model to fit particular nesting populations and testing further whether or not it may be used to predict observed nesting numbers and remigration intervals.

  19. Development of Teaching Materials Based on Contextual Video to Improve the Student Higher Order Thingking Skills of Animal Physiology Course

    Directory of Open Access Journals (Sweden)

    Ari Indriana Hapsari

    2016-03-01

    Full Text Available he important demands in learning in college is the lecturer should empower the potential of students with various skills primarily related to Higher Order Thinking Skills (HOTS. These aspects need to attention by the lecture, seeing that in the 21st century learning skills, critical thinking, creative, make decisions, and solve problems is required in the work. Through the development based on contextual video teaching materials is expected to increase HOTS students of animal physiology subjects. The method used in this research is the ADDIE (Analysis, Design, Development, Implementation and Evaluation. Results of this study was an increase in the average value HOTS activity after treatment where the value of the average highest and lowest C41 analysis indicators are C52 evaluation indicators. Ngain value calculation is equal to 0.2 with a low category. While the results of the validation of two experts in a row both material and media experts in the amount of 3.2 and 3.12 in both categories.

  20. The effect of flipped teaching combined with modified team-based learning on student performance in physiology.

    Science.gov (United States)

    Gopalan, Chaya; Klann, Megan C

    2017-09-01

    Flipped classroom is a hybrid educational format that shifts guided teaching out of class, thus allowing class time for student-centered learning. Although this innovative teaching format is gaining attention, there is limited evidence on the effectiveness of flipped teaching on student performance. We compared student performance and student attitudes toward flipped teaching with that of traditional lectures using a partial flipped study design. Flipped teaching expected students to have completed preclass material, such as assigned reading, instructor-prepared lecture video(s), and PowerPoint slides. In-class activities included the review of difficult topics, a modified team-based learning (TBL) session, and an individual assessment. In the unflipped teaching format, students were given PowerPoint slides and reading assignment before their scheduled lectures. The class time consisted of podium-style lecture, which was captured in real time and was made available for students to use as needed. Comparison of student performance between flipped and unflipped teaching showed that flipped teaching improved student performance by 17.5%. This was true of students in both the upper and lower half of the class. A survey conducted during this study indicated that 65% of the students changed the way they normally studied, and 69% of the students believed that they were more prepared for class with flipped learning than in the unflipped class. These findings suggest that flipped teaching, combined with TBL, is more effective than the traditional lecture. Copyright © 2017 the American Physiological Society.

  1. In vitro physiologically based extraction test (PBET) and bioaccessibility of arsenic and lead from various mine waste materials.

    Science.gov (United States)

    Bruce, Scott; Noller, Barry; Matanitobua, Vitukawalu; Ng, Jack

    2007-10-01

    In vivo models show that the bioavailability of soil contaminants varies between site and type of matrix. Studies demonstrated that assuming 100% bioavailability of arsenic (As) and lead (Pb) from soils and mine waste materials overestimates the risk associated with human exposure. In in vitro systems, the simulated bioavailability of a contaminant is referred to as the "bioaccessibility" and is used as an alternative quantitative indicator for in vivo derived bioavailability estimates. The general concept of the in vitro extraction test is to predict the bioavailability of inorganic substances from solid matrices by simulating the gastrointestinal tract (GIT) environment. The aims of this study were to: (1) investigate the bioaccessibility of As and Pb from various mine wastes, including tailings, heap leach, and waste rock, using a physiologically based extraction test (PBET); (2) validate the bioaccessibility values from PBET with in vivo bioavailability values measured using animal models; and (3) correlate PBET results with the bioavailability values measured from alternative in vivo models (rats and cattle, from Bruce, 2004). Significant correlation was observed between bioaccessibility values from PBET, and bioavailability values generated for both rats and cattle, demonstrating the potential to utilize PBET as a relatively inexpensive alternative to in vivo models for bioavailability assessment.

  2. Evidence-Based Evaluation of Physiological Effects of Standing and Walking in Individuals with Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Mohammad Taghi Karimi

    2011-12-01

    Full Text Available Spinal Cord Injury (SCI is damage to spinal cord, which is categorized according to the extent of functional loss, sensation loss and inability of the subjects to stand and walk. The patients use two transportation systems including orthosis and wheelchair. It was claimed that standing and walking bring some benefits such as decreasing bone osteoporosis, prevention of pressure sores, and improvement of the function of the digestive system for SCI patients. Nevertheless, the question of wether or not there is enough evidence to support the effect of walking with orthosis on the health status of the subjects with SCI remains unanswered. In order to answer this question a review of the relevant literature was carried out. The review of the literature showed that evidence reported in the literature regarding the effectiveness of orthoses for improving the health condition of SCI patients was controversial. Many investigators had only used the comments of the users of orthoses. The benefits mentioned in various research studies regarding the use of orthosis included decreasing bone osteoprosis, preventing joint deformity, improving bowl and bladder function, improving digestive system function, decreasing muscle spasm, improving independent living, and improving respiratory and cardiovascular systems function. The findings of the studies reviewed also showed that improving the independent living and physiological health of the subjects were the only two benefits, which were supported by strong evidence. The review of the literature suggests that most published studies are in fact surveys, which collected questionnaire-based information from the users of orthosis

  3. Normal and Pathological NCAT Image and PhantomData Based onPhysiologically Realistic Left Ventricle Finite-Element Models

    Energy Technology Data Exchange (ETDEWEB)

    Veress, Alexander I.; Segars, W. Paul; Weiss, Jeffrey A.; Tsui,Benjamin M.W.; Gullberg, Grant T.

    2006-08-02

    The 4D NURBS-based Cardiac-Torso (NCAT) phantom, whichprovides a realistic model of the normal human anatomy and cardiac andrespiratory motions, is used in medical imaging research to evaluate andimprove imaging devices and techniques, especially dynamic cardiacapplications. One limitation of the phantom is that it lacks the abilityto accurately simulate altered functions of the heart that result fromcardiac pathologies such as coronary artery disease (CAD). The goal ofthis work was to enhance the 4D NCAT phantom by incorporating aphysiologically based, finite-element (FE) mechanical model of the leftventricle (LV) to simulate both normal and abnormal cardiac motions. Thegeometry of the FE mechanical model was based on gated high-resolutionx-ray multi-slice computed tomography (MSCT) data of a healthy malesubject. The myocardial wall was represented as transversely isotropichyperelastic material, with the fiber angle varying from -90 degrees atthe epicardial surface, through 0 degreesat the mid-wall, to 90 degreesat the endocardial surface. A time varying elastance model was used tosimulate fiber contraction, and physiological intraventricular systolicpressure-time curves were applied to simulate the cardiac motion over theentire cardiac cycle. To demonstrate the ability of the FE mechanicalmodel to accurately simulate the normal cardiac motion as well abnormalmotions indicative of CAD, a normal case and two pathologic cases weresimulated and analyzed. In the first pathologic model, a subendocardialanterior ischemic region was defined. A second model was created with atransmural ischemic region defined in the same location. The FE baseddeformations were incorporated into the 4D NCAT cardiac model through thecontrol points that define the cardiac structures in the phantom whichwere set to move according to the predictions of the mechanical model. Asimulation study was performed using the FE-NCAT combination toinvestigate how the differences in contractile function

  4. Psycho-physiological assessment of a prosthetic hand sensory feedback system based on an auditory display: a preliminary study

    Directory of Open Access Journals (Sweden)

    Gonzalez Jose

    2012-06-01

    Full Text Available Abstract Background Prosthetic hand users have to rely extensively on visual feedback, which seems to lead to a high conscious burden for the users, in order to manipulate their prosthetic devices. Indirect methods (electro-cutaneous, vibrotactile, auditory cues have been used to convey information from the artificial limb to the amputee, but the usability and advantages of these feedback methods were explored mainly by looking at the performance results, not taking into account measurements of the user’s mental effort, attention, and emotions. The main objective of this study was to explore the feasibility of using psycho-physiological measurements to assess cognitive effort when manipulating a robot hand with and without the usage of a sensory substitution system based on auditory feedback, and how these psycho-physiological recordings relate to temporal and grasping performance in a static setting. Methods 10 male subjects (26+/-years old, participated in this study and were asked to come for 2 consecutive days. On the first day the experiment objective, tasks, and experiment setting was explained. Then, they completed a 30 minutes guided training. On the second day each subject was tested in 3 different modalities: Auditory Feedback only control (AF, Visual Feedback only control (VF, and Audiovisual Feedback control (AVF. For each modality they were asked to perform 10 trials. At the end of each test, the subject had to answer the NASA TLX questionnaire. Also, during the test the subject’s EEG, ECG, electro-dermal activity (EDA, and respiration rate were measured. Results The results show that a higher mental effort is needed when the subjects rely only on their vision, and that this effort seems to be reduced when auditory feedback is added to the human-machine interaction (multimodal feedback. Furthermore, better temporal performance and better grasping performance was obtained in the audiovisual modality. Conclusions The performance

  5. Biokinetics and dosimetry of {sup 111}In-DOTA-NOC-ATE compared with {sup 111}In-DTPA-octreotide

    Energy Technology Data Exchange (ETDEWEB)

    Boubaker, Ariane; Prior, John O.; Champendal, Melanie; Bischof Delaloye, Angelika [Lausanne University Hospital, CHUV, Department of Nuclear Medicine, Lausanne (Switzerland); Willi, Jean-Pierre [University Hospital of Geneva, Department of Nuclear Medicine, Geneva 14 (Switzerland); Kosinski, Marek; Baechler, Sebastien [Lausanne University Hospital, Institute of Radiation Physics, Lausanne (Switzerland); Maecke, Helmut R. [University Hospital of Freiburg, Department of Nuclear Medicine, Freiburg (Germany); Ginj, Mihaela [University Health Network, Joint Department of Medical Imaging, Toronto, ON (Canada); Buchegger, Franz [Lausanne University Hospital, CHUV, Department of Nuclear Medicine, Lausanne (Switzerland); University Hospital of Geneva, Department of Nuclear Medicine, Geneva 14 (Switzerland)

    2012-12-15

    The biokinetics and dosimetry of {sup 111}In-DOTA-NOC-ATE (NOCATE), a high-affinity ligand of SSTR-2 and SSTR-5, and {sup 111}In-DTPA-octreotide (Octreoscan trademark, OCTREO) were compared in the same patients. Seventeen patients (10 men, 7 women; mean age 60 years), referred for an OCTREO scan for imaging of a neuroendocrine tumour (15), thymoma (1) or medullary thyroid carcinoma (1), agreed to undergo a second study with NOCATE. Whole-body anterior-posterior scans were recorded 0.5 (100 % reference scan), 4, 24 and 48 h (17 patients) and 120 h (5 patients) after injection. In 16 patients the OCTREO scan (178 {+-} 15 MBq) was performed 16 {+-} 5 days before the NOCATE scan (108 {+-} 14 MBq) with identical timing; 1 patient had the NOCATE scan before the OCTREO scan. Blood samples were obtained from 14 patients 5 min to 48 h after injection. Activities expressed as percent of the initial (reference) activity in the whole body, lung, kidney, liver, spleen and blood were fitted to biexponential or single exponential functions. Dosimetry was performed using OLINDA/EXM. Initial whole-body, lung and kidney activities were similar, but retention of NOCATE was higher than that of OCTREO. Liver and spleen uptakes of NOCATE were higher from the start (p < 0.001) and remained so over time. Whole-body activity showed similar {alpha} and {beta} half-lives, but the {beta} fraction of NOCATE was double that of OCTREO. Blood T{sub 1/2}{beta} for NOCATE was longer (19 vs. 6 h). As a result, the effective dose of NOCATE (105 {mu}Sv/MBq) exceeded that of OCTREO (52 {mu}Sv/MBq), and the latter result was similar to the ICRP 106 value of 54 {mu}Sv/MBq. Differential activity measurement in blood cells and plasma showed an average of <5 % of NOCATE and OCTREO attached to globular blood components. NOCATE showed a slower clearance from normal tissues and its effective dose was roughly double that of OCTREO. (orig.)

  6. Biokinetics and dosimetry of 111In-DOTA-NOC-ATE compared with 111In-DTPA-octreotide.

    Science.gov (United States)

    Boubaker, Ariane; Prior, John O; Willi, Jean-Pierre; Champendal, Melanie; Kosinski, Marek; Bischof Delaloye, Angelika; Maecke, Helmut R; Ginj, Mihaela; Baechler, Sébastien; Buchegger, Franz

    2012-12-01

    The biokinetics and dosimetry of (111)In-DOTA-NOC-ATE (NOCATE), a high-affinity ligand of SSTR-2 and SSTR-5, and (111)In-DTPA-octreotide (Octreoscan™, OCTREO) were compared in the same patients. Seventeen patients (10 men, 7 women; mean age 60 years), referred for an OCTREO scan for imaging of a neuroendocrine tumour (15), thymoma (1) or medullary thyroid carcinoma (1), agreed to undergo a second study with NOCATE. Whole-body anterior-posterior scans were recorded 0.5 (100 % reference scan), 4, 24 and 48 h (17 patients) and 120 h (5 patients) after injection. In 16 patients the OCTREO scan (178 ± 15 MBq) was performed 16 ± 5 days before the NOCATE scan (108 ± 14 MBq) with identical timing; 1 patient had the NOCATE scan before the OCTREO scan. Blood samples were obtained from 14 patients 5 min to 48 h after injection. Activities expressed as percent of the initial (reference) activity in the whole body, lung, kidney, liver, spleen and blood were fitted to biexponential or single exponential functions. Dosimetry was performed using OLINDA/EXM. Initial whole-body, lung and kidney activities were similar, but retention of NOCATE was higher than that of OCTREO. Liver and spleen uptakes of NOCATE were higher from the start (p < 0.001) and remained so over time. Whole-body activity showed similar α and β half-lives, but the β fraction of NOCATE was double that of OCTREO. Blood T (1/2)β for NOCATE was longer (19 vs. 6 h). As a result, the effective dose of NOCATE (105 μSv/MBq) exceeded that of OCTREO (52 μSv/MBq), and the latter result was similar to the ICRP 106 value of 54 μSv/MBq. Differential activity measurement in blood cells and plasma showed an average of <5 % of NOCATE and OCTREO attached to globular blood components. NOCATE showed a slower clearance from normal tissues and its effective dose was roughly double that of OCTREO.

  7. Development of a simple proton nuclear magnetic resonance-based procedure to estimate the approximate distribution coefficient at physiological pH (logD7.4)

    DEFF Research Database (Denmark)

    Stéen, E Johanna L; Nyberg, Nils; Lehel, Szabolcs

    2017-01-01

    In drug discovery, lipophilicity is a key parameter for drug optimization. Lipophilicity determinations can be both work and time consuming, especially for non-UV active compounds. Herein, an improved and simple 1H NMR-based method is described to estimate the lipophilicity at physiological pH (l...

  8. Use of novel inhalation kinetic studies to refine physiologically-based-pharmacokinetic models for ethanol in non-pregnant and pregnant rats

    Science.gov (United States)

    Ethanol (EtOH) exposure induces a variety of concentration-dependent neurological and developmental effects in the rat. Physiologically-based pharmacokinetic (PBPK) models have been used to predict the inhalation exposure concentrations necessary to produce blood EtOH concentrat...

  9. Integration of Life-Stage Physiologically Based Pharmacokinetic Models with Adverse Outcome Pathways and Environmental Exposure Models to Screen for Environmental Hazards

    Science.gov (United States)

    A Life-stage Physiologically-Based Pharmacokinetic (PBPK) model was developed to include descriptions of several life-stage events such as pregnancy, fetal development, the neonate and child growth. The overall modeling strategy was used for in vitro to in vivo (IVIVE) extrapolat...

  10. Application of physiologically based toxicokinetic modelling to study the impact of the exposure scenario on the toxicokinetics and the behavioural effects of toluene in rats

    NARCIS (Netherlands)

    Asperen, J. van; Rijcken, W.R.P.; Lammers, J.H.C.M.

    2003-01-01

    The toxicity of inhalatory exposure to organic solvents may not only be related to the total external dose, but also to the pattern of exposure. In this study physiologically based toxicokinetic (PBTK) modelling has been used to study the impact of the exposure scenario on the toxicokinetics and the

  11. Use of a physiologically based pharmacokinetic model to simulate drug-drug interactions between antineoplastic and antiretroviral drugs.

    Science.gov (United States)

    Moltó, José; Rajoli, Rajith; Back, David; Valle, Marta; Miranda, Cristina; Owen, Andrew; Clotet, Bonaventura; Siccardi, Marco

    2017-03-01

    Co-administration of antineoplastics with ART is challenging due to potential drug-drug interactions (DDIs). However, trials specifically assessing such DDIs are lacking. Our objective was to simulate DDIs between the antineoplastics erlotinib and gefitinib with key antiretroviral drugs and to predict dose adjustments using a physiologically based pharmacokinetic (PBPK) model. In vitro data describing chemical properties and pharmacokinetic processes of each drug and their effect on cytochrome P450 isoforms were obtained from the literature. Plasma drug-concentration profiles were simulated in a virtual population of 50 individuals receiving erlotinib or gefitinib alone or with darunavir/ritonavir, efavirenz or etravirine. Simulated pharmacokinetic parameters and the magnitude of DDIs with probe drugs (midazolam, maraviroc) were compared with literature values. Erlotinib and gefitinib pharmacokinetics with and without antiretrovirals were compared and dose-adjustment strategies were evaluated. Simulated parameters of each drug and the magnitude of DDIs with probe drugs were in agreement with reference values. Darunavir/ritonavir increased erlotinib and gefitinib exposure, while efavirenz and etravirine decreased erlotinib and gefitinib concentrations. Based on our predictions, dose-adjustment strategies may consist of once-daily dosing erlotinib at 25 mg and gefitinib at 125 mg with darunavir/ritonavir; or erlotinib at 200 mg and gefitinib at 375 mg with etravirine. The interaction with efavirenz was not overcome even after doubling erlotinib or gefitinib doses. PBPK models predicted the in vivo pharmacokinetics of erlotinib, gefitinib and the antiretrovirals darunavir/ritonavir, efavirenz and etravirine, and the DDIs between them. The simulated dose-adjustments may represent valuable strategies to optimize antineoplastic therapy in HIV-infected patients.

  12. Physiological properties of neurons derived from human embryonic stem cells using a dibutyryl cyclic AMP-based protocol.

    Science.gov (United States)

    Belinsky, Glenn S; Moore, Anna R; Short, Shaina M; Rich, Matthew T; Antic, Srdjan D

    2011-10-01

    Neurons derived from human embryonic stem cells hold promise for the therapy of neurological diseases. Quality inspection of human embryonic stem cell-derived neurons has often been based on immunolabeling for neuronal markers. Here we put emphasis on their physiological properties. Electrophysiological measurements were carried out systematically at different stages of neuronal in vitro development, including the very early stage, neuroepithelial rosettes. Developing human neurons are able to generate action potentials (APs) as early as 10 days after the start of differentiation. Tyrosine hydroxylase (TH)-positive (putative dopaminergic, DA) neurons tend to aggregate into clumps, and their overall yield per coverslip is relatively low (8.3%) because of areas void of DA neurons. On the same in vitro day, neighboring neurons can be in very different stages of differentiation, including repetitive AP firing, single full-size AP, and abortive AP. Similarly, the basic electrophysiological parameters (resting membrane potential, input resistance, peak sodium, and peak potassium currents) are scattered in a wide range. Visual appearance of differentiating neurons, and number of primary and secondary dendrites cannot be used to predict the peak sodium current or AP firing properties of cultured neurons. Approximately 13% of neurons showed evidence of hyperpolarization-induced current (I(h)), a characteristic of DA neurons; however, no neurons with repetitive APs showed I(h). The electrophysiological measurements thus indicate that a standard DA differentiation (dibutyryl cyclic AMP-based) protocol, applied for 2-5 weeks, produces a heterogeneous ensemble of mostly immature neurons. The overall quality of human neurons under present conditions (survival factors were not used) begins to deteriorate after 12 days of differentiation.

  13. Formulation and physiological and biopharmaceutical issues in the development of oral lipid-based drug delivery systems.

    Science.gov (United States)

    Wasan, K M

    2001-04-01

    The rapidly increasing availability of drug receptor structural characteristics has permitted the receptor-guided synthesis of potential new drug molecules. This synthesis strategy frequently results in the creation of polycyclic and highly hydrophobic compounds, with attendant poor oral bioavailability resulting from low solubility and slow dissolution rate in the primarily aqueous contents of the gastrointestinal (GI) tract. In an attempt to improve the solubility-limited bioavailabiliy associated with these compounds, formulators have turned to the use of lipid excipients in which the compounds can be solubilized prior to oral administration. This new class of excipients presents the pharmaceutical scientist with a number of new challenges at all stages of the formulation development process, beginning with the excipient selection and stability assessment of the prototype formulation, up to and including scale-up and mass production of the final market-image product. The interaction of lipid-based formulations with the gastrointestinal system and associated digestive processes presents additional challenges and opportunities that will be understood more fully as we begin to unravel the intricacies of the GI processing of lipid excipients. For example, an increasing body of evidence has shown that certain lipids are capable of inhibiting both presystemic drug metabolism and drug efflux by the gut wall mediated by p-glycoprotein (PGP). And, it is well known that lipids are capable of enhancing lymphatic transport of hydrophobic drugs, thereby reducing drug clearance resulting from hepatic first-pass metabolism. This review addresses the current state of knowledge regarding oral lipid-based formulation development and scale-up issues and the physiological and biopharmaceutical aspects pertinent to the development of an orally bioavailable and efficacious dosage form.

  14. A physiologically based in silico model for trans-2-hexenal detoxification and DNA adduct formation in rat.

    Science.gov (United States)

    Kiwamoto, Reiko; Rietjens, Ivonne M C M; Punt, Ans

    2012-12-17

    trans-2-Hexenal (2-hexenal) is an α,β-unsaturated aldehyde that occurs naturally in a wide range of fruits, vegetables, and spices. 2-Hexenal as well as other α,β-unsaturated aldehydes that are natural food constituents or flavoring agents may raise a concern for genotoxicity due to the ability of the α,β-unsaturated aldehyde moiety to react with DNA. Controversy remains, however, on whether α,β-unsaturated aldehydes result in significant DNA adduct formation in vivo at realistic dietary exposure. In this study, a rat physiologically based in silico model was developed for 2-hexenal as a model compound to examine the time- and dose-dependent detoxification and DNA adduct formation of this selected α,β-unsaturated aldehyde. The model was developed based on in vitro and literature-derived parameters, and its adequacy was evaluated by comparing predicted DNA adduct formation in the liver of rats exposed to 2-hexenal with reported in vivo data. The model revealed that at an exposure level of 0.04 mg/kg body weight, a value reflecting estimated daily human dietary intake, 2-hexenal is rapidly detoxified predominantly by conjugation with glutathione (GSH) by glutathione S-transferases. At higher dose levels, depletion of GSH results in a shift to 2-hexenal oxidation and reduction as the major pathways for detoxification. The level of DNA adduct formation at current levels of human dietary intake was predicted to be more than 3 orders of magnitude lower than endogenous DNA adduct levels. These results support that rapid detoxification of 2-hexenal reduces the risk arising from 2-hexenal exposure and that at current dietary exposure levels, DNA adduct formation is negligible.

  15. Models projecting the fate of fish populations under climate change need to be based on valid physiological mechanisms.

    Science.gov (United States)

    Lefevre, Sjannie; McKenzie, David J; Nilsson, Göran E

    2017-09-01

    Some recent modelling papers projecting smaller fish sizes and catches in a warmer future are based on erroneous assumptions regarding (i) the scaling of gills with body mass and (ii) the energetic cost of 'maintenance'. Assumption (i) posits that insurmountable geometric constraints prevent respiratory surface areas from growing as fast as body volume. It is argued that these constraints explain allometric scaling of energy metabolism, whereby larger fishes have relatively lower mass-specific metabolic rates. Assumption (ii) concludes that when fishes reach a certain size, basal oxygen demands will not be met, because of assumption (i). We here demonstrate unequivocally, by applying accepted physiological principles with reference to the existing literature, that these assumptions are not valid. Gills are folded surfaces, where the scaling of surface area to volume is not constrained by spherical geometry. The gill surface area can, in fact, increase linearly in proportion to gill volume and body mass. We cite the large body of evidence demonstrating that respiratory surface areas in fishes reflect metabolic needs, not vice versa, which explains the large interspecific variation in scaling of gill surface areas. Finally, we point out that future studies basing their predictions on models should incorporate factors for scaling of metabolic rate and for temperature effects on metabolism, which agree with measured values, and should account for interspecific variation in scaling and temperature effects. It is possible that some fishes will become smaller in the future, but to make reliable predictions the underlying mechanisms need to be identified and sought elsewhere than in geometric constraints on gill surface area. Furthermore, to ensure that useful information is conveyed to the public and policymakers about the possible effects of climate change, it is necessary to improve communication and congruity between fish physiologists and fisheries scientists. © 2017

  16. Dosimetric contribution of organs of biokinetics of {sup 99m}Tc and {sup 123}I to estimate radiation doses in thyroids of children of 1 and 5 years; Contribucion dosimetrica de organos de la biocinetica del {sup 99m}Tc y {sup 123}I para estimar dosis en tiroides de ninos de 1 y 5 anos

    Energy Technology Data Exchange (ETDEWEB)

    Vasquez, M.V.; Castillo, C.E.; Abanto, D.M.; Rocha, D.; Garcia, W.H.; Marin, K., E-mail: marvva@hotmail.com [Universidad Nacional de Trujillo (UNT), Trujillo (Peru); Quispe, R. [Centro de Ciencias Aplicadas y Desarrollo Tecnologico, UNAM, Mexico (Mexico)

    2015-07-01

    The absorbed doses by thyroids during uptake studies through biokinetics of radiopharmaceuticals containing {sup 123}I (iodine) or {sup 99m}Tc (pertechnetate) are estimated. Using the MIRD scheme and the representation of Cristy-Eckerman for thyroids in children of 1 and 5 years, the objective of the study was to determine whether the dosimetric biokinetic contributions of the organs of {sup 123}I (iodide) and {sup 99m}Tc (pertechnetate) biokinetic are significant in the estimated of the absorbed dose for thyroid uptake studies.

  17. Pain and distress caused by endotracheal suctioning in neonates is better quantified by behavioural than physiological items: a comparison based on item response theory modelling.

    Science.gov (United States)

    Välitalo, Pyry A J; van Dijk, Monique; Krekels, Elke H J; Gibbins, Sharyn; Simons, Sinno H P; Tibboel, Dick; Knibbe, Catherijne A J

    2016-08-01

    Pain cannot be directly measured in neonates. Therefore, scores based on indirect behavioural signals such as crying, or physiological signs such as blood pressure, are used to quantify neonatal pain both in clinical practice and in clinical studies. The aim of this study was to determine which of the physiological and behavioural items of 2 validated pain assessment scales (COMFORT and premature infant pain profile) are best able to detect pain during endotracheal and nasal suctioning in ventilated newborns. We analysed a total of 516 PIPP and COMFORT scores from 118 newborns. A graded response model was built to describe the data and item information was calculated for each of the behavioural and physiological items. We found that the graded response model was able to well describe the data, as judged by agreement between the observed data and model simulations. Furthermore, a good agreement was found between the pain estimated by the graded response model and the investigator-assessed visual analogue scale scores (Spearman rho correlation coefficient = 0.80). The information scores for the behavioural items ranged from 1.4 to 27.2 and from 0.0282 to 0.131 for physiological items. In these data with mild to moderate pain levels, behavioural items were vastly more informative of pain and distress than were physiological items. The items that were the most informative of pain are COMFORT items "calmness/agitation," "alertness," and "facial tension."

  18. A physiologically based toxicokinetic (PBTK) model for moderately hydrophobic organic chemicals in the European eel (Anguilla anguilla)

    Energy Technology Data Exchange (ETDEWEB)

    Brinkmann, Markus [Department of Ecosystem Analysis, Institute for Environmental Research, ABBt — Aachen Biology and Biotechnology, RWTH Aachen University, Aachen (Germany); Freese, Marko; Pohlmann, Jan-Dag; Kammann, Ulrike [Thünen Institute of Fisheries Ecology, Hamburg (Germany); Preuss, Thomas G. [Environmental Biology and Chemodynamics, Institute for Environmental Research, ABBt — Aachen Biology and Biotechnology, RWTH Aachen University, Aachen (Germany); Buchinger, Sebastian; Reifferscheid, Georg [Federal Institute of Hydrology (BFG), Department G3: Biochemistry, Ecotoxicology, Koblenz (Germany); Beiermeister, Anne; Hanel, Reinhold [Thünen Institute of Fisheries Ecology, Hamburg (Germany); Hollert, Henner, E-mail: Henner.hollert@bio5.rwth-aachen.de [Department of Ecosystem Analysis, Institute for Environmental Research, ABBt — Aachen Biology and Biotechnology, RWTH Aachen University, Aachen (Germany); State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing (China); College of Resources and Environmental Science, Chongqing University, Chongqing (China); Key Laboratory of Yangtze Water Environment, Ministry of Education, Tongji University, Shanghai 200092 (China)

    2015-12-01

    The European eel (Anguilla anguilla) is a facultatively catadromous fish species with a complex life cycle. Its current population status is alarming: recruitment has decreased drastically since the 1980s and its stock is still considered to be outside safe biological limits. Although there is no consensus on the reasons for this situation, it is currently thought to have resulted from a combination of different stressors, including anthropogenic contaminants. To deepen our understanding of the processes leading to the accumulation of lipophilic organic contaminants in yellow eels (i.e. the feeding, continental growth stage), we developed a physiologically based toxicokinetic model using our own data and values from the literature. Such models can predict the uptake and distribution of water-borne organic chemicals in the whole fish and in different tissues at any time during exposure. The predictive power of the model was tested against experimental data for six chemicals with n-octanol-water partitioning coefficient (log K{sub ow}) values ranging from 2.13–4.29. Model performance was excellent, with a root mean squared error of 0.28 log units. This model has the potential to help identify suitable habitats for restocking under eel management plans. - Highlights: • A PBTK model was developed for European eel (Anguilla anguilla). • Own experimental data and data from the literature were used for parameterization. • The predictive power of the model was excellent, with RMSE of 0.28 log units. • The developed model can be amended with sub-models for dietary and dermal exposure.

  19. In vivo validation of DNA adduct formation by estragole in rats predicted by physiologically based biodynamic modelling.

    Science.gov (United States)

    Paini, Alicia; Punt, Ans; Scholz, Gabriele; Gremaud, Eric; Spenkelink, Bert; Alink, Gerrit; Schilter, Benoît; van Bladeren, Peter J; Rietjens, Ivonne M C M

    2012-11-01

    Estragole is a naturally occurring food-borne genotoxic compound found in a variety of food sources, including spices and herbs. This results in human exposure to estragole via the regular diet. The objective of this study was to quantify the dose-dependent estragole-DNA adduct formation in rat liver and the urinary excretion of 1'-hydroxyestragole glucuronide in order to validate our recently developed physiologically based biodynamic (PBBD) model. Groups of male outbred Sprague Dawley rats (n = 10, per group) were administered estragole once by oral gavage at dose levels of 0 (vehicle control), 5, 30, 75, 150, and 300mg estragole/kg bw and sacrificed after 48h. Liver, kidney and lungs were analysed for DNA adducts by LC-MS/MS. Results obtained revealed a dose-dependent increase in DNA adduct formation in the liver. In lungs and kidneys DNA adducts were detected at lower levels than in the liver confirming the occurrence of DNA adducts preferably in the target organ, the liver. The results obtained showed that the PBBD model predictions for both urinary excretion of 1'-hydroxyestragole glucuronide and the guanosine adduct formation in the liver were comparable within less than an order of magnitude to the values actually observed in vivo. The PBBD model was refined using liver zonation to investigate whether its predictive potential could be further improved. The results obtained provide the first data set available on estragole-DNA adduct formation in rats and confirm their occurrence in metabolically active tissues, i.e. liver, lung and kidney, while the significantly higher levels found in liver are in accordance with the liver as the target organ for carcinogenicity. This opens the way towards future modelling of dose-dependent estragole liver DNA adduct formation in human.

  20. An Age-Dependent Physiologically-Based Pharmacokinetic/Pharmacodynamic Model for the Organophosphorus Insecticide Chlorpyrifos in the Preweanling Rat

    Energy Technology Data Exchange (ETDEWEB)

    Timchalk, Chuck; Kousba, Ahmed A.; Poet, Torka S.

    2007-08-01

    Juvenile rats are more susceptible than adults to the acute toxicity of organophosphorus insecticides like chlorpyrifos (CPF). Age- and dose-dependent differences in metabolism may be responsible. Of importance is CYP450 activation and detoxification of CPF to chlorpyrifos-oxon (CPF-oxon) and trichloropyridinol (TCP), as well as B-esterase (cholinesterase; ChE) and A-esterase (PON-1) detoxification of CPF-oxon to TCP. In the current study, a modified physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model incorporating age-dependent changes in CYP450, PON-1, and tissue ChE levels for rats was developed. In this model, age was used as a dependent function to estimate body weight which was then used to allometrically scale both metabolism and tissue ChE levels. Model simulations suggest that preweanling rats are particularly sensitive to CPF toxicity, with levels of CPF-oxon in blood and brain disproportionately increasing, relative to the response in adult rats. This age-dependent non-linear increase in CPF-oxon concentration may potentially result from the depletion of non-target B-esterases, and a lower PON-1 metabolic capacity in younger animals. These results indicate that the PBPK/PD model behaves consistently with the general understanding of CPF toxicity, pharmacokinetics and tissue ChE inhibition in neonatal and adult rats. Hence, this model represents an important starting point for developing a computational model to assess the neurotoxic potential of environmentally relevant organophosphate exposures in infants and children.

  1. Proposed mechanistic description of dose-dependent BDE-47 urinary elimination in mice using a physiologically based pharmacokinetic model

    Energy Technology Data Exchange (ETDEWEB)

    Emond, Claude, E-mail: claude.emond@umontreal.ca [BioSimulation Consulting Inc., Newark, DE (United States); Departments of Environmental and Occupational Health, Medicine Faculty, University of Montreal, Montreal, Quebec (Canada); Sanders, J. Michael, E-mail: sander10@mail.nih.gov [National Cancer Institute, Research Triangle Park, NC (United States); Wikoff, Daniele, E-mail: dwikoff@toxstrategies.com [ToxStrategies, Austin, TX (United States); Birnbaum, Linda S., E-mail: birnbaumls@niehs.nih.gov [National Cancer Institute, Research Triangle Park, NC (United States)

    2013-12-01

    Polybrominated diphenyl ethers (PBDEs) have been used in a wide variety of consumer applications as additive flame retardants. In North America, scientists have noted continuing increases in the levels of PBDE congeners measured in human serum. Some recent studies have found that PBDEs are associated with adverse health effects in humans, in experimental animals, and wildlife. This laboratory previously demonstrated that urinary elimination of 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) is saturable at high doses in mice; however, this dose-dependent urinary elimination has not been observed in adult rats or immature mice. Thus, the primary objective of this study was to examine the mechanism of urinary elimination of BDE-47 in adult mice using a physiologically based pharmacokinetic (PBPK) model. To support this objective, additional laboratory data were collected to evaluate the predictions of the PBPK model using novel information from adult multi-drug resistance 1a/b knockout mice. Using the PBPK model, the roles of mouse major urinary protein (a blood protein carrier) and P-glycoprotein (an apical membrane transporter in proximal tubule cells in the kidneys, brain, intestines, and liver) were investigated in BDE-47 elimination. The resulting model and new data supported the major role of m-MUP in excretion of BDE-47 in the urine of adult mice, and a lesser role of P-gp as a transporter of BDE-47 in mice. This work expands the knowledge of BDE-47 kinetics between species and provides information for determining the relevancy of these data for human risk assessment purposes. - Highlights: • We report the first study on PBPK model on flame retardant in mice for BDE-47. • We examine mechanism of urinary elimination of BDE-47 in mice using a PBPK model. • We investigated roles of m-MUP and P-gp as transporters in urinary elimination.

  2. Virtual population pharmacokinetic using physiologically based pharmacokinetic model for evaluating bioequivalence of oral lacidipine formulations in dogs

    Directory of Open Access Journals (Sweden)

    Bin Yang

    2017-01-01

    Full Text Available The aim of the present study was to investigate virtual population pharmacokinetic using physiologically based pharmacokinetic (PBPK model for evaluating bioequivalence of oral lacidipine formulations in dogs. The dissolution behaviors of three lacidipine formulations including one commercial product and two self-made amorphous solid dispersions (ASDs capsules were determined in 0.07% Tween 80 media. A randomized 3-period crossover design in 6 healthy beagle dogs after oral administration of the three formulations at a single dose of 4 mg was conducted. The PBPK modeling was utilized for the virtual bioequivalence study. In vitro dissolution experiment showed that the dissolution behaviors of lacidipine amorphous solid dispersions (ASDs capsules, which was respectively prepared by HPMC-E5 or Soluplus, as polymer displayed similar curves compared with the reference formulation in 0.07% Tween 80 media. In vivo pharmacokinetics experiments showed that three formulations had comparable maximum plasma drug concentration (Cmax, and the time (Tmax to reach Cmax of lacidipine tablet, which was prepared by Soluplus, as polymer was slower than other two formulations in consistency with the in vitro dissolution rate. The 90% confidence interval (CI for the Cmax, AUC0–24 h and AUC0–∞ of the ratio of the test drug to the referencedrug exceeded the acceptable bioequivalence (BE limits (0.80–1.25. However, the 90% CI of the AUC0–24 h, AUC0–∞ and Cmax of the ratio of test to reference drug were within the BE limit, calculated using PBPK modeling when the virtual subjects reached 24 dogs. The results all demonstrated that virtual bioequivalence study can overcome the inequivalence caused by inter-subject variability of the 6 beagle dogs involved in in vivo experiments.

  3. Reduction of a Whole-Body Physiologically Based Pharmacokinetic Model to Stabilise the Bayesian Analysis of Clinical Data.

    Science.gov (United States)

    Wendling, Thierry; Tsamandouras, Nikolaos; Dumitras, Swati; Pigeolet, Etienne; Ogungbenro, Kayode; Aarons, Leon

    2016-01-01

    Whole-body physiologically based pharmacokinetic (PBPK) models are increasingly used in drug development for their ability to predict drug concentrations in clinically relevant tissues and to extrapolate across species, experimental conditions and sub-populations. A whole-body PBPK model can be fitted to clinical data using a Bayesian population approach. However, the analysis might be time consuming and numerically unstable if prior information on the model parameters is too vague given the complexity of the system. We suggest an approach where (i) a whole-body PBPK model is formally reduced using a Bayesian proper lumping method to retain the mechanistic interpretation of the system and account for parameter uncertainty, (ii) the simplified model is fitted to clinical data using Markov Chain Monte Carlo techniques and (iii) the optimised reduced PBPK model is used for extrapolation. A previously developed 16-compartment whole-body PBPK model for mavoglurant was reduced to 7 compartments while preserving plasma concentration-time profiles (median and variance) and giving emphasis to the brain (target site) and the liver (elimination site). The reduced model was numerically more stable than the whole-body model for the Bayesian analysis of mavoglurant pharmacokinetic data in healthy adult volunteers. Finally, the reduced yet mechanistic model could easily be scaled from adults to children and predict mavoglurant pharmacokinetics in children aged from 3 to 11 years with similar performance compared with the whole-body model. This study is a first example of the practicality of formal reduction of complex mechanistic models for Bayesian inference in drug development.

  4. Speciation and cysteine-simplified physiological-based extraction technique (SBET) bioaccesibility of heavy metals in biosolids.

    Science.gov (United States)

    Tongesayi, Tsanangurayi; Dasilva, Patricia; Dilger, Katharine; Hollingsworth, Tristan; Mooney, Melissa

    2011-01-01

    Cysteine residues on proteins have a high affinity for metals yet formulations used to determine bioaccessibility do not contain cysteine or thiol-containing molecules. As a result, we used a cysteine-simplified physiological-based extraction technique (SBET) and, the conventional glycine-SBET to determine bioaccesibility of selected heavy metals in biosolids and compared the data. We also determined speciation of the selected metals in the biosolids to assess further the health risk posed the use of biosolids as a soil amendment in agricultural soils. Samples, including a certified reference standard were analyzed using x-ray fluorescence and flame atomic absorption. Bioaccessibility was higher in cysteine-SBET than glycine-SBET, and regression data show that the two methods give different sets of results. We proposed a bioaccessibility model that involves cysteine and the hydrogen ion complementing each other to dissolve metals. The model also includes a three mode-bioavailability mechanism: absorption of free metal ions; ligand-mediated transport of metal ions from solution; and ligand-mediated transport of metal ions directly from the biosolids into the cell. Low pH in the gut increases bioaccessibility but reduces bioavailability due to protonation of receptor ligands. With the exception of Fe, bioaccessibility was directly correlated to the sequential extraction availability which followed the order: Mn(90.3 %)>Zn(50.3 %)>Cd(26.5 %)>Cu(24.9 %)>Fe(0.367 %). We calculated bioavailability from bioaccessibility using literature estimates of percent bioavailabilities. The order of abundance of the analyzed metals in the biosolids was as follows: Fe>Mn>Zn>Cu>Pb>Cd.

  5. The Toxicological Geochemistry of Dusts, Soils, and Other Earth Materials: Insights From In Vitro Physiologically-based Geochemical Leach Tests

    Science.gov (United States)

    Plumlee, G. S.; Ziegler, T. L.; Lamothe, P.; Meeker, G. P.; Sutley, S.

    2003-12-01

    Exposure to mineral dusts, soils, and other earth materials results in chemical reactions between the materials and different body fluids that include, depending upon the exposure route, lung fluids, gastrointestinal fluids, and perspiration. In vitro physiologically-based geochemical leach tests provide useful insights into these chemical reactions and their potential toxicological implications. We have conducted such leach tests on a variety of earth materials, including asbestos, volcanic ash, dusts from dry lake beds, mine wastes, wastes left from the roasting of mercury ores, mineral processing wastes, coal dusts and coal fly ash, various soils, and complex dusts generated by the World Trade Center collapse. Size-fractionated samples of earth materials that have been well-characterized mineralogically and chemically are reacted at body temperature (37 C) for periods from 2 hours up to multiple days with various proportions of simulated lung, gastric, intestinal, and/or plasma-based fluids. Results indicate that different earth materials may have quite different solubility and dissolution behavior in vivo, depending upon a) the mineralogic makeup of the material, and b) the exposure route. For example, biodurable minerals such as asbestos and volcanic ash particles, whose health effects result because they dissolve very slowly in vivo, bleed off low levels of trace metals into the simulated lung fluids; these include metals such as Fe and Cr that are suspected by health scientists of contributing to the generation of reactive oxygen species and resulting DNA damage in vivo. In contrast, dry lake bed dusts and concrete-rich dusts are highly alkaline and bioreactive, and cause substantial pH increases and other chemical changes in the simulated body fluids. Many of the earth materials tested contain a variety of metals that can be quite soluble (bioaccessible), depending upon the material and the simulated body fluid composition. For example, due to their acidic

  6. From pest data to abundance-based risk maps combining eco-physiological knowledge, weather, and habitat variability.

    Science.gov (United States)

    Lacasella, Federica; Marta, Silvio; Singh, Aditya; Stack Whitney, Kaitlin; Hamilton, Krista; Townsend, Phil; Kucharik, Christopher J; Meehan, Timothy D; Gratton, Claudio

    2016-11-12

    Noxious species, i.e., crop pest or invasive alien species, are major threats to both natural and managed ecosystems. Invasive pests are of special importance, and knowledge about their distribution and abundance is fundamental to minimize economic losses and prioritize management activities. Occurrence models are a common tool used to identify suitable zones and map priority areas (i.e., risk maps) for noxious species management, although they provide a simplified description of species dynamics (i.e., no indication on species density). An alternative is to use abundance models, but translating abundance data into risk maps is often challenging. Here, we describe a general framework for generating abundance-based risk maps using multi-year pest data. We used an extensive data set of 3968 records collected between 2003 and 2013 in Wisconsin during annual surveys of soybean aphid (SBA), an exotic invasive pest in this region. By using an integrative approach, we modelled SBA responses to weather, seasonal, and habitat variability using generalized additive models (GAMs). Our models showed good to excellent performance in predicting SBA occurrence and abundance (TSS = 0.70, AUC = 0.92; R(2)  = 0.63). We found that temperature, precipitation, and growing degree days were the main drivers of SBA trends. In addition, a significant positive relationship between SBA abundance and the availability of overwintering habitats was observed. Our models showed aphid populations were also sensitive to thresholds associated with high and low temperatures, likely related to physiological tolerances of the insects. Finally, the resulting aphid predictions were integrated using a spatial prioritization algorithm ("Zonation") to produce an abundance-based risk map for the state of Wisconsin that emphasized the spatiotemporal consistency and magnitude of past infestation patterns. This abundance-based risk map can provide information on potential foci of pest outbreaks where

  7. Physiological Acoustics

    Science.gov (United States)

    Young, Eric D.

    The analysis of physiological sound in the peripheral auditory system solves three important problems. First, sound energy impinging on the head must be captured and presented to the transduction apparatus in the ear as a suitable mechanical signal; second, this mechanical signal needs to be transduced into a neural representation that can be used by the brain; third, the resulting neural representation needs to be analyzed by central neurons to extract information useful to the animal. This chapter provides an overview of some aspects of the first two of these processes. The description is entirely focused on the mammalian auditory system, primarily on human hearing and on the hearing of a few commonly used laboratory animals (mainly rodents and carnivores). Useful summaries of non-mammalian hearing are available [1]. Because of the large size of the literature, review papers are referenced wherever possible.

  8. Prediction of drug-drug interactions between various antidepressants and ritonavir using a physiologically based pharmacokinetic model

    Directory of Open Access Journals (Sweden)

    M Siccardi

    2012-11-01

    Full Text Available Depression can impact on the treatment of HIV infection, and effective treatment of depressive conditions can have a beneficial effect improving adherence. However antidepressant treatment requires long-term maintenance, and is prone to pharmacokinetic drug-drug interactions (DDI with antiretrovirals. The aim of this study was to predict the magnitude of DDI between ritonavir (RTV and the most commonly prescribed antidepressants using a physiologically based pharmacokinetic (PBPK model simulating virtual clinical trials. In vitro data describing the physiochemical properties, absorption, metabolism, induction and inhibitory potential of RTV and five antidepressants were obtained from published literature. Interactions between RTV and antidepressants were evaluated using the full PBPK model implemented in the Simcyp Population-based Simulator (Version 11.1, Simcyp Limited, UK and virtual clinical studies were simulated on 50 Caucasian subjects receiving 100mg bid of RTV for 21 days plus sertraline (100mg qd, citalopram (40mg qd, fluoxetine (20mg qd, venlafaxine (25mg qd and then from day 14–21. Simulated pharmacokinetic parameters were compared with observed values available in the literature. The simulated PK parameters of RTV, sertraline, citalopram, fluoxetine, mirtazepine and venlafaxine given alone at standard dosage were similar to reference values obtain from published clinical studies. The effect of simulated RTV co-administration on sertaline, fluoxetine and venlaflaxine was an AUC decrease of 40%, 26% and 6%, respectively and on mirtazepine and citalopram, an AUC increase of 60% and 20% respectively. The magnitude of the simulated DDI between RTV and the antidepressants was overall weak to moderate according to the classification of the FDA. The modest magnitude of these drug-drug interactions could be explained by the fact that antidepressants are substrates of multiple isoforms thus metabolism can still occur through CYPs that are

  9. Application of physiologically based pharmacokinetic modeling in predicting drug–drug interactions for sarpogrelate hydrochloride in humans

    Directory of Open Access Journals (Sweden)

    Min JS

    2016-09-01

    Full Text Available Jee Sun Min,1 Doyun Kim,1 Jung Bae Park,1 Hyunjin Heo,1 Soo Hyeon Bae,2 Jae Hong Seo,1 Euichaul Oh,1 Soo Kyung Bae1 1Integrated Research Institute of Pharmaceutical Sciences, College of Pharmacy, The Catholic University of Korea, Bucheon, 2Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seocho-gu, Seoul, South Korea Background: Evaluating the potential risk of metabolic drug–drug interactions (DDIs is clinically important. Objective: To develop a physiologically based pharmacokinetic (PBPK model for sarpogrelate hydrochloride and its active metabolite, (R,S-1-{2-[2-(3-methoxyphenylethyl]-phenoxy}-3-(dimethylamino-2-propanol (M-1, in order to predict DDIs between sarpogrelate and the clinically relevant cytochrome P450 (CYP 2D6 substrates, metoprolol, desipramine, dextromethorphan, imipramine, and tolterodine. Methods: The PBPK model was developed, incorporating the physicochemical and pharmacokinetic properties of sarpogrelate hydrochloride, and M-1 based on the findings from in vitro and in vivo studies. Subsequently, the model was verified by comparing the predicted concentration-time profiles and pharmacokinetic parameters of sarpogrelate and M-1 to the observed clinical data. Finally, the verified model was used to simulate clinical DDIs between sarpogrelate hydrochloride and sensitive CYP2D6 substrates. The predictive performance of the model was assessed by comparing predicted results to observed data after coadministering sarpogrelate hydrochloride and metoprolol. Results: The developed PBPK model accurately predicted sarpogrelate and M-1 plasma concentration profiles after single or multiple doses of sarpogrelate hydrochloride. The simulated ratios of area under the curve and maximum plasma concentration of metoprolol in the presence of sarpogrelate hydrochloride to baseline were in good agreement with the observed ratios. The predicted fold-increases in the area under the curve ratios of metoprolol

  10. Mode of action based risk assessment of the botanical food-borne alkenylbenzene apiol from parsley using physiologically based kinetic (PBK) modelling and read-across from safrole.

    Science.gov (United States)

    Alajlouni, Abdalmajeed M; Al Malahmeh, Amer J; Kiwamoto, Reiko; Wesseling, Sebastiaan; Soffers, Ans E M F; Al-Subeihi, Ala A A; Vervoort, Jacques; Rietjens, Ivonne M C M

    2016-03-01

    The present study developed physiologically-based kinetic (PBK) models for the alkenylbenzene apiol in order to facilitate risk assessment based on read-across from the related alkenylbenzene safrole. Model predictions indicate that in rat liver the formation of the 1'-sulfoxy metabolite is about 3 times lower for apiol than for safrole. These data support that the lower confidence limit of the benchmark dose resulting in a 10% extra cancer incidence (BMDL10) that would be obtained in a rodent carcinogenicity study with apiol may be 3-fold higher for apiol than for safrole. These results enable a preliminary risk assessment for apiol, for which tumor data are not available, using a BMDL10 value of 3 times the BMDL10 for safrole. Based on an estimated BMDL10 for apiol of 5.7-15.3 mg/kg body wt per day and an estimated daily intake of 4 × 10(-5) mg/kg body wt per day, the margin of exposure (MOE) would amount to 140,000-385,000. This indicates a low priority for risk management. The present study shows how PBK modelling can contribute to the development of alternatives for animal testing, facilitating read-across from compounds for which in vivo toxicity studies on tumor formation are available to compounds for which these data are unavailable.

  11. Effect of an Interactive Web-Based Instruction in the Performance of Undergraduate Anatomy and Physiology Lab Students

    Science.gov (United States)

    Gopal, Tamilselvi; Herron, Sherry S.; Mohn, Richard S.; Hartsell, Taralynn; Jawor, Jodie M.; Blickenstaff, Jacob C.

    2010-01-01

    This study provides an understanding of how different interactive technology tools that are integrated into a Website can be used for teaching undergraduate human anatomy and physiology laboratory students. Technology tools refer to a Website that the authors created to teach the Cardiovascular System that includes dynamic tools such as the…

  12. Effect of an Interactive Web-Based Instruction in the Performance of Undergraduate Anatomy and Physiology Lab Students

    Science.gov (United States)

    Gopal, Tamilselvi; Herron, Sherry S.; Mohn, Richard S.; Hartsell, Taralynn; Jawor, Jodie M.; Blickenstaff, Jacob C.

    2010-01-01

    This study provides an understanding of how different interactive technology tools that are integrated into a Website can be used for teaching undergraduate human anatomy and physiology laboratory students. Technology tools refer to a Website that the authors created to teach the Cardiovascular System that includes dynamic tools such as the…

  13. Biokinetics and radiation dosimetry of {sup 14}C-labelled triolein, urea, glycocholic acid and xylose in man. Studies related to nuclear medicine 'breath tests' using accelerator mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Gunnarsson, Mikael

    2002-08-01

    {sup 14}C-labelled substances have been used in biomedical research and clinical medicine for over 50 years. Physicians and scientists however, often hesitate to use these substances in patients and volunteers because the radiation dosimetry is unclear. In this work detailed long-term biokinetic and dosimetric estimation have been carried out for four clinically used {sup 14}C-breath tests: {sup 14}C-triolein (examination of fat malabsorption), urea (detection of Helicobacter pylori infection in the stomach), glycocholic acid and xylose (examination of bacterial overgrowth in the small intestine) by using the highly sensitive accelerator mass-spectrometry (AMS) technique. The AMS technique has been used to measure low {sup 14}C concentrations in small samples of exhaled air, urine, faeces and tissue samples and has improved the base for the estimation of the absorbed dose to various organs and tissues and the effective dose to man. The high sensitivity of the AMS system has also made it possible to perform {sup 14}C breath tests on patient groups which were earlier subject for restriction (e.g. small children). In summary, our results show that for adult patients - and in the case of {sup 14}C-urea breath test also for children down to 3 years of age - the dose contributions are comparatively low, both described as organ doses and as effective doses. For adults, the latter is: {sup 14}C-glycocholic acid - 0.4 mSv/MBq, {sup 14}C-triolein - 0.3 mSv/MBq, {sup 14}C-xylose - 0.1 mSv/MBq and {sup 14}C-urea - 0.04 mSv/MBq. Thus, from a radiation protection point of view there is no reason for restrictions in using any of the {sup 14}C-labelled radiopharmaceutical included in this work in the activities normally used (0.07-0.2 MBq for a 70 kg patient)

  14. Space Physiology within an Exercise Physiology Curriculum

    Science.gov (United States)

    Carter, Jason R.; West, John B.

    2013-01-01

    Compare and contrast strategies remain common pedagogical practices within physiological education. With the support of an American Physiological Society Teaching Career Enhancement Award, we have developed a junior- or senior-level undergraduate curriculum for exercise physiology that compares and contrasts the physiological adaptations of…

  15. Potassium physiology.

    Science.gov (United States)

    Thier, S O

    1986-04-25

    Potassium is the most abundant exchangeable cation in the body. It exists predominantly in the intracellular fluid at concentrations of 140 to 150 meq/liter and in the extracellular fluid at concentrations of 3.5 to 5 meq/liter. The maintenance of the serum potassium concentration is a complex bodily function and results from the balance between intake, excretion, and distribution between intracellular and extracellular space. Ingested potassium is virtually completely absorbed from and minimally excreted through the intestine under nonpathologic circumstances. Renal excretion of potassium, which is the major chronic protective mechanism against abnormalities in potassium balance, depends on filtration, reabsorption, and a highly regulated distal nephron secretory process. Factors regulating potassium secretion include prior potassium intake, intracellular potassium, delivery of sodium chloride and poorly reabsorbable anions to the distal nephron, the urine flow rate, hormones such as aldosterone and beta-catecholamines, and the integrity of the renal tubular cell. The maintenance of distribution between the inside and outside of cells depends on the integrity of the cell membrane and its pumps, osmolality, pH, and the hormones insulin, aldosterone, beta 2-catecholamines, alpha-catecholamines, and prostaglandins. Both distribution across cell membranes and/or renal excretion of potassium may be altered by pharmacologic agents such as diuretics, alpha- and beta-catechol antagonists and agonists, depolarizing agents, and digitalis. Problems with hypokalemia and hyperkalemia can be analyzed on the basis of potassium physiology and pharmacology; proper treatment depends on an accurate analysis.

  16. Biokinetics and dosimetry in patients of {sup 99m}Tc-EDDA/HYNIC-Tyr{sup 3}-octreotide prepared from lyophilized kits

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez-Vazquez, Armando [Departamento de Medicina Nuclear, Hospital Militar (Mexico); Facultad de Medicina, Universidad Autonoma del Estado de Mexico (Mexico); Ferro-Flores, Guillermina [Departamento de Materiales Radiactivos, Gerencia de Aplicaciones Nucleares en la Salud, Instituto Nacional de Investigaciones Nucleares, Km. 36.5 Carretera Mexico-Toluca, Ocoyoacac, Estado de Mexico, C.P. 52045 (Mexico)]. E-mail: gff@nuclear.inin.mx; Arteaga de Murphy, Consuelo [Departamento de Medicina Nuclear, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran (Mexico); Gutierrez-Garcia, Zohar [Departamento de Medicina Nuclear, Hospital Militar (Mexico)

    2006-07-15

    {sup 99m}Tc-EDDA/HYNIC-Tyr{sup 3}-octreotide ({sup 99m}Tc-HYNIC-TOC) has shown high in vitro and in vivo stability, rapid background clearance and rapid detection of somatostatin receptor-positive tumors. The aim of this study was to establish a biokinetic model for {sup 99m}Tc-HYNIC-TOC prepared from lyophilized kits, and to evaluate its dosimetry as a tumor imaging agent in patients with histologically confirmed neuroendocrine tumors. Whole-body images from eight patients were acquired at 5, 60, 90, 180 min and 24 h after {sup 99m}Tc-HYNIC-TOC administration obtained from instant freeze-dried kit formulations with radiochemical purities >95%. Regions of interest (ROIs) were drawn around source organs on each time frame. The same set of ROIs was used for all eight scans and the count per minute (cpm) of each ROI was converted to activity using the conjugate view counting method. The image sequence was used to extrapolate {sup 99m}Tc-HYNIC-TOC time-activity curves in each organ, to adjust a biokinetic model using the SAAM software, and to calculate the total number of disintegrations (N) that occurred in the source regions. N data were the input for the OLINDA/EXM code to calculate internal radiation dose estimates. Images showed an average tumor/blood (heart) ratio of 4.3{+-}0.7 in receptor-positive tumors at 1 h. The mean radiation absorbed dose calculated for a study using 740 MBq was 24, 21.5, 5.5 and 1.0 mSv for spleen, kidneys, liver and bone marrow respectively and the effective dose was 4.4 mSv.

  17. Using physiologically based pharmacokinetic modeling to address nonlinear kinetics and changes in rodent physiology and metabolism due to aging and adaptation in deriving reference values for propylene glycol methyl ether and propylene glycol methyl ether acetate.

    Energy Technology Data Exchange (ETDEWEB)

    Kirman, C R.; Sweeney, Lisa M.; Corley, Rick A.; Gargas, M L.

    2005-04-01

    Reference values, including an oral reference dose (RfD) and an inhalation reference concentration (RfC), were derived for propylene glycol methyl ether (PGME), and an oral RfD was derived for its acetate (PGMEA). These values were based upon transient sedation observed in F344 rats and B6C3F1 mice during a two-year inhalation study. The dose-response relationship for sedation was characterized using internal dose measures as predicted by a physiologically based pharmacokinetic (PBPK) model for PGME and its acetate. PBPK modeling was used to account for changes in rodent physiology and metabolism due to aging and adaptation, based on data collected during weeks 1, 2, 26, 52, and 78 of a chronic inhalation study. The peak concentration of PGME in richly perfused tissues was selected as the most appropriate internal dose measure based upon a consideration of the mode of action for sedation and similarities in tissue partitioning between brain and other richly perfused tissues. Internal doses (peak tissue concentrations of PGME) were designated as either no-observed-adverse-effect levels (NOAELs) or lowest-observed-adverse-effect levels (LOAELs) based upon the presence or absence of sedation at each time-point, species, and sex in the two year study. Distributions of the NOAEL and LOAEL values expressed in terms of internal dose were characterized using an arithmetic mean and standard deviation, with the mean internal NOAEL serving as the basis for the reference values, which was then divided by appropriate uncertainty factors. Where data were permitting, chemical-specific adjustment factors were derived to replace default uncertainty factor values of ten. Nonlinear kinetics are were predicted by the model in all species at PGME concentrations exceeding 100 ppm, which complicates interspecies and low-dose extrapolations. To address this complication, reference values were derived using two approaches which differ with respect to the order in which these extrapolations

  18. Using a Molecular-Genetic Approach to Investigate Bacterial Physiology in a Continuous, Research-Based, Semester-Long Laboratory for Undergraduates

    Directory of Open Access Journals (Sweden)

    Jeremiah Foster Ault

    2011-09-01

    Full Text Available Designing investigative laboratory exercises that encourage critical thinking, problem solving, and independent thought for upper-division biology courses is a difficult but worthwhile task. In an effort to do so, we developed a semester-long, continuous, research-based investigative laboratory that integrates numerous genetic and molecular biology methods into the investigation of a bacterial physiological process. In this lab, students use random Tn5 transposon mutagenesis to create prodigiosin pigment mutants in the bacterium, Serratia marcescens. This is followed by phenotypic characterization, cloning, and sequencing the Tn insertion site to identify genes involved in pigment biosynthesis. During this lab, students gain ample experience performing basic lab techniques while learning about — and applying — methods for elucidating gene function. The approach to the laboratory and the outcomes are intimately integrated into the teaching of many fundamental physiological processes underlying prodigiosin production in bacteria. The result is a cohesive course that integrates the theory and application of molecular genetic techniques with the study of bacterial physiology. Assessments of student learning objectives demonstrated that students greatly improved their understanding of both physiological processes and the genetic techniques used to investigate them. In addition, students felt that this semester-long exercise provided the necessary laboratory experience they needed and desired in preparation for careers in molecular biology, microbiology, and biochemistry.

  19. Using a molecular-genetic approach to investigate bacterial physiology in a continuous, research-based, semester-long laboratory for undergraduates.

    Science.gov (United States)

    Ault, Jeremiah Foster; Renfro, Betsey Marie; White, Andrea Kirsten

    2011-01-01

    Designing investigative laboratory exercises that encourage critical thinking, problem solving, and independent thought for upper-division biology courses is a difficult but worthwhile task. In an effort to do so, we developed a semester-long, continuous, research-based investigative laboratory that integrates numerous genetic and molecular biology methods into the investigation of a bacterial physiological process. In this lab, students use random Tn5 transposon mutagenesis to create prodigiosin pigment mutants in the bacterium, Serratia marcescens. This is followed by phenotypic characterization, cloning, and sequencing the Tn insertion site to identify genes involved in pigment biosynthesis. During this lab, students gain ample experience performing basic lab techniques while learning about - and applying - methods for elucidating gene function. The approach to the laboratory and the outcomes are intimately integrated into the teaching of many fundamental physiological processes underlying prodigiosin production in bacteria. The result is a cohesive course that integrates the theory and application of molecular genetic techniques with the study of bacterial physiology. Assessments of student learning objectives demonstrated that students greatly improved their understanding of both physiological processes and the genetic techniques used to investigate them. In addition, students felt that this semester-long exercise provided the necessary laboratory experience they needed and desired in preparation for careers in molecular biology, microbiology, and biochemistry.

  20. Estimation of parameters biokinetics from the resolution of a model compartment for I-131. Application to a patient with thyroid carcinoma hemodialysis; Estimacion de parametros bioceniticos a partir de la resolucion de un modelo compartimental para I-131. Aplicacion a un paciente hemodializado con carcinoma de torioides

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, R.; Jimenez Feltstrom, D.; Luis dimon, F. J.; Sanchez Carmona, G.; Herrador Cordoba, M.

    2013-07-01

    This work aims to define a biokinetic model for the I-131, and solve it for different conditions of the patient or person affected (normal, with cancer of the thyroid or hyperthyroid). Solve the model in the case of a patient treated with I-131 for ablation of thyroid remnants with undergoing renal insufficiency and hemodialysis . Get the parameters Biokinetic this model for different situations. (Author)

  1. Using a Molecular-Genetic Approach to Investigate Bacterial Physiology in a Continuous, Research-Based, Semester-Long Laboratory for Undergraduates †

    OpenAIRE

    Jeremiah Foster Ault; Betsey Marie Renfro; Andrea Kirsten White

    2011-01-01

    Designing investigative laboratory exercises that encourage critical thinking, problem solving, and independent thought for upper-division biology courses is a difficult but worthwhile task. In an effort to do so, we developed a semester-long, continuous, research-based investigative laboratory that integrates numerous genetic and molecular biology methods into the investigation of a bacterial physiological process. In this lab, students use random Tn5 transposon mutagenesis to create prodigi...

  2. Physiologically based pharmacokinetics in Drug Development and Regulatory Science: A workshop report (Georgetown University, Washington, DC, May 29–30, 2002)

    OpenAIRE

    Rowland, Malcolm; Balant, Luc; Peck,Carl

    2004-01-01

    A 2-day workshop on “Physiologically Based Pharmacokinetics (PBPK) in Drug Development and Regulatory Science” came to a successful conclusion on May 30, 2002, in Washington, DC. More than 120 international participants from the environmental and predominantly pharmaceutical industries, Food and Drug Administration (FDA), and universities attended this workshop, organized by the Center for Drug Development Science, Georgetown University, Washington, DC. The first of its kind specifically devo...

  3. Multi-sensor fusion system using wavelet-based detection algorithm applied to physiological monitoring under high-G environment

    Science.gov (United States)

    Ryoo, Han Chool

    2000-06-01

    A significant problem in physiological state monitoring systems with single data channels is high rates of false alarm. In order to reduce false alarm probability, several data channels can be integrated to enhance system performance. In this work, we have investigated a sensor fusion methodology applicable to physiological state monitoring, which combines local decisions made from dispersed detectors. Difficulties in biophysical signal processing are associated with nonstationary signal patterns and individual characteristics of human physiology resulting in nonidentical observation statistics. Thus a two compartment design, a modified version of well established fusion theory in communication systems, is presented and applied to biological signal processing where we combine discrete wavelet transforms (DWT) with sensor fusion theory. The signals were decomposed in time-frequency domain by discrete wavelet transform (DWT) to capture localized transient features. Local decisions by wavelet power analysis are followed by global decisions at the data fusion center operating under an optimization criterion, i.e., minimum error criterion (MEC). We used three signals acquired from human volunteers exposed to high-G forces at the human centrifuge/dynamic flight simulator facility in Warminster, PA. The subjects performed anti-G straining maneuvers to protect them from the adverse effects of high-G forces. These maneuvers require muscular tensing and altered breathing patterns. We attempted to determine the subject's state by detecting the presence or absence of the voluntary anti-G straining maneuvers (AGSM). During the exposure to high G force the respiratory patterns, blood pressure and electroencephalogram (EEG) were measured to determine changes in the subject's state. Experimental results show that the probability of false alarm under MEC can be significantly reduced by applying the same rule found at local thresholds to all subjects, and MEC can be employed as a

  4. The effects of orange juice clarification on the physiology of Escherichia coli; growth-based and flow cytometric analysis.

    Science.gov (United States)

    Anvarian, Amir H P; Smith, Madeleine P; Overton, Tim W

    2016-02-16

    Orange juice (OJ) is a food product available in various forms which can be processed to a greater or lesser extent. Minimally-processed OJ has a high consumer perception but presents a potential microbiological risk due to acid-tolerant bacteria. Clarification of OJ (such as removal of cloud) is a common processing step in many OJ products. However, many of the antimicrobial components of OJ such as essential oils are present in the cloud fraction. Here, the effect of clarification by filtration on the viability and physiology of Escherichia coli K-12 was tested using total viable count (TVC) and flow cytometric (FCM) analysis. The latter technique was also used to monitor intracellular pH during incubation in OJ. Removal of the OJ cloud fraction was shown to have dramatic effects on bacterial viability and physiology during storage at a range of incubation temperatures. For instance, at 4 °C, a significantly lower number of healthy cells and a significantly higher number of injured cells were observed in 0.22 μm-filtered OJ at 24h post-inoculation, compared to filtered OJ samples containing particles between 0.22 μm and 11 μm in size. Similarly, there was a significant difference between the number of healthy bacteria in the 0.7 μm-filtered OJ and both 0.22 μm-filtered and 1.2 μm-filtered OJ after 24 hour incubation at 22.5 °C. This indicated that OJ cloud between 0.7 μm and 0.22 μm in size might have an adverse effect on the viability of E. coli K-12. Furthermore, FCM allowed the rapid analysis of bacterial physiology without the requirement for growth on agar plates, and revealed the extent of the viable but non-culturable (VBNC) population. For example, at 4 °C, while the FCM viable count did not substantially decrease until 48 h, decreases in TVC were observed between 0 and 48 hour incubation, due to a subset of injured bacteria entering the VBNC state, hence being unable to grow on agar plates. This study highlights the application of FCM in

  5. Badminton training analysis system based on physiological computing%一个基于生理计算的羽毛球训练分析系统

    Institute of Scientific and Technical Information of China (English)

    袁中果; 罗文灿; 田丰

    2014-01-01

    Field studies are conducted in China Badminton Team and a badminton team in Beijing Sport University to inves-tigate current common problems in Badminton training. Based on the investigation, Physiological Plan system is designed. It has four levels, including hardware level, data processing level, algorithm level and the interface level. The hardware of Physiological Plan is based on the Berkeley Tricorder platform;data processing level is aiming to transform kinds of sensors to a uniform format;algorithm level includes algorithms of filter, peak finder, outlier detection, etc;coaches interact with the system through the interface level. Physiological Plan can collect ECG, EMG, bioimpedance, 3-axis accelerations of the player, provide real-time feedback of the data to coaches, and help them monitor and analyze the physiological states of the player. The experiment shows that Physiological Plan is valuable for coaches to monitor and analyze the states of players.%通过在国家羽毛球队和北京体育大学的现场调研分析了当前羽毛球训练中存在的问题,针对这些问题设计实现了Physiological Plan系统。系统分为硬件层、数据处理层、算法层和界面层。硬件层采用Berkeley Tricorder平台,数据处理层通过适配器模式将各个传感器的数据统一;算法层包括滤波算法、峰值检测算法以及Outlier检测算法等,界面层与教练进行交互,并将结果呈现给教练。该系统能同时采集和分析运动员的心电图(ECG)、肌电图(EMG)和3D加速度等信息,并将数据分析处理结果反馈给教练,解决了当前羽毛球训练中无法实时采集分析运动员生理数据的问题。实验结果表明该系统可以有效辅助教练员监控和分析运动员训练和比赛时的状态。

  6. Physiologically based pharmacokinetics joined with in vitro-in vivo extrapolation of ADME: a marriage under the arch of systems pharmacology.

    Science.gov (United States)

    Rostami-Hodjegan, A

    2012-07-01

    Classic pharmacokinetics (PK) rarely takes into account the full knowledge of physiology and biology of the human body. However, physiologically based PK (PBPK) is built mainly from drug-independent "system" information. PBPK is not a new concept, but it has shown a very rapid rise in recent years. This has been attributed to a greater connectivity to in vitro-in vivo extrapolation (IVIVE) techniques for predicting drug absorption, distribution, metabolism, and excretion (ADME) and their variability in humans. The marriage between PBPK and IVIVE under the overarching umbrella of "systems biology" has removed many constraints related to cutoff approaches on prediction of ADME. PBPK-IVIVE linked models have repeatedly shown their value in guiding decisions when predicting the effects of intrinsic and extrinsic factors on PK of drugs. A review of the achievements and shortcomings of the models might suggest better strategies in extending the success of PBPK-IVIVE to pharmacodynamics (PD) and drug safety.

  7. Prediction of in vivo developmental toxicity of all-trans-retinoic acid based on in vitro toxicity data and in silico physiologically based kinetic modeling.

    Science.gov (United States)

    Louisse, Jochem; Bosgra, Sieto; Blaauboer, Bas J; Rietjens, Ivonne M C M; Verwei, Miriam

    2015-07-01

    The use of laboratory animals for toxicity testing in chemical safety assessment meets increasing ethical, economic and legislative constraints. The development, validation and application of reliable alternatives for in vivo toxicity testing are therefore urgently needed. In order to use toxicity data obtained from in vitro assays for risk assessment, in vitro concentration-response data need to be translated into in vivo dose-response data that are needed to obtain points of departure for risk assessment, like a benchmark dose (BMD). In the present study, we translated in vitro concentration-response data of the retinoid all-trans-retinoic acid (ATRA), obtained in the differentiation assay of the embryonic stem cell test, into in vivo dose-response data using a physiologically based kinetic model for rat and human that is mainly based on kinetic model parameter values derived using in vitro techniques. The predicted in vivo dose-response data were used for BMD modeling, and the obtained BMDL10 values [lower limit of the 95 % confidence interval on the BMD at which a benchmark response equivalent to a 10 % effect size (BMR10) is reached (BMD10)] for rat were compared with BMDL10 values derived from in vivo developmental toxicity data in rats reported in the literature. The results show that the BMDL10 values from predicted dose-response data differ about sixfold from the BMDL10 values obtained from in vivo data, pointing at the feasibility of using a combined in vitro-in silico approach for defining a point of departure for toxicological risk assessment.

  8. [Human physiology: kidney].

    Science.gov (United States)

    Natochin, Iu V

    2010-01-01

    The content of human physiology as an independent part of current physiology is discussed. Substantiated is the point that subjects of human physiology are not only special sections of physiology where functions are inherent only in human (physiology of intellectual activity, speech, labor, sport), but also in peculiarities of functions, specificity of regulation of each of physiological systems. By the example of physiology of kidney and water-salt balance there are shown borders of norm, peculiarities of regulation in human, new chapters of renal physiology which have appeared in connection with achievements of molecular physiology.

  9. A critical care monitoring system for depth of anaesthesia analysis based on entropy analysis and physiological information database.

    Science.gov (United States)

    Wei, Qin; Li, Yang; Fan, Shou-Zen; Liu, Quan; Abbod, Maysam F; Lu, Cheng-Wei; Lin, Tzu-Yu; Jen, Kuo-Kuang; Wu, Shang-Ju; Shieh, Jiann-Shing

    2014-09-01

    Diagnosis of depth of anaesthesia (DoA) plays an important role in treatment and drug usage in the operating theatre and intensive care unit. With the flourishing development of analysis methods and monitoring devices for DoA, a small amount of physiological data had been stored and shared for further researches. In this paper, a critical care monitoring (CCM) system for DoA monitoring and analysis was designed and developed, which includes two main components: a physiologic information database (PID) and a DoA analysis subsystem. The PID, including biologic data and clinical information was constructed through a browser and server model so as to provide a safe and open platform for storage, sharing and further study of clinical anaesthesia information. In the analysis of DoA, according to our previous studies on approximate entropy, sample entropy (SampEn) and multi-scale entropy (MSE), the SampEn and MSE were integrated into the subsystem for indicating the state of patients underwent surgeries in real time because of their stability. Therefore, this CCM system not only supplies the original biological data and information collected from the operating room, but also shares our studies for improvement and innovation in the research of DoA.

  10. Theoretical Compartment Modeling of DCE-MRI Data Based on the Transport across Physiological Barriers in the Brain

    Directory of Open Access Journals (Sweden)

    Laura Fanea

    2012-01-01

    Full Text Available Neurological disorders represent major causes of lost years of healthy life and mortality worldwide. Development of their quantitative interdisciplinary in vivo evaluation is required. Compartment modeling (CM of brain data acquired in vivo using magnetic resonance imaging techniques with clinically available contrast agents can be performed to quantitatively assess brain perfusion. Transport of 1H spins in water molecules across physiological compartmental brain barriers in three different pools was mathematically modeled and theoretically evaluated in this paper and the corresponding theoretical compartment modeling of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI data was analyzed. The pools considered were blood, tissue, and cerebrospinal fluid (CSF. The blood and CSF data were mathematically modeled assuming continuous flow of the 1H spins in these pools. Tissue data was modeled using three CMs. Results in this paper show that transport across physiological brain barriers such as the blood to brain barrier, the extracellular space to the intracellular space barrier, or the blood to CSF barrier can be evaluated quantitatively. Statistical evaluations of this quantitative information may be performed to assess tissue perfusion, barriers' integrity, and CSF flow in vivo in the normal or disease-affected brain or to assess response to therapy.

  11. Corrosion-fatigue study of a Zr-based bulk-metallic glass in a physiologically relevant environment

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Lu [Key Laboratory of Aerospace Materials and Performance (Ministry of Education), School of Materials Science and Engineering, Beijing University of Aeronautics and Astronautics, XueYuan Road No. 37, HaiDian District, Beijing 100191 (China); Department of Materials Science and Engineering, The University of Tennessee, Knoxville, TN 37996-2200 (United States); Wang, Gongyao; Qiao, Dongchun; Liaw, Peter K. [Department of Materials Science and Engineering, The University of Tennessee, Knoxville, TN 37996-2200 (United States); Pang, Shujie; Wang, Jianfeng [Key Laboratory of Aerospace Materials and Performance (Ministry of Education), School of Materials Science and Engineering, Beijing University of Aeronautics and Astronautics, XueYuan Road No. 37, HaiDian District, Beijing 100191 (China); Zhang, Tao, E-mail: zhangtao@buaa.edu.c [Key Laboratory of Aerospace Materials and Performance (Ministry of Education), School of Materials Science and Engineering, Beijing University of Aeronautics and Astronautics, XueYuan Road No. 37, HaiDian District, Beijing 100191 (China)

    2010-08-15

    Four-point-bend corrosion-fatigue experiments were conducted in a physiologically relevant environment to study the environmental effects on the fatigue behavior of (Zr{sub 0.55}Al{sub 0.10}Ni{sub 0.05}Cu{sub 0.30}){sub 99}Y{sub 1} (at.%) bulk-metallic glasses (BMGs), and the results were compared with those obtained in air at room temperature. At high stress ranges, the corrosive environment did not significantly affect the fatigue lifetime; while at low stress ranges, the corrosive environment exhibited a detrimental effect on the fatigue resistance. The fatigue strength was decreased by 40% in the physiologically relevant environment. Fracture morphologies after fatigue tests were studied by the scanning electron microscopy. The mechanism for the environmental effects on the fatigue life of the (Zr{sub 0.55}Al{sub 0.10}Ni{sub 0.05}Cu{sub 0.30}){sub 99}Y{sub 1} BMG was determined to be anodic dissolution.

  12. Physiological attributes of triathletes.

    Science.gov (United States)

    Suriano, R; Bishop, D

    2010-05-01

    Triathlons of all distances can be considered endurance events and consist of the individual disciplines of swimming, cycling and running which are generally completed in this sequential order. While it is expected that elite triathletes would possess high values for submaximal and maximal measures of aerobic fitness, little is known about how these values compare with those of single-sport endurance athletes. Earlier reviews, conducted in the 1980s, concluded that triathletes possessed lower V(O2(max)) values than other endurance athletes. An update of comparisons is of interest to determine if the physiological capacities of elite triathletes now reflect those of single-sport athletes or whether these physiological capacities are compromised by the requirement to cross-train for three different disciplines. It was found that although differences in the physiological attributes during swimming, cycling and running are evident among triathletes, those who compete at an international level possess V(O2(max)) values that are indicative of success in endurance-based individual sports. Furthermore, various physiological parameters at submaximal workloads have been used to describe the capacities of these athletes. Only a few studies have reported the lactate threshold among triathletes with the majority of studies reporting the ventilatory threshold. Although observed differences among triathletes for both these submaximal measures are complicated by the various methods used to determine them, the reported values for triathletes are similar to those for trained cyclists and runners. Thus, from the limited data available, it appears that triathletes are able to obtain similar physiological values as single-sport athletes despite dividing their training time among three disciplines.

  13. Puzzle-based versus traditional lecture: comparing the effects of pedagogy on academic performance in an undergraduate human anatomy and physiology II lab.

    Science.gov (United States)

    Stetzik, Lucas; Deeter, Anthony; Parker, Jamie; Yukech, Christine

    2015-06-23

    A traditional lecture-based pedagogy conveys information and content while lacking sufficient development of critical thinking skills and problem solving. A puzzle-based pedagogy creates a broader contextual framework, and fosters critical thinking as well as logical reasoning skills that can then be used to improve a student's performance on content specific assessments. This paper describes a pedagogical comparison of traditional lecture-based teaching and puzzle-based teaching in a Human Anatomy and Physiology II Lab. Using a single subject/cross-over design half of the students from seven sections of the course were taught using one type of pedagogy for the first half of the semester, and then taught with a different pedagogy for the second half of the semester. The other half of the students were taught the same material but with the order of the pedagogies reversed. Students' performance on quizzes and exams specific to the course, and in-class assignments specific to this study were assessed for: learning outcomes (the ability to form the correct conclusion or recall specific information), and authentic academic performance as described by (Am J Educ 104:280-312, 1996). Our findings suggest a significant improvement in students' performance on standard course specific assessments using a puzzle-based pedagogy versus a traditional lecture-based teaching style. Quiz and test scores for students improved by 2.1 and 0.4% respectively in the puzzle-based pedagogy, versus the traditional lecture-based teaching. Additionally, the assessments of authentic academic performance may only effectively measure a broader conceptual understanding in a limited set of contexts, and not in the context of a Human Anatomy and Physiology II Lab. In conclusion, a puzzle-based pedagogy, when compared to traditional lecture-based teaching, can effectively enhance the performance of students on standard course specific assessments, even when the assessments only test a limited

  14. Assessment of Bioequivalence of Weak Base Formulations Under Various Dosing Conditions Using Physiologically Based Pharmacokinetic Simulations in Virtual Populations. Case Examples: Ketoconazole and Posaconazole.

    Science.gov (United States)

    Cristofoletti, Rodrigo; Patel, Nikunjkumar; Dressman, Jennifer B

    2017-02-01

    Postabsorptive factors which can affect systemic drug exposure are assumed to be dependent on the active pharmaceutical ingredient (API), and thus independent of formulation. In contrast, preabsorptive factors, for example, hypochlorhydria, might affect systemic exposure in both an API and a formulation-dependent way. The aim of this study was to evaluate whether the oral absorption of 2 poorly soluble, weakly basic APIs, ketoconazole (KETO) and posaconazole (POSA), would be equally sensitive to changes in dissolution rate under the following dosing conditions-coadministration with water, with food, with carbonated drinks, and in drug-induced hypochlorhydria. The systems-components of validated absorption and PBPK models for KETO and POSA were modified to simulate the above-mentioned clinical scenarios. Virtual bioequivalence studies were then carried out to investigate whether formulation effects on the plasma profile vary with the dosing conditions. The slow precipitation of KETO upon reaching the upper part of the small intestine renders its absorption more sensitive to the completeness of gastric dissolution and thus to the gastric environment than POSA, which is subject to extensive precipitation in response to a pH shift. The virtual bioequivalence studies showed that hypothetical test and reference formulations containing KETO would be bioequivalent only if the microenvironment in the stomach enables complete gastric dissolution. We conclude that physiologically based pharmacokinetic modeling and simulation has excellent potential to address issues close to bedside such as optimizing dosing conditions. By studying virtual populations adapted to various clinical situations, clinical strategies to reduce therapeutic failures can be identified.

  15. Using physiologically-based pharmacokinetic-guided "body-on-a-chip" systems to predict mammalian response to drug and chemical exposure.

    Science.gov (United States)

    Sung, Jong Hwan; Srinivasan, Balaji; Esch, Mandy Brigitte; McLamb, William T; Bernabini, Catia; Shuler, Michael L; Hickman, James J

    2014-09-01

    The continued development of in vitro systems that accurately emulate human response to drugs or chemical agents will impact drug development, our understanding of chemical toxicity, and enhance our ability to respond to threats from chemical or biological agents. A promising technology is to build microscale replicas of humans that capture essential elements of physiology, pharmacology, and/or toxicology (microphysiological systems). Here, we review progress on systems for microscale models of mammalian systems that include two or more integrated cellular components. These systems are described as a "body-on-a-chip", and utilize the concept of physiologically-based pharmacokinetic (PBPK) modeling in the design. These microscale systems can also be used as model systems to predict whole-body responses to drugs as well as study the mechanism of action of drugs using PBPK analysis. In this review, we provide examples of various approaches to construct such systems with a focus on their physiological usefulness and various approaches to measure responses (e.g. chemical, electrical, or mechanical force and cellular viability and morphology). While the goal is to predict human response, other mammalian cell types can be utilized with the same principle to predict animal response. These systems will be evaluated on their potential to be physiologically accurate, to provide effective and efficient platform for analytics with accessibility to a wide range of users, for ease of incorporation of analytics, functional for weeks to months, and the ability to replicate previously observed human responses. © 2014 by the Society for Experimental Biology and Medicine.

  16. Database of Physiological Parameters for Early Life Rats and Mice

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Database of Physiological Parameters for Early Life Rats and Mice provides information based on scientific literature about physiological parameters. Modelers...

  17. The dynamics of p53 in single cells: physiologically based ODE and reaction-diffusion PDE models

    Science.gov (United States)

    Eliaš, Ján; Dimitrio, Luna; Clairambault, Jean; Natalini, Roberto

    2014-08-01

    The intracellular signalling network of the p53 protein plays important roles in genome protection and the control of cell cycle phase transitions. Recently observed oscillatory behaviour in single cells under stress conditions has inspired several research groups to simulate and study the dynamics of the protein with the aim of gaining a proper understanding of the physiological meanings of the oscillations. We propose compartmental ODE and PDE models of p53 activation and regulation in single cells following DNA damage and we show that the p53 oscillations can be retrieved by plainly involving p53-Mdm2 and ATM-p53-Wip1 negative feedbacks, which are sufficient for oscillations experimentally, with no further need to introduce any delays into the protein responses and without considering additional positive feedback.

  18. Anti-aggregation-based spectrometric detection of Hg(II) at physiological pH using gold nanorods

    Energy Technology Data Exchange (ETDEWEB)

    Rajeshwari, A.; Karthiga, D.; Chandrasekaran, Natarajan; Mukherjee, Amitava, E-mail: amit.mookerjea@gmail.com

    2016-10-01

    An efficient detection method for Hg (II) ions at physiological pH (pH 7.4) was developed using tween 20-modified gold nanorods (NRs) in the presence of dithiothreitol (DTT). Thiol groups (-SH) at the end of DTT have a higher affinity towards gold atoms, and they can covalently interact with gold NRs and leads to their aggregation. The addition of Hg(II) ions prevents the aggregation of gold NRs due to the covalent bond formation between the -SH group of DTT and Hg(II) ions in the buffer system. The changes in the longitudinal surface plasmon resonance peak of gold NRs were characterized using a UV–visible spectrophotometer. The absorption intensity peak of gold NRs at 679 nm was observed to reduce after interaction with DTT, and the absorption intensity was noted to increase by increasing the concentration of Hg(II) ions. The TEM analysis confirms the morphological changes of gold NRs before and after addition of Hg(II) ions in the presence of DTT. Further, the aggregation and disaggregation of gold NRs were confirmed by particle size and zeta potential analysis. The developed method shows an excellent linearity (y = 0.001 x + 0.794) for the graph plotted between the absorption ratio and Hg(II) concentration (1 to 100 pM) under the optimized conditions. The limit of detection was noted to be 0.42 pM in the buffer system. The developed method was tested in simulated body fluid, and it was found to have a good recovery rate. - Highlights: • Tween-20 modified gold NRs used as a probe for Hg(II) at physiological pH. • TEM, particle size and surface charge analysis confirm the aggregation and • disaggregation of NRs • The sensitivity of the probe for Hg(II) ions detection was 0.42 pM. • Hg(II) estimation in simulated body fluids with good recovery.

  19. Reification of abstract concepts to improve comprehension using interactive virtual environments and a knowledge-based design: a renal physiology model.

    Science.gov (United States)

    Alverson, Dale C; Saiki, Stanley M; Caudell, Thomas P; Goldsmith, Timothy; Stevens, Susan; Saland, Linda; Colleran, Kathleen; Brandt, John; Danielson, Lee; Cerilli, Lisa; Harris, Alexis; Gregory, Martin C; Stewart, Randall; Norenberg, Jeffery; Shuster, George; Panaoitis; Holten, James; Vergera, Victor M; Sherstyuk, Andrei; Kihmm, Kathleen; Lui, Jack; Wang, Kin Lik

    2006-01-01

    Several abstract concepts in medical education are difficult to teach and comprehend. In order to address this challenge, we have been applying the approach of reification of abstract concepts using interactive virtual environments and a knowledge-based design. Reification is the process of making abstract concepts and events, beyond the realm of direct human experience, concrete and accessible to teachers and learners. Entering virtual worlds and simulations not otherwise easily accessible provides an opportunity to create, study, and evaluate the emergence of knowledge and comprehension from the direct interaction of learners with otherwise complex abstract ideas and principles by bringing them to life. Using a knowledge-based design process and appropriate subject matter experts, knowledge structure methods are applied in order to prioritize, characterize important relationships, and create a concept map that can be integrated into the reified models that are subsequently developed. Applying these principles, our interdisciplinary team has been developing a reified model of the nephron into which important physiologic functions can be integrated and rendered into a three dimensional virtual environment called Flatland, a virtual environments development software tool, within which a learners can interact using off-the-shelf hardware. The nephron model can be driven dynamically by a rules-based artificial intelligence engine, applying the rules and concepts developed in conjunction with the subject matter experts. In the future, the nephron model can be used to interactively demonstrate a number of physiologic principles or a variety of pathological processes that may be difficult to teach and understand. In addition, this approach to reification can be applied to a host of other physiologic and pathological concepts in other systems. These methods will require further evaluation to determine their impact and role in learning.

  20. Estimating 131I biokinetics and radiation doses to the red marrow and whole body in thyroid cancer patients: probe detection versus image quantification

    Directory of Open Access Journals (Sweden)

    José Willegaignon

    2016-06-01

    Full Text Available Abstract Objective: To compare the probe detection method with the image quantification method when estimating 131I biokinetics and radiation doses to the red marrow and whole body in the treatment of thyroid cancer patients. Materials and Methods: Fourteen patients with metastatic thyroid cancer, without metastatic bone involvement, were submitted to therapy planning in order to tailor the therapeutic amount of 131I to each individual. Whole-body scans and probe measurements were performed at 4, 24, 48, 72, and 96 h after 131I administration in order to estimate the effective half-life (Teff and residence time of 131I in the body. Results: The mean values for Teff and residence time, respectively, were 19 ± 9 h and 28 ± 12 h for probe detection, compared with 20 ± 13 h and 29 ± 18 h for image quantification. The average dose to the red marrow and whole body, respectively, was 0.061 ± 0.041 mGy/MBq and 0.073 ± 0.040 mGy/MBq for probe detection, compared with 0.066 ± 0.055 mGy/MBq and 0.078 ± 0.056 mGy/MBq for image quantification. Statistical analysis proved that there were no significant differences between the two methods for estimating the Teff (p = 0.801, residence time (p = 0.801, dose to the red marrow (p = 0.708, and dose to the whole body (p = 0.811, even when we considered an optimized approach for calculating doses only at 4 h and 96 h after 131I administration (p > 0.914. Conclusion: There is full agreement as to the feasibility of using probe detection and image quantification when estimating 131I biokinetics and red-marrow/whole-body doses. However, because the probe detection method is inefficacious in identifying tumor sites and critical organs during radionuclide therapy and therefore liable to skew adjustment of the amount of 131I to be administered to patients under such therapy, it should be used with caution.

  1. Estimating 131I biokinetics and radiation doses to the red marrow and whole body in thyroid cancer patients: probe detection versus image quantification*

    Science.gov (United States)

    Willegaignon, José; Pelissoni, Rogério Alexandre; Lima, Beatriz Christine de Godoy Diniz; Sapienza, Marcelo Tatit; Coura-Filho, George Barberio; Queiroz, Marcelo Araújo; Buchpiguel, Carlos Alberto

    2016-01-01

    Objective To compare the probe detection method with the image quantification method when estimating 131I biokinetics and radiation doses to the red marrow and whole body in the treatment of thyroid cancer patients. Materials and Methods Fourteen patients with metastatic thyroid cancer, without metastatic bone involvement, were submitted to therapy planning in order to tailor the therapeutic amount of 131I to each individual. Whole-body scans and probe measurements were performed at 4, 24, 48, 72, and 96 h after 131I administration in order to estimate the effective half-life (Teff) and residence time of 131I in the body. Results The mean values for Teff and residence time, respectively, were 19 ± 9 h and 28 ± 12 h for probe detection, compared with 20 ± 13 h and 29 ± 18 h for image quantification. The average dose to the red marrow and whole body, respectively, was 0.061 ± 0.041 mGy/MBq and 0.073 ± 0.040 mGy/MBq for probe detection, compared with 0.066 ± 0.055 mGy/MBq and 0.078 ± 0.056 mGy/MBq for image quantification. Statistical analysis proved that there were no significant differences between the two methods for estimating the Teff (p = 0.801), residence time (p = 0.801), dose to the red marrow (p = 0.708), and dose to the whole body (p = 0.811), even when we considered an optimized approach for calculating doses only at 4 h and 96 h after 131I administration (p > 0.914). Conclusion There is full agreement as to the feasibility of using probe detection and image quantification when estimating 131I biokinetics and red-marrow/whole-body doses. However, because the probe detection method is inefficacious in identifying tumor sites and critical organs during radionuclide therapy and therefore liable to skew adjustment of the amount of 131I to be administered to patients under such therapy, it should be used with caution. PMID:27403014

  2. Estimating {sup 131}I biokinetics and radiation doses to the red marrow and whole body in thyroid cancer patients: probe detection versus image quantification

    Energy Technology Data Exchange (ETDEWEB)

    Willegaignon, Jose; Pelissoni, Rogerio Alexandre; Lima, Beatriz Christine de Godoy Diniz; Coura-Filho, George Barberio; Queiroz, Marcelo Araujo, E-mail: j.willegaignon@gmail.com [Instituto do Cancer do Estado de Sao Paulo Octavio Frias de Oliveira (ICESP), Sao Paulo, SP (Brazil); Sapienza, Marcelo Tatit; Buchpiguel, Carlos Alberto [Universidade de Sao Paulo (FM/USP), Sao Paulo, SP (Brazil). Faculdade de Medicina. Departamento de Radiologia

    2016-05-15

    Objective: to compare the probe detection method with the image quantification method when estimating {sup 131}I biokinetics and radiation doses to the red marrow and whole body in the treatment of thyroid cancer patients. Materials and methods: fourteen patients with metastatic thyroid cancer, without metastatic bone involvement, were submitted to therapy planning in order to tailor the therapeutic amount of {sup 131}I to each individual. Whole-body scans and probe measurements were performed at 4, 24, 48, 72, and 96 h after {sup 131}I administration in order to estimate the effective half-life (T{sub eff}) and residence time of {sup 131}I in the body. Results: the mean values for T{sub eff} and residence time, respectively, were 19 ± 9 h and 28 ± 12 h for probe detection, compared with 20 ± 13 h and 29 ± 18 h for image quantification. The average dose to the red marrow and whole body, respectively, was 0.061 ± 0.041 mGy/MBq and 0.073 ± 0.040 mGy/MBq for probe detection, compared with 0.066 ± 0.055 mGy/MBq and 0.078 ± 0.056 mGy/MBq for image quantification. Statistical analysis proved that there were no significant differences between the two methods for estimating the T{sub eff} (p = 0.801), residence time (p = 0.801), dose to the red marrow (p = 0.708), and dose to the whole body (p = 0.811), even when we considered an optimized approach for calculating doses only at 4 h and 96 h after {sup 131}I administration (p > 0.914). Conclusion: there is full agreement as to the feasibility of using probe detection and image quantification when estimating {sup 131}I biokinetics and red-marrow/whole-body doses. However, because the probe detection method is ineffective in identifying tumor sites and critical organs during radionuclide therapy and therefore liable to skew adjustment of the amount of {sup 131}I to be administered to patients under such therapy, it should be used with caution. (author)

  3. Use of Physiologically-Based Pharmacokinetic Modeling to Simulate the Profiles of 3-Hydroxybenzo(a)pyrene in Workers Exposed to Polycyclic Aromatic Hydrocarbons

    OpenAIRE

    Roberto Heredia Ortiz; Anne Maître; Damien Barbeau; Michel Lafontaine; Michèle Bouchard

    2014-01-01

    Biomathematical modeling has become an important tool to assess xenobiotic exposure in humans. In the present study, we have used a human physiologically-based pharmacokinetic (PBPK) model and an simple compartmental toxicokinetic model of benzo(a)pyrene (BaP) kinetics and its 3-hydroxybenzo(a)pyrene (3-OHBaP) metabolite to reproduce the time-course of this biomarker of exposure in the urine of industrially exposed workers and in turn predict the most plausible exposure scenarios. The models ...

  4. Bengt Saltin and exercise physiology: a perspective.

    Science.gov (United States)

    Joyner, Michael J

    2017-01-01

    This perspective highlights some of the key contributions of Professor Bengt Saltin (1935-2014) to exercise physiology. The emergence of exercise physiology from work physiology as his career began is discussed as are his contributions in a number of areas. Saltin's open and question-based style of leadership is a model for the future of our field.

  5. Reproductive performance in East Greenland polar bears (Ursus maritimus) may be affected by organohalogen contaminants as shown by physiologically-based pharmacokinetic (PBPK) modelling

    DEFF Research Database (Denmark)

    Sonne, Christian; Gustavson, Kim; Rigét, Frank F.

    2009-01-01

    quotient (RQ) evaluation to more quantitatively evaluate the effect risk on reproduction (embryotoxicity and teratogenicity) based on the critical body residue (CBR) concept and using a physiologically-based pharmacokinetic (PBPK) model. We applied modelling approaches to PCBs, p,p′-DDE, dieldrin......, oxychlordane, HCHs, HCB, PBDEs and PFOS in East Greenland polar bears based on known OHC pharmacokinetics and dynamics in laboratory rats (Rattus rattus). The results showed that subcutaneous adipose tissue concentrations of dieldrin (range: 79–1271 ng g−1 lw) and PCBs (range: 4128–53 923 ng g−1 lw) reported...... and for dieldrin (range: 43–640 ng g−1 lw), PCBs (range: 3491–13 243 ng g−1 lw) and PFOS (range: 1332–6160 ng g−1 ww) in the year 2006. The concentrations of oxychlordane, DDTs, HCB and HCHs in polar bears resulted in RQs

  6. Mimicking the functional hematopoietic stem cell niche in vitro: recapitulation of marrow physiology by hydrogel-based three-dimensional cultures of mesenchymal stromal cells.

    Science.gov (United States)

    Sharma, Monika B; Limaye, Lalita S; Kale, Vaijayanti P

    2012-05-01

    A culture system that closely recapitulates marrow physiology is essential to study the niche-mediated regulation of hematopoietic stem cell fate at a molecular level. We investigated the key features that play a crucial role in the formation of a functional niche in vitro. Hydrogel-based cultures of human placenta-derived mesenchymal stromal cells were established to recapitulate the fibrous three-dimensional architecture of the marrow. Plastic-adherent mesenchymal stromal cells were used as controls. Human bone marrow-derived CD34(+) cells were co-cultured with them. The output hematopoietic cells were characterized by various stem cell-specific phenotypic and functional parameters. The hydrogel-cultures harbored a large pool of primitive hematopoietic stem cells with superior phenotypic and functional attributes. Most importantly, like the situation in vivo, a significant fraction of these cells remained quiescent in the face of a robust multi-lineage hematopoiesis. The retention of a high percentage of primitive stem cells by the hydrogel-cultures was attributed to the presence of CXCR4-SDF1α axis and integrin beta1-mediated adhesive interactions. The hydrogel-grown mesenchymal stromal cells expressed high levels of several molecules that are known to support the maintenance of hematopoietic stem cells. Yet another physiologically relevant property exhibited by the hydrogel cultures was the formation of hypoxia-gradient. Destruction of hypoxia-gradient by incubating these cultures in a hypoxia chamber destroyed their specialized niche properties. Our data show that hydrogel-based cultures of mesenchymal stromal cells form a functional in vitro niche by mimicking key features of marrow physiology.

  7. Physiology of the fetal circulation.

    Science.gov (United States)

    Kiserud, Torvid

    2005-12-01

    Our understanding of fetal circulatory physiology is based on experimental animal data, and this continues to be an important source of new insight into developmental mechanisms. A growing number of human studies have investigated the human physiology, with results that are similar but not identical to those from animal studies. It is time to appreciate these differences and base more of our clinical approach on human physiology. Accordingly, the present review focuses on distributional patterns and adaptational mechanisms that were mainly discovered by human studies. These include cardiac output, pulmonary and placental circulation, fetal brain and liver, venous return to the heart, and the fetal shunts (ductus venosus, foramen ovale and ductus arteriosus). Placental compromise induces a set of adaptational and compensational mechanisms reflecting the plasticity of the developing circulation, with both short- and long-term implications. Some of these aspects have become part of the clinical physiology of today with consequences for surveillance and treatment.

  8. Support vector machines to detect physiological patterns for EEG and EMG-based human-computer interaction: a review

    Science.gov (United States)

    Quitadamo, L. R.; Cavrini, F.; Sbernini, L.; Riillo, F.; Bianchi, L.; Seri, S.; Saggio, G.

    2017-02-01

    Support vector machines (SVMs) are widely used classifiers for detecting physiological patterns in human-computer interaction (HCI). Their success is due to their versatility, robustness and large availability of free dedicated toolboxes. Frequently in the literature, insufficient details about the SVM implementation and/or parameters selection are reported, making it impossible to reproduce study analysis and results. In order to perform an optimized classification and report a proper description of the results, it is necessary to have a comprehensive critical overview of the applications of SVM. The aim of this paper is to provide a review of the usage of SVM in the determination of brain and muscle patterns for HCI, by focusing on electroencephalography (EEG) and electromyography (EMG) techniques. In particular, an overview of the basic principles of SVM theory is outlined, together with a description of several relevant literature implementations. Furthermore, details concerning reviewed papers are listed in tables and statistics of SVM use in the literature are presented. Suitability of SVM for HCI is discussed and critical comparisons with other classifiers are reported.

  9. Is repeated-sprint ability of soccer players predictable from field-based or laboratory physiological tests?

    Science.gov (United States)

    Psotta, R; Bunc, V; Hendl, J; Tenney, D; Heller, J

    2011-03-01

    The aim of this study was to investigate multiple regression models with prediction equations that would enable a valid estimate of running repeated-sprint ability (RSA) in soccer players from the variables measured in field and laboratory physiological tests. Adolescent soccer players (N=33) performed five field performance tests and two laboratory tests for assessment of muscle strength of legs, sprint ability, anaerobic power and capacity, aerobic power and capacity, and running economy. These tests served as potential predictors of RSA. RSA was assessed by a intermittent anaerobic running test (IAnRT) consisted of ten 20 m sprints. Multiple regression analysis revealed that the mean speed in the 20 m sprint test and the 2 km endurance running test accounted for 89% of total variation in the mean running speed in the IAnRT (VIAnRT) as the indicator of capacity for multiple sprint work (R2=0.89, SEM=0.09 m.s-1). Using the variables from the laboratory tests, the best prediction of the VIAnRT was obtained from the running speed at the ventilatory threshold level (VVT) and anaerobic power (Pmax.kg-1) (R2=0.49, SEM=0.21 m.s-1). Performance in the multiple-sprint exercise as an indicator of RSA can be estimated by the regression equation with two predictors - mean speed in the 20 m sprint and 2 km running test with an error of 4%.

  10. A hypothesis for a possible synergy between ghrelin and exercise in patients with cachexia: Biochemical and physiological bases.

    Science.gov (United States)

    Fuoco, Domenico; Kilgour, Robert D; Vigano, Antonio

    2015-12-01

    This article reviews the biochemical and physiological observations underpinning the synergism between ghrelin and ghrelin agonists with exercise, especially progressive resistance training that has been shown to increase muscle mass. The synergy of ghrelin agonists and physical exercise could be beneficial in conditions where muscle wasting is present, such as that found in patients with advanced cancer. The principal mechanism that controls muscle anabolism following the activation of the ghrelin receptor in the central nervous system involves the release of growth hormone/insulin-like growth factor-1 (GH/IGF-1). GH/IGF-1 axis has a dual pathway of action on muscle growth: (a) a direct action on muscle, bone and fat tissue and (b) an indirect action via the production of both muscle-restricted mIGF-1 and anti-cachectic cytokines. Progressive resistance training is a potent inducer of the secretion the muscle-restricted IGF-1 (mIGF-1) that enhances protein synthesis, increases lean body mass and eventually leads to the improvement of muscle strength. Thus, the combination of ghrelin administration with progressive resistance training may serve to circumvent ghrelin resistance and further reduce muscle wasting, which are commonly associated with cachexia. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Uniaxial and Multiaxial Fatigue Life Prediction of the Trabecular Bone Based on Physiological Loading: A Comparative Study.

    Science.gov (United States)

    Fatihhi, S J; Harun, M N; Abdul Kadir, Mohammed Rafiq; Abdullah, Jaafar; Kamarul, T; Öchsner, Andreas; Syahrom, Ardiyansyah

    2015-10-01

    Fatigue assessment of the trabecular bone has been developed to give a better understanding of bone properties. While most fatigue studies are relying on uniaxial compressive load as the method of assessment, in various cases details are missing, or the uniaxial results are not very realistic. In this paper, the effect of three different load histories from physiological loading applied on the trabecular bone were studied in order to predict the first failure surface and the fatigue lifetime. The fatigue behaviour of the trabecular bone under uniaxial load was compared to that of multiaxial load using a finite element simulation. The plastic strain was found localized at the trabecular structure under multiaxial load. On average, applying multiaxial loads reduced more than five times the fatigue life of the trabecular bone. The results provide evidence that multiaxial loading is dominated in the low cycle fatigue in contrast to the uniaxial one. Both bone volume fraction and structural model index were best predictors of failure (p < 0.05) in fatigue for both types of loading, whilst uniaxial loading has indicated better values in most cases.

  12. Human Blood Concentrations of Cotinine, a Biomonitoring Marker for Tobacco Smoke, Extrapolated from Nicotine Metabolism in Rats and Humans and Physiologically Based Pharmacokinetic Modeling

    Directory of Open Access Journals (Sweden)

    Masato Kitajima

    2010-09-01

    Full Text Available The present study defined a simplified physiologically based pharmacokinetic (PBPK model for nicotine and its primary metabolite cotinine in humans, based on metabolic parameters determined in vitro using relevant liver microsomes, coefficients derived in silico, physiological parameters derived from the literature, and an established rat PBPK model. The model consists of an absorption compartment, a metabolizing compartment, and a central compartment for nicotine and three equivalent compartments for cotinine. Evaluation of a rat model was performed by making comparisons with predicted concentrations in blood and in vivo experimental pharmacokinetic values obtained from rats after oral treatment with nicotine (1.0 mg/kg, a no-observed-adverse-effect level for 14 days. Elimination rates of nicotine in vitro were established from data from rat liver microsomes and from human pooled liver microsomes. Human biomonitoring data (17 ng nicotine and 150 ng cotinine per mL plasma 1 h after smoking from pooled five male Japanese smokers (daily intake of 43 mg nicotine by smoking revealed that these blood concentrations could be calculated using a human PBPK model. These results indicate that a simplified PBPK model for nicotine/cotinine is useful for a forward dosimetry approach in humans and for estimating blood concentrations of other related compounds resulting from exposure to low chemical doses.

  13. A COMPARATIVE STUDY OF TEAM-BASED LEARNING ON THE TRADITIONAL METHOD OF CONDUCTING TUTORIALS IN PHYSIOLOGY FOR FIRST YEAR MBBS STUDENTS

    Directory of Open Access Journals (Sweden)

    Ashwini Vishweshwar Amalladinna

    2017-05-01

    Full Text Available BACKGROUND In medical education, didactic lectures, tutorials, bedside clinics, etc. are some of the teaching-learning method incorporated in the curriculum. Most of the methods are teacher oriented where students are not involved much. Active participation of the students, i.e. student centered approach increases the understanding of the subject. In physiology, the tutorials are conducted to discuss the individual topics. It was observed that active participation of students in physiology tutorials is less. This study was undertaken to actively involve the students during tutorials and to assess their understanding by Team-Based Learning (TBL. MATERIALS AND METHODS In this study, the performance of the students in team-based learning was compared with the traditional learning. The pretest and post-test was conducted at the beginning and at the end of the tutorial in both the groups. In the study group, the tutorial topics were discussed in teams, whereas in control group, the tutorial was conducted by traditional method. RESULTS There was a significant increase in performance in post-test in study group compared to control group (p <0.001. TBL sessions will be more interesting and interacting compared to traditional method. TBL method improves the student’s understanding of the topics in detail and hence enhances the performance. CONCLUSION The different teaching-learning methods, which increase the student’s involvement should be implemented in the medical education to facilitate the learning process.

  14. Population Physiologically-Based Pharmacokinetic Modeling for the Human Lactational Transfer of PCB 153 with Consideration of Worldwide Human Biomonitoring Results

    Energy Technology Data Exchange (ETDEWEB)

    Redding, Laurel E.; Sohn, Michael D.; McKone, Thomas E.; Wang, Shu-Li; Hsieh, Dennis P. H.; Yang, Raymond S. H.

    2008-03-01

    We developed a physiologically based pharmacokinetic model of PCB 153 in women, and predict its transfer via lactation to infants. The model is the first human, population-scale lactational model for PCB 153. Data in the literature provided estimates for model development and for performance assessment. Physiological parameters were taken from a cohort in Taiwan and from reference values in the literature. We estimated partition coefficients based on chemical structure and the lipid content in various body tissues. Using exposure data in Japan, we predicted acquired body burden of PCB 153 at an average childbearing age of 25 years and compare predictions to measurements from studies in multiple countries. Forward-model predictions agree well with human biomonitoring measurements, as represented by summary statistics and uncertainty estimates. The model successfully describes the range of possible PCB 153 dispositions in maternal milk, suggesting a promising option for back estimating doses for various populations. One example of reverse dosimetry modeling was attempted using our PBPK model for possible exposure scenarios in Canadian Inuits who had the highest level of PCB 153 in their milk in the world.

  15. Evaluating functional roles of phase resetting in generation of adaptive human bipedal walking with a physiologically based model of the spinal pattern generator.

    Science.gov (United States)

    Aoi, Shinya; Ogihara, Naomichi; Funato, Tetsuro; Sugimoto, Yasuhiro; Tsuchiya, Kazuo

    2010-05-01

    The central pattern generators (CPGs) in the spinal cord strongly contribute to locomotor behavior. To achieve adaptive locomotion, locomotor rhythm generated by the CPGs is suggested to be functionally modulated by phase resetting based on sensory afferent or perturbations. Although phase resetting has been investigated during fictive locomotion in cats, its functional roles in actual locomotion have not been clarified. Recently, simulation studies have been conducted to examine the roles of phase resetting during human bipedal walking, assuming that locomotion is generated based on prescribed kinematics and feedback control. However, such kinematically based modeling cannot be used to fully elucidate the mechanisms of adaptation. In this article we proposed a more physiologically based mathematical model of the neural system for locomotion and investigated the functional roles of phase resetting. We constructed a locomotor CPG model based on a two-layered hierarchical network model of the rhythm generator (RG) and pattern formation (PF) networks. The RG model produces rhythm information using phase oscillators and regulates it by phase resetting based on foot-contact information. The PF model creates feedforward command signals based on rhythm information, which consists of the combination of five rectangular pulses based on previous analyses of muscle synergy. Simulation results showed that our model establishes adaptive walking against perturbing forces and variations in the environment, with phase resetting playing important roles in increasing the robustness of responses, suggesting that this mechanism of regulation may contribute to the generation of adaptive human bipedal locomotion.

  16. Radiation fields, dosimetry, biokinetics and biophysical models for cancer induction by ionising radiation 1996 - 1999. Mid-term reports for the period 1996-1997

    Energy Technology Data Exchange (ETDEWEB)

    Jacob, P.; Paretzke, H.G.; Roth, P. [GSF - Forschungszentrum fuer Umwelt und Gesundheit Neuherberg GmbH, Oberschleissheim (Germany). Inst. fuer Strahlenschutz; Michael, B.D. [Mount Vernon Hospital, Northwood (United Kingdom). Gray Lab.; O`Sullivan, D. [Dublin Inst. for Advanced Studies (Ireland)

    1998-12-31

    The main objectives of the first dosimetry project are the measurement of neutron and charged particle flux and energy spectra at altitudes in civil aviation, the determination of response characteristics for detectors, the investigation of calibration procedures, and the evaluation of exposures of aircrews. The overall objective of the second dosimetry project is to improve estimates of dose following the intake of radionuclides by adults and children. The work includes the development of biokinetic and dosimetric models, including models of the gastrointestinal tract, for the systemic behaviour of radionuclides, and for the developing embryo and foetus. Further subjects are target cell dosimetry for short-range particles and the development of computational tools for sensitivity and uncertainty analysis models. The third dosimetry project encompasses the study of different methods for retrospective dose assessments for individuals or groups of individuals accidentally exposed to increased levels of radiation. The methods investigated include electron paramagnetic resonance (EPR) of tooth enamel and chromosome painting (FISH) for lymphocytes in peripheral blood for individual retrospective dose assessments, luminescence techniques on materials in inhabited environment (ceramics, bricks) and model calculations using environmental data as input. (orig.)

  17. Physiological effects in aromatherapy

    OpenAIRE

    2004-01-01

    The effects of aromas on humans are divided into physiological and psychological effects. The physiological effect acts directly on the physical organism, the psychological effect acts via the sense of smell or olfactory system, which in turn may cause a physiological effect. This paper reviews on the physiological effects which are used for the evaluation of the effects of aromas. Physiological parameters, i.e. heart rate blood pressure, electrodermal activity, electroencephalogram, slow pot...

  18. Anti-aggregation-based spectrometric detection of Hg(II) at physiological pH using gold nanorods.

    Science.gov (United States)

    Rajeshwari, A; Karthiga, D; Chandrasekaran, Natarajan; Mukherjee, Amitava

    2016-10-01

    An efficient detection method for Hg (II) ions at physiological pH (pH7.4) was developed using tween 20-modified gold nanorods (NRs) in the presence of dithiothreitol (DTT). Thiol groups (-SH) at the end of DTT have a higher affinity towards gold atoms, and they can covalently interact with gold NRs and leads to their aggregation. The addition of Hg(II) ions prevents the aggregation of gold NRs due to the covalent bond formation between the -SH group of DTT and Hg(II) ions in the buffer system. The changes in the longitudinal surface plasmon resonance peak of gold NRs were characterized using a UV-visible spectrophotometer. The absorption intensity peak of gold NRs at 679nm was observed to reduce after interaction with DTT, and the absorption intensity was noted to increase by increasing the concentration of Hg(II) ions. The TEM analysis confirms the morphological changes of gold NRs before and after addition of Hg(II) ions in the presence of DTT. Further, the aggregation and disaggregation of gold NRs were confirmed by particle size and zeta potential analysis. The developed method shows an excellent linearity (y=0.001x+0.794) for the graph plotted between the absorption ratio and Hg(II) concentration (1 to 100pM) under the optimized conditions. The limit of detection was noted to be 0.42pM in the buffer system. The developed method was tested in simulated body fluid, and it was found to have a good recovery rate. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Ventilation onset prior to umbilical cord clamping (physiological-based cord clamping) improves systemic and cerebral oxygenation in preterm lambs.

    Science.gov (United States)

    Polglase, Graeme R; Dawson, Jennifer A; Kluckow, Martin; Gill, Andrew W; Davis, Peter G; Te Pas, Arjan B; Crossley, Kelly J; McDougall, Annie; Wallace, Euan M; Hooper, Stuart B

    2015-01-01

    As measurement of arterial oxygen saturation (SpO2) is common in the delivery room, target SpO2 ranges allow clinicians to titrate oxygen therapy for preterm infants in order to achieve saturation levels similar to those seen in normal term infants in the first minutes of life. However, the influence of the onset of ventilation and the timing of cord clamping on systemic and cerebral oxygenation is not known. We investigated whether the initiation of ventilation, prior to, or after umbilical cord clamping, altered systemic and cerebral oxygenation in preterm lambs. Systemic and cerebral blood-flows, pressures and peripheral SpO2 and regional cerebral tissue oxygenation (SctO2) were measured continuously in apnoeic preterm lambs (126±1 day gestation). Positive pressure ventilation was initiated either 1) prior to umbilical cord clamping, or 2) after umbilical cord clamping. Lambs were monitored intensively prior to intervention, and for 10 minutes following umbilical cord clamping. Clamping the umbilical cord prior to ventilation resulted in a rapid decrease in SpO2 and SctO2, and an increase in arterial pressure, cerebral blood flow and cerebral oxygen extraction. Ventilation restored oxygenation and haemodynamics by 5-6 minutes. No such disturbances in peripheral or cerebral oxygenation and haemodynamics were observed when ventilation was initiated prior to cord clamping. The establishment of ventilation prior to umbilical cord clamping facilitated a smooth transition to systemic and cerebral oxygenation following birth. SpO2 nomograms may need to be re-evaluated to reflect physiological management of preterm infants in the delivery room.

  20. Ventilation onset prior to umbilical cord clamping (physiological-based cord clamping improves systemic and cerebral oxygenation in preterm lambs.

    Directory of Open Access Journals (Sweden)

    Graeme R Polglase

    Full Text Available As measurement of arterial oxygen saturation (SpO2 is common in the delivery room, target SpO2 ranges allow clinicians to titrate oxygen therapy for preterm infants in order to achieve saturation levels similar to those seen in normal term infants in the first minutes of life. However, the influence of the onset of ventilation and the timing of cord clamping on systemic and cerebral oxygenation is not known.We investigated whether the initiation of ventilation, prior to, or after umbilical cord clamping, altered systemic and cerebral oxygenation in preterm lambs.Systemic and cerebral blood-flows, pressures and peripheral SpO2 and regional cerebral tissue oxygenation (SctO2 were measured continuously in apnoeic preterm lambs (126±1 day gestation. Positive pressure ventilation was initiated either 1 prior to umbilical cord clamping, or 2 after umbilical cord clamping. Lambs were monitored intensively prior to intervention, and for 10 minutes following umbilical cord clamping.Clamping the umbilical cord prior to ventilation resulted in a rapid decrease in SpO2 and SctO2, and an increase in arterial pressure, cerebral blood flow and cerebral oxygen extraction. Ventilation restored oxygenation and haemodynamics by 5-6 minutes. No such disturbances in peripheral or cerebral oxygenation and haemodynamics were observed when ventilation was initiated prior to cord clamping.The establishment of ventilation prior to umbilical cord clamping facilitated a smooth transition to systemic and cerebral oxygenation following birth. SpO2 nomograms may need to be re-evaluated to reflect physiological management of preterm infants in the delivery room.

  1. Perspective: Does Laboratory-Based Maximal Incremental Exercise Testing Elicit Maximum Physiological Responses in Highly-Trained Athletes with Cervical Spinal Cord Injury?

    Science.gov (United States)

    West, Christopher R; Leicht, Christof A; Goosey-Tolfrey, Victoria L; Romer, Lee M

    2015-01-01

    The physiological assessment of highly-trained athletes is a cornerstone of many scientific support programs. In the present article, we provide original data followed by our perspective on the topic of laboratory-based incremental exercise testing in elite athletes with cervical spinal cord injury. We retrospectively reviewed our data on Great Britain Wheelchair Rugby athletes collected during the last two Paralympic cycles. We extracted and compared peak cardiometabolic (heart rate and blood lactate) responses between a standard laboratory-based incremental exercise test on a treadmill and two different maximal field tests (4 min and 40 min maximal push). In the nine athletes studied, both field tests elicited higher peak responses than the laboratory-based test. The present data imply that laboratory-based incremental protocols preclude the attainment of true peak cardiometabolic responses. This may be due to the different locomotor patterns required to sustain wheelchair propulsion during treadmill exercise or that maximal incremental treadmill protocols only require individuals to exercise at or near maximal exhaustion for a relatively short period of time. We acknowledge that both field- and laboratory-based testing have respective merits and pitfalls and suggest that the choice of test be dictated by the question at hand: if true peak responses are required then field-based testing is warranted, whereas laboratory-based testing may be more appropriate for obtaining cardiometabolic responses across a range of standardized exercise intensities.

  2. Perspective: Does laboratory-based maximal incremental exercise testing elicit maximum physiological responses in highly-trained athletes with cervical spinal cord injury?

    Directory of Open Access Journals (Sweden)

    Christopher R West

    2016-01-01

    Full Text Available The physiological assessment of highly-trained athletes is a cornerstone of many scientific support programs. In the present article, we provide original data followed by our perspective on the topic of laboratory-based incremental exercise testing in elite athletes with cervical spinal cord injury. We retrospectively reviewed our data on Great Britain Wheelchair Rugby athletes collected during the last two Paralympic cycles. We extracted and compared peak cardiometabolic (heart rate and blood lactate responses between a standard laboratory-based incremental exercise test on a treadmill and two different maximal field tests (4 min and 40 min maximal push. In the nine athletes studied, both field tests elicited higher peak responses than the laboratory-based test. The present data imply that laboratory-based incremental protocols preclude the attainment of true peak cardiometabolic responses. This may be due to the different locomotor patterns required to sustain wheelchair propulsion during treadmill exercise or that maximal incremental treadmill protocols only require individuals to exercise at or near maximal exhaustion for a relatively short period of time. We acknowledge that both field- and laboratory-based testing have respective merits and pitfalls and suggest that the choice of test be dictated by the question at hand: if true peak responses are required then field-based testing is warranted, whereas laboratory-based testing may be more appropriate for obtaining cardiometabolic responses across a range of standardised exercise intensities.

  3. Effects of aqueous and dietary preexposure and resulting body burden on silver biokinetics in the green mussel Perma viridis.

    Science.gov (United States)

    Shi, Dalin; Blackmore, Graham; Wang, Wen-Xiong

    2003-03-01

    To determine whether preexposure of green mussel Perna viridis to Ag influenced metal uptake kinetics we compared various physiological indicators of metal uptake kinetics between the control mussels and mussels preexposed to Ag in both diet and water at different levels (up to 5 weeks). In all preexposed mussels, the assimilation of Ag increased by 1.1-3.0 times with increasing Ag body concentration (0.651-19.3 microg g(-1)) as compared with the controls (Ag body concentration of 0.311-0.479 microg g(-1)), whereas the efflux rate constants decreased by 45-88%. There was no significant increase in Ag associated with the metallothionein-like protein (MTLP) fraction following exposure of the mussels to Ag through either the dissolved or food phase. The clearance rates were little affected or depressed byAg preexposure, and the relationship between the Ag influx rate from the dissolved phase and the Ag preexposure was somewhat complicated. The influx rate decreased with increasing Ag body burden at <2.5 microg g(-1), above which it increased with increasing Ag body burden. Our results indicate that the mussels may modify physiological processes to ambient chronic Ag exposure, consequently accumulating more Ag. Ag body concentration in these mussels may therefore increase disproportionally in response to increasing Ag concentration in the ambient environments. Ag preexposure and resulting body burden should be considered carefully when interpreting the observed Ag concentration in biomonitoring animals to evaluate the Ag pollution in seawater.

  4. Toxic Effects of Ethyl Cinnamate on the Photosynthesis and Physiological Characteristics of Chlorella vulgaris Based on Chlorophyll Fluorescence and Flow Cytometry Analysis.

    Science.gov (United States)

    Jiao, Yang; Ouyang, Hui-Ling; Jiang, Yu-Jiao; Kong, Xiang-Zhen; He, Wei; Liu, Wen-Xiu; Yang, Bin; Xu, Fu-Liu

    2015-01-01

    The toxic effects of ethyl cinnamate on the photosynthetic and physiological characteristics of Chlorella vulgaris were studied based on chlorophyll fluorescence and flow cytometry analysis. Parameters, including biomass, F(v)/F(m) (maximal photochemical efficiency of PSII), Ф(PSII) (actual photochemical efficiency of PSII in the light), FDA, and PI staining fluorescence, were measured. The results showed the following: (1) The inhibition on biomass increased as the exposure concentration increased. 1 mg/L ethyl cinnamate was sufficient to reduce the total biomass of C. vulgaris. The 48-h and 72-h EC50 values were 2.07 mg/L (1.94-2.20) and 1.89 mg/L (1.82-1.97). (2) After 24 h of exposure to 2-4 mg/L ethyl cinnamate, the photosynthesis of C. vulgaris almost ceased, manifesting in Ф(PSII) being close to zero. After 72 h of exposure to 4 mg/L ethyl cinnamate, the Fv /Fm of C. vulgaris dropped to zero. (3) Ethyl cinnamate also affected the cellular physiology of C. vulgaris, but these effects resulted in the inhibition of cell yield rather than cell death. Exposure to ethyl cinnamate resulted in decreased esterase activities in C. vulgaris, increased average cell size, and altered intensities of chlorophyll a fluorescence. Overall, esterase activity was the most sensitive variable.

  5. Toxic Effects of Ethyl Cinnamate on the Photosynthesis and Physiological Characteristics of Chlorella vulgaris Based on Chlorophyll Fluorescence and Flow Cytometry Analysis

    Directory of Open Access Journals (Sweden)

    Yang Jiao

    2015-01-01

    Full Text Available The toxic effects of ethyl cinnamate on the photosynthetic and physiological characteristics of Chlorella vulgaris were studied based on chlorophyll fluorescence and flow cytometry analysis. Parameters, including biomass, Fv/Fm (maximal photochemical efficiency of PSII, ФPSII (actual photochemical efficiency of PSII in the light, FDA, and PI staining fluorescence, were measured. The results showed the following: (1 The inhibition on biomass increased as the exposure concentration increased. 1 mg/L ethyl cinnamate was sufficient to reduce the total biomass of C. vulgaris. The 48-h and 72-h EC50 values were 2.07 mg/L (1.94–2.20 and 1.89 mg/L (1.82–1.97. (2 After 24 h of exposure to 2–4 mg/L ethyl cinnamate, the photosynthesis of C. vulgaris almost ceased, manifesting in ФPSII being close to zero. After 72 h of exposure to 4 mg/L ethyl cinnamate, the Fv/Fm of C. vulgaris dropped to zero. (3 Ethyl cinnamate also affected the cellular physiology of C. vulgaris, but these effects resulted in the inhibition of cell yield rather than cell death. Exposure to ethyl cinnamate resulted in decreased esterase activities in C. vulgaris, increased average cell size, and altered intensities of chlorophyll a fluorescence. Overall, esterase activity was the most sensitive variable.

  6. 基于LabVIEW的人体生理参数采集系统设计%Design of LabVIEW-based acquisition system for human physiological parameters

    Institute of Scientific and Technical Information of China (English)

    张凌飞; 王圣禹; 郑黄敏; 王雪梅

    2014-01-01

    In order to enable people to understand their own physiological parameters in time,a human physiological pa-rameter acquisition system based on virtual instrument was designed. The method to compile system software with LabVIEW, the system hardware composed of sensor,alignment circuit and data acquisition card as well as the method to display the temper-ature,pulse wave and heart rate on the PC screen are described in this paper briefly. Experimental results shows that this sys-tem achieves good effect.%为了使人们能更加及时地了解自己的一些生理参数,设计了一种基于虚拟仪器的人体生理参数采集系统。在此简单叙述了利用LabVIEW编写系统软件,由传感器、调理电路和数据采集卡构成系统硬件,并将采集到体温、脉搏波和心率显示在PC机上的原理和方法。通过实践,系统达到了较好的效果。

  7. Effects of dietary nitrate supplementation on symptoms of acute mountain sickness and basic physiological responses in a group of male adolescents during ascent to Mount Everest Base Camp.

    Science.gov (United States)

    Hennis, Philip J; Mitchell, Kay; Gilbert-Kawai, Edward; Bountziouka, Vassiliki; Wade, Angie; Feelisch, Martin; Grocott, Michael P; Martin, Daniel S

    2016-11-30

    The purpose of this study was to investigate the effects of dietary nitrate supplementation, in the form of beetroot juice, on acute mountain sickness (AMS) symptoms and physiological responses, in a group of young males trekking to Mount Everest Base Camp (EBC). Forty healthy male students (mean age (SD): 16 (1) yrs) trekked to EBC over 11 days. Following an overnight fast, each morning participants completed the Lake Louise AMS questionnaire and underwent a series of physiological tests: resting blood pressure as well as resting and exercising heart rate, respiratory rate, and peripheral oxygen saturation. The exercise test consisted of a standardised 2-min stepping protocol and measurements were taken in the last 10 s. Participants in the intervention arm of the study consumed 140 ml of concentrated beetroot juice daily, containing approximately 10 mmol of nitrate, while those in the control arm consumed 140 ml of concentrated blackcurrant cordial with negligible nitrate content. Drinks were taken for the first seven days at high altitude (days 2-8), in two equal doses; one with breakfast, and one with the evening meal. Mixed modelling revealed no significant between-groups difference in the incidence of AMS (Odds Ratio - nitrate vs.

  8. Inversion analysis of estimating interannual variability and its uncertainties in biotic and abiotic parameters of a parsimonious physiologically based model after wind disturbance

    Science.gov (United States)

    Toda, M.; Yokozawa, M.; Richardson, A. D.; Kohyama, T.

    2011-12-01

    The effects of wind disturbance on interannual variability in ecosystem CO2 exchange have been assessed in two forests in northern Japan, i.e., a young, even-aged, monocultured, deciduous forest and an uneven-aged mixed forest of evergreen and deciduous trees, including some over 200 years old using eddy covariance (EC) measurements during 2004-2008. The EC measurements have indicated that photosynthetic recovery of trees after a huge typhoon occurred during early September in 2004 activated annual carbon uptake of both forests due to changes in physiological response of tree leaves during their growth stages. However, little have been resolved about what biotic and abiotic factors regulated interannual variability in heat, water and carbon exchange between an atmosphere and forests. In recent years, an inverse modeling analysis has been utilized as a powerful tool to estimate biotic and abiotic parameters that might affect heat, water and CO2 exchange between the atmosphere and forest of a parsimonious physiologically based model. We conducted the Bayesian inverse model analysis for the model with the EC measurements. The preliminary result showed that the above model-derived NEE values were consistent with observed ones on the hourly basis with optimized parameters by Baysian inversion. In the presentation, we would examine interannual variability in biotic and abiotic parameters related to heat, water and carbon exchange between the atmosphere and forests after disturbance by typhoon.

  9. The use of team-based, guided inquiry learning to overcome educational disadvantages in learning human physiology: a structural equation model.

    Science.gov (United States)

    Rathner, Joseph A; Byrne, Graeme

    2014-09-01

    The study of human bioscience is viewed as a crucial curriculum in allied health. Nevertheless, bioscience (and particularly physiology) is notoriously difficult for undergraduates, particularly academically disadvantaged students. So endemic are the high failure rates (particularly in nursing) that it has come to be known as "the human bioscience problem." In the present report, we describe the outcomes for individual success in studying first-year human physiology in a subject that emphasises team-based active learning as the major pedagogy for mastering subject learning outcomes. Structural equation modeling was used to develop a model of the impact team learning had on individual performance. Modeling was consistent with the idea that students with similar academic abilities (as determined by tertiary entrance rank) were advantaged (scored higher on individual assessment items) by working in strong teams (teams that scored higher in team-based assessments). Analysis of covariance revealed that students who studied the subject with active learning as the major mode of learning activities outperformed students who studied the subject using the traditional didactic teaching format (lectures and tutorials, P = 0.000). After adjustment for tertiary entrance rank (via analysis of covariance) on two individual tests (the final exam and a late-semester in-class test), individual student grades improved by 8% (95% confidence interval: 6-10%) and 12% (95% confidence interval: 10-14%) when students engaged in team-based active learning. These data quantitatively support the notion that weaker students working in strong teams can overcome their educational disadvantages.

  10. Recent technological advances in sound-based approaches to tinnitus treatment: a review of efficacy considered against putative physiological mechanisms.

    Science.gov (United States)

    Hoare, Derek J; Adjamian, Peyman; Sereda, Magdalena; Hall, Deborah A

    2013-01-01

    The past decade has seen an escalating enthusiasm to comprehend chronic tinnitus from the perspective of both scientific understanding and clinical management. At the same time, there is a significant interest and commercial investment in providing targeted and individualized approaches to care, which incorporate novel sound-based technologies, with standard audiological and psychological strategies. Commercially produced sound-based devices for the tinnitus market include Co-ordinated Reset Neuromodulation ® , Neuromonics © , Serenade ® , and Widex ® Zen. Additionally, experimental interventions such as those based on frequency-discrimination training are of current interest. Many of these interventions overtly claim to target the underlying neurological causes of tinnitus. Here, we briefly summarize current perspectives on the pathophysiology of tinnitus and evaluate claims made by the device supporters from a critical point of view. We provide an opinion on how future research in the field of individualized sound-based interventions might best provide a reliable evidence-base in this growing area of translational medicine.

  11. Recent technological advances in sound-based approaches to tinnitus treatment: A review of efficacy considered against putative physiological mechanisms

    Directory of Open Access Journals (Sweden)

    Derek J Hoare

    2013-01-01

    Full Text Available The past decade has seen an escalating enthusiasm to comprehend chronic tinnitus from the perspective of both scientific understanding and clinical management. At the same time, there is a significant interest and commercial investment in providing targeted and individualized approaches to care, which incorporate novel sound-based technologies, with standard audiological and psychological strategies. Commercially produced sound-based devices for the tinnitus market include Co-ordinated Reset Neuromodulation ® , Neuromonics © , Serenade ® , and Widex ® Zen. Additionally, experimental interventions such as those based on frequency-discrimination training are of current interest. Many of these interventions overtly claim to target the underlying neurological causes of tinnitus. Here, we briefly summarize current perspectives on the pathophysiology of tinnitus and evaluate claims made by the device supporters from a critical point of view. We provide an opinion on how future research in the field of individualized sound-based interventions might best provide a reliable evidence-base in this growing area of translational medicine.

  12. Physiology of bile secretion

    Institute of Scientific and Technical Information of China (English)

    Alejandro Esteller

    2008-01-01

    The formation of bile depends on the structural and functional integrity of the bile-secretory apparatus and its impairment,in different situations,results in the syndrome of cholestasis.The structural bases that permit bile secretion as well as various aspects related with its composition