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Sample records for human physiologically based

  1. [Human physiology: kidney].

    PubMed

    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.

  2. Complexity analysis of human physiological signals based on case studies

    NASA Astrophysics Data System (ADS)

    Angelova, Maia; Holloway, Philip; Ellis, Jason

    2015-04-01

    This work focuses on methods for investigation of physiological time series based on complexity analysis. It is a part of a wider programme to determine non-invasive markers for healthy ageing. We consider two case studies investigated with actigraphy: (a) sleep and alternations with insomnia, and (b) ageing effects on mobility patterns. We illustrate, using these case studies, the application of fractal analysis to the investigation of regulation patterns and control, and change of physiological function. In the first case study, fractal analysis techniques were implemented to study the correlations present in sleep actigraphy for individuals suffering from acute insomnia in comparison with healthy controls. The aim was to investigate if complexity analysis can detect the onset of adverse health-related events. The subjects with acute insomnia displayed significantly higher levels of complexity, possibly a result of too much activity in the underlying regulatory systems. The second case study considered mobility patterns during night time and their variations with age. It showed that complexity metrics can identify change in physiological function with ageing. Both studies demonstrated that complexity analysis can be used to investigate markers of health, disease and healthy ageing.

  3. PHYSIOLOGICALLY BASED PHARMACOKINETIC MODEL FOR HUMAN EXPOSURES TO METHYL TERTIARY-BUTYL ETHER

    EPA Science Inventory

    Humans can be exposed by inhalation, ingestion, or dermal absorption to methyl tertiary-butyl ether (MTBE), an oxygenated fuel additive, from contaminated water sources. The purpose of this research was to develop a physiologically based pharmacokinetic model describing in human...

  4. PHYSIOLOGICALLY BASED PHARMACOKINETIC MODEL FOR HUMAN EXPOSURES TO METHYL TERTIARY-BUTYL ETHER

    EPA Science Inventory

    Humans can be exposed by inhalation, ingestion, or dermal absorption to methyl tertiary-butyl ether (MTBE), an oxygenated fuel additive, from contaminated water sources. The purpose of this research was to develop a physiologically based pharmacokinetic model describing in human...

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

    PubMed

    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.

  6. Validation of Human Physiologically Based Pharmacokinetic Model for Vinyl Acetate Against Human Nasal Dosimetry Data

    SciTech Connect

    Hinderliter, Paul M.; Thrall, Karla D.; Corley, Rick A.; Bloemen, Louis 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 13 C1 , 13 C2 vinyl acetate via inhalation. A probe inserted into thenasopharyngeal region sampled both 13 C1 , 13 C2 vinyl acetate and the major metabolite 13 C1 , 13 C2 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.

  7. Physiologically-based pharmacokinetic (PBPK) models in human exposure assessment

    SciTech Connect

    Krishnan, K.

    1995-12-31

    The potential dose received by an individual during defined exposure situations can be determined using personal dosimeters or estimated by combining information on exposure scenarios with the environmental concentration (C.) of chemicals. With the latter approach, not only the potential dose but also the internal dose (i.e., amount of chemical that has been absorbed and available for interaction with receptors) and biologically-effective dose (i.e., amount of chemical that actually reaches the cellular sites where interaction with macromolecules occur) can be estimated if C. is provided as an input to PBPK models. These models are mathematical representations of the interrelationships among the critical determinants of the absorption, distribution, metabolism and excretion of chemicals in biota. Since the compartments in this model correspond to biologically relevant tissues or tissue groups, the amount of chemical reaching specific target organ(s) can be estimated. Further, the PBPK models permit the use of biological monitoring data such as urinary levels of metabolites, hemoglobin adduct levels, and alveolar air concentrations, to reconstruct the exposure levels and scenarios for specific subgroups of populations. These models are also useful in providing estimates of target tissue dose in humans simultaneously exposed to chemicals in various media (air, water, soil, food) by different routes (oral, dermal, inhalation). Several examples of exposure assessment for volatile organic chemicals using PBPK models for mammals will be presented, and the strategies for development of these models for other classes of chemicals highlighted.

  8. The Virtual Physiological Human

    PubMed Central

    Coveney, Peter V.; Diaz, Vanessa; Hunter, Peter; Kohl, Peter; Viceconti, Marco

    2011-01-01

    The Virtual Physiological Human is synonymous with a programme in computational biomedicine that aims to develop a framework of methods and technologies to investigate the human body as a whole. It is predicated on the transformational character of information technology, brought to bear on that most crucial of human concerns, our own health and well-being.

  9. Human physiology in space

    NASA Technical Reports Server (NTRS)

    Vernikos, J.

    1996-01-01

    The universality of gravity (1 g) in our daily lives makes it difficult to appreciate its importance in morphology and physiology. Bone and muscle support systems were created, cellular pumps developed, neurons organised and receptors and transducers of gravitational force to biologically relevant signals evolved under 1g gravity. Spaceflight provides the only microgravity environment where systematic experimentation can expand our basic understanding of gravitational physiology and perhaps provide new insights into normal physiology and disease processes. These include the surprising extent of our body's dependence on perceptual information, and understanding the effect and importance of forces generated within the body's weightbearing structures such as muscle and bones. Beyond this exciting prospect is the importance of this work towards opening the solar system for human exploration. Although both appear promising, we are only just beginning to taste what lies ahead.

  10. Human physiology in space

    NASA Technical Reports Server (NTRS)

    Vernikos, J.

    1996-01-01

    The universality of gravity (1 g) in our daily lives makes it difficult to appreciate its importance in morphology and physiology. Bone and muscle support systems were created, cellular pumps developed, neurons organised and receptors and transducers of gravitational force to biologically relevant signals evolved under 1g gravity. Spaceflight provides the only microgravity environment where systematic experimentation can expand our basic understanding of gravitational physiology and perhaps provide new insights into normal physiology and disease processes. These include the surprising extent of our body's dependence on perceptual information, and understanding the effect and importance of forces generated within the body's weightbearing structures such as muscle and bones. Beyond this exciting prospect is the importance of this work towards opening the solar system for human exploration. Although both appear promising, we are only just beginning to taste what lies ahead.

  11. Human physiology in space.

    PubMed

    Vernikos, J

    1996-12-01

    The universality of gravity (1 g) in our daily lives makes it difficult to appreciate its importance in morphology and physiology. Bone and muscle support systems were created, cellular pumps developed, neurons organised and receptors and transducers of gravitational force to biologically relevant signals evolved under 1g gravity. Spaceflight provides the only microgravity environment where systematic experimentation can expand our basic understanding of gravitational physiology and perhaps provide new insights into normal physiology and disease processes. These include the surprising extent of our body's dependence on perceptual information, and understanding the effect and importance of forces generated within the body's weightbearing structures such as muscle and bones. Beyond this exciting prospect is the importance of this work towards opening the solar system for human exploration. Although both appear promising, we are only just beginning to taste what lies ahead.

  12. Electronic Textbook in Human Physiology.

    ERIC Educational Resources Information Center

    Broering, Naomi C.; Lilienfield, Lawrence S.

    1994-01-01

    Describes the development of an electronic textbook in human physiology at the Georgetown University Medical Center Library that was designed to enhance learning and visualization through a prototype knowledge base of core instructional materials stored in digital format on Macintosh computers. The use of computers in the medical curriculum is…

  13. AN EXAMPLE OF MODEL STRUCTURE DIFFERENCES USING SENSITIVITY ANALYSES IN PHYSIOLOGICALLY BASED PHARMACOKINETIC MODELS OF TRICHLOROETHYLENE IN HUMANS

    EPA Science Inventory

    Abstract Trichloroethylene (TCE) is an industrial chemical and an environmental contaminant. TCE and its metabolites may be carcinogenic and affect human health. Physiologically based pharmacokinetic (PBPK) models that differ in compartmentalization are developed for TCE metabo...

  14. Calculation of physiological acid-base parameters in multicompartment systems with application to human blood.

    PubMed

    Wooten, E Wrenn

    2003-12-01

    A general formalism for calculating parameters describing physiological acid-base balance in single compartments is extended to multicompartment systems and demonstrated for the multicompartment example of human whole blood. Expressions for total titratable base, strong ion difference, change in total titratable base, change in strong ion difference, and change in Van Slyke standard bicarbonate are derived, giving calculated values in agreement with experimental data. The equations for multicompartment systems are found to have the same mathematical interrelationships as those for single compartments, and the relationship of the present formalism to the traditional form of the Van Slyke equation is also demonstrated. The multicompartment model brings the strong ion difference theory to the same quantitative level as the base excess method.

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

    NASA Astrophysics Data System (ADS)

    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.

  16. Screening of chemicals for human bioaccumulative potential with a physiologically based toxicokinetic model.

    PubMed

    Tonnelier, Arnaud; Coecke, Sandra; Zaldívar, José-Manuel

    2012-03-01

    Human bioaccumulative potential is an important element in the risk assessment of chemicals. Due to the high number of synthetic chemicals, there exists the need to develop prioritisation strategies. The purpose of this study was to develop a predictive tool for human bioaccumulation risk assessment that incorporates not only the chemical properties of the compounds, but also the processes that tend to decrease the concentration of the compound such as metabolisation. We used a generic physiologically based toxicokinetic model that based on in vitro human liver metabolism data, minimal renal excretion and a constant exposure was able to assess the bioaccumulative potential of a chemical. The approach has been analysed using literature data on well-known bioaccumulative compounds and liver metabolism data from the ECVAM database and a subset of the ToxCast phase I chemical library-in total 94 compounds covering pharmaceuticals, plant protection products and industrial chemicals. Our results provide further evidence that partitioning properties do not allow for a reliable screening criteria for human chemical hazard. Our model, based on a 100% intestinal absorption assumption, suggests that metabolic clearance, plasma protein-binding properties and renal excretion are the main factors in determining whether bioaccumulation will occur and its amount. It is essential that in vitro metabolic clearance tests with metabolic competent cell lines as well as plasma protein-binding assays be performed for suspected bioaccumulative compounds.

  17. Physiologically based pharmacokinetic model parameter estimation and sensitivity and variability analyses for acrylonitrile disposition in humans.

    PubMed

    Sweeney, Lisa M; Gargas, Michael L; Strother, Dale E; Kedderis, Gregory L

    2003-01-01

    A physiologically based pharmacokinetic (PBPK) model of acrylonitrile (ACN) and cyanoethylene oxide (CEO) disposition in humans was developed and is based on human in vitro data and scaling from a rat model (G. L. Kedderis et al., 1996, TOXICOL: Appl. Pharmacol.140, 422-435) for application to risk assessment. All of the major biotransformation and reactivity pathways, including metabolism of ACN to glutathione conjugates and CEO, reaction rates of ACN and CEO with glutathione and tissues, and the metabolism of CEO by hydrolysis and glutathione conjugation, were described in the human PBPK model. Model simulations indicated that predicted blood and brain ACN and CEO concentrations were similar in rats and humans exposed to ACN by inhalation. In contrast, rats consuming ACN in drinking water had higher predicted blood concentrations of ACN than humans exposed to the same concentration in water. Sensitivity and variability analyses were conducted on the model. While many parameters contributed to the estimated variability of the model predictions, the reaction rate of CEO with glutathione, hydrolysis rate for CEO, and blood:brain partition coefficient of CEO were the parameters predicted to make the greatest contributions to variability of blood and brain CEO concentrations in humans. The main contributor to predicted variance in human blood ACN concentrations in people exposed through drinking water was the Vmax for conversion of ACN to CEO. In contrast, the main contributors for variance in people exposed by inhalation were expected to be the rate of blood flow to the liver and alveolar ventilation rate, with the brain:blood partition coefficient also contributing to variability in predicted concentrations of ACN in the brain. Expected variability in blood CEO concentrations (peak or average) in humans exposed by inhalation or drinking water was modest, with a 95th-percentile individual expected to have blood concentrations 1.8-times higher than an average

  18. Physiologically Based Pharmacokinetic Model of Rifapentine and 25-Desacetyl Rifapentine Disposition in Humans.

    PubMed

    Zurlinden, Todd J; Eppers, Garrett J; Reisfeld, Brad

    2016-08-01

    Rifapentine (RPT) is a rifamycin antimycobacterial and, as part of a combination therapy, is indicated for the treatment of pulmonary tuberculosis (TB) caused by Mycobacterium tuberculosis Although the results from a number of studies indicate that rifapentine has the potential to shorten treatment duration and enhance completion rates compared to other rifamycin agents utilized in antituberculosis drug regimens (i.e., regimens 1 to 4), its optimal dose and exposure in humans are unknown. To help inform such an optimization, a physiologically based pharmacokinetic (PBPK) model was developed to predict time course, tissue-specific concentrations of RPT and its active metabolite, 25-desacetyl rifapentine (dRPT), in humans after specified administration schedules for RPT. Starting with the development and verification of a PBPK model for rats, the model was extrapolated and then tested using human pharmacokinetic data. Testing and verification of the models included comparisons of predictions to experimental data in several rat tissues and time course RPT and dRPT plasma concentrations in humans from several single- and repeated-dosing studies. Finally, the model was used to predict RPT concentrations in the lung during the intensive and continuation phases of a current recommended TB treatment regimen. Based on these results, it is anticipated that the PBPK model developed in this study will be useful in evaluating dosing regimens for RPT and for characterizing tissue-level doses that could be predictors of problems related to efficacy or safety.

  19. Physiologically Based Pharmacokinetic Model of Rifapentine and 25-Desacetyl Rifapentine Disposition in Humans

    PubMed Central

    Zurlinden, Todd J.; Eppers, Garrett J.

    2016-01-01

    Rifapentine (RPT) is a rifamycin antimycobacterial and, as part of a combination therapy, is indicated for the treatment of pulmonary tuberculosis (TB) caused by Mycobacterium tuberculosis. Although the results from a number of studies indicate that rifapentine has the potential to shorten treatment duration and enhance completion rates compared to other rifamycin agents utilized in antituberculosis drug regimens (i.e., regimens 1 to 4), its optimal dose and exposure in humans are unknown. To help inform such an optimization, a physiologically based pharmacokinetic (PBPK) model was developed to predict time course, tissue-specific concentrations of RPT and its active metabolite, 25-desacetyl rifapentine (dRPT), in humans after specified administration schedules for RPT. Starting with the development and verification of a PBPK model for rats, the model was extrapolated and then tested using human pharmacokinetic data. Testing and verification of the models included comparisons of predictions to experimental data in several rat tissues and time course RPT and dRPT plasma concentrations in humans from several single- and repeated-dosing studies. Finally, the model was used to predict RPT concentrations in the lung during the intensive and continuation phases of a current recommended TB treatment regimen. Based on these results, it is anticipated that the PBPK model developed in this study will be useful in evaluating dosing regimens for RPT and for characterizing tissue-level doses that could be predictors of problems related to efficacy or safety. PMID:27270284

  20. Simulation of monoclonal antibody pharmacokinetics in humans using a minimal physiologically based model.

    PubMed

    Li, Linzhong; Gardner, Iain; Dostalek, Miroslav; Jamei, Masoud

    2014-09-01

    Compared to small chemical molecules, monoclonal antibodies and Fc-containing derivatives (mAbs) have unique pharmacokinetic behaviour characterised by relatively poor cellular permeability, minimal renal filtration, binding to FcRn, target-mediated drug disposition, and disposition via lymph. A minimal physiologically based pharmacokinetic (PBPK) model to describe the pharmacokinetics of mAbs in humans was developed. Within the model, the body is divided into three physiological compartments; plasma, a single tissue compartment and lymph. The tissue compartment is further sub-divided into vascular, endothelial and interstitial spaces. The model simultaneously describes the levels of endogenous IgG and exogenous mAbs in each compartment and sub-compartment and, in particular, considers the competition of these two species for FcRn binding in the endothelial space. A Monte-Carlo sampling approach is used to simulate the concentrations of endogenous IgG and mAb in a human population. Existing targeted-mediated drug disposition (TMDD) models are coupled with the minimal PBPK model to provide a general platform for simulating the pharmacokinetics of therapeutic antibodies using primarily pre-clinical data inputs. The feasibility of utilising pre-clinical data to parameterise the model and to simulate the pharmacokinetics of adalimumab and an anti-ALK1 antibody (PF-03446962) in a population of individuals was investigated and results were compared to published clinical data.

  1. A physiologically based biokinetic model for cesium in the human body.

    PubMed

    Leggett, R W; Williams, L R; Melo, D R; Lipsztein, J L

    2003-12-30

    A physiologically descriptive model of the biological behavior of cesium in the human body has been constructed around a detailed blood flow model. The rate of transfer from plasma into a tissue is determined by the blood perfusion rate and the tissue-specific extraction fraction of Cs during passage from arterial to venous plasma. Information on tissue-specific extraction of Cs is supplemented with information on the Cs analogues, K and Rb, and known patterns of discrimination between these metals by tissues. The rate of return from a tissue to plasma is estimated from the relative contents of Cs in plasma and the tissue at equilibrium as estimated from environmental studies. Transfers of Cs other than exchange between plasma and tissues (e.g. secretions into the gastrointestinal tract) are based on a combination of physiological considerations and empirical data on Cs or related elements. Model predictions are consistent with the sizable database on the time-dependent distribution and retention of radiocesium in the human body.

  2. Physiologically based pharmacokinetic modeling of ethyl acetate and ethanol in rodents and humans.

    PubMed

    Crowell, S R; Smith, J N; Creim, J A; Faber, W; Teeguarden, J G

    2015-10-01

    A physiologically based pharmacokinetic (PBPK) model was developed and applied to a metabolic series approach for the ethyl series (i.e., ethyl acetate, ethanol, acetaldehyde, and acetate). This approach bases toxicity information on dosimetry analyses for metabolically linked compounds using pharmacokinetic data for each compound and toxicity data for parent or individual compounds. In vivo pharmacokinetic studies of ethyl acetate and ethanol were conducted in rats following IV and inhalation exposure. Regardless of route, ethyl acetate was rapidly converted to ethanol. Blood concentrations of ethyl acetate and ethanol following both IV bolus and infusion suggested linear kinetics across blood concentrations from 0.1 to 10 mM ethyl acetate and 0.01-0.8 mM ethanol. Metabolic parameters were optimized and evaluated based on available pharmacokinetic data. The respiratory bioavailability of ethyl acetate and ethanol were estimated from closed chamber inhalation studies and measured ventilation rates. The resulting ethyl series model successfully reproduces blood ethyl acetate and ethanol kinetics following IV administration and inhalation exposure in rats, and blood ethanol kinetics following inhalation exposure to ethanol in humans. The extrapolated human model was used to derive human equivalent concentrations for the occupational setting of 257-2120 ppm ethyl acetate and 72-517 ppm ethyl acetate for continuous exposure, corresponding to rat LOAELs of 350 and 1500 ppm. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. A physiologically-based pharmacokinetic (PBPK) model of squalene-containing adjuvant in human vaccines.

    PubMed

    Tegenge, Million A; Mitkus, Robert J

    2013-10-01

    Squalene is used in the oil phase of certain emulsion vaccine adjuvants, but its fate as a vaccine component following intramuscular (IM) injection in humans is unknown. In this study, we constructed a physiologically-based pharmacokinetic (PBPK) model for intramuscularly injected squalene-in-water (SQ/W) emulsion, in order to make a quantitative estimation of the tissue distribution of squalene following a single IM injection in humans. The PBPK model incorporates relevant physicochemical properties of squalene; estimates of the time course of cracking of a SQ/W emulsion; anatomical and physiological parameters at the injection site and beyond; and local, preferential lymphatic transport. The model predicts that a single dose of SQ/W emulsion will be removed from human deltoid muscle within six days following IM injection. The major proportion of the injected squalene will be distributed to draining lymph nodes and adipose tissues. The model indicates slow decay from the latter compartment most likely due to partitioning into neutral lipids and a low rate of squalene biotransformation there. Parallel pharmacokinetic modeling for mouse muscle suggests that the kinetics of SQ/W emulsion correspond to the immunodynamic time course of a commercial squalene-containing adjuvant reported in that species. In conclusion, this study makes important pharmacokinetic predictions of the fate of a squalene-containing emulsion in humans. The results of this study may be relevant for understanding the immunodynamics of this new class of vaccine adjuvants and may be useful in future quantitative risk analyses that incorporate mode-of-action data.

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

    SciTech Connect

    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.

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed Central

    Abaci, Hasan Erbil; Shuler, Michael L.

    2015-01-01

    Advances in maintaining multiple human tissues on microfluidic platforms has led to a growing interest in developing microphysiological systems for drug development studies. Determining 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 model (PD) -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 current PBPK modeling-based drug discovery to provide a conceptual model. We propose two types of platforms that can be involved in different stages of PBPK modeling and drug development; these are a μOrgans-on-a-chip and a μHuman-on-a-chip. Then we establish 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 on 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 designing microphysiological platforms for PBPK/PD based drug discovery. PMID:25739725

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

    PubMed

    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. Copyright © 2013 IPEM. Published by Elsevier Ltd. All rights reserved.

  9. A physiologically based model for temporal envelope encoding in human primary auditory cortex.

    PubMed

    Dugué, Pierre; Le Bouquin-Jeannès, Régine; Edeline, Jean-Marc; Faucon, Gérard

    2010-09-01

    Communication sounds exhibit temporal envelope fluctuations in the low frequency range (<70 Hz) and human speech has prominent 2-16 Hz modulations with a maximum at 3-4 Hz. Here, we propose a new phenomenological model of the human auditory pathway (from cochlea to primary auditory cortex) to simulate responses to amplitude-modulated white noise. To validate the model, performance was estimated by quantifying temporal modulation transfer functions (TMTFs). Previous models considered either the lower stages of the auditory system (up to the inferior colliculus) or only the thalamocortical loop. The present model, divided in two stages, is based on anatomical and physiological findings and includes the entire auditory pathway. The first stage, from the outer ear to the colliculus, incorporates inhibitory interneurons in the cochlear nucleus to increase performance at high stimuli levels. The second stage takes into account the anatomical connections of the thalamocortical system and includes the fast and slow excitatory and inhibitory currents. After optimizing the parameters of the model to reproduce the diversity of TMTFs obtained from human subjects, a patient-specific model was derived and the parameters were optimized to effectively reproduce both spontaneous activity and the oscillatory part of the evoked response.

  10. Physiologically based pharmacokinetic modeling of deltamethrin: Development of a rat and human diffusion-limited model

    EPA Science Inventory

    Mirfazaelian et al. (2006) developed a physiologically based pharmacokinetic (PBPK) model for the pyrethroid pesticide deltamethrin in the rat. This model describes gastrointestinal tract absorption as a saturable process mediated by phase III efflux transporters which pump delta...

  11. Physiologically based pharmacokinetic modeling of deltamethrin: Development of a rat and human diffusion-limited model

    EPA Science Inventory

    Mirfazaelian et al. (2006) developed a physiologically based pharmacokinetic (PBPK) model for the pyrethroid pesticide deltamethrin in the rat. This model describes gastrointestinal tract absorption as a saturable process mediated by phase III efflux transporters which pump delta...

  12. Development of a Physiologically Based Pharmacokinetic Model for Triadimefon and Triadimenol in Rats and Humans

    EPA Science Inventory

    A physiologically based pharmacokinetic (PBPK) model was developed for the conazole fungicide triadimefon and its primary metabolite, triadimenol. Rat tissue:blood partition coefficients and metabolic constants were measured in vitro for both compounds. Kinetic time course data...

  13. Development of a Physiologically Based Pharmacokinetic Model for Triadimefon and Triadimenol in Rats and Humans

    EPA Science Inventory

    A physiologically based pharmacokinetic (PBPK) model was developed for the conazole fungicide triadimefon and its primary metabolite, triadimenol. Rat tissue:blood partition coefficients and metabolic constants were measured in vitro for both compounds. Kinetic time course data...

  14. A physiologically based assessment of human exposure to radon released from groundwater.

    PubMed

    Yu, Donghan; Kim, Jin Kyu

    2004-02-01

    Most of the indoor radon comes directly from the soil beneath the foundation of a basement. Recently, radon from groundwater was found to make some contribution to the total inhalation risk associated with radon in indoor air. This study presents a realistic exposure assessment of a human to indoor radon released from groundwater. First, the prediction of indoor radon concentration released from groundwater was based on a three-compartment model that was developed to describe the transfer and distribution of the radon released from groundwater in a house through showers, washing clothes, and flushing toilets. Second, a physiologically based pharmacokinetic (PBPK) model for inhaled radon was developed and used to estimate tissue group concentrations in a human body. The PBPK model provides reasonable predictions of uptake, excretion, and distribution of retained radon among tissue groups in the body. Hence, the approach using the PBPK model combined with realistic indoor exposure scenarios predicts the radon concentrations in tissue groups in the body associated with the indoor radon pollution. The results obtained from the study will help increase the quantitative understanding of the risk assessment issues associated with the indoor radon released from the groundwater.

  15. Development and application of a multiroute physiologically based pharmacokinetic model for oxytetracycline in dogs and humans.

    PubMed

    Lin, Zhoumeng; Li, Mengjie; Gehring, Ronette; Riviere, Jim E

    2015-01-01

    Oxytetracycline (OTC) is a commonly used tetracycline antibiotic in veterinary and human medicine. To establish a quantitative model for predicting OTC plasma and tissue exposure, a permeability-limited multiroute physiologically based pharmacokinetic model was developed in dogs. The model was calibrated with plasma pharmacokinetic data in beagle dogs following single intravenous (5 mg/kg), oral (100 mg/kg), and intramuscular (20 mg/kg) administrations. The model predicted other available dog data well, including drug concentrations in the liver, kidney, and muscle after repeated exposure, and data in the mixed-breed dog. The model was extrapolated to humans and the human model adequately simulated measured plasma OTC concentrations after intravenous (7.14 mg/kg) and oral exposures (6.67 mg/kg). The dog model was applied to predict 24-h OTC area-under-the-curve after three therapeutic treatments. Results were 27.75, 51.76, and 64.17 μg/mL*h in the plasma, and 120.93, 225.64, and 279.67 μg/mL*h in the kidney for oral (100 mg/kg), intravenous (10 mg/kg), and intramuscular (20 mg/kg) administrations, respectively. This model can be used to predict plasma and tissue concentrations to aid in designing optimal therapeutic regimens with OTC in veterinary, and potentially, human medicine; and as a foundation for scaling to other tetracycline antibiotics and to other animal species. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:233-243, 2015. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

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

    NASA Astrophysics Data System (ADS)

    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.

  17. Development of a physiologically based pharmacokinetic (PBPK) model for methyl iodide in rats, rabbits, and humans.

    PubMed

    Sweeney, Lisa M; Kirman, Christopher R; Gannon, Shawn A; Thrall, Karla D; Gargas, Michael L; Kinzell, John H

    2009-05-01

    Methyl iodide (MeI) has been proposed as an alternative to methyl bromide as a pre-plant soil fumigant that does not deplete stratospheric ozone. In inhalation toxicity studies performed in animals as part of the registration process, three effects have been identified that warrant consideration in developing toxicity reference values for human risk assessment: nasal lesions (rat), acute neurotoxicity (rat), and fetal loss (rabbit). Uncertainties in the risk assessment can be reduced by using an internal measure of target tissue dose that is linked to the likely mode of action (MOA) for the toxicity of MeI, rather than the external exposure concentration. Physiologically based pharmacokinetic (PBPK) models have been developed for MeI and used to reduce uncertainties in the risk assessment extrapolations (e.g. interspecies, high to low dose, exposure scenario). PBPK model-derived human equivalent concentrations comparable to the animal study NOAELs (no observed adverse effect levels) for the endpoints of interest were developed for a 1-day, 24-hr exposure of bystanders or 8 hr/day exposure of workers. Variability analyses of the PBPK models support application of uncertainty factors (UF) of approximately 2 for intrahuman pharmacokinetic variability for the nasal effects and acute neurotoxicity.

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

    SciTech Connect

    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.

  19. A physiology based inverse dynamic analysis of human gait: potential and perspectives.

    PubMed

    De Groote, F; Pipeleers, G; Jonkers, I; Demeulenaere, B; Patten, C; Swevers, J; De Schutter, J

    2009-10-01

    One approach to compute the musculotendon forces that underlie human motion is to combine an inverse dynamic analysis with a static optimisation procedure. Although computationally efficient, this classical inverse approach fails to incorporate constraints imposed by muscle physiology. The present paper reports on a physiological inverse approach (PIA) that combines an inverse dynamic analysis with a dynamic optimisation procedure. This allows the incorporation of a full description of muscle activation and contraction dynamics, without loss of computational efficiency. A comparison of muscle excitations and MT-forces predicted by the classical and the PIA is presented for normal and pathological gait. Inclusion of muscle physiology primarily affects the rate of active muscle force build-up and decay and allows the estimation of passive muscle force. Consequently, it influences the onset and cessation of the predicted muscle excitations as well as the level of co-contraction.

  20. A physiologically based model for ethanol and acetaldehyde metabolism in human beings.

    PubMed

    Umulis, David M; Gürmen, Nihat M; Singh, Prashant; Fogler, H Scott

    2005-01-01

    Pharmacokinetic models for ethanol metabolism have contributed to the understanding of ethanol clearance in human beings. However, these models fail to account for ethanol's toxic metabolite, acetaldehyde. Acetaldehyde accumulation leads to signs and symptoms, such as cardiac arrhythmias, nausea, anxiety, and facial flushing. Nevertheless, it is difficult to determine the levels of acetaldehyde in the blood or other tissues because of artifactual formation and other technical issues. Therefore, we have constructed a promising physiologically based pharmacokinetic (PBPK) model, which is an excellent match for existing ethanol and acetaldehyde concentration-time data. The model consists of five compartments that exchange material: stomach, gastrointestinal tract, liver, central fluid, and muscle. All compartments except the liver are modeled as stirred reactors. The liver is modeled as a tubular flow reactor. We derived average enzymatic rate laws for alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH), determined kinetic parameters from the literature, and found best-fit parameters by minimizing the squared error between our profiles and the experimental data. The model's transient output correlates strongly with the experimentally observed results for healthy individuals and for those with reduced ALDH activity caused by a genetic deficiency of the primary acetaldehyde-metabolizing enzyme ALDH2. Furthermore, the model shows that the reverse reaction of acetaldehyde back into ethanol is essential and keeps acetaldehyde levels approximately 10-fold lower than if the reaction were irreversible.

  1. Melatonin: Physiological effects in humans.

    PubMed

    Claustrat, B; Leston, J

    2015-01-01

    Melatonin is a methoxyindole synthesized and secreted principally by the pineal gland at night under normal light/dark conditions. The endogenous rhythm of secretion is generated by the suprachiasmatic nuclei and entrained to the light/dark cycle. Light is able to either suppress or synchronize melatonin production according to the light schedule. The nycthohemeral rhythm of this hormone can be evaluated by repeated measurement of plasma or saliva melatonin or urine sulfatoxymelatonin, the main hepatic metabolite. The primary physiological function of melatonin, whose secretion adjusts to night length, is to convey information concerning the daily cycle of light and darkness to body structures. This information is used for the organisation of functions, which respond to changes in the photoperiod such as the seasonal rhythms. Seasonal rhythmicity of physiological functions in humans related to possible alteration of the melatonin message remains, however, of limited evidence in temperate areas under field conditions. Also, the daily melatonin secretion, which is a very robust biochemical signal of night, can be used for the organisation of circadian rhythms. Although functions of this hormone in humans are mainly based on correlations between clinical observations and melatonin secretion, there is some evidence that melatonin stabilises and strengthens coupling of circadian rhythms, especially of core temperature and sleep-wake rhythms. The circadian organisation of other physiological functions depend also on the melatonin signal, for instance immune, antioxidant defences, haemostasis and glucose regulation. The difference between physiological and pharmacological effects of melatonin is not always clear but is based upon consideration of dose and not of duration of the hormone message. It is admitted that a "physiological" dose provides plasma melatonin levels in the same order of magnitude as a nocturnal peak. Since the regulating system of melatonin secretion

  2. Assessing prebaccalaureate human physiology courses.

    PubMed

    McCleary, V L

    1998-12-01

    Two surveys were conducted between 1994 and 1996. The purpose of the initial survey was to obtain demographic information about prebaccaulareate human physiology courses. Of the 117 responding physiology departments, 50% offered human physiology at the prebaccalaureate level to 14,185 students during the 1994-1995 academic year. The mean was 245 students per year (+/- 30 SE). Class size was limited by 44% of the respondents. Prebaccaluareate human physiology was offered as a separate course from anatomy by 93% of the departments. Sixty-one percent scheduled the course once a year. The purpose of the second survey was to determine how physiology departments evaluated prebaccalaureate physiology courses and faculty. All responding departments utilized student feedback; 38% of the departments included physiology chair review, 38% peer review, and 9% allied health faculty review. Twenty-eight percent of allied health programs evaluated the course. Results indicated that, whereas a significant number of undergraduate students are enrolled in prebaccaluareate physiology courses annually, those courses appear to lack formal, consistent formative evaluation.

  3. Physiologically Based Simulations of Deuterated Glucose for Quantifying Cell Turnover in Humans

    PubMed Central

    Lahoz-Beneytez, Julio; Schaller, Stephan; Macallan, Derek; Eissing, Thomas; Niederalt, Christoph; Asquith, Becca

    2017-01-01

    In vivo [6,6-2H2]-glucose labeling is a state-of-the-art technique for quantifying cell proliferation and cell disappearance in humans. However, there are discrepancies between estimates of T cell proliferation reported in short (1-day) versus long (7-day) 2H2-glucose studies and very-long (9-week) 2H2O studies. It has been suggested that these discrepancies arise from underestimation of true glucose exposure from intermittent blood sampling in the 1-day study. Label availability in glucose studies is normally approximated by a “square pulse” (Sq pulse). Since the body glucose pool is small and turns over rapidly, the availability of labeled glucose can be subject to large fluctuations and the Sq pulse approximation may be very inaccurate. Here, we model the pharmacokinetics of exogenous labeled glucose using a physiologically based pharmacokinetic (PBPK) model to assess the impact of a more complete description of label availability as a function of time on estimates of CD4+ and CD8+ T cell proliferation and disappearance. The model enabled us to predict the exposure to labeled glucose during the fasting and de-labeling phases, to capture the fluctuations of labeled glucose availability caused by the intake of food or high-glucose beverages, and to recalculate the proliferation and death rates of immune cells. The PBPK model was used to reanalyze experimental data from three previously published studies using different labeling protocols. Although using the PBPK enrichment profile decreased the 1-day proliferation estimates by about 4 and 7% for CD4 and CD8+ T cells, respectively, differences with the 7-day and 9-week studies remained significant. We conclude that the approximations underlying the “square pulse” approach—recently suggested as the most plausible hypothesis—only explain a component of the discrepancy in published T cell proliferation rate estimates. PMID:28487698

  4. Human physiologically based pharmacokinetic model for ACE inhibitors: ramipril and ramiprilat

    PubMed Central

    Levitt, David G; Schoemaker, Rik C

    2006-01-01

    Background The angiotensin-converting enzyme (ACE) inhibitors have complicated and poorly characterized pharmacokinetics. There are two binding sites per ACE (high affinity "C", lower affinity "N") that have sub-nanomolar affinities and dissociation rates of hours. Most inhibitors are given orally in a prodrug form that is systemically converted to the active form. This paper describes the first human physiologically based pharmacokinetic (PBPK) model of this drug class. Methods The model was applied to the experimental data of van Griensven et. al for the pharmacokinetics of ramiprilat and its prodrug ramipril. It describes the time course of the inhibition of the N and C ACE sites in plasma and the different tissues. The model includes: 1) two independent ACE binding sites; 2) non-equilibrium time dependent binding; 3) liver and kidney ramipril intracellular uptake, conversion to ramiprilat and extrusion from the cell; 4) intestinal ramipril absorption. The experimental in vitro ramiprilat/ACE binding kinetics at 4°C and 300 mM NaCl were assumed for most of the PBPK calculations. The model was incorporated into the freely distributed PBPK program PKQuest. Results The PBPK model provides an accurate description of the individual variation of the plasma ramipril and ramiprilat and the ramiprilat renal clearance following IV ramiprilat and IV and oral ramipril. Summary of model features: Less than 2% of total body ACE is in plasma; 35% of the oral dose is absorbed; 75% of the ramipril metabolism is hepatic and 25% of this is converted to systemic ramiprilat; 100% of renal ramipril metabolism is converted to systemic ramiprilat. The inhibition was long lasting, with 80% of the C site and 33% of the N site inhibited 24 hours following a 2.5 mg oral ramipril dose. The plasma ACE inhibition determined by the standard assay is significantly less than the true in vivo inhibition because of assay dilution. Conclusion If the in vitro plasma binding kinetics of the ACE

  5. Evaluation of an integrated in vitro-in silico PBPK (physiologically based pharmacokinetic) model to provide estimates of human bioavailability.

    PubMed

    Cai, Hongliang; Stoner, Chad; Reddy, Anita; Freiwald, Sascha; Smith, Danielle; Winters, Roger; Stankovic, Charles; Surendran, Narayanan

    2006-02-03

    PK express module is a physiologically based model of first pass metabolism, which integrates in vitro data with an in silico physiologically based pharmacokinetic (PBPK) model to predict human bioavailability (F(H)). There are three required inputs: FDp (Fraction dose absorbed, final parameter from iDEA absorption module), protein binding (fu) and disappearance kinetics in human hepatocytes. Caco-2 permeability, aqueous solubility (at multiple pH's), estimated dose and chemical structure are inputs required for the estimation of FDp (Norris et al., 2000; Stoner et al., 2004) and were determined for all compounds in our laboratory or obtained from literature. Protein binding data was collected from literature references and/or Pfizer database. Human hepatocyte data was generated in-house using an automated human hepatocyte method (using Tecan Genesis Workstation) as described previously (). Sixteen compounds (commercial and Pfizer compounds) were chosen to evaluate the PK express model and the bioavailability predicted from the module was compared with known clinical endpoints. For majority of the 16 compounds (approximately 80%), the PK express model F(H) values were comparable to the known human bioavailability (F(H)) (within 23.7 units of the known human (true) F, except for PF 3, PF 4, PF 6). In conclusion, the PK express model integrates a number of key readily available discovery parameters and provides estimates of human performance by integrating in silico and experimental variables built on a physiological based pharmacokinetic model. Information from this model in conjunction with other ADME data (e.g., P450 inhibition) will enable progression of most promising compounds for further in vivo PK and/or efficacy studies.

  6. Human plasma concentrations of cytochrome P450 probes extrapolated from pharmacokinetics in cynomolgus monkeys using physiologically based pharmacokinetic modeling.

    PubMed

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed Central

    Carter, Kirtigandha Salwe; Carter III, Robert

    2016-01-01

    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

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

    PubMed

    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

  10. Physiologically based pharmacokinetic modeling of fetal and neonatal manganese exposure in humans: describing manganese homeostasis during development.

    PubMed

    Yoon, Miyoung; Schroeter, Jeffry D; Nong, Andy; Taylor, Michael D; Dorman, David C; Andersen, Melvin E; Clewell, Harvey J

    2011-08-01

    Concerns for potential vulnerability to manganese (Mn) neurotoxicity during fetal and neonatal development have been raised due to increased needs for Mn for normal growth, different sources of exposure to Mn, and pharmacokinetic differences between the young and adults. A physiologically based pharmacokinetic (PBPK) model for Mn during human gestation and lactation was developed to predict Mn in fetal and neonatal brain using a parallelogram approach based upon extrapolation across life stages in rats and cross-species extrapolation to humans. Based on the rodent modeling, key physiological processes controlling Mn kinetics during gestation and lactation were incorporated, including alterations in Mn uptake, excretion, tissue-specific distributions, and placental and lactational transfer of Mn. Parameters for Mn kinetics were estimated based on human Mn data for milk, placenta, and fetal/neonatal tissues, along with allometric scaling from the human adult model. The model was evaluated by comparison with published Mn levels in cord blood, milk, and infant blood. Maternal Mn homeostasis during pregnancy and lactation, placenta and milk Mn, and fetal/neonatal tissue Mn were simulated for normal dietary intake and with inhalation exposure to environmental Mn. Model predictions indicate similar or lower internal exposures to Mn in the brains of fetus/neonate compared with the adult at or above typical environmental air Mn concentrations. This PBPK approach can assess expected Mn tissue concentration during early life and compares contributions of different Mn sources, such as breast or cow milk, formula, food, drinking water, and inhalation, with tissue concentration.

  11. Human Body (Physiology), K-6.

    ERIC Educational Resources Information Center

    Bethlehem Area Schools, PA.

    The physiology of the human body is one of eight subject areas covered in the K-6 Science Program of the Bethlehem Area School District. This manual is a teacher's guide to activities for each grade level. "Awareness of Senses" is treated in Kindergarten, "Body Growth and Development" in grade 1, "The Senses and Their…

  12. Physiologically based pharmacokinetic modeling of hydrogen cyanide levels in human breath.

    PubMed

    Stamyr, Kristin; Mörk, Anna-Karin; Johanson, Gunnar

    2015-08-01

    Hydrogen cyanide (HCN) is a potent and fast-acting toxin increasingly recognized as an important cause of death in fire victims. Prompt diagnosis and treatment of cyanide poisoning are essential to avoid fatalities. Unfortunately, there are at present few rapid diagnostic methods. A noninvasive methodology would be to use HCN in exhaled air as a marker for systemic exposure. To explore this possibility, we developed a preliminary physiologically based pharmacokinetic model. The model suggests that breath HCN levels following inhalation exposure at near-lethal and lethal conditions are 0.1-1 ppm, i.e., one to two orders of magnitude higher than the background breath level of about 0.01 ppm in unexposed subjects. Hence, our results imply that breath analysis may be used as a rapid diagnostic method for cyanide poisoning.

  13. The bioaccessibility of soil-based mercury as determined by physiological based extraction tests and human biomonitoring in children.

    PubMed

    Safruk, Adam M; Berger, Robert G; Jackson, Blair J; Pinsent, Celine; Hair, Alan T; Sigal, Elliot A

    2015-06-15

    Environmental contaminants associated with soil particles are generally less bioavailable than contaminants associated with other exposure media where chemicals are often found in more soluble forms. In vitro methods, such as Physiological Based Extraction Tests (PBET), can provide estimates of bioaccessibility for soil-based contaminants. The results of these tests can be used to predict exposure to contaminants from soil ingestion pathways within human health risk assessment (HHRA). In the current investigation, an HHRA was conducted to examine the risks associated with elevated concentrations of mercury in soils in the northern Canadian smelter community of Flin Flon, Manitoba. A PBET was completed for residential soils and indicated mean bioaccessibilities of 1.2% and 3.0% for total mercury using gastric phase and gastric+intestinal phase methodologies, respectively. However, as many regulators only allow for the consideration of in vitro results for lead and arsenic in the HHRA process, in vitro bioaccessibility results for mercury were not utilized in the current HHRA. Based on the need to assume 100% bioaccessibility for inorganic mercury in soil, results from the HHRA indicated the need for further assessment of exposure and risk. A biomonitoring study was undertaken for children between 2 and 15 years of age in the community to examine urinary inorganic mercury concentrations. Overall, 375 children provided valid urine samples for analysis. Approximately 50% of urine samples had concentrations of urinary inorganic mercury below the limit of detection (0.1 μg/L), with an average creatinine adjusted concentration of 0.11 μg/g. Despite high variability in mercury soil concentrations within sub-communities, soil concentrations did not appear to influence urinary mercury concentrations. The results of the current investigation indicate that mercury bioaccessibility in residential soils in the Flin Flon area was likely limited and that HHRA estimates would

  14. Home-based vs. laboratory-based practical activities in the learning of human physiology: the perception of students.

    PubMed

    Neves, Ben-Hur S; Altermann, Caroline; Gonçalves, Rithiele; Lara, Marcus Vinícius; Mello-Carpes, Pâmela B

    2017-03-01

    Different tools have been used to facilitate the teaching and learning process in different areas of knowledge. Practical activities represent a form of teaching in which students not only listen to theoretical concepts but are also able to link theory and practice, and their importance in the biological sciences is notable. Sometimes, however, there is neither the time nor the resources to promote laboratory practices in physiology classes. In this sense, home-based practical activities may be an interesting alternative. Here, different approaches of practical activities were used and students' perceptions of the contributions of home-based practical activities (HBPA) and laboratory-based practical activities (LBPA) for physiology learning were collected. After each approach, the students evaluated the activities through an anonymous questionnaire. A total of 49 students completed the questionnaires, and the results demonstrate that both HBPA and LBPA were considered important contributors to physiology learning but that this contribution was more significant in the case of LBPA (χ(2) = 4.356, P = 0.037). Copyright © 2017 the American Physiological Society.

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

    PubMed

    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.

  16. Application of physiologically based pharmacokinetic modeling in the prediction of pharmacokinetics of bicyclol controlled-release formulation in human.

    PubMed

    Wang, Baolian; Liu, Zhihao; Li, Dan; Yang, Shuang; Hu, Jinping; Chen, Hui; Sheng, Li; Li, Yan

    2015-09-18

    Physiologically based pharmacokinetic (PBPK) modeling can assist in formulation development. Bicyclol is a novel anti-hepatitis drug. A bilayer osmotic pump table of bicyclol is being developed. PBPK models for bicyclol immediate-release (IR) and controlled-release (CR) tablets in beagle dog, as well as PBPK model for IR tablets in human were constructed. These models incorporated physicochemical properties and in vitro preclinical data. Parameter sensitivity analysis was performed for the effects of solubility and dissolution on pharmacokinetic (PK) parameters. Models were refined by comparing simulated results to experimental measurements. Furthermore, the clinical PK for bicyclol CR tablets was predicted using the in vivo dissolution profile by deconvolution of the mean PK profile of CR tablets in dogs. In summary, the present study described a strategy employing PBPK models to evaluate the effects of formulation factors on PK profiles and predict the performance of bicyclol CR tablets in human. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Development of a Physiologically Based Model to Describe the Pharmacokinetics of Methylphenidate in Juvenile and Adult Humans and Nonhuman Primates

    PubMed Central

    Yang, Xiaoxia; Morris, Suzanne M.; Gearhart, Jeffery M.; Ruark, Christopher D.; Paule, Merle G.; Slikker, William; Mattison, Donald R.; Vitiello, Benedetto; Twaddle, Nathan C.; Doerge, Daniel R.; Young, John F.; Fisher, Jeffrey W.

    2014-01-01

    The widespread usage of methylphenidate (MPH) in the pediatric population has received considerable attention due to its potential effect on child development. For the first time a physiologically based pharmacokinetic (PBPK) model has been developed in juvenile and adult humans and nonhuman primates to quantitatively evaluate species- and age-dependent enantiomer specific pharmacokinetics of MPH and its primary metabolite ritalinic acid. The PBPK model was first calibrated in adult humans using in vitro enzyme kinetic data of MPH enantiomers, together with plasma and urine pharmacokinetic data with MPH in adult humans. Metabolism of MPH in the small intestine was assumed to account for the low oral bioavailability of MPH. Due to lack of information, model development for children and juvenile and adult nonhuman primates primarily relied on intra- and interspecies extrapolation using allometric scaling. The juvenile monkeys appear to metabolize MPH more rapidly than adult monkeys and humans, both adults and children. Model prediction performance is comparable between juvenile monkeys and children, with average root mean squared error values of 4.1 and 2.1, providing scientific basis for interspecies extrapolation of toxicity findings. Model estimated human equivalent doses in children that achieve similar internal dose metrics to those associated with pubertal delays in juvenile monkeys were found to be close to the therapeutic doses of MPH used in pediatric patients. This computational analysis suggests that continued pharmacovigilance assessment is prudent for the safe use of MPH. PMID:25184666

  18. Development of a Human Physiologically Based Pharmacokinetics (PBPK) Model For Dermal Permeability for Lindane

    EPA Science Inventory

    Lindane is a neurotoxicant used for the treatment of lice and scabies present on human skin. Due to its pharmaceutical application, an extensive pharmacokinetic database exists in humans. Mathematical diffusion models allow for calculation of lindane skin permeability coefficient...

  19. Development of a Human Physiologically Based Pharmacokinetics (PBPK) Model For Dermal Permeability for Lindane

    EPA Science Inventory

    Lindane is a neurotoxicant used for the treatment of lice and scabies present on human skin. Due to its pharmaceutical application, an extensive pharmacokinetic database exists in humans. Mathematical diffusion models allow for calculation of lindane skin permeability coefficient...

  20. Use of Physiologically Based Biokinetic (PBBK) Modeling to Study Estragole Bioactivation and Detoxification in Humans as Compared with Male Rats

    PubMed Central

    Punt, Ans; Paini, Alicia; Boersma, Marelle G.; Freidig, Andreas P.; Delatour, Thierry; Scholz, Gabriele; Schilter, Benoît; van Bladeren, Peter J.; Rietjens, Ivonne M. C. M.

    2009-01-01

    The extent of bioactivation of the herbal constituent estragole to its ultimate carcinogenic metabolite 1′-sulfooxyestragole depends on the relative levels of bioactivation and detoxification pathways. The present study investigated the kinetics of the metabolic reactions of both estragole and its proximate carcinogenic metabolite 1′-hydroxyestragole in humans in incubations with relevant tissue fractions. Based on the kinetic data obtained a physiologically based biokinetic (PBBK) model for estragole in human was defined to predict the relative extent of bioactivation and detoxification at different dose levels of estragole. The outcomes of the model were subsequently compared with those previously predicted by a PBBK model for estragole in male rat to evaluate the occurrence of species differences in metabolic activation. The results obtained reveal that formation of 1′-oxoestragole, which represents a minor metabolic route for 1′-hydroxyestragole in rat, is the main detoxification pathway of 1′-hydroxyestragole in humans. Due to a high level of this 1′-hydroxyestragole oxidation pathway in human liver, the predicted species differences in formation of 1′-sulfooxyestragole remain relatively low, with the predicted formation of 1′-sulfooxyestragole being twofold higher in human compared with male rat, even though the formation of its precursor 1′-hydroxyestragole was predicted to be fourfold higher in human. Overall, it is concluded that in spite of significant differences in the relative extent of different metabolic pathways between human and male rat there is a minor influence of species differences on the ultimate overall bioactivation of estragole to 1′-sulfooxyestragole. PMID:19447879

  1. Human plasma concentrations of herbicidal carbamate molinate extrapolated from the pharmacokinetics established in in vivo experiments with chimeric mice with humanized liver and physiologically based pharmacokinetic modeling.

    PubMed

    Yamashita, Masanao; Suemizu, Hiroshi; Murayama, Norie; Nishiyama, Sayako; Shimizu, Makiko; Yamazaki, Hiroshi

    2014-10-01

    To predict concentrations in humans of the herbicidal carbamate molinate, used exclusively in rice cultivation, a forward dosimetry approach was carried out using data from lowest-observed-adverse-effect-level doses orally administered to rats, wild type mice, and chimeric mice with humanized liver and from in vitro human and rodent experiments. Human liver microsomes preferentially mediated hydroxylation of molinate, but rat livers additionally produced molinate sulfoxide and an unidentified metabolite. Adjusted animal biomonitoring equivalents for molinate and its primary sulfoxide from animal studies were scaled to human biomonitoring equivalents using known species allometric scaling factors and human metabolic data with a simple physiologically based pharmacokinetic (PBPK) model. The slower disposition of molinate and accumulation of molinate sulfoxide in humans were estimated by modeling after single and multiple doses compared with elimination in rodents. The results from simplified PBPK modeling in combination with chimeric mice with humanized liver suggest that ratios of estimated parameters of molinate sulfoxide exposure in humans to those in rats were three times as many as general safety factor of 10 for species difference in toxicokinetics. Thus, careful regulatory decision is needed when evaluating the human risk resulting from exposure to low doses of molinate and related carbamates based on data obtained from rats.

  2. A Physiologically Based Pharmacokinetic Model for the Oxime TMB-4: Simulation of Rodent and Human Data

    DTIC Science & Technology

    2013-01-13

    blood, urine and tissue kinetics in non-human primates would allow some insight into the magnitude of species differences in tissue/blood PCs...parameters in laboratory animals and humans. Pharm Res 10:1093–1095 de Miranda P, Feitknecht UF, Gibbon SL, Burrows GE, Way JL (1972) Urinary metabolite of 1

  3. Quantitative Evaluation of Dichloroacetic Acid Kinetics in Human -- A Physiologically-Based Pharmacokinetic Modeling Investigation

    DTIC Science & Technology

    2008-01-01

    use include mild liver dysfunction, transient central neuropathy , peripheral neuropathy and hypocalcemia. The clinical effects are generally...metabolite of trichloroethylene. DCA liver carcinogenicity has been demonstrated in rodents but epidemiological evidence in humans is not available. High...probable minor metabolite of trichloroethylene. DCA liver carcinogenicity has been demonstrated in rodents but epidemiological evidence in humans is not

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

    SciTech Connect

    Al-Subeihi, Ala' A.A.; Spenkelink, Bert; Punt, Ans; Boersma, Marelle G.; Bladeren, Peter J. van; Rietjens, Ivonne M.C.M.

    2012-05-01

    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 current model were compared with those of a previously developed PBK model for methyleugenol (ME) in male rat. The results obtained reveal that formation of 1′-hydroxymethyleugenol glucuronide (1′HMEG), a major metabolic pathway in male rat liver, appears to represent a minor metabolic pathway in human liver whereas in human liver a significantly higher formation of 1′-oxomethyleugenol (1′OME) compared with male rat liver is observed. Furthermore, formation of 1′-sulfooxymethyleugenol (1′HMES), which readily undergoes desulfonation to a reactive carbonium ion (CA) that can form DNA or protein adducts (DA), is predicted to be the same in the liver of both human and male rat at oral doses of 0.0034 and 300 mg/kg bw. Altogether despite a significant difference in especially the metabolic pathways of the proximate carcinogenic metabolite 1′-hydroxymethyleugenol (1′HME) between human and male rat, the influence of species differences on the ultimate overall bioactivation of methyleugenol (ME) to 1′-sulfooxymethyleugenol (1′HMES) appears to be negligible. Moreover, the PBK model predicted the formation of 1′-sulfooxymethyleugenol (1′HMES) in the liver of human and rat to be linear from doses as high as the benchmark dose (BMD{sub 10}) down to as low as the virtual safe dose (VSD). This study shows that kinetic data do not provide a reason to argue against linear extrapolation from the rat tumor data to the human situation. -- Highlights: ► A PBK model is made for bioactivation and detoxification of methyleugenol in human. ► Comparison to the PBK model in male rat revealed species differences. ► PBK results support linear extrapolation from high to low

  5. Development of a Physiologically Based Pharmacokinetic Model for Triadimefon and its Metabolite Triandimenol in Rats and Humans

    EPA Science Inventory

    physiologically based pharmacokinetic (PBPK) model was developed for the conazole fungicide triadimefon and its primary metabolite, triadimenol. Rat tissue:blood partition coefficients and metabolic constants were measured in vitro for both compounds. Pharmacokinetic data for par...

  6. Physiological cross-sectional area of human leg muscles based on magnetic resonance imaging

    NASA Technical Reports Server (NTRS)

    Fukunaga, T.; Roy, R. R.; Shellock, F. G.; Hodgson, J. A.; Day, M. K.; Lee, P. L.; Kwong-Fu, H.; Edgerton, V. R.

    1992-01-01

    Magnetic resonance imaging techniques were used to determine the physiological cross-sectional areas (PCSAs) of the major muscles or muscle groups of the lower leg. For 12 healthy subjects, the boundaries of each muscle or muscle group were digitized from images taken at 1-cm intervals along the length of the leg. Muscle volumes were calculated from the summation of each anatomical CSA (ACSA) and the distance between each section. Muscle length was determined as the distance between the most proximal and distal images in which the muscle was visible. The PCSA of each muscle was calculated as muscle volume times the cosine of the angle of fiber pinnation divided by fiber length, where published fiber length:muscle length ratios were used to estimate fiber lengths. The mean volumes of the major plantarflexors were 489, 245, and 140 cm3 for the soleus and medial (MG) and lateral (LG) heads of the gastrocnemius. The mean PCSA of the soleus was 230 cm2, about three and eight times larger than the MG (68 cm2) and LG (28 cm2), respectively. These PCSA values were eight (soleus), four (MG), and three (LG) times larger than their respective maximum ACSA. The major dorsiflexor, the tibialis anterior (TA), had a muscle volume of 143 cm2, a PCSA of 19 cm2, and an ACSA of 9 cm2. With the exception of the soleus, the mean fiber length of all subjects was closely related to muscle volume across muscles. The soleus fibers were unusually short relative to the muscle volume, thus potentiating its force potential.(ABSTRACT TRUNCATED AT 250 WORDS).

  7. Physiological cross-sectional area of human leg muscles based on magnetic resonance imaging

    NASA Technical Reports Server (NTRS)

    Fukunaga, T.; Roy, R. R.; Shellock, F. G.; Hodgson, J. A.; Day, M. K.; Lee, P. L.; Kwong-Fu, H.; Edgerton, V. R.

    1992-01-01

    Magnetic resonance imaging techniques were used to determine the physiological cross-sectional areas (PCSAs) of the major muscles or muscle groups of the lower leg. For 12 healthy subjects, the boundaries of each muscle or muscle group were digitized from images taken at 1-cm intervals along the length of the leg. Muscle volumes were calculated from the summation of each anatomical CSA (ACSA) and the distance between each section. Muscle length was determined as the distance between the most proximal and distal images in which the muscle was visible. The PCSA of each muscle was calculated as muscle volume times the cosine of the angle of fiber pinnation divided by fiber length, where published fiber length:muscle length ratios were used to estimate fiber lengths. The mean volumes of the major plantarflexors were 489, 245, and 140 cm3 for the soleus and medial (MG) and lateral (LG) heads of the gastrocnemius. The mean PCSA of the soleus was 230 cm2, about three and eight times larger than the MG (68 cm2) and LG (28 cm2), respectively. These PCSA values were eight (soleus), four (MG), and three (LG) times larger than their respective maximum ACSA. The major dorsiflexor, the tibialis anterior (TA), had a muscle volume of 143 cm2, a PCSA of 19 cm2, and an ACSA of 9 cm2. With the exception of the soleus, the mean fiber length of all subjects was closely related to muscle volume across muscles. The soleus fibers were unusually short relative to the muscle volume, thus potentiating its force potential.(ABSTRACT TRUNCATED AT 250 WORDS).

  8. Evolutionary Medicine: The Ongoing Evolution of Human Physiology and Metabolism.

    PubMed

    Rühli, Frank; van Schaik, Katherine; Henneberg, Maciej

    2016-11-01

    The field of evolutionary medicine uses evolutionary principles to understand changes in human anatomy and physiology that have occurred over time in response to environmental changes. Through this evolutionary-based approach, we can understand disease as a consequence of anatomical and physiological "trade-offs" that develop to facilitate survival and reproduction. We demonstrate how diachronic study of human anatomy and physiology is fundamental for an increased understanding of human health and disease.

  9. A physiologically based pharmacokinetic (PBPK) model for methyl mercury (MeHg) in monkey and human

    SciTech Connect

    Gearhart, J.M.; Clewall, H.J. III; Shipp, A.M.

    1995-12-31

    A PBPK model for MeHg was developed which coherently describes MeHg pharmacokinetics in the adult rat, monkey and man, and predicts fetal levels of MeHg from in utero exposure. The model includes a description of enterohepatic recirculation of MeHg, conversion to inorganic mercury in tissues and intestinal flora, slowly reversible incorporation of mercury in tissues, and excretion of both organic and inorganic mercury into urine, feces, and hair. The adult submodel includes compartments representing the red blood tells (RBC), plasma, brain, liver, kidney, gut intestinal lumen, gut tissue, hair, richly and slowly perfused tissues, and placenta. The fetal submodel includes compartments representing RBC`s, plasma, brain, and remaining body mass. Two features of the model structure which are critical to prediction of the kinetics of MeHg in different species is the use of separate RBC and plasma compartments, allowing the use of species specific RBC/plasma ratios, and biliary excretion with enterohepatic recirculation. Published tissue and blood MeHg concentrations were used to derive the partition coefficients and RBC/plasma ratios to adjust for species differences in MeHg distribution. Validation involved comparing the model simulations with data from repeated dosing studies in animals and humans, and from accidental human exposures. The model will be used to investigate maternal MeHg intake as it relates to measured blood and hair MeHg concentrations, and to fetal exposure.

  10. [Heat exchange between human body and environment (theoretical bases of physiological measurement and evaluation)].

    PubMed

    Pezzagno, G

    1999-01-01

    In the first part of this report the theory of the heat exchange between human body and external environment is developed. In particular, the problems concerning energy expenditure and heat production [metabolic heat] during physical activity, the heat exchange between internal organs and body surface, and its elimination are considered. Proposal of heat exchange equations (in case of conduction, convection, evaporation, radiation transport) are made, and the involved parameters and constants are indicated. Some pages are devoted to heat exchange through the lung and to "perspiratio insensibilis". In the second part the problems concerning the wellbeing and the thermal discomfort are discussed. A description of some widely employed indices of thermal stress, strain and comfort concludes the report [P4SR index, HSI index, ITS index, TTL index, HR index, WBGT index, TE indices]. In the end, the Fanger equations of thermal comfort are presented and discussed.

  11. A DYNAMIC PHYSIOLOGICALLY-BASED TOXICOKINETIC (DPBTK) MODEL FOR SIMULATION OF COMPLEX TOLUENE EXPOSURE SCENARIOS IN HUMANS

    EPA Science Inventory

    A GENERAL PHYSIOLOGICAL AND TOXICOKINETIC (GPAT) MODEL FOR SIMULATION OF COMPLEX TOLUENE EXPOSURE SCENARIOS IN HUMANS. E M Kenyon1, T Colemen2, C R Eklund1 and V A Benignus3. 1U.S. EPA, ORD, NHEERL, ETD, PKB, RTP, NC, USA; 2Biological Simulators, Inc., Jackson MS, USA, 3U.S. EP...

  12. A DYNAMIC PHYSIOLOGICALLY-BASED TOXICOKINETIC (DPBTK) MODEL FOR SIMULATION OF COMPLEX TOLUENE EXPOSURE SCENARIOS IN HUMANS

    EPA Science Inventory

    A GENERAL PHYSIOLOGICAL AND TOXICOKINETIC (GPAT) MODEL FOR SIMULATION OF COMPLEX TOLUENE EXPOSURE SCENARIOS IN HUMANS. E M Kenyon1, T Colemen2, C R Eklund1 and V A Benignus3. 1U.S. EPA, ORD, NHEERL, ETD, PKB, RTP, NC, USA; 2Biological Simulators, Inc., Jackson MS, USA, 3U.S. EP...

  13. Derivation of human Biomonitoring Guidance Values for chlorpyrifos using a physiologically based pharmacokinetic and pharmacodynamic model of cholinesterase inhibition.

    PubMed

    Arnold, Scott M; Morriss, Alistair; Velovitch, Joseph; Juberg, Daland; Burns, Carol J; Bartels, Michael; Aggarwal, Manoj; Poet, Torka; Hays, Sean; Price, Paul

    2015-03-01

    A number of biomonitoring surveys have been performed for chlorpyrifos (CPF) and its metabolite (3,5,6-trichloro-2-pyridinol, TCPy); however, there is no available guidance on how to interpret these data in a health risk assessment context. To address this gap, Biomonitoring Guidance Values (BGVs) are developed using a physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model. The PBPK/PD model is used to predict the impact of age and human variability on the relationship between an early marker of cholinesterase (ChE) inhibition in the peripheral and central nervous systems [10% red blood cell (RBC) ChE inhibition] and levels of systemic biomarkers. Since the PBPK/PD model characterizes variation of sensitivity to CPF in humans, interspecies and intraspecies uncertainty factors are not needed. Derived BGVs represent the concentration of blood CPF and urinary TCPy associated with 95% of the population having less than or equal to 10% RBC ChE inhibition. Blood BGV values for CPF in adults and infants are 6100 ng/L and 4200 ng/L, respectively. Urinary TCPy BGVs for adults and infants are 2100 μg/L and 520 μg/L, respectively. The reported biomonitoring data are more than 150-fold lower than the BGVs suggesting that current US population exposures to CPF are well below levels associated with any adverse health effect. Copyright © 2015. Published by Elsevier Inc.

  14. Physiologically based modeling of the pharmacokinetics of acetaminophen and its major metabolites in humans using a Bayesian population approach.

    PubMed

    Zurlinden, Todd J; Reisfeld, Brad

    2016-06-01

    The principal aim of this study was to develop, validate, and demonstrate a physiologically based pharmacokinetic (PBPK) model to predict and characterize the absorption, distribution, metabolism, and excretion of acetaminophen (APAP) in humans. A PBPK model was created that included pharmacologically and toxicologically relevant tissue compartments and incorporated mechanistic descriptions of the absorption and metabolism of APAP, such as gastric emptying time, cofactor kinetics, and transporter-mediated movement of conjugated metabolites in the liver. Through the use of a hierarchical Bayesian framework, unknown model parameters were estimated using a large training set of data from human pharmacokinetic studies, resulting in parameter distributions that account for data uncertainty and inter-study variability. Predictions from the model showed good agreement to a diverse test set of data across several measures, including plasma concentrations over time, renal clearance, APAP absorption, and pharmacokinetic and exposure metrics. The utility of the model was then demonstrated through predictions of cofactor depletion, dose response of several pharmacokinetic endpoints, and the relationship between APAP biomarker levels in the plasma and those in the liver. The model addressed several limitations in previous PBPK models for APAP, and it is anticipated that it will be useful in predicting the pharmacokinetics of APAP in a number of contexts, such as extrapolating across doses, estimating internal concentrations, quantifying population variability, assessing possible impacts of drug coadministration, and, when coupled with a suitable pharmacodynamic model, predicting toxicity.

  15. A first-generation physiologically based pharmacokinetic (PBPK) model of alpha-tocopherol in human influenza vaccine adjuvant.

    PubMed

    Tegenge, Million A; Mitkus, Robert J

    2015-04-01

    Alpha (α)-tocopherol is a component of a new generation of squalene-containing oil-in-water (SQ/W) emulsion adjuvants that have been licensed for use in certain influenza vaccines. Since regulatory pharmacokinetic studies are not routinely required for influenza vaccines, the in vivo fate of this vaccine constituent is largely unknown. In this study, we constructed a physiologically based pharmacokinetic (PBPK) model for emulsified α-tocopherol in human adults and infants. An independent sheep PBPK model was also developed to inform the local preferential lymphatic transfer and for the purpose of model evaluation. The PBPK model predicts that α-tocopherol will be removed from the injection site within 24h and rapidly transfer predominantly into draining lymph nodes. A much lower concentration of α-tocopherol was estimated to peak in plasma within 8h. Any systemically absorbed α-tocopherol was predicted to accumulate slowly in adipose tissue, but not in other tissues. Model evaluation and uncertainty analyses indicated acceptable fit, with the fraction of dose taken up into the lymphatics as most influential on plasma concentration. In summary, this study estimates the in vivo fate of α-tocopherol in adjuvanted influenza vaccine, may be relevant in explaining its immunodynamics in humans, and informs current regulatory risk-benefit analyses. Published by Elsevier Inc.

  16. Impact of human emotions on physiological characteristics

    NASA Astrophysics Data System (ADS)

    Partila, P.; Voznak, M.; Peterek, T.; Penhaker, M.; Novak, V.; Tovarek, J.; Mehic, Miralem; Vojtech, L.

    2014-05-01

    Emotional states of humans and their impact on physiological and neurological characteristics are discussed in this paper. This problem is the goal of many teams who have dealt with this topic. Nowadays, it is necessary to increase the accuracy of methods for obtaining information about correlations between emotional state and physiological changes. To be able to record these changes, we focused on two majority emotional states. Studied subjects were psychologically stimulated to neutral - calm and then to the stress state. Electrocardiography, Electroencephalography and blood pressure represented neurological and physiological samples that were collected during patient's stimulated conditions. Speech activity was recording during the patient was reading selected text. Feature extraction was calculated by speech processing operations. Classifier based on Gaussian Mixture Model was trained and tested using Mel-Frequency Cepstral Coefficients extracted from the patient's speech. All measurements were performed in a chamber with electromagnetic compatibility. The article discusses a method for determining the influence of stress emotional state on the human and his physiological and neurological changes.

  17. Virtual physiological human: training challenges.

    PubMed

    Lawford, Patricia V; Narracott, Andrew V; McCormack, Keith; Bisbal, Jesus; Martin, Carlos; Bijnens, Bart; Brook, Bindi; Zachariou, Margarita; Freixa, Jordi Villà I; Kohl, Peter; Fletcher, Katherine; Diaz-Zuccarini, Vanessa

    2010-06-28

    The virtual physiological human (VPH) initiative encompasses a wide range of activities, including structural and functional imaging, data mining, knowledge discovery tool and database development, biomedical modelling, simulation and visualization. The VPH community is developing from a multitude of relatively focused, but disparate, research endeavours into an integrated effort to bring together, develop and translate emerging technologies for application, from academia to industry and medicine. This process initially builds on the evolution of multi-disciplinary interactions and abilities, but addressing the challenges associated with the implementation of the VPH will require, in the very near future, a translation of quantitative changes into a new quality of highly trained multi-disciplinary personnel. Current strategies for undergraduate and on-the-job training may soon prove insufficient for this. The European Commission seventh framework VPH network of excellence is exploring this emerging need, and is developing a framework of novel training initiatives to address the predicted shortfall in suitably skilled VPH-aware professionals. This paper reports first steps in the implementation of a coherent VPH training portfolio.

  18. Prediction of Deoxypodophyllotoxin Disposition in Mouse, Rat, Monkey, and Dog by Physiologically Based Pharmacokinetic Model and the Extrapolation to Human

    PubMed Central

    Chen, Yang; Zhao, Kaijing; Liu, Fei; Xie, Qiushi; Zhong, Zeyu; Miao, Mingxing; Liu, Xiaodong; Liu, Li

    2016-01-01

    Deoxypodophyllotoxin (DPT) is a potential anti-tumor candidate prior to its clinical phase. The aim of the study was to develop a physiologically based pharmacokinetic (PBPK) model consisting of 13 tissue compartments to predict DPT disposition in mouse, rat, monkey, and dog based on in vitro and in silico inputs. Since large interspecies difference was found in unbound fraction of DPT in plasma, we assumed that Kt:pl,u (unbound tissue-to-plasma concentration ratio) was identical across species. The predictions of our model were then validated by in vivo data of corresponding preclinical species, along with visual predictive checks. Reasonable matches were found between observed and predicted plasma concentrations and pharmacokinetic parameters in all four animal species. The prediction in the related seven tissues of mouse was also desirable. We also attempted to predict human pharmacokinetic profile by both the developed PBPK model and interspecies allometric scaling across mouse, rat and monkey, while dog was excluded from the scaling. The two approaches reached similar results. We hope the study will help in the efficacy and safety assessment of DPT in future clinical studies and provide a reference to the preclinical screening of similar compounds by PBPK model. PMID:28018224

  19. Population Physiologically-Based Pharmacokinetic Modeling for the Human Lactational Transfer of PCB 153 with Consideration of Worldwide Human Biomonitoring Results

    SciTech Connect

    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.

  20. Development of a physiologically based kinetic model for 99m-technetium-labelled carbon nanoparticles inhaled by humans.

    PubMed

    Péry, Alexandre R R; Brochot, Céline; Hoet, Peter H M; Nemmar, Abderrahim; Bois, Frédéric Y

    2009-11-01

    Particulate air pollution is associated with respiratory and cardiovascular morbidity and mortality. Recent studies investigated whether and to which extent inhaled ultrafine particles are able to translocate into the bloodstream in humans. However, their conclusions were conflicting. We developed a physiologically based kinetic model for (99m)technetium-labelled carbon nanoparticles (Technegas). The model was designed to analyse imaging data. It includes different translocation rates and kinetics for free technetium, and small and large technetium-labelled particles. It was calibrated with data from an experiment designed to assess the fate of nanoparticles in humans after inhalation of Technegas. The data provided time courses of radioactivity in the liver, stomach, urine, and blood. Parameter estimation was performed in a Bayesian context with Markov chain Monte Carlo (MCMC) techniques. Our analysis points to a likely translocation of particle-bound technetium from lung to blood, at a rate about twofold lower than the transfer rate of free technetium. Notably, restricting the model so that only free technetium would have been able to reach blood circulation resulted in much poorer fits to the experimental data. The percentage of small particles able to translocate was estimated at 12.7% of total particles. The percentage of unbound technetium was estimated at 6.7% of total technetium. To our knowledge, our model is the first PBPK model able to use imaging data to describe the absorption and distribution of nanoparticles. We believe that our modeling approach using Bayesian and MCMC techniques provides a reasonable description on which to base further model refinement.

  1. Design Projects in Human Anatomy & Physiology

    ERIC Educational Resources Information Center

    Polizzotto, Kristin; Ortiz, Mary T.

    2008-01-01

    Very often, some type of writing assignment is required in college entry-level Human Anatomy and Physiology courses. This assignment can be anything from an essay to a research paper on the literature, focusing on a faculty-approved topic of interest to the student. As educators who teach Human Anatomy and Physiology at an urban community college,…

  2. Design Projects in Human Anatomy & Physiology

    ERIC Educational Resources Information Center

    Polizzotto, Kristin; Ortiz, Mary T.

    2008-01-01

    Very often, some type of writing assignment is required in college entry-level Human Anatomy and Physiology courses. This assignment can be anything from an essay to a research paper on the literature, focusing on a faculty-approved topic of interest to the student. As educators who teach Human Anatomy and Physiology at an urban community college,…

  3. Physiologically based pharmacokinetics of radioiodinated human beta-endorphin in rats. An application of the capillary membrane-limited model

    SciTech Connect

    Sato, H.; Sugiyama, Y.; Sawada, Y.; Iga, T.; Hanano, M.

    1987-07-01

    In order to simulate the distribution and elimination of radioiodinated human beta-endorphin (/sup 125/I-beta-EP) after iv bolus injection in rats, we proposed a physiologically based pharmacokinetic model incorporating diffusional transport of /sup 125/I-beta-EP across the capillary membrane. This model assumes that the distribution of /sup 125/I-beta-EP is restricted only within the blood and the tissue interstitial fluid, and that a diffusional barrier across the capillary membrane exists in each tissue except the liver. The tissue-to-blood partition coefficients were estimated from the ratios of the concentration in tissues to that in arterial plasma at the terminal (pseudoequilibrium) phase. The total body plasma clearance (9.0 ml/min/kg) was appropriately assigned to the liver and kidney. The transcapillary diffusion clearances of /sup 125/I-beta-EP were also estimated and shown to correlate linearly with that of inulin in several tissues. Numerically solving the mass-balance differential equations as to plasma and each tissue simultaneously, simulated concentration curves of /sup 125/I-beta-EP corresponded well with the observed data. It was suggested by the simulation that the initial rapid disappearance of /sup 125/I-beta-EP from plasma after iv injection could be attributed in part to the transcapillary diffusion of the peptide.

  4. Physiologically based pharmacokinetic modeling with dichloromethane, its metabolite, carbon monoxide, and blood carboxyhemoglobin in rats and humans.

    PubMed

    Andersen, M E; Clewell, H J; Gargas, M L; MacNaughton, M G; Reitz, R H; Nolan, R J; McKenna, M J

    1991-03-15

    Dichloromethane (methylene chloride, DCM) and other dihalomethanes are metabolized to carbon monoxide (CO) which reversibly binds hemoglobin and is eliminated by exhalation. We have developed a physiologically based pharmacokinetic (PB-PK) model which describes the kinetics of CO, carboxyhemoglobin (HbCO), and parent dihalomethane, and have applied this model to examine the inhalation kinetics of CO and of DCM in rats and humans. The portion of the model describing CO and HbCO kinetics was adapted from the Coburn-Forster-Kane equation, after modification to include production of CO by DCM oxidation. DCM kinetics and metabolism were described by a generic PB-PK model for volatile chemicals (RAMSEY AND ANDERSEN, Toxicol. Appl. Pharmacol. 73, 159-175, 1984). Physiological and biochemical constants for CO were first estimated by exposing rats to 200 ppm CO for 2 hr and examining the time course of HbCO after cessation of CO exposure. These CO inhalation studies provided estimates of CO diffusing capacity under free breathing and for the Haldane coefficient, the relative equilibrium distribution ratio for hemoglobin between CO and O2. The CO model was then coupled to a PB-PK model for DCM to predict HbCO time course behavior during and after DCM exposures in rats. By coupling the models it was possible to estimate the yield of CO from oxidation of DCM. In rats only about 0.7 mol of CO are produced from 1 mol of DCM during oxidation. The combined model adequately represented HbCO and DCM behavior following 4-hr exposures to 200 or 1000 ppm DCM, and HbCO behavior following 1/2-hr exposure to 5160 ppm DCM or 5000 ppm bromochloromethane. The rat PB-PK model was scaled to predict DCM, HbCO, and CO kinetics in humans exposed either to DCM or to CO. Three human data sets from the literature were examined: (1) inhalation of CO at 50, 100, 250, and 500 ppm; (2) seven 1/2-hr inhalation exposures to 50, 100, 250, and 500 ppm DCM; and (3) 2-hr inhalation exposures to 986 ppm DCM

  5. DEVELOPMENT OF A HUMAN PHYSIOLOGICALLY-BASED PHARMACOKINETIC (PBPK) MODEL FOR INORGANIC ARSENIC AND ITS MONO- AND DI-METHYLATED METABOLITES

    EPA Science Inventory

    A physiologically-based pharmacokinetic (PBPK) model was developed to estimate levels of arsenic and its metabolites in human tissues and urine after oral exposure to either arsenate (AsV) or arsnite (AsIII). The model consists of interconnected individual ...

  6. DEVELOPMENT OF A HUMAN PHYSIOLOGICALLY-BASED PHARMACOKINETIC (PBPK) MODEL FOR INORGANIC ARSENIC AND ITS MONO- AND DI-METHYLATED METABOLITES

    EPA Science Inventory

    A physiologically-based pharmacokinetic (PBPK) model was developed to estimate levels of arsenic and its metabolites in human tissues and urine after oral exposure to either arsenate (AsV) or arsnite (AsIII). The model consists of interconnected individual ...

  7. A Novel Physiology-Based Mathematical Model to Estimate Red Blood Cell Lifespan in Different Human Age Groups.

    PubMed

    An, Guohua; Widness, John A; Mock, Donald M; Veng-Pedersen, Peter

    2016-09-01

    Direct measurement of red blood cell (RBC) survival in humans has improved from the original accurate but limited differential agglutination technique to the current reliable, safe, and accurate biotin method. Despite this, all of these methods are time consuming and require blood sampling over several months to determine the RBC lifespan. For situations in which RBC survival information must be obtained quickly, these methods are not suitable. With the exception of adults and infants, RBC survival has not been extensively investigated in other age groups. To address this need, we developed a novel, physiology-based mathematical model that quickly estimates RBC lifespan in healthy individuals at any age. The model is based on the assumption that the total number of RBC recirculations during the lifespan of each RBC (denoted by N max) is relatively constant for all age groups. The model was initially validated using the data from our prior infant and adult biotin-labeled red blood cell studies and then extended to the other age groups. The model generated the following estimated RBC lifespans in 2-year-old, 5-year-old, 8-year-old, and 10-year-old children: 62, 74, 82, and 86 days, respectively. We speculate that this model has useful clinical applications. For example, HbA1c testing is not reliable in identifying children with diabetes because HbA1c is directly affected by RBC lifespan. Because our model can estimate RBC lifespan in children at any age, corrections to HbA1c values based on the model-generated RBC lifespan could improve diabetes diagnosis as well as therapy in children.

  8. DEVELOPMENT OF A PHYSIOLOGICALLY BASED PHARMACOKINETIC MODEL FOR ETHYLENE GLYCOL AND ITS MAJOR METABOLITE, GLYCOLIC ACID, IN RATS AND HUMANS

    SciTech Connect

    Corley, Rick A.; Bartels, M J.; Carney, E W.; Weitz, Karl K.; Soelberg, Jolen J.; Gies, Richard A.; Thrall, Karla D.

    2005-05-19

    An extensive database on the toxicity and modes of action of the major industrial chemical, ethylene glycol (EG), has been developed over the past several decades. These studies have consistently identified the kidney as a primary target organ, with rats being more sensitive than mice and males more sensitive than females following chronic exposure. Renal toxicity has been associated with the terminal metabolite, oxalic acid which can precipitate with calcium to form crystals. EG also induces developmental toxicity, although these effects appear to require high-doses or accelerated dose-rates, and have been reported only in rats and mice. The developmental toxicity of EG has been attributed to the intermediate metabolite, glycolic acid (GA). The developmental toxicity of EG has been the subject of extensive research and regulatory review in recent years. Therefore, a physiologically based pharmacokinetic (PBPK) model was developed to integrate the extensive mode of action and pharmacokinetic data on EG and GA for use in developmental risk assessment. Metabolic rate constants and partition coefficients for EG and GA were estimated from in vitro studies. Other biochemical constants were optimized from appropriate in vivo pharmacokinetic studies. The resulting PBPK model includes inhalation, oral, dermal, intravenous and subcutaneous routes of administration. Metabolism of EG and GA were described in the liver with elimination via the kidneys. Several rat and human metabolism studies were used to validate the resulting PBPK model. Consistent with these studies, simulations indicated that the metabolism of EG to GA was essentially first-order (linear) up to 2500 mg/kg/day while the metabolism of GA saturated between bolus ethylene glycol doses of 200 and 1000 mg/kg/day. This saturation results in non-linear increases in blood GA concentrations, correlating with the developmental toxicity of EG. Pregnancy had no effect on maternal EG and GA kinetics over a broad dose

  9. [Design of the data recorder outside body based on FAT file system in a noninvasive measuring system for human GI physiological signals].

    PubMed

    Li, Hongwei; Yan, Guozheng; Huang, Biao; Wang, Wenxing

    2009-02-01

    A noninvasive measuring system for human GI physiological signals has been designed, and human GI physiological realtime parameters are acquired in the normal physiological state of human. In this paper is mainly discussed the design of "In-vitro data recorder" of a noninvasive measuring system for human GI physiological signals. By experiments, the portable "In-vitro data recorder" works normally and reliably; it can meet the needs of clinical application.

  10. Cosmic Rays Variations and Human Physiological State

    NASA Astrophysics Data System (ADS)

    Dimitrova, S.

    2009-12-01

    It was obtained in our previous investigations that geomagnetic activity as an indirect indicator of solar activity correlates with some human physiological and psycho-physiological parameters. A lot of studies indicate that other parameters of space weather like cosmic rays Forbush decreases affect myocardial infarction, brain stroke, car accidents, etc. The purpose of that work was to study the effect of cosmic rays variations on human physiological status. It was established that the decrease in cosmic rays intensity was related to an increase in systolic and diastolic blood pressure and reported subjective psycho-physiological complaints in healthy volunteers.

  11. Quantitative Circulatory Physiology: an integrative mathematical model of human physiology for medical education.

    PubMed

    Abram, Sean R; Hodnett, Benjamin L; Summers, Richard L; Coleman, Thomas G; Hester, Robert L

    2007-06-01

    We have developed Quantitative Circulatory Physiology (QCP), a mathematical model of integrative human physiology containing over 4,000 variables of biological interactions. This model provides a teaching environment that mimics clinical problems encountered in the practice of medicine. The model structure is based on documented physiological responses within peer-reviewed literature and serves as a dynamic compendium of physiological knowledge. The model is solved using a desktop, Windows-based program, allowing students to calculate time-dependent solutions and interactively alter over 750 parameters that modify physiological function. The model can be used to understand proposed mechanisms of physiological function and the interactions among physiological variables that may not be otherwise intuitively evident. In addition to open-ended or unstructured simulations, we have developed 30 physiological simulations, including heart failure, anemia, diabetes, and hemorrhage. Additional stimulations include 29 patients in which students are challenged to diagnose the pathophysiology based on their understanding of integrative physiology. In summary, QCP allows students to examine, integrate, and understand a host of physiological factors without causing harm to patients. This model is available as a free download for Windows computers at http://physiology.umc.edu/themodelingworkshop.

  12. HUMAN--A Comprehensive Physiological Model.

    ERIC Educational Resources Information Center

    Coleman, Thomas G.; Randall, James E.

    1983-01-01

    Describes computer program (HUMAN) used to simulate physiological experiments on patient pathology. Program (available from authors, including versions for microcomputers) consists of dynamic interactions of over 150 physiological variables and integrating approximations of cardiovascular, renal, lung, temperature regulation, and some hormone…

  13. HUMAN--A Comprehensive Physiological Model.

    ERIC Educational Resources Information Center

    Coleman, Thomas G.; Randall, James E.

    1983-01-01

    Describes computer program (HUMAN) used to simulate physiological experiments on patient pathology. Program (available from authors, including versions for microcomputers) consists of dynamic interactions of over 150 physiological variables and integrating approximations of cardiovascular, renal, lung, temperature regulation, and some hormone…

  14. Cognitive and physiological responses in humans exposed to a TETRA base station signal in relation to perceived electromagnetic hypersensitivity.

    PubMed

    Wallace, Denise; Eltiti, Stacy; Ridgewell, Anna; Garner, Kelly; Russo, Riccardo; Sepulveda, Francisco; Walker, Stuart; Quinlan, Terence; Dudley, Sandra; Maung, Sithu; Deeble, Roger; Fox, Elaine

    2012-01-01

    Terrestrial Trunked Radio (TETRA) technology ("Airwave") has led to public concern because of its potential interference with electrical activity in the brain. The present study is the first to examine whether acute exposure to a TETRA base station signal has an impact on cognitive functioning and physiological responses. Participants were exposed to a 420 MHz TETRA signal at a power flux density of 10 mW/m(2) as well as sham (no signal) under double-blind conditions. Fifty-one people who reported a perceived sensitivity to electromagnetic fields as well as 132 controls participated in a double-blind provocation study. Forty-eight sensitive and 132 control participants completed all three sessions. Measures of short-term memory, working memory, and attention were administered while physiological responses (blood volume pulse, heart rate, skin conductance) were monitored. After applying exclusion criteria based on task performance for each aforementioned cognitive measure, data were analyzed for 36, 43, and 48 sensitive participants for these respective tasks and, likewise, 107,125, and 129 controls. We observed no differences in cognitive performance between sham and TETRA exposure in either group; physiological response also did not differ between the exposure conditions. These findings are similar to previous double-blind studies with other mobile phone signals (900-2100 MHz), which could not establish any clear evidence that mobile phone signals affect health or cognitive function.

  15. [Immune response genes products in human physiology].

    PubMed

    Khaitov, R M; Alekseev, L P

    2012-09-01

    Current data on physiological role of human immune response genes' proteomic products (antigens) are discussed. The antigens are specified by a very high level of diversity that mediates a wide specter ofphysiological functions. They actually provide integrity and biological stability of human as species. These data reveal new ideas on many pathological processes as well as drafts new approaches for prophylaxis and treatment.

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

    ERIC Educational Resources Information Center

    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…

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

    ERIC Educational Resources Information Center

    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…

  18. Gravitational Effects on Human Physiology.

    PubMed

    Atomi, Yoriko

    2015-01-01

    Physical working capacity decreases with age and also in microgravity. Regardless of age, increased physical activity can always improve the physical adaptability of the body, although the mechanisms of this adaptability are unknown. Physical exercise produces various mechanical stimuli in the body, and these stimuli may be essential for cell survival in organisms. The cytoskeleton plays an important role in maintaining cell shape and tension development, and in various molecular and/or cellular organelles involved in cellular trafficking. Both intra and extracellular stimuli send signals through the cytoskeleton to the nucleus and modulate gene expression via an intrinsic property, namely the "dynamic instability" of cytoskeletal proteins. αB-crystallin is an important chaperone for cytoskeletal proteins in muscle cells. Decreases in the levels of αB-crystallin are specifically associated with a marked decrease in muscle mass (atrophy) in a rat hindlimb suspension model that mimics muscle and bone atrophy that occurs in space and increases with passive stretch. Moreover, immunofluorescence data show complete co-localization of αB-crystallin and the tubulin/microtubule system in myoblast cells. This association was further confirmed in biochemical experiments carried out in vitro showing that αB-crystallin acts as a chaperone for heat-denatured tubulin and prevents microtubule disassembly induced by calcium. Physical activity induces the constitutive expression of αB-crystallin, which helps to maintain the homeostasis of cytoskeleton dynamics in response to gravitational forces. This relationship between chaperone expression levels and regulation of cytoskeletal dynamics observed in slow anti-gravitational muscles as well as in mammalian striated muscles, such as those in the heart, diaphragm and tongue, may have been especially essential for human evolution in particular. Elucidation of the intrinsic properties of the tubulin/microtubule and chaperone

  19. Improved physiologically based pharmacokinetic model for oral exposures to chromium in mice, rats, and humans to address temporal variation and sensitive populations.

    PubMed

    Kirman, C R; Suh, M; Proctor, D M; Hays, S M

    2017-06-15

    A physiologically based pharmacokinetic (PBPK) model for hexavalent chromium [Cr(VI)] in mice, rats, and humans developed previously (Kirman et al., 2012, 2013), was updated to reflect an improved understanding of the toxicokinetics of the gastrointestinal tract following oral exposures. Improvements were made to: (1) the reduction model, which describes the pH-dependent reduction of Cr(VI) to Cr(III) in the gastrointestinal tract under both fasted and fed states; (2) drinking water pattern simulations, to better describe dosimetry in rodents under the conditions of the NTP cancer bioassay; and (3) parameterize the model to characterize potentially sensitive human populations. Important species differences, sources of non-linear toxicokinetics, and human variation are identified and discussed within the context of human health risk assessment. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Development and evaluation of a harmonized physiologically based pharmacokinetic (PBPK) model for perchloroethylene toxicokinetics in mice, rats, and humans

    SciTech Connect

    Chiu, Weihsueh A.; Ginsberg, Gary L.

    2011-06-15

    reconciles the disparity between those previously published PBPK models that concluded low perc metabolism in humans and those that predicted high perc metabolism in humans. In essence, both conclusions are consistent with the data if augmented with some additional qualifications: in humans, oxidative metabolism is low, while GSH conjugation metabolism may be high or low, with uncertainty and/or interindividual variability spanning three orders of magnitude. More direct data on the internal kinetics of perc GSH conjugation, such as trichlorovinyl glutathione or tricholorvinyl cysteine in blood and/or tissues, would be needed to better characterize the uncertainty and variability in GSH conjugation in humans. - Research Highlights: >We analyze perchloroethylene (perc) toxicokinetics with a physiological model. >Results from previous analyses lumping metabolic pathways are inconsistent. >Separately tracking oxidation and conjugation pathways reconciles these results. >Available data are adequate for predicting perc blood levels and oxidation by P450. >High uncertainty remains for human conjugation of perc with glutathione.

  1. Support vector machines to detect physiological patterns for EEG and EMG-based human-computer interaction: a review

    NASA Astrophysics Data System (ADS)

    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.

  2. Support vector machines to detect physiological patterns for EEG and EMG-based human-computer interaction: a review.

    PubMed

    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.

  3. Study on inter-ethnic human differences in bioactivation and detoxification of estragole using physiologically based kinetic modeling.

    PubMed

    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.

  4. Evaluation of the interindividual human variation in bioactivation of methyleugenol using physiologically based kinetic modeling and Monte Carlo simulations.

    PubMed

    Al-Subeihi, Ala A A; Alhusainy, Wasma; Kiwamoto, Reiko; Spenkelink, Bert; van Bladeren, Peter J; Rietjens, Ivonne M C M; Punt, Ans

    2015-03-01

    The present study aims at predicting the level of formation of the ultimate carcinogenic metabolite of methyleugenol, 1'-sulfooxymethyleugenol, in the human population by taking variability in key bioactivation and detoxification reactions into account using Monte Carlo simulations. Depending on the metabolic route, variation was simulated based on kinetic constants obtained from incubations with a range of individual human liver fractions or by combining kinetic constants obtained for specific isoenzymes with literature reported human variation in the activity of these enzymes. The results of the study indicate that formation of 1'-sulfooxymethyleugenol is predominantly affected by variation in i) P450 1A2-catalyzed bioactivation of methyleugenol to 1'-hydroxymethyleugenol, ii) P450 2B6-catalyzed epoxidation of methyleugenol, iii) the apparent kinetic constants for oxidation of 1'-hydroxymethyleugenol, and iv) the apparent kinetic constants for sulfation of 1'-hydroxymethyleugenol. Based on the Monte Carlo simulations a so-called chemical-specific adjustment factor (CSAF) for intraspecies variation could be derived by dividing different percentiles by the 50th percentile of the predicted population distribution for 1'-sulfooxymethyleugenol formation. The obtained CSAF value at the 90th percentile was 3.2, indicating that the default uncertainty factor of 3.16 for human variability in kinetics may adequately cover the variation within 90% of the population. Covering 99% of the population requires a larger uncertainty factor of 6.4. In conclusion, the results showed that adequate predictions on interindividual human variation can be made with Monte Carlo-based PBK modeling. For methyleugenol this variation was observed to be in line with the default variation generally assumed in risk assessment.

  5. Evaluation of the interindividual human variation in bioactivation of methyleugenol using physiologically based kinetic modeling and Monte Carlo simulations

    SciTech Connect

    Al-Subeihi, Ala' A.A.; Alhusainy, Wasma; Kiwamoto, Reiko; Spenkelink, Bert; Bladeren, Peter J. van; Rietjens, Ivonne M.C.M.; Punt, Ans

    2015-03-01

    The present study aims at predicting the level of formation of the ultimate carcinogenic metabolite of methyleugenol, 1′-sulfooxymethyleugenol, in the human population by taking variability in key bioactivation and detoxification reactions into account using Monte Carlo simulations. Depending on the metabolic route, variation was simulated based on kinetic constants obtained from incubations with a range of individual human liver fractions or by combining kinetic constants obtained for specific isoenzymes with literature reported human variation in the activity of these enzymes. The results of the study indicate that formation of 1′-sulfooxymethyleugenol is predominantly affected by variation in i) P450 1A2-catalyzed bioactivation of methyleugenol to 1′-hydroxymethyleugenol, ii) P450 2B6-catalyzed epoxidation of methyleugenol, iii) the apparent kinetic constants for oxidation of 1′-hydroxymethyleugenol, and iv) the apparent kinetic constants for sulfation of 1′-hydroxymethyleugenol. Based on the Monte Carlo simulations a so-called chemical-specific adjustment factor (CSAF) for intraspecies variation could be derived by dividing different percentiles by the 50th percentile of the predicted population distribution for 1′-sulfooxymethyleugenol formation. The obtained CSAF value at the 90th percentile was 3.2, indicating that the default uncertainty factor of 3.16 for human variability in kinetics may adequately cover the variation within 90% of the population. Covering 99% of the population requires a larger uncertainty factor of 6.4. In conclusion, the results showed that adequate predictions on interindividual human variation can be made with Monte Carlo-based PBK modeling. For methyleugenol this variation was observed to be in line with the default variation generally assumed in risk assessment. - Highlights: • Interindividual human differences in methyleugenol bioactivation were simulated. • This was done using in vitro incubations, PBK modeling

  6. Physiological basis for human autonomic rhythms.

    PubMed

    Eckberg, D L

    2000-07-01

    Oscillations of arterial pressures, heart periods, and muscle sympathetic nerve activity have been studied intensively in recent years to explore otherwise obscure human neurophysiological mechanisms. The best-studied rhythms are those occurring at breathing frequencies. Published evidence indicates that respiratory fluctuations of muscle sympathetic nerve activity and electrocardiographic R-R intervals result primarily from the action of a central 'gate' that opens during expiration and closes during inspiration. Parallel respiratory fluctuations of arterial pressures and R-R intervals are thought to be secondary to arterial baroreflex physiology: changes in systolic pressure provoke changes in the R-R interval. However, growing evidence suggests that these parallel oscillations result from the influence of respiration on sympathetic and vagal-cardiac motoneurones rather than from baroreflex physiology. There is a rapidly growing literature on the use of mathematical models of low- and high-frequency (respiratory) R-R interval fluctuations in characterizing instantaneous 'sympathovagal balance'. The case for this approach is based primarily on measurements made with patients in upright tilt. However, the strong linear relation between such measures as the ratio of low- to high-frequency R-R interval oscillations and the angle of the tilt reflects exclusively the reductions of the vagal (high-frequency) component. As the sympathetic component does not change in tilt, the low- to high-frequency R-R interval ratio provides no proof that sympathetic activity increases. Moreover, the validity of extrapolating from measurements performed during upright tilt to measurements during supine rest has not been established. Nonetheless, it is clear that measures of heart rate variability provide important prognostic information in patients with cardiovascular diseases. It is not known whether reduced heart rate variability is merely a marker for the severity of disease or a

  7. Physiological basis for human autonomic rhythms

    NASA Technical Reports Server (NTRS)

    Eckberg, D. L.

    2000-01-01

    Oscillations of arterial pressures, heart periods, and muscle sympathetic nerve activity have been studied intensively in recent years to explore otherwise obscure human neurophysiological mechanisms. The best-studied rhythms are those occurring at breathing frequencies. Published evidence indicates that respiratory fluctuations of muscle sympathetic nerve activity and electrocardiographic R-R intervals result primarily from the action of a central 'gate' that opens during expiration and closes during inspiration. Parallel respiratory fluctuations of arterial pressures and R-R intervals are thought to be secondary to arterial baroreflex physiology: changes in systolic pressure provoke changes in the R-R interval. However, growing evidence suggests that these parallel oscillations result from the influence of respiration on sympathetic and vagal-cardiac motoneurones rather than from baroreflex physiology. There is a rapidly growing literature on the use of mathematical models of low- and high-frequency (respiratory) R-R interval fluctuations in characterizing instantaneous 'sympathovagal balance'. The case for this approach is based primarily on measurements made with patients in upright tilt. However, the strong linear relation between such measures as the ratio of low- to high-frequency R-R interval oscillations and the angle of the tilt reflects exclusively the reductions of the vagal (high-frequency) component. As the sympathetic component does not change in tilt, the low- to high-frequency R-R interval ratio provides no proof that sympathetic activity increases. Moreover, the validity of extrapolating from measurements performed during upright tilt to measurements during supine rest has not been established. Nonetheless, it is clear that measures of heart rate variability provide important prognostic information in patients with cardiovascular diseases. It is not known whether reduced heart rate variability is merely a marker for the severity of disease or a

  8. Physiological basis for human autonomic rhythms

    NASA Technical Reports Server (NTRS)

    Eckberg, D. L.

    2000-01-01

    Oscillations of arterial pressures, heart periods, and muscle sympathetic nerve activity have been studied intensively in recent years to explore otherwise obscure human neurophysiological mechanisms. The best-studied rhythms are those occurring at breathing frequencies. Published evidence indicates that respiratory fluctuations of muscle sympathetic nerve activity and electrocardiographic R-R intervals result primarily from the action of a central 'gate' that opens during expiration and closes during inspiration. Parallel respiratory fluctuations of arterial pressures and R-R intervals are thought to be secondary to arterial baroreflex physiology: changes in systolic pressure provoke changes in the R-R interval. However, growing evidence suggests that these parallel oscillations result from the influence of respiration on sympathetic and vagal-cardiac motoneurones rather than from baroreflex physiology. There is a rapidly growing literature on the use of mathematical models of low- and high-frequency (respiratory) R-R interval fluctuations in characterizing instantaneous 'sympathovagal balance'. The case for this approach is based primarily on measurements made with patients in upright tilt. However, the strong linear relation between such measures as the ratio of low- to high-frequency R-R interval oscillations and the angle of the tilt reflects exclusively the reductions of the vagal (high-frequency) component. As the sympathetic component does not change in tilt, the low- to high-frequency R-R interval ratio provides no proof that sympathetic activity increases. Moreover, the validity of extrapolating from measurements performed during upright tilt to measurements during supine rest has not been established. Nonetheless, it is clear that measures of heart rate variability provide important prognostic information in patients with cardiovascular diseases. It is not known whether reduced heart rate variability is merely a marker for the severity of disease or a

  9. A comprehensive physiologically based pharmacokinetic ...

    EPA Pesticide Factsheets

    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 parameters and in vivo pharmacokinetic data used to calibrate these published models can act as valuable starting points for model development of new chemicals with similar molecular structures. A knowledgebase for published PBPK-related articles was compiled to support PBPK model construction for new chemicals based on their close analogues within the knowledgebase, and a web-based interface was developed to allow users to query those close analogues. A list of 689 unique chemicals and their corresponding 1751 articles was created after analysis of 2,245 PBPK-related articles. For each model, the PMID, chemical name, major metabolites, species, gender, life stages and tissue compartments were extracted from the published articles. PaDEL-Descriptor, a Chemistry Development Kit based software, was used to calculate molecular fingerprints. Tanimoto index was implemented in the user interface as measurement of structural similarity. The utility of the PBPK knowledgebase and web-based user interface was demonstrated using two case studies with ethylbenzene and gefitinib. Our PBPK knowledgebase is a novel tool for ranking chemicals based on similarities to other chemicals associated with existi

  10. A comprehensive physiologically based pharmacokinetic ...

    EPA Pesticide Factsheets

    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 parameters and in vivo pharmacokinetic data used to calibrate these published models can act as valuable starting points for model development of new chemicals with similar molecular structures. A knowledgebase for published PBPK-related articles was compiled to support PBPK model construction for new chemicals based on their close analogues within the knowledgebase, and a web-based interface was developed to allow users to query those close analogues. A list of 689 unique chemicals and their corresponding 1751 articles was created after analysis of 2,245 PBPK-related articles. For each model, the PMID, chemical name, major metabolites, species, gender, life stages and tissue compartments were extracted from the published articles. PaDEL-Descriptor, a Chemistry Development Kit based software, was used to calculate molecular fingerprints. Tanimoto index was implemented in the user interface as measurement of structural similarity. The utility of the PBPK knowledgebase and web-based user interface was demonstrated using two case studies with ethylbenzene and gefitinib. Our PBPK knowledgebase is a novel tool for ranking chemicals based on similarities to other chemicals associated with existi

  11. The use of team-based, guided inquiry learning to overcome educational disadvantages in learning human physiology: a structural equation model.

    PubMed

    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. Copyright © 2014 The American Physiological Society.

  12. Puzzle-based versus traditional lecture: comparing the effects of pedagogy on academic performance in an undergraduate human anatomy and physiology II lab.

    PubMed

    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

  13. Predictors of success in undergraduate human physiology.

    PubMed

    McCleary, V L; Aasen, G; Slotnick, H B

    1999-12-01

    This study tested the hypothesis that measurable attributes in students' backgrounds are related to their successful completion of an undergraduate human physiology course. Demographic, general academic performance, and science achievement data were obtained from student records for students enrolled during the 1995-1996 academic year, and additional demographic data were obtained from students enrolled during the 1996-1998 academic years. A hierarchical logistic regression analysis explored the relationship fo these variables to the percentage of students passing the human physiology course. Predicted passing versus failing showed a sensitivity of 85.5% and specificity of 69.7%. Two independent validations of the logistical regression equation correctly predicted the performance of subsequent groups of students 75.9% and 77.6% of the time.

  14. A simple physiologically based pharmacokinetic model evaluating the effect of anti-nicotine antibodies on nicotine disposition in the brains of rats and humans.

    PubMed

    Saylor, Kyle; Zhang, Chenming

    2016-09-15

    Physiologically based pharmacokinetic (PBPK) modeling was applied to investigate the effects of anti-nicotine antibodies on nicotine disposition in the brains of rats and humans. Successful construction of both rat and human models was achieved by fitting model outputs to published nicotine concentration time course data in the blood and in the brain. Key parameters presumed to have the most effect on the ability of these antibodies to prevent nicotine from entering the brain were selected for investigation using the human model. These parameters, which included antibody affinity for nicotine, antibody cross-reactivity with cotinine, and antibody concentration, were broken down into different, clinically-derived in silico treatment levels and fed into the human PBPK model. Model predictions suggested that all three parameters, in addition to smoking status, have a sizable impact on anti-nicotine antibodies' ability to prevent nicotine from entering the brain and that the antibodies elicited by current human vaccines do not have sufficient binding characteristics to reduce brain nicotine concentrations. If the antibody binding characteristics achieved in animal studies can similarly be achieved in human studies, however, nicotine vaccine efficacy in terms of brain nicotine concentration reduction is predicted to meet threshold values for alleviating nicotine dependence. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Application of physiologically based pharmacokinetic modeling in predicting drug–drug interactions for sarpogrelate hydrochloride in humans

    PubMed Central

    Min, Jee Sun; Kim, Doyun; Park, Jung Bae; Heo, Hyunjin; Bae, Soo Hyeon; Seo, Jae Hong; Oh, Euichaul; Bae, Soo Kyung

    2016-01-01

    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-methoxyphenyl)ethyl]-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, desipramine, imipramine, dextromethorphan, and tolterodine following single and multiple sarpogrelate hydrochloride oral doses were within the range of ≥1.25, but <2-fold, indicating that sarpogrelate hydrochloride is a weak inhibitor of CYP2D6 in vivo. Collectively, the predicted low DDIs suggest that sarpogrelate hydrochloride has limited potential for causing

  16. Use of Physiologically Based Pharmacokinetic (PBPK) Models ...

    EPA Pesticide Factsheets

    EPA announced the availability of the final report, Use of Physiologically Based Pharmacokinetic (PBPK) Models to Quantify the Impact of Human Age and Interindividual Differences in Physiology and Biochemistry Pertinent to Risk Final Report for Cooperative Agreement. This report describes and demonstrates techniques necessary to extrapolate and incorporate in vitro derived metabolic rate constants in PBPK models. It also includes two case study examples designed to demonstrate the applicability of such data for health risk assessment and addresses the quantification, extrapolation and interpretation of advanced biochemical information on human interindividual variability of chemical metabolism for risk assessment application. It comprises five chapters; topics and results covered in the first four chapters have been published in the peer reviewed scientific literature. Topics covered include: Data Quality ObjectivesExperimental FrameworkRequired DataTwo example case studies that develop and incorporate in vitro metabolic rate constants in PBPK models designed to quantify human interindividual variability to better direct the choice of uncertainty factors for health risk assessment. This report is intended to serve as a reference document for risk assors to use when quantifying, extrapolating, and interpretating advanced biochemical information about human interindividual variability of chemical metabolism.

  17. Malathion dermal permeability in relation to dermal load: Assessment by physiologically based pharmacokinetic modeling of in vivo human data.

    PubMed

    Bogen, Kenneth T; Singhal, Ankur

    2017-02-01

    Estimates of dermal permeability (Kp), obtained by fitting an updated human PBPK model for malathion to previously reported data on excreted urinary metabolites after 29 volunteers were dermally exposed to measured values of [(14)C]malathion dermal load (L), were used to examine the empirical relationship between Kp and L. The PBPK model was adapted from previously reported human biokinetic and PBPK models for malathion, fit to previously reported urinary excretion data after oral [(14)C]malathion intake by volunteers, and then augmented to incorporate a standard Kp approach to modeling dermal-uptake kinetics. Good to excellent PBPK-model fits were obtained to all of 29 sets of cumulative urinary metabolite-excretion data (ave. [±1 SD] R(2) = 0.953 [±0.064]). Contrary to the assumption that Kp and L are independent typically applied for dermally administered liquids or solutions, the 29 PBPK-based estimates of Kp obtained for malathion exhibit a strong positive association with the 2/3rds power of L (log-log Pearson correlation = 0.925, p = ∼0). Possible explanations of this observation involving physico-chemical characteristics and/or in vivo cutaneous effects of malathion are discussed. The PBPK model presented, and our observation that Kp estimates obtained by fitting this model to human experimental urinary-excretion data correlate well with L(2/3), allow more realistic assessments of absorbed and metabolized dose during or after a variety of scenarios involving actual or potential dermal or multi-route malathion exposures, including for pesticide workers or farmers who apply malathion to crops.

  18. The Importance of the Ionic Product for Water to Understand the Physiology of the Acid-Base Balance in Humans

    PubMed Central

    Adeva-Andany, María M.; Carneiro-Freire, Natalia; Donapetry-García, Cristóbal; Rañal-Muíño, Eva; López-Pereiro, Yosua

    2014-01-01

    Human plasma is an aqueous solution that has to abide by chemical rules such as the principle of electrical neutrality and the constancy of the ionic product for water. These rules define the acid-base balance in the human body. According to the electroneutrality principle, plasma has to be electrically neutral and the sum of its cations equals the sum of its anions. In addition, the ionic product for water has to be constant. Therefore, the plasma concentration of hydrogen ions depends on the plasma ionic composition. Variations in the concentration of plasma ions that alter the relative proportion of anions and cations predictably lead to a change in the plasma concentration of hydrogen ions by driving adaptive adjustments in water ionization that allow plasma electroneutrality while maintaining constant the ionic product for water. The accumulation of plasma anions out of proportion of cations induces an electrical imbalance compensated by a fall of hydroxide ions that brings about a rise in hydrogen ions (acidosis). By contrast, the deficiency of chloride relative to sodium generates plasma alkalosis by increasing hydroxide ions. The adjustment of plasma bicarbonate concentration to these changes is an important compensatory mechanism that protects plasma pH from severe deviations. PMID:24877130

  19. Comparative Risks of Aldehyde Constituents in Cigarette Smoke Using Transient Computational Fluid Dynamics/Physiologically Based Pharmacokinetic Models of the Rat and Human Respiratory Tracts

    PubMed Central

    Corley, Richard A.; Kabilan, Senthil; Kuprat, Andrew P.; Carson, James P.; Jacob, Richard E.; Minard, Kevin R.; Teeguarden, Justin G.; Timchalk, Charles; Pipavath, Sudhakar; Glenny, Robb; Einstein, Daniel R.

    2015-01-01

    Computational fluid dynamics (CFD) modeling is well suited for addressing species-specific anatomy and physiology in calculating respiratory tissue exposures to inhaled materials. In this study, we overcame prior CFD model limitations to demonstrate the importance of realistic, transient breathing patterns for predicting site-specific tissue dose. Specifically, extended airway CFD models of the rat and human were coupled with airway region-specific physiologically based pharmacokinetic (PBPK) tissue models to describe the kinetics of 3 reactive constituents of cigarette smoke: acrolein, acetaldehyde and formaldehyde. Simulations of aldehyde no-observed-adverse-effect levels for nasal toxicity in the rat were conducted until breath-by-breath tissue concentration profiles reached steady state. Human oral breathing simulations were conducted using representative aldehyde yields from cigarette smoke, measured puff ventilation profiles and numbers of cigarettes smoked per day. As with prior steady-state CFD/PBPK simulations, the anterior respiratory nasal epithelial tissues received the greatest initial uptake rates for each aldehyde in the rat. However, integrated time- and tissue depth-dependent area under the curve (AUC) concentrations were typically greater in the anterior dorsal olfactory epithelium using the more realistic transient breathing profiles. For human simulations, oral and laryngeal tissues received the highest local tissue dose with greater penetration to pulmonary tissues than predicted in the rat. Based upon lifetime average daily dose comparisons of tissue hot-spot AUCs (top 2.5% of surface area-normalized AUCs in each region) and numbers of cigarettes smoked/day, the order of concern for human exposures was acrolein > formaldehyde > acetaldehyde even though acetaldehyde yields were 10-fold greater than formaldehyde and acrolein. PMID:25858911

  20. Incorporation of therapeutic interventions in physiologically based pharmacokinetic modeling of human clinical case reports of accidental or intentional overdosing with ethylene glycol.

    PubMed

    Corley, R A; McMartin, K E

    2005-05-01

    Although occupational uses of the high production volume (HPV) chemical ethylene glycol (EG) have not been associated with adverse effects, there are case reports where humans have either intentionally or accidentally ingested large quantities of EG, primarily from antifreeze. The acute toxicity of EG can proceed through three stages, each associated with a different metabolite: central nervous system depression (ethylene glycol), cardiopulmonary effects associated with metabolic acidosis (glycolic acid), and ultimately renal toxicity (oxalic acid), depending on the total amounts consumed and the effectiveness of therapeutic interventions. A physiologically based pharmacokinetic (PBPK) model developed in a companion paper (Corley et al., 2005). Development of a physiologically based pharmacokinetic model for ethylene glycol and its metabolite, glycolic acid, in rats and humans. Toxicol. Sci., in press 2005) was refined in this study to include clinically relevant treatment regimens for EG poisoning such as hemodialysis or metabolic inhibition with either ethanol or fomepizole. Such modifications enabled the model to describe data from several human case reports, confirming the ability of the previous model to describe the pharmacokinetics of EG and its metabolite, glycolic acid, in humans across a broad range of doses and multiple exposure routes. By integrating the case report data sets with controlled studies in this PBPK model, it was demonstrated that fomepizole, if administered early enough in a clinical situation, can be more effective than ethanol or hemodialysis in preventing the metabolism of EG to more toxic metabolites. Hemodialysis remains an important option, however, if treatment is instituted after a significant amount of EG is metabolized or if renal toxicity has occurred.

  1. Development of a Combined In Vitro Physiologically Based Kinetic (PBK) and Monte Carlo Modelling Approach to Predict Interindividual Human Variation in Phenol-Induced Developmental Toxicity.

    PubMed

    Strikwold, Marije; Spenkelink, Bert; Woutersen, Ruud A; Rietjens, Ivonne M C M; Punt, Ans

    2017-06-01

    With our recently developed in vitro physiologically based kinetic (PBK) modelling approach, we could extrapolate in vitro toxicity data to human toxicity values applying PBK-based reverse dosimetry. Ideally information on kinetic differences among human individuals within a population should be considered. In the present study, we demonstrated a modelling approach that integrated in vitro toxicity data, PBK modelling and Monte Carlo simulations to obtain insight in interindividual human kinetic variation and derive chemical specific adjustment factors (CSAFs) for phenol-induced developmental toxicity. The present study revealed that UGT1A6 is the primary enzyme responsible for the glucuronidation of phenol in humans followed by UGT1A9. Monte Carlo simulations were performed taking into account interindividual variation in glucuronidation by these specific UGTs and in the oral absorption coefficient. Linking Monte Carlo simulations with PBK modelling, population variability in the maximum plasma concentration of phenol for the human population could be predicted. This approach provided a CSAF for interindividual variation of 2.0 which covers the 99th percentile of the population, which is lower than the default safety factor of 3.16 for interindividual human kinetic differences. Dividing the dose-response curve data obtained with in vitro PBK-based reverse dosimetry, with the CSAF provided a dose-response curve that reflects the consequences of the interindividual variability in phenol kinetics for the developmental toxicity of phenol. The strength of the presented approach is that it provides insight in the effect of interindividual variation in kinetics for phenol-induced developmental toxicity, based on only in vitro and in silico testing. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. The use of team-based, guided inquiry learning to overcome educational disadvantages in learning human physiology: a structural equation model

    PubMed Central

    Byrne, Graeme

    2014-01-01

    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. PMID:25179611

  3. Human plasma concentrations of cytochrome P450 probe cocktails extrapolated from pharmacokinetics in mice transplanted with human hepatocytes and from pharmacokinetics in common marmosets using physiologically based pharmacokinetic modeling.

    PubMed

    Utoh, Masahiro; Suemizu, Hiroshi; Mitsui, Marina; Kawano, Mirai; Toda, Akiko; Uehara, Shotaro; Uno, Yasuhiro; Shimizu, Makiko; Sasaki, Erika; Yamazaki, Hiroshi

    2016-12-01

    1. The pharmacokinetic data of cytochrome P450 probes in humans can be extrapolated from corresponding data in cynomolgus monkeys, dogs and minipigs using simplified physiologically based pharmacokinetic (PBPK) modeling. In this study, the modeling methodology was further adapted to estimate human plasma concentrations of P450 probes based on data from mice transplanted with human hepatocytes or based on data from marmosets. 2. Using known species allometric scaling factors, the observed plasma concentrations of caffeine, warfarin, omeprazole, metoprolol, and midazolam in chimeric TK-NOG mice with humanized liver were scaled to human oral monitoring equivalents. Using the same approach, the previously reported pharmacokinetics of the five P450 probes in marmosets were also scaled to reported equivalents in humans using in vitro metabolic clearance data. 3. Human plasma concentration profiles of the five P450 probes estimated by simplified human PBPK models based on the observed pharmacokinetics in mice with humanized liver and on the reported pharmacokinetics in marmosets were consistent with previously published pharmacokinetic data in Caucasians. 4. These results suggest that mice with humanized liver and/or marmosets could be suitable pharmacokinetic models for humans during research into new drugs, especially when used in combination with simple PBPK models.

  4. Use of physiologically based kinetic (PBK) modeling to study interindividual human variation and species differences in plasma concentrations of quercetin and its metabolites.

    PubMed

    Boonpawa, Rungnapa; Moradi, Nooshin; Spenkelink, Albertus; Rietjens, Ivonne M C M; Punt, Ans

    2015-12-15

    Biological activities of flavonoids in vivo ultimately depend on the systemic bioavailability of the aglycones and their metabolites. We aimed to develop physiologically based kinetic (PBK) models to predict plasma concentrations of the flavonoid quercetin and its metabolites in individual human subjects and to define species differences compared with male rat. The human models were developed based on in vitro metabolic parameters derived from incubations with pooled and 20 individual human tissue fractions and by fitting kinetic parameters to available in vivo data. The outcomes obtained were compared to a previously developed model for quercetin and its metabolites formation in male rat. Quercetin-3'-O-glucuronide was predicted to be the major circulating metabolite in 19 out of 20 individuals, while in male rat di- and tri-conjugates of quercetin containing a glucuronic acid, sulfate and/or methyl moieties are the major metabolites. Significant species differences occur in major circulating metabolites of quercetin suggesting that rat is not an adequate model to study effects of quercetin in man. The defined PBK models can be used to guide the experimental design of in vitro experiments with flavonoids, especially to better take into account the relevance of metabolism and the contribution of metabolites to the biological activity in humans.

  5. Physiological bases of mosquito ecology.

    PubMed

    Briegel, Hans

    2003-06-01

    The research carried out during more than 30 years in the author's laboratory is briefly reviewed. Quantitative analyses of basic physiological processes, such as growth and development, digestion and excretion, oogenesis and fecundity, reserve synthesis and resulting flight-potentials of Aedes aegypti were summarized and compared with several other mosquito species, particularly with Anopheles. These studies led to the recognition of distinctly different physiological strategies, for which the term "physiotype" has been coined, providing a basis for understanding the different ecotypes.

  6. Uncertainty and Variability in Physiologically-Based ...

    EPA Pesticide Factsheets

    EPA announced the availability of the final report, Uncertainty and Variability in Physiologically-Based Pharmacokinetic (PBPK) Models: Key Issues and Case Studies. This report summarizes some of the recent progress in characterizing uncertainty and variability in physiologically-based pharmacokinetic models and their predictions for use in risk assessment. This report summarizes some of the recent progress in characterizing uncertainty and variability in physiologically-based pharmacokinetic models and their predictions for use in risk assessment.

  7. Development of a hybrid physiologically based pharmacokinetic model with drug-specific scaling factors in rat to improve prediction of human pharmacokinetics.

    PubMed

    Sayama, Hiroyuki; Komura, Hiroshi; Kogayu, Motohiro; Iwaki, Masahiro

    2013-11-01

    Accurate prediction of pharmacokinetics (PK) in humans has been a vital part of drug discovery. The aims of this study are to verify the usefulness of scaling factors for clearance (CL) and apparent volume of distribution at the steady state (Vss ) estimated from the difference between observed and predicted PK profiles in rats for human PK prediction, and to develop a novel hybrid physiologically based pharmacokinetic (PBPK) model with the two scaling factors. The human prediction accuracies for CL with in vitro-in vivo extrapolation and Vss with a tissue composition model were improved by using rat-scaling factors. This improvement was explainable by data that the scaling factors for CL and Vss in rats were correlated with those in humans. The predictability of plasma concentration-time profiles by the hybrid PBPK model incorporating two scaling factors was compared mainly with that by the conventional PBPK model. The hybrid PBPK model yielded higher prediction accuracy for plasma concentrations than the conventional method. Furthermore, we proposed a tiered approach using the three prediction methods, including the hybrid Dedrick approach, that were previously reported (Sayama H, Komura H, Kogayu M. 2013. Drug Metab Dispos 41:498-507), taking the available information in the individual stages of drug discovery and development into consideration.

  8. A physiologically based pharmacokinetic model of mitoxantrone in mice and scale-up to humans: a semi-mechanistic model incorporating DNA and protein binding.

    PubMed

    An, Guohua; Morris, Marilyn E

    2012-06-01

    We conducted a pharmacokinetic (PK) study of mitoxantrone (Novantrone®), a clinically well-established anticancer agent, in mice and developed a mechanism-based PBPK (physiologically based pharmacokinetic) model to describe its disposition. Mitoxantrone concentrations in plasma and six organs (lung, heart, liver, kidney, spleen, and brain) were determined after a 5 mg/kg i.v. dose. We evaluated three different PBPK models in order to characterize our experimental data: model 1 containing Kp values, model 2 incorporating a deep binding compartment, and model 3 incorporating binding of mitoxantrone to DNA and protein. Among the three models, only model 3 with DNA and protein binding captured all the experimental data well. The estimated binding affinity for DNA (K (DNA)) and protein (K (macro)) were 0.0013 and 1.44 μM, respectively. Predicted plasma and tissue AUC values differed from observed values by <19 %, except for heart (60 %). Model 3 was further used to simulate plasma mitoxantrone concentrations in humans for a 12-mg/m(2) dose, using human physiological parameters. The simulated results generally agreed with the observed time course of mitoxantrone plasma concentrations in patients after a standard dose of 12 mg/m(2). In summary, we reported for the first time a mechanism-based PBPK model of mitoxantrone incorporating macromolecule binding which may have clinical applicability in optimizing clinical therapy. Since mitoxantrone is a substrate of the efflux transporters ABCG2 and ABCB1, the incorporation of efflux transporters may also be necessary to characterize the data obtained in low-dose studies.

  9. Earthing the Human Body Influences Physiologic Processes

    PubMed Central

    Sokal, Karol

    2011-01-01

    Abstract Objectives This study was designed to answer the question: Does the contact of the human organism with the Earth via a copper conductor affect physiologic processes? Subjects and experiments Five (5) experiments are presented: experiment 1—effect of earthing on calcium–phosphate homeostasis and serum concentrations of iron (N = 84 participants); experiment 2—effect of earthing on serum concentrations of electrolytes (N = 28); experiment 3—effect of earthing on thyroid function (N = 12); experiment 4—effect of earthing on glucose concentration (N = 12); experiment 5—effect of earthing on immune response to vaccine (N = 32). Subjects were divided into two groups. One (1) group of people was earthed, while the second group remained without contact with the Earth. Blood and urine samples were examined. Results Earthing of an electrically insulated human organism during night rest causes lowering of serum concentrations of iron, ionized calcium, inorganic phosphorus, and reduction of renal excretion of calcium and phosphorus. Earthing during night rest decreases free tri-iodothyronine and increases free thyroxine and thyroid-stimulating hormone. The continuous earthing of the human body decreases blood glucose in patients with diabetes. Earthing decreases sodium, potassium, magnesium, iron, total protein, and albumin concentrations while the levels of transferrin, ferritin, and globulins α1, α2, β, and γ increase. These results are statistically significant. Conclusions Earthing the human body influences human physiologic processes. This influence is observed during night relaxation and during physical activity. Effect of the earthing on calcium–phosphate homeostasis is the opposite of that which occurs in states of weightlessness. It also increases the activity of catabolic processes. It may be the primary factor regulating endocrine and nervous systems. PMID:21469913

  10. Earthing the human body influences physiologic processes.

    PubMed

    Sokal, Karol; Sokal, Pawel

    2011-04-01

    This study was designed to answer the question: Does the contact of the human organism with the Earth via a copper conductor affect physiologic processes? Subjects and experiments: Five (5) experiments are presented: experiment 1-effect of earthing on calcium-phosphate homeostasis and serum concentrations of iron (N = 84 participants); experiment 2-effect of earthing on serum concentrations of electrolytes (N = 28); experiment 3-effect of earthing on thyroid function (N = 12); experiment 4-effect of earthing on glucose concentration (N = 12); experiment 5-effect of earthing on immune response to vaccine (N = 32). Subjects were divided into two groups. One (1) group of people was earthed, while the second group remained without contact with the Earth. Blood and urine samples were examined. Earthing of an electrically insulated human organism during night rest causes lowering of serum concentrations of iron, ionized calcium, inorganic phosphorus, and reduction of renal excretion of calcium and phosphorus. Earthing during night rest decreases free tri-iodothyronine and increases free thyroxine and thyroid-stimulating hormone. The continuous earthing of the human body decreases blood glucose in patients with diabetes. Earthing decreases sodium, potassium, magnesium, iron, total protein, and albumin concentrations while the levels of transferrin, ferritin, and globulins α1, α2, β, and γ increase. These results are statistically significant. Earthing the human body influences human physiologic processes. This influence is observed during night relaxation and during physical activity. Effect of the earthing on calcium-phosphate homeostasis is the opposite of that which occurs in states of weightlessness. It also increases the activity of catabolic processes. It may be the primary factor regulating endocrine and nervous systems.

  11. The human hair: from anatomy to physiology.

    PubMed

    Buffoli, Barbara; Rinaldi, Fabio; Labanca, Mauro; Sorbellini, Elisabetta; Trink, Anna; Guanziroli, Elena; Rezzani, Rita; Rodella, Luigi F

    2014-03-01

    Hair is a unique character of mammals and has several functions, from protection of the skin to sexual and social communication. In literature, there are various studies about hair that take into consideration different aspects within many fields of science, including biology, dermatology, cosmetics, forensic sciences, and medicine. We carried out a search of studies published in PubMed up to 2013. In this review, we summarized the principal anatomical and physiological aspects of the different types of human hair, and we considered the clinical significance of the different structures and the distribution of the hair in the human body. This review could be the basis for improvement and progression in the field of hair research. © 2013 The International Society of Dermatology.

  12. The human physiological impact of global deoxygenation.

    PubMed

    Martin, Daniel; McKenna, Helen; Livina, Valerie

    2017-01-01

    There has been a clear decline in the volume of oxygen in Earth's atmosphere over the past 20 years. Although the magnitude of this decrease appears small compared to the amount of oxygen in the atmosphere, it is difficult to predict how this process may evolve, due to the brevity of the collected records. A recently proposed model predicts a non-linear decay, which would result in an increasingly rapid fall-off in atmospheric oxygen concentration, with potentially devastating consequences for human health. We discuss the impact that global deoxygenation, over hundreds of generations, might have on human physiology. Exploring the changes between different native high-altitude populations provides a paradigm of how humans might tolerate worsening hypoxia over time. Using this model of atmospheric change, we predict that humans may continue to survive in an unprotected atmosphere for ~3600 years. Accordingly, without dramatic changes to the way in which we interact with our planet, humans may lose their dominance on Earth during the next few millennia.

  13. Leptin in human physiology and pathophysiology

    PubMed Central

    Magkos, Faidon; Brinkoetter, Mary; Sienkiewicz, Elizabeth; Dardeno, Tina A.; Kim, Sang-Yong; Hamnvik, Ole-Petter R.; Koniaris, Anastasia

    2011-01-01

    Leptin, discovered through positional cloning 15 years ago, is an adipocyte-secreted hormone with pleiotropic effects in the physiology and pathophysiology of energy homeostasis, endocrinology, and metabolism. Studies in vitro and in animal models highlight the potential for leptin to regulate a number of physiological functions. Available evidence from human studies indicates that leptin has a mainly permissive role, with leptin administration being effective in states of leptin deficiency, less effective in states of leptin adequacy, and largely ineffective in states of leptin excess. Results from interventional studies in humans demonstrate that leptin administration in subjects with congenital complete leptin deficiency or subjects with partial leptin deficiency (subjects with lipoatrophy, congenital or related to HIV infection, and women with hypothalamic amenorrhea) reverses the energy homeostasis and neuroendocrine and metabolic abnormalities associated with these conditions. More specifically, in women with hypothalamic amenorrhea, leptin helps restore abnormalities in hypothalamic-pituitary-peripheral axes including the gonadal, thyroid, growth hormone, and to a lesser extent adrenal axes. Furthermore, leptin results in resumption of menses in the majority of these subjects and, in the long term, may increase bone mineral content and density, especially at the lumbar spine. In patients with congenital or HIV-related lipoatrophy, leptin treatment is also associated with improvements in insulin sensitivity and lipid profile, concomitant with reduced visceral and ectopic fat deposition. In contrast, leptin's effects are largely absent in the obese hyperleptinemic state, probably due to leptin resistance or tolerance. Hence, another emerging area of research pertains to the discovery and/or usefulness of leptin sensitizers. Results from ongoing studies are expected to further increase our understanding of the role of leptin and the potential clinical

  14. Leptin in human physiology and pathophysiology.

    PubMed

    Mantzoros, Christos S; Magkos, Faidon; Brinkoetter, Mary; Sienkiewicz, Elizabeth; Dardeno, Tina A; Kim, Sang-Yong; Hamnvik, Ole-Petter R; Koniaris, Anastasia

    2011-10-01

    Leptin, discovered through positional cloning 15 years ago, is an adipocyte-secreted hormone with pleiotropic effects in the physiology and pathophysiology of energy homeostasis, endocrinology, and metabolism. Studies in vitro and in animal models highlight the potential for leptin to regulate a number of physiological functions. Available evidence from human studies indicates that leptin has a mainly permissive role, with leptin administration being effective in states of leptin deficiency, less effective in states of leptin adequacy, and largely ineffective in states of leptin excess. Results from interventional studies in humans demonstrate that leptin administration in subjects with congenital complete leptin deficiency or subjects with partial leptin deficiency (subjects with lipoatrophy, congenital or related to HIV infection, and women with hypothalamic amenorrhea) reverses the energy homeostasis and neuroendocrine and metabolic abnormalities associated with these conditions. More specifically, in women with hypothalamic amenorrhea, leptin helps restore abnormalities in hypothalamic-pituitary-peripheral axes including the gonadal, thyroid, growth hormone, and to a lesser extent adrenal axes. Furthermore, leptin results in resumption of menses in the majority of these subjects and, in the long term, may increase bone mineral content and density, especially at the lumbar spine. In patients with congenital or HIV-related lipoatrophy, leptin treatment is also associated with improvements in insulin sensitivity and lipid profile, concomitant with reduced visceral and ectopic fat deposition. In contrast, leptin's effects are largely absent in the obese hyperleptinemic state, probably due to leptin resistance or tolerance. Hence, another emerging area of research pertains to the discovery and/or usefulness of leptin sensitizers. Results from ongoing studies are expected to further increase our understanding of the role of leptin and the potential clinical

  15. Physiologically-based pharmacokinetic analysis of grepafloxacin.

    PubMed

    Nakajima, Y; Hattori, K; Shinsei, M; Matsunaga, N; Iizasa, H; Sasabe, H; Akiyama, H; Miyanmoto, G; Nakashima, E

    2000-09-01

    Grepafloxacin (GPFX) is a synthetic new quinolone antimicrobial agent that possesses an extensive tissue distribution and exhibits a strong antibacterial activity in vivo. In this study, the tissue distribution characteristics of GPFX were examined using tissue concentration-time profiles following intravenous administration to rats. Subsequently, the pharmacokinetics of GPFX were analyzed based on the physiological pharmacokinetic model. The tissue-to-plasma partition coefficients (Kp) of GPFX in rats were high in all tissues except brain. A pharmacokinetic model for rabbits, monkeys and dogs was constructed using the tissue-to-plasma free concentration ratio (Kp,f) of GPFX in rats to simulate the GPFX concentration-time profile in plasma following intravenous administration of GPFX to each animal. The calculation-derived concentrations correlated well with the experimentally-derived data, suggesting that there are no interspecies differences in the high tissue distribution characteristics of GPFX. The clearance rates of GPFX in humans were predicted from the pharmacokinetic parameters of rats, rabbits, monkeys and dogs by an animal scale-up method and a pharmacokinetic model for humans was constructed. The GPFX concentration-time profiles in plasma, following oral administration of GPFX to humans, were predicted within 0.5-1.0 h of mean absorption time and the calculation-derived results were in good agreement with the experimental data. Thus, it is suggested that the concentration-time profile in plasma and all human organs can be predicted from the pharmacokinetic data of animals.

  16. DigitalHuman (DH): An Integrative Mathematical Model ofHuman Physiology

    NASA Technical Reports Server (NTRS)

    Hester, Robert L.; Summers, Richard L.; lIescu, Radu; Esters, Joyee; Coleman, Thomas G.

    2010-01-01

    Mathematical models and simulation are important tools in discovering the key causal relationships governing physiological processes and improving medical intervention when physiological complexity is a central issue. We have developed a model of integrative human physiology called DigitalHuman (DH) consisting of -5000 variables modeling human physiology describing cardiovascular, renal, respiratory, endocrine, neural and metabolic physiology. Users can view time-dependent solutions and interactively introduce perturbations by altering numerical parameters to investigate new hypotheses. The variables, parameters and quantitative relationships as well as all other model details are described in XML text files. All aspects of the model, including the mathematical equations describing the physiological processes are written in XML open source, text-readable files. Model structure is based upon empirical data of physiological responses documented within the peer-reviewed literature. The model can be used to understand proposed physiological mechanisms and physiological interactions that may not be otherwise intUitively evident. Some of the current uses of this model include the analyses of renal control of blood pressure, the central role of the liver in creating and maintaining insulin resistance, and the mechanisms causing orthostatic hypotension in astronauts. Additionally the open source aspect of the modeling environment allows any investigator to add detailed descriptions of human physiology to test new concepts. The model accurately predicts both qualitative and more importantly quantitative changes in clinically and experimentally observed responses. DigitalHuman provides scientists a modeling environment to understand the complex interactions of integrative physiology. This research was supported by.NIH HL 51971, NSF EPSCoR, and NASA

  17. DEVELOPMENT OF A PHYSIOLOGICALLY BASED PHARMACOKINETIC MODEL FOR PROPYLENE GLYCOL MONOMETHYL ETHER AND ITS ACETATE IN RATS AND HUMANS

    SciTech Connect

    Corley, Rick A.; Gies, Richard A.; Wu, Hong; Weitz, Karl K.

    2005-03-05

    Propylene glycol monomethyl ether (PM), along with its acetate, is the most widely used of the propylene glycol ether family of solvents. The most common toxic effects of PM observed in animal studies include sedation, very slight alpha2u globulin-mediated nephropathy (male rats only) and hepatomegally at high exposures (typically >1000 ppm). Sedation in animal studies usually resolves within a few exposures to 3000 ppm (the highest concentration used in subchronic and chronic inhalation studies) due to the induction of metabolizing enzymes. Data from a variety of pharmacokinetic and mechanistic studies have been incorporated into a PBPK model for PM and its acetate in rats and mice. Published controlled exposure and workplace biomonitoring studies have also been included for comparisons of the internal dosimetry of PM and its acetate between laboratory animals and humans. PM acetate is rapidly hydrolyzed to PM, which is further metabolized to either glucuronide or sulphate conjugates (minor pathways) or propylene glycol (major pathway). In vitro half-lives for PM acetate range from 14-36 min depending upon the tissue and species. In vivo half-lives are considerably faster, reflecting the total contributions of esterases in the blood and tissues of the body, and are on the order of just a few minutes. Thus, very little PM acetate is found in vivo and, other than potential portal of entry irritation, the toxicity of PM acetate is related to PM. Regardless of the source for PM (either PM or its acetate), rats were predicted to have a higher Cmax and AUC for PM in blood than humans, especially at concentrations greater than the current ACGIH TLV of 100 ppm. This would indicate that the major systemic effects of PM would be expected to be less severe in humans than rats at comparable inhalation exposures.

  18. [Physiological features of skin ageing in human].

    PubMed

    Tikhonova, I V; Tankanag, A V; Chemeris, N K

    2013-01-01

    The issue deals with the actual problem of gerontology, notably physiological features of human skin ageing. In the present review the authors have considered the kinds of ageing, central factors, affected on the ageing process (ultraviolet radiation and oxidation stress), as well as the research guidelines of the ageing changes in the skin structure and fuctions: study of mechanical properties, microcirculation, pH and skin thickness. The special attention has been payed to the methods of assessment of skin blood flow, and to results of investigations of age features of peripheral microhemodynamics. The laser Doppler flowmetry technique - one of the modern, noninvasive and extensively used methods for the assessmant of skin blood flow microcirculation system has been expanded in the review. The main results of the study of the ageing changes of skin blood perfusion using this method has been also presented.

  19. The Use of Team-Based, Guided Inquiry Learning to Overcome Educational Disadvantages in Learning Human Physiology: A Structural Equation Model

    ERIC Educational Resources Information Center

    Rathner, Joseph A.; Byrne, Graeme

    2014-01-01

    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…

  20. The Use of Team-Based, Guided Inquiry Learning to Overcome Educational Disadvantages in Learning Human Physiology: A Structural Equation Model

    ERIC Educational Resources Information Center

    Rathner, Joseph A.; Byrne, Graeme

    2014-01-01

    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…

  1. The application of global sensitivity analysis in the development of a physiologically based pharmacokinetic model for m-xylene and ethanol co-exposure in humans

    PubMed Central

    Loizou, George D.; McNally, Kevin; Jones, Kate; Cocker, John

    2015-01-01

    Global sensitivity analysis (SA) was used during the development phase of a binary chemical physiologically based pharmacokinetic (PBPK) model used for the analysis of m-xylene and ethanol co-exposure in humans. SA was used to identify those parameters which had the most significant impact on variability of venous blood and exhaled m-xylene and urinary excretion of the major metabolite of m-xylene metabolism, 3-methyl hippuric acid. This analysis informed the selection of parameters for estimation/calibration by fitting to measured biological monitoring (BM) data in a Bayesian framework using Markov chain Monte Carlo (MCMC) simulation. Data generated in controlled human studies were shown to be useful for investigating the structure and quantitative outputs of PBPK models as well as the biological plausibility and variability of parameters for which measured values were not available. This approach ensured that a priori knowledge in the form of prior distributions was ascribed only to those parameters that were identified as having the greatest impact on variability. This is an efficient approach which helps reduce computational cost. PMID:26175688

  2. A dynamic model of human physiology

    NASA Astrophysics Data System (ADS)

    Green, Melissa; Kaplan, Carolyn; Oran, Elaine; Boris, Jay

    2010-11-01

    To study the systems-level transport in the human body, we develop the Computational Man (CMAN): a set of one-dimensional unsteady elastic flow simulations created to model a variety of coupled physiological systems including the circulatory, respiratory, excretory, and lymphatic systems. The model systems are collapsed from three spatial dimensions and time to one spatial dimension and time by assuming axisymmetric vessel geometry and a parabolic velocity profile across the cylindrical vessels. To model the actions of a beating heart or expanding lungs, the flow is driven by user-defined changes to the equilibrium areas of the elastic vessels. The equations are then iteratively solved for pressure, area, and average velocity. The model is augmented with valves and contractions to resemble the biological structure of the different systems. CMAN will be used to track material transport throughout the human body for diagnostic and predictive purposes. Parameters will be adjustable to match those of individual patients. Validation of CMAN has used both higher-dimensional simulations of similar geometries and benchmark measurement from medical literature.

  3. Leptin in Human Physiology and Therapeutics

    PubMed Central

    Dardeno, Tina A.; Chou, Sharon H.; Moon, Hyun-Seuk; Chamberland, John P.; Fiorenza, Christina G.; Mantzoros, Christos S.

    2010-01-01

    Leptin regulates energy homeostasis and reproductive, neuroendocrine, immune, and metabolic functions. In this review, we describe the role of leptin in human physiology and review evidence from recent “proof of concept” clinical trials using recombinant human leptin in subjects with congenital leptin deficiency, hypoleptinemia associated with energy-deficient states, and hyperleptinemia associated with garden-variety obesity. Since most obese individuals are largely leptin-tolerant or -resistant, therapeutic uses of leptin are currently limited to patients with complete or partial leptin deficiency, including hypothalamic amenorrhea and lipoatrophy. Leptin administration in these energy-deficient states may help restore associated neuroendocrine, metabolic, and immune function and bone metabolism. Leptin treatment is currently available for individuals with congenital leptin deficiency and congenital lipoatrophy. The long-term efficacy and safety of leptin treatment in hypothalamic amenorrhea and acquired lipoatrophy are currently under investigation. Whether combination therapy with leptin and potential leptin sensitizers will prove effective in the treatment of garden-variety obesity and whether leptin may have a role in weight loss maintenance is being greatly anticipated. PMID:20600241

  4. Leptin in human physiology and therapeutics.

    PubMed

    Dardeno, Tina A; Chou, Sharon H; Moon, Hyun-Seuk; Chamberland, John P; Fiorenza, Christina G; Mantzoros, Christos S

    2010-07-01

    Leptin regulates energy homeostasis and reproductive, neuroendocrine, immune, and metabolic functions. In this review, we describe the role of leptin in human physiology and review evidence from recent "proof of concept" clinical trials using recombinant human leptin in subjects with congenital leptin deficiency, hypoleptinemia associated with energy-deficient states, and hyperleptinemia associated with garden-variety obesity. Since most obese individuals are largely leptin-tolerant or -resistant, therapeutic uses of leptin are currently limited to patients with complete or partial leptin deficiency, including hypothalamic amenorrhea and lipoatrophy. Leptin administration in these energy-deficient states may help restore associated neuroendocrine, metabolic, and immune function and bone metabolism. Leptin treatment is currently available for individuals with congenital leptin deficiency and congenital lipoatrophy. The long-term efficacy and safety of leptin treatment in hypothalamic amenorrhea and acquired lipoatrophy are currently under investigation. Whether combination therapy with leptin and potential leptin sensitizers will prove effective in the treatment of garden-variety obesity and whether leptin may have a role in weight loss maintenance is being greatly anticipated.

  5. An Extended Minimal Physiologically Based Pharmacokinetic Model: Evaluation of Type II Diabetes Mellitus and Diabetic Nephropathy on Human IgG Pharmacokinetics in Rats.

    PubMed

    Chadha, Gurkishan S; Morris, Marilyn E

    2015-11-01

    Although many studies have evaluated the effects of type 2 diabetes mellitus (T2DM) on the pharmacokinetics (PK) of low molecular weight molecules, there is limited information regarding effects on monoclonal antibodies. Our previous studies have reported significant increases in total (2-4 fold) and renal (100-300 fold) clearance of human IgG, an antibody isotype, in Zucker diabetic fatty (ZDF) rats. Pioglitazone treatment incompletely reversed the disease-related PK changes. The objective of this study was to construct a mechanistic model for simultaneous fitting plasma and urine data, to yield physiologically relevant PK parameters. We propose an extended minimal physiologically based PK (mPBPK) model specifically for IgG by classifying organs as either leaky or tight vascular tissues, and adding a kidney compartment. The model incorporates convection as the primary mechanism of IgG movement from plasma into tissues, interstitial fluid (ISF) in extravascular distribution space, and glomerular filtration rate (GFR), sieving coefficient and fraction reabsorbed in the kidney. The model captured the plasma and urine PK profiles well, and simulated concentrations in ISF. The model estimated a 2-4 fold increase in nonrenal clearance from plasma and 30-120 fold increase in renal clearance with T2DM, consistent with the experimental findings, and these differences in renal clearance were related to changes in GFR, sieving coefficient, and proximal tubular reabsorption. In conclusion, the mPBPK model offers a more relevant approach for analyzing plasma and urine IgG concentration-time data than conventional models and provides insight regarding alterations in distributional and elimination parameters occurring with T2DM.

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

    EPA Pesticide Factsheets

    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:

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

    EPA Pesticide Factsheets

    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:

  8. Mathematical modeling of human brain physiological data

    NASA Astrophysics Data System (ADS)

    Böhm, Matthias; Faltermeier, Rupert; Brawanski, Alexander; Lang, Elmar W.

    2013-12-01

    Recently, a mathematical model of the basic physiological processes regulating the cerebral perfusion and oxygen supply was introduced [Jung , J. Math. Biol.JMBLAJ0303-681210.1007/s00285-005-0343-5 51, 491 (2005)]. Although this model correctly describes the interdependence of arterial blood pressure (ABP) and intracranial pressure (ICP), it fails badly when it comes to explaining certain abnormal correlations seen in about 80% of the recordings of ABP together with ICP and the partial oxygen pressure (TiPO2) of the neuronal tissue, taken at an intensive care unit during neuromonitoring of patients with a severe brain trauma. Such recordings occasionally show segments, where the mean arterial blood pressure is correlated with the partial oxygen pressure in tissue but anticorrelated with the intracranial pressure. The origin of such abnormal correlations has not been fully understood yet. Here, two extensions to the previous approach are proposed which can reproduce such abnormal correlations in simulations quantitatively. Furthermore, as the simulations are based on a mathematical model, additional insight into the physiological mechanisms from which such abnormal correlations originate can be gained.

  9. Simulating human space physiology with bed rest.

    PubMed

    Jost, P D

    2008-08-01

    In a recent review on bed rest studies of the past 20 years, it was concluded that head-down bed rest has proved its usefulness as a reliable simulation model for most physiological effects of spaceflight. Much of this research has been conducted to find countermeasures against the negative effects, which are associated with gravitational unloading. There have been partial successes in the prevention of, for example muscle wasting, cardio-vascular deconditioning, adverse metabolic changes, and bone demineralization. Reviews refer to bone-related measurements of the U.S. and Russian space programmes, as well as data from bed rest analogues, and conclude that in spite of the wealth of knowledge obtained thus far, many questions remain regarding bone loss, bone recovery, and the factors affecting these skeletal processes. Bed rest research has also direct relevance for medical science on Earth. Valuable data on physiology and early reversible pathological changes that are associated with a sedentary lifestyle on Earth can be obtained. A good example is the conclusion from a metabolic protocol implemented during the 2001/2002 90-day ESA/CNES/NASDA male bed rest study. The results of that experiment on fatty acid oxidation suggest that Mediterranean diets should be recommended in recumbent patients. Some other unexpected results obtained during the ESA/NASA/CNES/CSA 60-day female bed rest study WISE-2005 may well prompt the development of a treatment for certain cardiac diseases. A nutritional supplement that was designed to alleviate skeletal muscle atrophy turned out to preserve cardiac muscle mass. In order to optimise bed rest research, a systematic and standardised approach will be beneficial. During the last years, serious efforts have been made towards such standardisation on an international level. It is expected that results from future studies, combined with in-flight validation, will provide the answers to many biomedical problems that currently limit safe

  10. Incorporation of Therapeutic Interventions in Physiologically Based Pharmacokinetic Modeling of Human Clinical Case Reports of Accidental or Intentional Overdosing with Ethylene Glycol

    SciTech Connect

    Corley, Rick A.; McMartin, K. E.

    2005-05-16

    Ethylene glycol is a high production volume chemical used in the manufacture of resins and fibers, antifreeze, deicing fluids, heat transfer and hydraulic fluids. Although occupational uses of ethylene glycol have not been associated with adverse effects, there are case reports where humans have either intentionally or accidentally ingested large quantities of ethylene glycol, primarily from antifreeze. The acute toxicity of ethylene glycol in humans and animals and can proceed through three stages, each associated with a different metabolite: central nervous system depression (ethylene glycol), cardiopulmonary effects associated with metabolic acidosis (glycolic acid) and ultimately renal toxicity (oxalic acid), depending upon the total amounts consumed and effectiveness of therapeutic interventions. A physiologically based pharmacokinetic (PBPK) model developed in a companion paper (Corley et al., 2004) was refined in this study to include clinically relevant treatment regimens for ethylene glycol poisoning such as hemodialysis or metabolic inhibition with either ethanol or fomepizole. Such modifications enabled the model to describe several human case reports which included analysis of ethylene glycol and/or glycolic acid. Such data and model simulations provide important confirmation that the PBPK model developed previously can adequately describe the pharmacokinetics of ethylene glycol in humans following low, occupational or environmentally relevant inhalation exposures, as well as massive oral doses even under conditions where treatments have been employed that markedly affect the disposition of ethylene glycol and glycolic acid. By integrating the case report data sets with controlled studies in this PBPK model, it was demonstrated that fomepizole, if administered early enough in a clinical situation, can be more effective than ethanol or hemodialysis in preventing the metabolism of ethylene glycol to more toxic metabolites. Hemodialysis remains an

  11. Space Cabin Landing Impact Vector Effects on Human Physiology

    DTIC Science & Technology

    1964-12-01

    December 1964 Journal Article 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Space Cabin Landing Impact Vector Effects on Human Physiology 5b. GRANT NUMBER 5c...Landing Impact Vector Effects on Human Physiology COLONEL JOHN P. STAPP, USAF, MC, and MAJOR ELLIS R. TAYLOR, USAF, MC ABSTRACT stimulation of carotid...LANDING IMPACT VECTOR EFFECTS ON HUMAN PHYSIOLOGY -STAPP AND TAYLOR tion and pallor occurred on exposure to more than 30 facing seated and bottom

  12. Knowledge environments representing molecular entities for the virtual physiological human.

    PubMed

    Hofmann-Apitius, Martin; Fluck, Juliane; Furlong, Laura; Fornes, Oriol; Kolárik, Corinna; Hanser, Susanne; Boeker, Martin; Schulz, Stefan; Sanz, Ferran; Klinger, Roman; Mevissen, Theo; Gattermayer, Tobias; Oliva, Baldo; Friedrich, Christoph M

    2008-09-13

    In essence, the virtual physiological human (VPH) is a multiscale representation of human physiology spanning from the molecular level via cellular processes and multicellular organization of tissues to complex organ function. The different scales of the VPH deal with different entities, relationships and processes, and in consequence the models used to describe and simulate biological functions vary significantly. Here, we describe methods and strategies to generate knowledge environments representing molecular entities that can be used for modelling the molecular scale of the VPH. Our strategy to generate knowledge environments representing molecular entities is based on the combination of information extraction from scientific text and the integration of information from biomolecular databases. We introduce @neuLink, a first prototype of an automatically generated, disease-specific knowledge environment combining biomolecular, chemical, genetic and medical information. Finally, we provide a perspective for the future implementation and use of knowledge environments representing molecular entities for the VPH.

  13. [Research progress on emotion recognition based on physiological signals].

    PubMed

    Zhang, Di; Wan, Baikun; Ming, Dong

    2015-02-01

    Emotion recognition will be prosperious in multifarious applications, like distance education, healthcare, and human-computer interactions, etc. Emotions can be recognized from the behavior signals such as speech, facial expressions, gestures or the physiological signals such as electroencephalogram and electrocardiogram. Contrast to other methods, the physiological signals based emotion recognition can achieve more objective and effective results because it is almost impossible to be disguised. This paper introduces recent advancements in emotion research using physiological signals, specified to its emotion model, elicitation stimuli, feature extraction and classification methods. Finally the paper also discusses some research challenges and future developments.

  14. The Virtual Physiological Human ToolKit.

    PubMed

    Cooper, Jonathan; Cervenansky, Frederic; De Fabritiis, Gianni; Fenner, John; Friboulet, Denis; Giorgino, Toni; Manos, Steven; Martelli, Yves; Villà-Freixa, Jordi; Zasada, Stefan; Lloyd, Sharon; McCormack, Keith; Coveney, Peter V

    2010-08-28

    The Virtual Physiological Human (VPH) is a major European e-Science initiative intended to support the development of patient-specific computer models and their application in personalized and predictive healthcare. The VPH Network of Excellence (VPH-NoE) project is tasked with facilitating interaction between the various VPH projects and addressing issues of common concern. A key deliverable is the 'VPH ToolKit'--a collection of tools, methodologies and services to support and enable VPH research, integrating and extending existing work across Europe towards greater interoperability and sustainability. Owing to the diverse nature of the field, a single monolithic 'toolkit' is incapable of addressing the needs of the VPH. Rather, the VPH ToolKit should be considered more as a 'toolbox' of relevant technologies, interacting around a common set of standards. The latter apply to the information used by tools, including any data and the VPH models themselves, and also to the naming and categorizing of entities and concepts involved. Furthermore, the technologies and methodologies available need to be widely disseminated, and relevant tools and services easily found by researchers. The VPH-NoE has thus created an online resource for the VPH community to meet this need. It consists of a database of tools, methods and services for VPH research, with a Web front-end. This has facilities for searching the database, for adding or updating entries, and for providing user feedback on entries. Anyone is welcome to contribute.

  15. Flexible and wearable electronic silk fabrics for human physiological monitoring

    NASA Astrophysics Data System (ADS)

    Mao, Cuiping; Zhang, Huihui; Lu, Zhisong

    2017-09-01

    The development of textile-based devices for human physiological monitoring has attracted tremendous interest in recent years. However, flexible physiological sensing elements based on silk fabrics have not been realized. In this paper, ZnO nanorod arrays are grown in situ on reduced graphene oxide-coated silk fabrics via a facile electro-deposition method for the fabrication of silk-fabric-based mechanical sensing devices. The data show that well-aligned ZnO nanorods with hexagonal wurtzite crystalline structures are synthesized on the conductive silk fabric surface. After magnetron sputtering of gold electrodes, silk-fabric-based devices are produced and applied to detect periodic bending and twisting. Based on the electric signals, the deformation and release processes can be easily differentiated. Human arterial pulse and respiration can also be real-time monitored to calculate the pulse rate and respiration frequency, respectively. Throat vibrations during coughing and singing are detected to demonstrate the voice recognition capability. This work may not only help develop silk-fabric-based mechanical sensing elements for potential applications in clinical diagnosis, daily healthcare monitoring and voice recognition, but also provide a versatile method for fabricating textile-based flexible electronic devices.

  16. Physiologically based pharmacokinetic-pharmacodynamic modeling to predict concentrations and actions of sodium-dependent glucose transporter 2 inhibitor canagliflozin in human intestines and renal tubules.

    PubMed

    Mori, Kazumi; Saito, Ryuta; Nakamaru, Yoshinobu; Shimizu, Makiko; Yamazaki, Hiroshi

    2016-11-01

    Canagliflozin is a recently developed sodium-glucose cotransporter (SGLT) 2 inhibitor that promotes renal glucose excretion and is considered to inhibit renal SGLT2 from the luminal side of proximal tubules. Canagliflozin reportedly inhibits SGLT1 weakly and suppresses postprandial plasma glucose, suggesting that it also inhibits intestinal SGLT1. However, it is difficult to measure the drug concentrations of these assumed sites of action directly. The pharmacokinetic-pharmacodynamic (PK/PD) relationships of canagliflozin remain poorly characterized. Therefore, a physiologically based pharmacokinetic (PBPK) model of canagliflozin was developed based on clinical data from healthy volunteers and it was used to simulate luminal concentrations in intestines and renal tubules. In small intestine simulations, the inhibition ratios for SGLT1 were predicted to be 40%-60% after the oral administration of clinical doses (100-300 mg/day). In contrast, inhibition ratios of canagliflozin for renal SGLT2 and SGLT1 were predicted to be approximately 100% and 0.2%-0.4%, respectively. These analyses suggest that canagliflozin only inhibits SGLT2 in the kidney. Using the simulated proximal tubule luminal concentrations of canagliflozin, the urinary glucose excretion rates in canagliflozin-treated diabetic patients were accurately predicted using the renal glucose reabsorption model as a PD model. Because the simulation of canagliflozin pharmacokinetics was successful, this PBPK methodology was further validated by successfully simulating the pharmacokinetics of dapagliflozin, another SGLT2 inhibitor. The present results suggest the utility of this PBPK/PD model for predicting canagliflozin concentrations at target sites and help to elucidate the pharmacological effects of SGLT1/2 inhibition in humans. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  17. Wearable Systems for Service based on Physiological Signals.

    PubMed

    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.

  18. Physiological concentrations of DHEA in human hair.

    PubMed

    Kintz, P; Cirimele, V; Ludes, B

    1999-10-01

    In 1974, steroids were added to the list of doping agents banned by the International Olympic Committee because of their effects on the performance of the athletes. Dehydroepiandrosterone (DHEA) is a steroid hormone naturally produced by the adrenal glands and by the ovaries. DHEA can be converted into other hormones, including estrogen and testosterone. In the United States, DHEA is classified as a nutritional supplement. This is not the case in France, where the drug is listed as a doping agent. As athletes can abuse DHEA to benefit from its conversion to testosterone, there is a need to establish the physiological range of DHEA concentrations in human hair. DHEA was investigated in hair obtained from 27 control subjects, including 15 males and 12 females aged 17-42 years. After decontamination with dichloromethane, 100 mg of hair was incubated in 1 M NaOH in presence of 1 ng of testosterone-d3. After neutralization, the extract was purified using solid-phase extraction with Isolute C18 columns and subsequent liquid-liquid extraction with pentane. After silylation, DHEA was analyzed by gas chromatography-mass spectrometry. Results were linear in the range 1-20 pg/mg. Relative extraction recovery was 91.6% with a limit of detection of 0.5 pg/mg. Concentrations were in the range 1.2-6.7 pg/mg (mean value of 4.3 pg/mg) and 0.5 to 10.6 pg/mg (mean value of 5.3 pg/mg) for the males and females, respectively. Extensive chromatographic procedures (two purification steps by solid-phase and liquid-liquid extraction, combined with injection of 4 microL through the column in pulsed mode) were analytical prerequisites for successful identification of DHEA in hair because of the low target concentrations. This new technology may find useful applications in anabolic abuse control.

  19. Structural physiology based on electron crystallography

    PubMed Central

    Fujiyoshi, Yoshinori

    2011-01-01

    There are many questions in brain science, which are extremely interesting but very difficult to answer. For example, how do education and other experiences during human development influence the ability and personality of the adult? The molecular mechanisms underlying such phenomena are still totally unclear. However, technological and instrumental advancements of electron microscopy have facilitated comprehension of the structures of biological components, cells, and organelles. Electron crystallography is especially good for studying the structure and function of membrane proteins, which are key molecules of signal transduction in neural and other cells. Electron crystallography is now an established technique to analyze the structures of membrane proteins in lipid bilayers, which are close to their natural biological environment. By utilizing cryo-electron microscopes with helium cooled specimen stages, which were developed through a personal motivation to understand functions of neural systems from a structural point of view, structures of membrane proteins were analyzed at a resolution higher than 3 Å. This review has four objectives. First, it is intended to introduce the new research field of structural physiology. Second, it introduces some of the personal struggles, which were involved in developing the cryo-electron microscope. Third, it discusses some of the technology for the structural analysis of membrane proteins based on cryo-electron microscopy. Finally, it reviews structural and functional analyses of membrane proteins. PMID:21416541

  20. Physiologically based pharmacokinetic modeling of human exposure to perfluorooctanoic acid suggests historical non drinking-water exposures are important for predicting current serum concentrations.

    PubMed

    Worley, Rachel Rogers; Yang, Xiaoxia; Fisher, Jeffrey

    2017-09-01

    Manufacturing of perfluorooctanoic acid (PFOA), a synthetic chemical with a long half-life in humans, peaked between 1970 and 2002, and has since diminished. In the United States, PFOA is detected in the blood of >99% of people tested, but serum concentrations have decreased since 1999. Much is known about exposure to PFOA in drinking water; however, the impact of non-drinking water PFOA exposure on serum PFOA concentrations is not well characterized. The objective of this research is to apply physiologically based pharmacokinetic (PBPK) modeling and Monte Carlo analysis to evaluate the impact of historic non-drinking water PFOA exposure on serum PFOA concentrations. In vitro to in vivo extrapolation was utilized to inform descriptions of PFOA transport in the kidney. Monte Carlo simulations were incorporated to evaluate factors that account for the large inter-individual variability of serum PFOA concentrations measured in individuals from North Alabama in 2010 and 2016, and the Mid-Ohio River Valley between 2005 and 2008. Predicted serum PFOA concentrations were within two-fold of experimental data. With incorporation of Monte Carlo simulations, the model successfully tracked the large variability of serum PFOA concentrations measured in populations from the Mid-Ohio River Valley. Simulation of exposure in a population of 45 adults from North Alabama successfully predicted 98% of individual serum PFOA concentrations measured in 2010 and 2016, respectively, when non-drinking water ingestion of PFOA exposure was included. Variation in serum PFOA concentrations may be due to inter-individual variability in the disposition of PFOA and potentially elevated historical non-drinking water exposures. Published by Elsevier Inc.

  1. Human Physiology in an Aquatic Environment.

    PubMed

    Pendergast, David R; Moon, Richard E; Krasney, John J; Held, Heather E; Zamparo, Paola

    2015-09-20

    Water covers over 70% of the earth, has varying depths and temperatures and contains much of the earth's resources. Head-out water immersion (HOWI) or submersion at various depths (diving) in water of thermoneutral (TN) temperature elicits profound cardiorespiratory, endocrine, and renal responses. The translocation of blood into the thorax and elevation of plasma volume by autotransfusion of fluid from cells to the vascular compartment lead to increased cardiac stroke volume and output and there is a hyperperfusion of some tissues. Pulmonary artery and capillary hydrostatic pressures increase causing a decline in vital capacity with the potential for pulmonary edema. Atrial stretch and increased arterial pressure cause reflex autonomic responses which result in endocrine changes that return plasma volume and arterial pressure to preimmersion levels. Plasma volume is regulated via a reflex diuresis and natriuresis. Hydrostatic pressure also leads to elastic loading of the chest, increasing work of breathing, energy cost, and thus blood flow to respiratory muscles. Decreases in water temperature in HOWI do not affect the cardiac output compared to TN; however, they influence heart rate and the distribution of muscle and fat blood flow. The reduced muscle blood flow results in a reduced maximal oxygen consumption. The properties of water determine the mechanical load and the physiological responses during exercise in water (e.g. swimming and water based activities). Increased hydrostatic pressure caused by submersion does not affect stroke volume; however, progressive bradycardia decreases cardiac output. During submersion, compressed gas must be breathed which introduces the potential for oxygen toxicity, narcosis due to nitrogen, and tissue and vascular gas bubbles during decompression and after may cause pain in joints and the nervous system.

  2. Human physiological responses to wooden indoor environment.

    PubMed

    Zhang, Xi; Lian, Zhiwei; Wu, Yong

    2017-03-02

    Previous studies are mainly focused on non-wooden environments, whereas few are concerned with wooden ones. How wooden indoor environments impact the physiology of the occupants is still unclear. The purpose of this study was to explore the distinct physiological responses to wooden and non-wooden indoor environments, assessed by physiological parameters tests including blood pressure, electrocardiogram measurements, electro-dermal activity, oxyhemoglobin saturation, skin temperature, and near distance vision. Twenty healthy adults participated in this experiment, and their physiological responses were evaluated in a 90minute investigation. The results illustrated that; less tension and fatigue were generated in the wooden rooms than in the non-wooden rooms when the participants did their work. In addition, the study also found that the wooden environments benefit the autonomic nervous system, respiratory system, and visual system. Moreover, wooden rooms play a valuable role in physiological regulation and ease function especially after a consecutive period of work. These results provide an experimental basis to support that wooden environment is beneficial to indoor occupants than the non-wooden indoor environment.

  3. Possible heliogeophysical effects on human physiological state

    NASA Astrophysics Data System (ADS)

    Dimitrova, Svetla

    2009-03-01

    A group of 86 healthy volunteers was examined in periods of high solar and geomagnetic activity. In this study hourly Dst-index values and hourly data about intensity of cosmic rays were used. Results revealed statistically significant increments for the mean systolic and diastolic blood pressure, pulse pressure and subjective psycho-physiological complaints of the group with geomagnetic activity increase and cosmic rays intensity decrease.

  4. Physiologically based pharmacokinetic model for acetone.

    PubMed Central

    Kumagai, S; Matsunaga, I

    1995-01-01

    OBJECTIVE--This study aimed to develop a physiologically based pharmacokinetic model for acetone and to predict the kinetic behaviour of acetone in the human body with that model. METHODS--The model consists of eight tissue groups in which acetone can be distributed: the mucous layer of the inhaled air tract, the mucous layer of the exhaled air tract, a compartment for gas exchange (alveolus of the lung), a group of blood vessel rich tissues including the brain and heart, a group of tissues including muscles and skin that have low perfusion rates, a group of fatty tissues, an organ for metabolism (liver), and a compartment for urinary excretion (kidney). A mucous layer in the model is only the outermost layer of the mucus lining the wall of the air tract during inhalation and exhalation. To check the relevance of the model, the simulated results were compared with the experimental data. Next, simulation was conducted by changing the volume of the mucous layer and the respiratory rate to clarify the effect of these variables. Finally, simulation of an occupational situation was performed. RESULTS--With an appropriate value for the volume of mucous layer, the simulated acetone concentrations in arterial blood, end exhaled air, urine, and fatty tissue were found to agree well with the experimental data. The volume of mucous layer and rate of respiration were critical for the appropriate simulation. The simulated occupational situation fitted the observed regression line in field studies quite well. The simulation also enabled predictions to be made about the characteristic kinetics for water soluble solvents. CONCLUSION--The model is useful for understanding and explaining the kinetics of acetone. PMID:7795758

  5. Human Adaptation to Space: Space Physiology and Countermeasures

    NASA Technical Reports Server (NTRS)

    Fogarty, Jennifer

    2009-01-01

    This viewgraph presentation reviews human physiological responses to spaceflight, and the countermeasures taken to prevent adverse effects of manned space flight. The topics include: 1) Human Spaceflight Experience; 2) Human Response to Spaceflight; 3) ISS Expeditions 1-16; 4) Countermeasure; and 5) Biomedical Data;

  6. [Human physiology: images and practices of the reflex].

    PubMed

    Wübben, Yvonne

    2010-01-01

    The essay examines the function of visualizations and practices in the formation of the reflex concept from Thomas Willis to Marshall Hall. It focuses on the specific form of reflex knowledge that images and practices can contain. In addition, the essay argues that it is through visual representations and experimental practices that technical knowledge is transferred to the field of human reflex physiology. When using technical metaphors in human physiology authors often seem to feel obliged to draw distinctions between humans, machines and animals. On closer scrutiny, these distinctions sometimes fail to establish firm borders between the human and the technical.

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

    EPA Pesticide Factsheets

    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

  8. Integrative Physiology: At the Crossroads of Nutrition, Microbiota, Animal Physiology, and Human Health.

    PubMed

    Leulier, François; MacNeil, Lesley T; Lee, Won-Jae; Rawls, John F; Cani, Patrice D; Schwarzer, Martin; Zhao, Liping; Simpson, Stephen J

    2017-03-07

    Nutrition is paramount in shaping all aspects of animal biology. In addition, the influence of the intestinal microbiota on physiology is now widely recognized. Given that diet also shapes the intestinal microbiota, this raises the question of how the nutritional environment and microbial assemblages together influence animal physiology. This research field constitutes a new frontier in the field of organismal biology that needs to be addressed. Here we review recent studies using animal models and humans and propose an integrative framework within which to define the study of the diet-physiology-microbiota systems and ultimately link it to human health. Nutritional Geometry sits centrally in the proposed framework and offers means to define diet compositions that are optimal for individuals and populations. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Physiological Based Simulator Fidelity Design Guidance

    NASA Technical Reports Server (NTRS)

    Schnell, Thomas; Hamel, Nancy; Postnikov, Alex; Hoke, Jaclyn; McLean, Angus L. M. Thom, III

    2012-01-01

    The evolution of the role of flight simulation has reinforced assumptions in aviation that the degree of realism in a simulation system directly correlates to the training benefit, i.e., more fidelity is always better. The construct of fidelity has several dimensions, including physical fidelity, functional fidelity, and cognitive fidelity. Interaction of different fidelity dimensions has an impact on trainee immersion, presence, and transfer of training. This paper discusses research results of a recent study that investigated if physiological-based methods could be used to determine the required level of simulator fidelity. Pilots performed a relatively complex flight task consisting of mission task elements of various levels of difficulty in a fixed base flight simulator and a real fighter jet trainer aircraft. Flight runs were performed using one forward visual channel of 40 deg. field of view for the lowest level of fidelity, 120 deg. field of view for the middle level of fidelity, and unrestricted field of view and full dynamic acceleration in the real airplane. Neuro-cognitive and physiological measures were collected under these conditions using the Cognitive Avionics Tool Set (CATS) and nonlinear closed form models for workload prediction were generated based on these data for the various mission task elements. One finding of the work described herein is that simple heart rate is a relatively good predictor of cognitive workload, even for short tasks with dynamic changes in cognitive loading. Additionally, we found that models that used a wide range of physiological and neuro-cognitive measures can further boost the accuracy of the workload prediction.

  10. Physiological Determinants of Human Acute Hypoxia Tolerance

    DTIC Science & Technology

    2013-11-01

    Ernsting , 1963; Lilienthal, Riley, Proemmel, & Franke, 1946) but not the causes of variation among individuals, per se. In this study, we tested the...hemoglobin oxygen saturation falls when human subjects breathe a gas mixture with reduced oxygen tension. Previous work by Ernsting (1963...Determination of PO2 from saturation. J Appl Physiol 67: 902, 1989. Ernsting J. The effect of brief profound hypoxia upon the arte- rial and venous

  11. MEGen: A Physiologically Based Pharmacokinetic Model Generator

    PubMed Central

    Loizou, George; Hogg, Alex

    2011-01-01

    Physiologically based pharmacokinetic models are being used in an increasing number of different areas. However, they 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 web application called MEGen for the rapid construction and documentation of bespoke deterministic PBPK model code is under development. MEGen comprises a parameter database and a model code generator that produces code for use in several commercial software packages and one that is freely available. Here we present an overview of the current capabilities of MEGen, and discuss future developments. PMID:22084631

  12. LINKING 'OMIC AND GENETIC DATA TO PHYSIOLOGICALLY-BASED PHARMACOKINETIC AND PHARMACODYNAMIC MODELING TO ENHANCE ECOLOGICAL AND HUMAN HEALTH RISK ASSESSMENT

    EPA Science Inventory

    A great deal of academic, private sector, and government research has been initiated to apply advanced molecular biological methods to the discovery of toxicity pathways in wildlife and humans. One aim is the prediction of health outcomes based on the combination of refined chemi...

  13. LINKING 'OMIC AND GENETIC DATA TO PHYSIOLOGICALLY-BASED PHARMACOKINETIC AND PHARMACODYNAMIC MODELING TO ENHANCE ECOLOGICAL AND HUMAN HEALTH RISK ASSESSMENT

    EPA Science Inventory

    A great deal of academic, private sector, and government research has been initiated to apply advanced molecular biological methods to the discovery of toxicity pathways in wildlife and humans. One aim is the prediction of health outcomes based on the combination of refined chemi...

  14. Mitochondrial uncoupling proteins in human physiology and disease.

    PubMed

    Hagen, T; Vidal-Puig, A

    2002-02-01

    Uncoupling proteins are mitochondrial carrier proteins that catalyse a regulated proton leak across the inner mitochondrial membrane, diverting free energy from ATP synthesis by the mitochondrial F0F1-ATP synthase to the production of heat. Uncoupling protein 1 (UCP1), which is exclusively expressed in brown adipose tissue, is the mediator of thermogenesis in response to beta-adrenergic stimulation. Using gene a knockout mouse model, UCP1 has been shown to be required for cold acclimation. Two homologues of UCP1, UCP2 and UCP3, have been identified recently and show a much wider tissue distribution. UCP2 and UCP3 have been postulated to play a role in the regulation of cold acclimation, energy expenditure and diet-induced thermogenesis in humans, who, in contrast to rodents, have very little brown fat in adult life. However, evidence is accumulating that thermogenesis and regulation of body weight may not be the physiological functions of UCP2 and UCP3. For instance, mice deficient for UCP2 or UCP3 are not cold-intolerant and do not develop obesity. Alternative functions were suggested, primarily based on findings in UCP2 and UCP3 gene knockout mice. Both UCP2- and UCP3-deficient mice were found to overproduce reactive oxygen species and UCP2-deficient mice to hypersecrete insulin. Thus, the UCP1 homologues may play a role in regulating mitochondrial production of reactive oxygen species and b-cell function. In this review, we discuss the role of UCP1, UCP2 and UCP3 in human physiology and disease, primarily based on findings from the various animal models that have been generated.

  15. User Interactive Software for Analysis of Human Physiological Data

    NASA Technical Reports Server (NTRS)

    Cowings, Patricia S.; Toscano, William; Taylor, Bruce C.; Acharya, Soumydipta

    2006-01-01

    Ambulatory physiological monitoring has been used to study human health and performance in space and in a variety of Earth-based environments (e.g., military aircraft, armored vehicles, small groups in isolation, and patients). Large, multi-channel data files are typically recorded in these environments, and these files often require the removal of contaminated data prior to processing and analyses. Physiological data processing can now be performed with user-friendly, interactive software developed by the Ames Psychophysiology Research Laboratory. This software, which runs on a Windows platform, contains various signal-processing routines for both time- and frequency- domain data analyses (e.g., peak detection, differentiation and integration, digital filtering, adaptive thresholds, Fast Fourier Transform power spectrum, auto-correlation, etc.). Data acquired with any ambulatory monitoring system that provides text or binary file format are easily imported to the processing software. The application provides a graphical user interface where one can manually select and correct data artifacts utilizing linear and zero interpolation and adding trigger points for missed peaks. Block and moving average routines are also provided for data reduction. Processed data in numeric and graphic format can be exported to Excel. This software, PostProc (for post-processing) requires the Dadisp engineering spreadsheet (DSP Development Corp), or equivalent, for implementation. Specific processing routines were written for electrocardiography, electroencephalography, electromyography, blood pressure, skin conductance level, impedance cardiography (cardiac output, stroke volume, thoracic fluid volume), temperature, and respiration

  16. Development of a Physiological Model for the Human Spine

    NASA Astrophysics Data System (ADS)

    Kvitnitsky, Michael; Thangam, Siva

    2011-11-01

    The intervertebral disc in a human spine is a complex structure consisting of three distinct parts: the nucleus pulposus, the annulus fibrosus, and the cartilaginous end-plates. The Nucleus Pulposus is centrally located within the disc surrounded by annulus fibrosus. It consists of a loose network of fibers and cells in a proteoglycan gel, which merges indistinctly at its outer margin with the annulus fibrosus. A viscoelastic constitutive model is proposed for the nucleus pulposus of the human spine to facilitate the development of a flexible intervetebral device designed for application in the thoraco-lumbar region of the human spine during surgery. A novel experimental set up was designed to establish application limits of the design concept for different approaches in spinal surgery. Both static and fatigue mechanical tests based on the ASTM standards provided a basis for the comparison with some existing clinically successful spinal implants designed for similar applications. Also, these mechanical tests and in-vitro comparison with normal spine provided the application limits of this design in surgery to maintain physiologic functional performance at the affected spinal level. The model is used to investigate the effect of the various design parameters on the biomechanical environment of the spine segment.

  17. Assessing human variability in kinetics for exposures to multiple environmental chemicals: a physiologically based pharmacokinetic modeling case study with dichloromethane, benzene, toluene, ethylbenzene, and m-xylene.

    PubMed

    Valcke, Mathieu; Haddad, Sami

    2015-01-01

    The objective of this study was to compare the magnitude of interindividual variability in internal dose for inhalation exposure to single versus multiple chemicals. Physiologically based pharmacokinetic models for adults (AD), neonates (NEO), toddlers (TODD), and pregnant women (PW) were used to simulate inhalation exposure to "low" (RfC-like) or "high" (AEGL-like) air concentrations of benzene (Bz) or dichloromethane (DCM), along with various levels of toluene alone or toluene with ethylbenzene and xylene. Monte Carlo simulations were performed and distributions of relevant internal dose metrics of either Bz or DCM were computed. Area under the blood concentration of parent compound versus time curve (AUC)-based variability in AD, TODD, and PW rose for Bz when concomitant "low" exposure to mixtures of increasing complexities occurred (coefficient of variation (CV) = 16-24%, vs. 12-15% for Bz alone), but remained unchanged considering DCM. Conversely, AUC-based CV in NEO fell (15 to 5% for Bz; 12 to 6% for DCM). Comparable trends were observed considering production of metabolites (AMET), except for NEO's CYP2E1-mediated metabolites of Bz, where an increased CV was observed (20 to 71%). For "high" exposure scenarios, Cmax-based variability of Bz and DCM remained unchanged in AD and PW, but decreased in NEO (CV= 11-16% to 2-6%) and TODD (CV= 12-13% to 7-9%). Conversely, AMET-based variability for both substrates rose in every subpopulation. This study analyzed for the first time the impact of multiple exposures on interindividual variability in toxicokinetics. Evidence indicates that this impact depends upon chemical concentrations and biochemical properties, as well as the subpopulation and internal dose metrics considered.

  18. HumMod: A Modeling Environment for the Simulation of Integrative Human Physiology.

    PubMed

    Hester, Robert L; Brown, Alison J; Husband, Leland; Iliescu, Radu; Pruett, Drew; Summers, Richard; Coleman, Thomas G

    2011-01-01

    Mathematical models and simulations are important tools in discovering key causal relationships governing physiological processes. Simulations guide and improve outcomes of medical interventions involving complex physiology. We developed HumMod, a Windows-based model of integrative human physiology. HumMod consists of 5000 variables describing cardiovascular, respiratory, renal, neural, endocrine, skeletal muscle, and metabolic physiology. The model is constructed from empirical data obtained from peer-reviewed physiological literature. All model details, including variables, parameters, and quantitative relationships, are described in Extensible Markup Language (XML) files. The executable (HumMod.exe) parses the XML and displays the results of the physiological simulations. The XML description of physiology in HumMod's modeling environment allows investigators to add detailed descriptions of human physiology to test new concepts. Additional or revised XML content is parsed and incorporated into the model. The model accurately predicts both qualitative and quantitative changes in clinical and experimental responses. The model is useful in understanding proposed physiological mechanisms and physiological interactions that are not evident, allowing one to observe higher level emergent properties of the complex physiological systems. HumMod has many uses, for instance, analysis of renal control of blood pressure, central role of the liver in creating and maintaining insulin resistance, and mechanisms causing orthostatic hypotension in astronauts. Users simulate different physiological and pathophysiological situations by interactively altering numerical parameters and viewing time-dependent responses. HumMod provides a modeling environment to understand the complex interactions of integrative physiology. HumMod can be downloaded at http://hummod.org.

  19. Drawing on student knowledge in human anatomy and physiology

    NASA Astrophysics Data System (ADS)

    Slominski, Tara Nicole

    Prior to instruction, students may have developed alternative conceptions about the mechanics behind human physiology. To help students re-shape these ideas into correct reasoning, the faulty characteristics reinforcing the alternative conceptions need to made explicit. This study used student-generated drawings to expose alternative conceptions Human Anatomy and Physiology students had prior to instruction on neuron physiology. Specifically, we investigated how students thought about neuron communication across a synapse (n=355) and how neuron activity can be modified (n=311). When asked to depict basic communication between two neurons, at least 80% of students demonstrated incorrect ideas about synaptic transmission. When targeting spatial and temporal summation, only eleven students (3.5%) were able to accurately depict at least one form of summation. In response to both drawing questions, student drawings revealed multiple alternative conceptions that resulted in a deeper analysis and characterization of the wide variation of student ideas.

  20. Physiologically Based Pharmacokinetic (PBPK) Models for Ethanol

    PubMed Central

    Plawecki, Martin H.; Han, Jae-Joon; Doerschuk, Peter C.; Ramchandani, Vijay A.; O'Connor, Sean J.

    2012-01-01

    Physiologically based pharmacokinetic models have been used to describe the distribution and elimination of ethanol after intravenous administration. These models have been used to estimate the ethanol infusion profile that is sufficient for achieving a prescribed breath ethanol concentration time course in individuals, providing a useful platform for several pharmacokinetic and pharmacodynamic investigations. Mathematical foundations of these models are examined, including the derivation of an explicit set of governing equations in the form of a system of nonlinear ordinary differential equations. These equations can then be used to formulate and refine parameter identification and control strategies. Finally, a framework in which models related to this model can be constructed and analyzed is described. PMID:19126448

  1. A Physiologically Based Pharmacokinetic Model for Capreomycin

    PubMed Central

    Metzler, C. P.; Lyons, M. A.; Mayeno, A. N.; Brooks, E. J.; DeGroote, M. A.

    2012-01-01

    The emergence of multidrug-resistant tuberculosis (MDR-TB) has led to a renewed interest in the use of second-line antibiotic agents. Unfortunately, there are currently dearths of information, data, and computational models that can be used to help design rational regimens for administration of these drugs. To help fill this knowledge gap, an exploratory physiologically based pharmacokinetic (PBPK) model, supported by targeted experimental data, was developed to predict the absorption, distribution, metabolism, and excretion (ADME) of the second-line agent capreomycin, a cyclic peptide antibiotic often grouped with the aminoglycoside antibiotics. To account for interindividual variability, Bayesian inference and Monte Carlo methods were used for model calibration, validation, and testing. Along with the predictive PBPK model, the first for an antituberculosis agent, this study provides estimates of various key pharmacokinetic parameter distributions and supports a hypothesized mechanism for capreomycin transport into the kidney. PMID:22143528

  2. Colonic Fermentation: A Neglected Topic in Human Physiology Education

    ERIC Educational Resources Information Center

    Valeur, Jorgen; Berstad, Arnold

    2010-01-01

    Human physiology textbooks tend to limit their discussion of colonic functions to those of absorbing water and electrolytes and storing waste material. However, the colon is a highly active metabolic organ, containing an exceedingly complex society of microbes. By means of fermentation, gastrointestinal microbes break down nutrients that cannot be…

  3. Colonic Fermentation: A Neglected Topic in Human Physiology Education

    ERIC Educational Resources Information Center

    Valeur, Jorgen; Berstad, Arnold

    2010-01-01

    Human physiology textbooks tend to limit their discussion of colonic functions to those of absorbing water and electrolytes and storing waste material. However, the colon is a highly active metabolic organ, containing an exceedingly complex society of microbes. By means of fermentation, gastrointestinal microbes break down nutrients that cannot be…

  4. Development and Implementation of a PSI Course in Human Physiology.

    ERIC Educational Resources Information Center

    Giese, Maurine; Lawler, Michael

    1978-01-01

    The paper describes the Personalized System of Instruction (PSI) used in an allied health course in human physiology at the University of Texas. Distinguishing features of the PSI system of individualizing courses are mastery learning, self-pacing, and immediate feedback, with the instructor as class manager rather than lecturer. (MF)

  5. Human Physiology: Improving Students' Achievements through Intelligent Studyware.

    ERIC Educational Resources Information Center

    Dori, Yehudit J.; Yochim, Jerome M.

    1994-01-01

    A studyware comprising a set of interconnected modules on human physiology has been developed and used to improve undergraduate students' achievements. Study results show the scores of students who used the optional computer laboratory sessions were enhanced over those who did not use the studyware. Presents examples from the modules. (LZ)

  6. HuPSON: the human physiology simulation ontology

    PubMed Central

    2013-01-01

    Background Large biomedical simulation initiatives, such as the Virtual Physiological Human (VPH), are substantially dependent on controlled vocabularies to facilitate the exchange of information, of data and of models. Hindering these initiatives is a lack of a comprehensive ontology that covers the essential concepts of the simulation domain. Results We propose a first version of a newly constructed ontology, HuPSON, as a basis for shared semantics and interoperability of simulations, of models, of algorithms and of other resources in this domain. The ontology is based on the Basic Formal Ontology, and adheres to the MIREOT principles; the constructed ontology has been evaluated via structural features, competency questions and use case scenarios. The ontology is freely available at: http://www.scai.fraunhofer.de/en/business-research-areas/bioinformatics/downloads.html (owl files) and http://bishop.scai.fraunhofer.de/scaiview/ (browser). Conclusions HuPSON provides a framework for a) annotating simulation experiments, b) retrieving relevant information that are required for modelling, c) enabling interoperability of algorithmic approaches used in biomedical simulation, d) comparing simulation results and e) linking knowledge-based approaches to simulation-based approaches. It is meant to foster a more rapid uptake of semantic technologies in the modelling and simulation domain, with particular focus on the VPH domain. PMID:24267822

  7. HuPSON: the human physiology simulation ontology.

    PubMed

    Gündel, Michaela; Younesi, Erfan; Malhotra, Ashutosh; Wang, Jiali; Li, Hui; Zhang, Bijun; de Bono, Bernard; Mevissen, Heinz-Theodor; Hofmann-Apitius, Martin

    2013-11-22

    Large biomedical simulation initiatives, such as the Virtual Physiological Human (VPH), are substantially dependent on controlled vocabularies to facilitate the exchange of information, of data and of models. Hindering these initiatives is a lack of a comprehensive ontology that covers the essential concepts of the simulation domain. We propose a first version of a newly constructed ontology, HuPSON, as a basis for shared semantics and interoperability of simulations, of models, of algorithms and of other resources in this domain. The ontology is based on the Basic Formal Ontology, and adheres to the MIREOT principles; the constructed ontology has been evaluated via structural features, competency questions and use case scenarios.The ontology is freely available at: http://www.scai.fraunhofer.de/en/business-research-areas/bioinformatics/downloads.html (owl files) and http://bishop.scai.fraunhofer.de/scaiview/ (browser). HuPSON provides a framework for a) annotating simulation experiments, b) retrieving relevant information that are required for modelling, c) enabling interoperability of algorithmic approaches used in biomedical simulation, d) comparing simulation results and e) linking knowledge-based approaches to simulation-based approaches. It is meant to foster a more rapid uptake of semantic technologies in the modelling and simulation domain, with particular focus on the VPH domain.

  8. Linking adult hippocampal neurogenesis with human physiology and disease.

    PubMed

    Bowers, Megan; Jessberger, Sebastian

    2016-07-01

    We here review the existing evidence linking adult hippocampal neurogenesis and human brain function in physiology and disease. Furthermore, we aim to point out where evidence is missing, highlight current promising avenues of investigation, and suggest future tools and approaches to foster the link between life-long neurogenesis and human brain function. Developmental Dynamics 245:702-709, 2016. © 2016 Wiley Periodicals, Inc.

  9. Combining in vitro embryotoxicity data with physiologically based kinetic (PBK) modelling to define in vivo dose-response curves for developmental toxicity of phenol in rat and human.

    PubMed

    Strikwold, Marije; Spenkelink, Bert; Woutersen, Ruud A; Rietjens, Ivonne M C M; Punt, Ans

    2013-09-01

    In vitro assays are often used for the hazard characterisation of compounds, but their application for quantitative risk assessment purposes is limited. This is because in vitro assays cannot provide a complete in vivo dose-response curve from which a point of departure (PoD) for risk assessment can be derived, like the no observed adverse effect level (NOAEL) or the 95 % lower confidence limit of the benchmark dose (BMDL). To overcome this constraint, the present study combined in vitro data with a physiologically based kinetic (PBK) model applying reverse dosimetry. To this end, embryotoxicity of phenol was evaluated in vitro using the embryonic stem cell test (EST), revealing a concentration-dependent inhibition of differentiation into beating cardiomyocytes. In addition, a PBK model was developed on the basis of in vitro and in silico data and data available from the literature only. After evaluating the PBK model performance, effective concentrations (ECx) obtained with the EST served as an input for in vivo plasma concentrations in the PBK model. Applying PBK-based reverse dosimetry provided in vivo external effective dose levels (EDx) from which an in vivo dose-response curve and a PoD for risk assessment were derived. The predicted PoD lies within the variation of the NOAELs obtained from in vivo developmental toxicity data from the literature. In conclusion, the present study showed that it was possible to accurately predict a PoD for the risk assessment of phenol using in vitro toxicity data combined with reverse PBK modelling.

  10. EPM - The European Facility for human physiology research on ISS.

    PubMed

    Rieschel, Mats; Nasca, Rosario; Junk, Peter; Gerhard, Ingo

    2002-07-01

    The European Physiology Modules (EPM) Facility is one of the four major Space Station facilities being developed within the framework of ESA's Microgravity Facilities for Columbus (MFC) programme. In order to allow a wide spectrum of physiological studies in weightlessness conditions, the facility provides the infrastructure to accommodate a variable set of scientific equipment. The initial EPM configuration supports experiments in the fields of neuroscience, bone & muscle research, cardiovascular research and metabolism. The International Space Life Science Working Group (ISLSWG) has recommended co-locating EPM with the 2 NASA Human Research Facility racks.

  11. Dunbar's number: group size and brain physiology in humans reexamined.

    PubMed

    de Ruiter, Jan; Weston, Gavin; Lyon, Stephen M

    2011-01-01

    Popular academic ideas linking physiological adaptations to social behaviors are spreading disconcertingly into wider societal contexts. In this article, we note our skepticism with one particularly popular—in our view, problematic—supposed causal correlation between neocortex size and social group size. The resulting Dunbar's Number, as it has come to be called, has been statistically tested against observed group size in different primate species. Although there may be reason to doubt the Dunbar's Number hypothesis among nonhuman primate species, we restrict ourselves here to the application of such an explanatory hypothesis to human, culture-manipulating populations. Human information process management, we argue, cannot be understood as a simple product of brain physiology. Cross-cultural comparison of not only group size but also relationship-reckoning systems like kinship terminologies suggests that although neocortices are undoubtedly crucial to human behavior, they cannot be given such primacy in explaining complex group composition, formation, or management.

  12. Human inhalation exposures to toluene, ethylbenzene, and m-xylene and physiologically based pharmacokinetic modeling of exposure biomarkers in exhaled air, blood, and urine.

    PubMed

    Marchand, Axelle; Aranda-Rodriguez, Rocio; Tardif, Robert; Nong, Andy; Haddad, Sami

    2015-04-01

    Urinary biomarkers of exposure are used widely in biomonitoring studies. The commonly used urinary biomarkers for the aromatic solvents toluene (T), ethylbenzene (E), and m-xylene (X) are o-cresol, mandelic acid, and m-methylhippuric acid. The toxicokinetics of these biomarkers following inhalation exposure have yet to be described by physiologically based pharmacokinetic (PBPK) modeling. Five male volunteers were exposed for 6 h in an inhalation chamber to 1/8 or 1/4 of the time-weighted average exposure value (TWAEV) for each solvent: toluene, ethylbenzene, and m-xylene were quantified in blood and exhaled air and their corresponding urine biomarkers were measured in urine. Published PBPK model for parent compounds was used and simulations were compared with experimental blood and exhaled air concentration data. If discrepancies existed, Vmax and Km were optimized. Urinary excretion was modeled using parameters found in literature assuming simply stoichiometric yields from parent compound metabolism and first-order urinary excretion rate. Alternative models were also tested for (1) the possibility that CYP1A2 is the only enzyme implicated in o-cresol and (2) a 2-step model for describing serial metabolic steps for mandelic acid. Models adapted in this study for urinary excretion will be further used to interpret urinary biomarker kinetic data from mixed exposures of these solvents. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Physiological Bases of Bulimia, and Antidepressant Treatment.

    ERIC Educational Resources Information Center

    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…

  14. Evolutionary change in physiological phenotypes along the human lineage

    PubMed Central

    Vining, Alexander Q.; Nunn, Charles L.

    2016-01-01

    Background and Objectives: Research in evolutionary medicine provides many examples of how evolution has shaped human susceptibility to disease. Traits undergoing rapid evolutionary change may result in associated costs or reduce the energy available to other traits. We hypothesize that humans have experienced more such changes than other primates as a result of major evolutionary change along the human lineage. We investigated 41 physiological traits across 50 primate species to identify traits that have undergone marked evolutionary change along the human lineage. Methodology: We analysed the data using two Bayesian phylogenetic comparative methods. One approach models trait covariation in non-human primates and predicts human phenotypes to identify whether humans are evolutionary outliers. The other approach models adaptive shifts under an Ornstein-Uhlenbeck model of evolution to assess whether inferred shifts are more common on the human branch than on other primate lineages. Results: We identified four traits with strong evidence for an evolutionary increase on the human lineage (amylase, haematocrit, phosphorus and monocytes) and one trait with strong evidence for decrease (neutrophilic bands). Humans exhibited more cases of distinct evolutionary change than other primates. Conclusions and Implications: Human physiology has undergone increased evolutionary change compared to other primates. Long distance running may have contributed to increases in haematocrit and mean corpuscular haemoglobin concentration, while dietary changes are likely related to increases in amylase. In accordance with the pathogen load hypothesis, human monocyte levels were increased, but many other immune-related measures were not. Determining the mechanisms underlying conspicuous evolutionary change in these traits may provide new insights into human disease. PMID:27615376

  15. Emerging role of mitophagy in human diseases and physiology.

    PubMed

    Um, Jee-Hyun; Yun, Jeanho

    2017-04-03

    Mitophagy is a process of selective removal of damaged or unnecessary mitochondria using autophagic machineries. Mitophagy plays an essential role in mitochondria quality control and mitochondria homeostasis. Mitochondria dysfunctions and mitophagy defects in neurodegenerative diseases, cancer, metabolic diseases indicate a close link between human disease and mitophagy activity. Furthermore, recent studies showing the involvement of mitophagy in differentiation and development, suggest that mitophagy may play a more active role in controlling cellular functions. The better understanding of mitophagy will provide insight about human disease and offering novel chance for treatment. This review mainly focuses on the recent implications of mitophagy in human diseases and normal physiology.

  16. Dietary boron: progress in establishing essential roles in human physiology.

    PubMed

    Hunt, Curtiss D

    2012-06-01

    This review summarizes the progress made in establishing essential roles for boron in human physiology and assesses that progress in view of criteria for essentiality of elements. The evidence to date suggests that humans and at least some higher animals may use boron to support normal biological functions. These include roles in calcium metabolism, bone growth and maintenance, insulin metabolism, and completion of the life cycle. The biochemical mechanisms responsible for these effects are poorly understood but the nature of boron biochemistry suggests further characterization of the cell signaling molecules capable of complexing with boron. Such characterization may provide insights into the biochemical function(s) of boron in humans.

  17. Life-Stage Physiologically-Based Pharmacokinetic (PBPK) ...

    EPA Pesticide Factsheets

    This presentation discusses methods used to extrapolate from in vitro high-throughput screening (HTS) toxicity data for an endocrine pathway to in vivo for early life stages in humans, and the use of a life stage PBPK model to address rapidly changing physiological parameters. Adverse outcome pathways (AOPs), in this case endocrine disruption during development, provide a biologically-based framework for linking molecular initiating events triggered by chemical exposures to key events leading to adverse outcomes. The application of AOPs to human health risk assessment requires extrapolation of in vitro HTS toxicity data to in vivo exposures (IVIVE) in humans, which can be achieved through the use of a PBPK/PD model. Exposure scenarios for chemicals in the PBPK/PD model will consider both placental and lactational transfer of chemicals, with a focus on age dependent dosimetry during fetal development and after birth for a nursing infant. This talk proposes a universal life-stage computational model that incorporates changing physiological parameters to link environmental exposures to in vitro levels of HTS assays related to a developmental toxicological AOP for vascular disruption. In vitro toxicity endpoints discussed are based on two mechanisms: 1) Fetal vascular disruption, and 2) Neurodevelopmental toxicity induced by altering thyroid hormone levels in neonates via inhibition of thyroperoxidase in the thyroid gland. Application of our Life-stage computati

  18. Life-Stage Physiologically-Based Pharmacokinetic (PBPK) ...

    EPA Pesticide Factsheets

    This presentation discusses methods used to extrapolate from in vitro high-throughput screening (HTS) toxicity data for an endocrine pathway to in vivo for early life stages in humans, and the use of a life stage PBPK model to address rapidly changing physiological parameters. Adverse outcome pathways (AOPs), in this case endocrine disruption during development, provide a biologically-based framework for linking molecular initiating events triggered by chemical exposures to key events leading to adverse outcomes. The application of AOPs to human health risk assessment requires extrapolation of in vitro HTS toxicity data to in vivo exposures (IVIVE) in humans, which can be achieved through the use of a PBPK/PD model. Exposure scenarios for chemicals in the PBPK/PD model will consider both placental and lactational transfer of chemicals, with a focus on age dependent dosimetry during fetal development and after birth for a nursing infant. This talk proposes a universal life-stage computational model that incorporates changing physiological parameters to link environmental exposures to in vitro levels of HTS assays related to a developmental toxicological AOP for vascular disruption. In vitro toxicity endpoints discussed are based on two mechanisms: 1) Fetal vascular disruption, and 2) Neurodevelopmental toxicity induced by altering thyroid hormone levels in neonates via inhibition of thyroperoxidase in the thyroid gland. Application of our Life-stage computati

  19. Physiological correlates and emotional specificity of human piloerection

    PubMed Central

    Benedek, Mathias; Kaernbach, Christian

    2011-01-01

    Piloerection is known as an indicator of strong emotional experiences. However, little is known about the physiological and emotional specificity of this psychophysiological response. In the presented study, piloerection was elicited by audio stimuli taken from music and film episodes. The physiological response accompanying the incidence of piloerection was recorded with respect to electrodermal, cardiovascular and respiratory measures and compared to a matched control condition. The employment of an optical recording system allowed for a direct and objective assessment of visible piloerection. The occurrence of piloerection was primarily accompanied by an increase of phasic electrodermal activity and increased respiration depth as compared to a matched control condition. This physiological response pattern is discussed in the context of dominant theories of human piloerection. Consideration of all available evidence suggests that emotional piloerection represents a valuable indicator of the state of being moved or touched. PMID:21276827

  20. Human Physiological Responses to Acute and Chronic Cold Exposure

    NASA Technical Reports Server (NTRS)

    Stocks, Jodie M.; Taylor, Nigel A. S.; Tipton, Michael J.; Greenleaf, John E.

    2001-01-01

    When inadequately protected humans are exposed to acute cold, excessive body heat is lost to the environment and unless heat production is increased and heat loss attenuated, body temperature will decrease. The primary physiological responses to counter the reduction in body temperature include marked cutaneous vasoconstriction and increased metabolism. These responses, and the hazards associated with such exposure, are mediated by a number of factors which contribute to heat production and loss. These include the severity and duration of the cold stimulus; exercise intensity; the magnitude of the metabolic response; and individual characteristics such as body composition, age, and gender. Chronic exposure to a cold environment, both natural and artificial, results in physiological alterations leading to adaptation. Three quite different, but not necessarily exclusive, patterns of human cold adaptation have been reported: metabolic, hypothermic, and insulative. Cold adaptation has also been associated with an habituation response, in which there is a desensitization, or damping, of the normal response to a cold stress. This review provides a comprehensive analysis of the human physiological and pathological responses to cold exposure. Particular attention is directed to the factors contributing to heat production and heat loss during acute cold stress, and the ability of humans to adapt to cold environments.

  1. Human Physiological Responses to Acute and Chronic Cold Exposure

    NASA Technical Reports Server (NTRS)

    Stocks, Jodie M.; Taylor, Nigel A. S.; Tipton, Michael J.; Greenleaf, John E.

    2001-01-01

    When inadequately protected humans are exposed to acute cold, excessive body heat is lost to the environment and unless heat production is increased and heat loss attenuated, body temperature will decrease. The primary physiological responses to counter the reduction in body temperature include marked cutaneous vasoconstriction and increased metabolism. These responses, and the hazards associated with such exposure, are mediated by a number of factors which contribute to heat production and loss. These include the severity and duration of the cold stimulus; exercise intensity; the magnitude of the metabolic response; and individual characteristics such as body composition, age, and gender. Chronic exposure to a cold environment, both natural and artificial, results in physiological alterations leading to adaptation. Three quite different, but not necessarily exclusive, patterns of human cold adaptation have been reported: metabolic, hypothermic, and insulative. Cold adaptation has also been associated with an habituation response, in which there is a desensitization, or damping, of the normal response to a cold stress. This review provides a comprehensive analysis of the human physiological and pathological responses to cold exposure. Particular attention is directed to the factors contributing to heat production and heat loss during acute cold stress, and the ability of humans to adapt to cold environments.

  2. The physiology of the normal human breast: an exploratory study.

    PubMed

    Mills, Dixie; Gordon, Eva J; Casano, Ashley; Lahti, Sarah Michelle; Nguyen, Tinh; Preston, Alex; Tondre, Julie; Wu, Kuan; Yanase, Tiffany; Chan, Henry; Chia, David; Esfandiari, Mahtash; Himmel, Tiffany; Love, Susan M

    2011-12-01

    The physiology of the nonlactating human breast likely plays a key role in factors that contribute to the etiology of breast cancer and other breast conditions. Although there has been extensive research into the physiology of lactation, few reports explore the physiology of the resting mammary gland, including mechanisms by which compounds such as hormones, drugs, and potential carcinogens enter the breast ducts. The purpose of this study was to explore transport of exogenous drugs into ductal fluid in nonlactating women and determine if their concentrations in the fluid are similar to those observed in the breast milk of lactating women. We selected two compounds that have been well characterized during lactation, caffeine and cimetidine. Caffeine passively diffuses into breast milk, but cimetidine is actively transported and concentrated in breast milk. After ingestion of caffeine and cimetidine, 14 nonlactating subjects had blood drawn and underwent ductal lavage at five time points over 12 h to measure drug levels in the fluid and blood. The concentrations of both caffeine and cimetidine in lavage fluid were substantially less than those observed in breast milk. Our results support recent evidence that the cimetidine transporter is not expressed in the nonlactating mammary gland, and highlight intriguing differences in the physiology and molecular transport of the lactating and nonlactating breast. The findings of this exploratory study warrant further exploration into the physiology of the nonlactating mammary gland to elucidate factors involved in disease initiation and progression.

  3. Sunspot Dynamics Are Reflected in Human Physiology and Pathophysiology

    PubMed Central

    Sothern, Robert B.; Du-Quiton, Jovelyn; Quiton, Dinah Faith T.; Rietveld, Wop; Boon, Mathilde E.

    2011-01-01

    Abstract Periodic episodes of increased sunspot activity (solar electromagnetic storms) occur with 10–11 and 5–6 year periodicities and may be associated with measurable biological events. We investigated whether this sunspot periodicity characterized the incidence of Pap smear-determined cervical epithelial histopathologies and human physiologic functions. From January 1983 through December 2003, monthly averages were obtained for solar flux and sunspot numbers; six infectious, premalignant and malignant changes in the cervical epithelium from 1,182,421 consecutive, serially independent, screening Pap smears (59°9″N, 4°29″E); and six human physiologic functions of a healthy man (oral temperature, pulse, systolic and diastolic blood pressure, respiration, and peak expiratory flow), which were measured ∼5 times daily during ∼34,500 self-measurement sessions (44°56″N, 93°8″W). After determining that sunspot numbers and solar flux, which were not annually rhythmic, occurred with a prominent 10-year and a less-prominent 5.75-year periodicity during this 21-year study span, each biological data set was analyzed with the same curve-fitting procedures. All six annually rhythmic Pap smear-detected infectious, premalignant and malignant cervical epithelial pathologies showed strong 10-year and weaker 5.75-year cycles, as did all six self-measured, annually rhythmic, physiologic functions. The phases (maxima) for the six histopathologic findings and five of six physiologic measurements were very near, or within, the first two quarters following the 10-year solar maxima. These findings add to the growing evidence that solar magnetic storm periodicities are mirrored by cyclic phase-locked rhythms of similar period length or lengths in human physiology and pathophysiology. Key Words: Cervical infections—Cervical premalignancy—Geo-solar magnetic interactions—Pap smear—Schwabe cycle—10-year rhythm. Astrobiology 11, 93–103. PMID:21391821

  4. Sunspot Dynamics Are Reflected in Human Physiology and Pathophysiology

    NASA Astrophysics Data System (ADS)

    Hrushesky, William J. M.; Sothern, Robert B.; Du-Quiton, Jovelyn; Quiton, Dinah Faith T.; Rietveld, Wop; Boon, Mathilde E.

    2011-03-01

    Periodic episodes of increased sunspot activity (solar electromagnetic storms) occur with 10-11 and 5-6 year periodicities and may be associated with measurable biological events. We investigated whether this sunspot periodicity characterized the incidence of Pap smear-determined cervical epithelial histopathologies and human physiologic functions. From January 1983 through December 2003, monthly averages were obtained for solar flux and sunspot numbers; six infectious, premalignant and malignant changes in the cervical epithelium from 1,182,421 consecutive, serially independent, screening Pap smears (59°9"N, 4°29"E); and six human physiologic functions of a healthy man (oral temperature, pulse, systolic and diastolic blood pressure, respiration, and peak expiratory flow), which were measured ∼5 times daily during ∼34,500 self-measurement sessions (44°56"N, 93°8"W). After determining that sunspot numbers and solar flux, which were not annually rhythmic, occurred with a prominent 10-year and a less-prominent 5.75-year periodicity during this 21-year study span, each biological data set was analyzed with the same curve-fitting procedures. All six annually rhythmic Pap smear-detected infectious, premalignant and malignant cervical epithelial pathologies showed strong 10-year and weaker 5.75-year cycles, as did all six self-measured, annually rhythmic, physiologic functions. The phases (maxima) for the six histopathologic findings and five of six physiologic measurements were very near, or within, the first two quarters following the 10-year solar maxima. These findings add to the growing evidence that solar magnetic storm periodicities are mirrored by cyclic phase-locked rhythms of similar period length or lengths in human physiology and pathophysiology.

  5. Sunspot dynamics are reflected in human physiology and pathophysiology.

    PubMed

    Hrushesky, William J M; Sothern, Robert B; Du-Quiton, Jovelyn; Quiton, Dinah Faith T; Rietveld, Wop; Boon, Mathilde E

    2011-03-01

    Periodic episodes of increased sunspot activity (solar electromagnetic storms) occur with 10-11 and 5-6 year periodicities and may be associated with measurable biological events. We investigated whether this sunspot periodicity characterized the incidence of Pap smear-determined cervical epithelial histopathologies and human physiologic functions. From January 1983 through December 2003, monthly averages were obtained for solar flux and sunspot numbers; six infectious, premalignant and malignant changes in the cervical epithelium from 1,182,421 consecutive, serially independent, screening Pap smears (59°9″N, 4°29″E); and six human physiologic functions of a healthy man (oral temperature, pulse, systolic and diastolic blood pressure, respiration, and peak expiratory flow), which were measured ∼5 times daily during ∼34,500 self-measurement sessions (44°56″N, 93°8″W). After determining that sunspot numbers and solar flux, which were not annually rhythmic, occurred with a prominent 10-year and a less-prominent 5.75-year periodicity during this 21-year study span, each biological data set was analyzed with the same curve-fitting procedures. All six annually rhythmic Pap smear-detected infectious, premalignant and malignant cervical epithelial pathologies showed strong 10-year and weaker 5.75-year cycles, as did all six self-measured, annually rhythmic, physiologic functions. The phases (maxima) for the six histopathologic findings and five of six physiologic measurements were very near, or within, the first two quarters following the 10-year solar maxima. These findings add to the growing evidence that solar magnetic storm periodicities are mirrored by cyclic phase-locked rhythms of similar period length or lengths in human physiology and pathophysiology. © Mary Ann Liebert, Inc.

  6. Helmet-based physiological signal monitoring system.

    PubMed

    Kim, Youn Sung; Baek, Hyun Jae; Kim, Jung Soo; Lee, Haet Bit; Choi, Jong Min; Park, Kwang Suk

    2009-02-01

    A helmet-based system that was able to monitor the drowsiness of a soldier was developed. The helmet system monitored the electrocardiogram, electrooculogram and electroencephalogram (alpha waves) without constraints. Six dry electrodes were mounted at five locations on the helmet: both temporal sides, forehead region and upper and lower jaw strips. The electrodes were connected to an amplifier that transferred signals to a laptop computer via Bluetooth wireless communication. The system was validated by comparing the signal quality with conventional recording methods. Data were acquired from three healthy male volunteers for 12 min twice a day whilst they were sitting in a chair wearing the sensor-installed helmet. Experimental results showed that physiological signals for the helmet user were measured with acceptable quality without any intrusions on physical activities. The helmet system discriminated between the alert and drowsiness states by detecting blinking and heart rate variability (HRV) parameters extracted from ECG. Blinking duration and eye reopening time were increased during the sleepiness state compared to the alert state. Also, positive peak values of the sleepiness state were much higher, and the negative peaks were much lower than that of the alert state. The LF/HF ratio also decreased during drowsiness. This study shows the feasibility for using this helmet system: the subjects' health status and mental states could be monitored without constraints whilst they were working.

  7. Prediction of a potentially effective dose in humans for BAY 60–5521, a potent inhibitor of cholesteryl ester transfer protein (CETP) by allometric species scaling and combined pharmacodynamic and physiologically-based pharmacokinetic modelling

    PubMed Central

    Weber, Olaf; Willmann, Stefan; Bischoff, Hilmar; Li, Volkhart; Vakalopoulos, Alexandros; Lustig, Klemens; Hafner, Frank-Thorsten; Heinig, Roland; Schmeck, Carsten; Buehner, Klaus

    2012-01-01

    AIMS The purpose of this work was to support the prediction of a potentially effective dose for the CETP-inhibitor, BAY 60–5521, in humans. METHODS A combination of allometric scaling of the pharmacokinetics of the CETP-inhibitor BAY 60–5521 with pharmacodynamic studies in CETP-transgenic mice and in human plasma with physiologically-based pharmacokinetic (PBPK) modelling was used to support the selection of the first-in-man dose. RESULTS The PBPK approach predicts a greater extent of distribution for BAY 60–5521 in humans compared with the allometric scaling method as reflected by a larger predicted volume of distribution and longer elimination half-life. The combined approach led to an estimate of a potentially effective dose for BAY 60–5521 of 51 mg in humans. CONCLUSION The approach described in this paper supported the prediction of a potentially effective dose for the CETP-inhibitor BAY 60–5521 in humans. Confirmation of the dose estimate was obtained in a first-in-man study. PMID:21762205

  8. Effects of weightlessness on human fluid and electrolyte physiology

    NASA Technical Reports Server (NTRS)

    Leach, Carolyn S.; Johnson, Philip C., Jr.

    1991-01-01

    Skylab and Spacelab data on changes occurring in human fluid and electrolyte physiology during the acute and adaptive phases of adaptation to spaceflight are summarized. The combined results for all three Spacelab studies show that hyponatremia developed within 20 h after the onset of weightlessness and continued throughout the flights, and hypokalemia developed by 40 h. Antidiuretic hormone was increased in plasma throughout the flights. Aldosterone decreased by 40 h, but after 7 days it had reached preflight levels.

  9. Effects of weightlessness on human fluid and electrolyte physiology

    NASA Technical Reports Server (NTRS)

    Leach, Carolyn S.; Johnson, Philip C., Jr.

    1991-01-01

    Skylab and Spacelab data on changes occurring in human fluid and electrolyte physiology during the acute and adaptive phases of adaptation to spaceflight are summarized. The combined results for all three Spacelab studies show that hyponatremia developed within 20 h after the onset of weightlessness and continued throughout the flights, and hypokalemia developed by 40 h. Antidiuretic hormone was increased in plasma throughout the flights. Aldosterone decreased by 40 h, but after 7 days it had reached preflight levels.

  10. Teaching renal physiology in the 21st century: focus on acid-base physiology.

    PubMed

    Leehey, David J; Daugirdas, John T

    2016-04-01

    A thorough understanding of renal physiology, and in particular acid-base physiology, is essential for an understanding of nephrology. Difficulties in both teaching and learning this material are major impediments to attracting medical trainees into nephrology. Approaches to teaching renal physiology include collaborative learning, computer-based learning and laboratory-based learning. Computer-based learning applications are becoming increasingly popular and can be useful, but are most successful when they incorporate interactive components. Students also note that the presence of a live instructor remains desirable. Some concepts of renal and in particular acid-base physiology can be taught using structured self-experimentation, a practice with a long tradition that possibly should be revitalized.

  11. Teaching renal physiology in the 21st century: focus on acid–base physiology

    PubMed Central

    Leehey, David J.; Daugirdas, John T.

    2016-01-01

    A thorough understanding of renal physiology, and in particular acid–base physiology, is essential for an understanding of nephrology. Difficulties in both teaching and learning this material are major impediments to attracting medical trainees into nephrology. Approaches to teaching renal physiology include collaborative learning, computer-based learning and laboratory-based learning. Computer-based learning applications are becoming increasingly popular and can be useful, but are most successful when they incorporate interactive components. Students also note that the presence of a live instructor remains desirable. Some concepts of renal and in particular acid–base physiology can be taught using structured self-experimentation, a practice with a long tradition that possibly should be revitalized. PMID:26985388

  12. Introduction to anatomy and physiology of human conception.

    PubMed

    Kably, A; Barroso, G

    2000-01-01

    Anatomical and physiological concepts of human reproduction currently in use have been developed over generations, following clinical and basic research guidelines that preceded modern technology. The application of new forms of research over recent decades, as in the case of molecular biology, has contributed to a more in-depth and accurate understanding of the interaction of each of the inter- and intracellular structures in the mechanics of human physiology. On the other hand the use of non-human primate models has provided invaluable information in the reproductive field. The information obtained through models and techniques that have changed over time has led to concepts that continue to have the same validity as when they were first described. The principal objective of this review is to develop an understanding of the physiological processes applied in the anatomical sphere, taking as a reference the fact that it is impossible to understand reproductive mechanics in terms of static phenomena, but rather they should be understood as dynamic and changing processes adaptable to the conditions of each individual's surroundings.

  13. Teaching Acid/Base Physiology in the Laboratory

    ERIC Educational Resources Information Center

    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…

  14. Teaching Acid/Base Physiology in the Laboratory

    ERIC Educational Resources Information Center

    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…

  15. Human Performance: Psychological and Physiological Sex Differences (A Selected Bibliography)

    DTIC Science & Technology

    1980-02-01

    Norwegian I men and women. Journal of Applied Physiology, 1965, _20, 425-431. 43. Heyward, V., & McCreary , L. Comparison of the relative endurance...inner space: A data-based reevaluatlon. American Journal of Qrthopsychiatry, 1979, 4_9, 100-108. 8. Carrigan, W. C., & Julian , J. W„ Sex and birth

  16. Dealing with noise and physiological artifacts in human EEG recordings: empirical mode methods

    NASA Astrophysics Data System (ADS)

    Runnova, Anastasiya E.; Grubov, Vadim V.; Khramova, Marina V.; Hramov, Alexander E.

    2017-04-01

    In the paper we propose the new method for removing noise and physiological artifacts in human EEG recordings based on empirical mode decomposition (Hilbert-Huang transform). As physiological artifacts we consider specific oscillatory patterns that cause problems during EEG analysis and can be detected with additional signals recorded simultaneously with EEG (ECG, EMG, EOG, etc.) We introduce the algorithm of the proposed method with steps including empirical mode decomposition of EEG signal, choosing of empirical modes with artifacts, removing these empirical modes and reconstructing of initial EEG signal. We show the efficiency of the method on the example of filtration of human EEG signal from eye-moving artifacts.

  17. Physiology

    ERIC Educational Resources Information Center

    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…

  18. Physiology

    ERIC Educational Resources Information Center

    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…

  19. How Do Humans Control Physiological Strain during Strenuous Endurance Exercise?

    PubMed Central

    Esteve-Lanao, Jonathan; Lucia, Alejandro; deKoning, Jos J.; Foster, Carl

    2008-01-01

    Background Distance running performance is a viable model of human locomotion. Methodology/Principal Findings To evaluate the physiologic strain during competitions ranging from 5–100 km, we evaluated heart rate (HR) records of competitive runners (n = 211). We found evidence that: 1) physiologic strain (% of maximum HR (%HRmax)) increased in proportional manner relative to distance completed, and was regulated by variations in running pace; 2) the %HRmax achieved decreased with relative distance; 3) slower runners had similar %HRmax response within a racing distance compared to faster runners, and despite differences in pace, the profile of %HRmax during a race was very similar in runners of differing ability; and 4) in cases where there was a discontinuity in the running performance, there was evidence that physiologic effort was maintained for some time even after the pace had decreased. Conclusions/Significance The overall results suggest that athletes are actively regulating their relative physiologic strain during competition, although there is evidence of poor regulation in the case of competitive failures. PMID:18698405

  20. Characteristics of an Intelligent Computer Assisted Instruction Shell with an Example in Human Physiology.

    ERIC Educational Resources Information Center

    Dori, Yehudit J.; Yochim, Jerome M.

    1992-01-01

    Discusses exemplary teacher and student characteristics that can provide the base to generate an Intelligent Computer Assisted Instruction (ICAI) shell. Outlines the expertise, learning, student-model, and inference modules of an ICAI shell. Describes the development of an ICAI shell for an undergraduate course in human physiology. (33 references)…

  1. Is Lutein a Physiologically Important Ligand for Transthyretin in Humans?

    SciTech Connect

    Chen, Liwei

    2003-01-01

    Lutein and zeaxanthin are the only carotenoids accumulated in the macula of the human retina and are known as the macular pigments (MP). These pigments account for the yellow color of the macula and appear to play an important role in protecting against age-related macular degeneration (AMD). The uptake of lutein and zeaxanthin in human eyes is remarkably specific. It is likely that specific transport or binding proteins are involved. The objective is to determine whether transthyretin (TTR) is a transport protein in human plasma and could thus deliver lutein from the blood to the retina. In this study, they used a biosynthetic 13C-lutein tracer and gas chromatography-combustion interfaced-isotope ratio mass spectrometry (GCC-IRMS) to gain the requisite sensitivity to detect the minute amounts of lutein expected as a physiological ligand for human transthyretin. The biosynthetic 13C-labeled lutein tracer was purified from algae. Healthy women (n = 4) each ingested 1 mg of 13C-labeled lutein daily for 3 days and a blood sample was collected 24 hours after the final dose. Plasma TTR was isolated by retinol-binding protein (RBP)-sepharose affinity chromatography and extracted with chloroform. The 13C/12C ratio in the TTR extract was measured by GCC-IRMS. There was no 13C-lutein enrichment in the pure TTR extract. This result indicated that lutein is not associated with TTR in human plasma after ingestion in physiological amounts. Some hydrophobic compounds with yellow color may bind to human TTR in the plasma. However, this association needs to be further proved by showing specificity. The study provides a new approach for carotenoid-binding protein studies using a stable isotope tracer method combined with the high precision of GCC-IRMS. The mechanism of selective transport, uptake, and accumulation of lutein in human macula remain to be determined.

  2. Clinical review: Reunification of acid–base physiology

    PubMed Central

    Kellum, John A

    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 tutorial is also provided. PMID:16277739

  3. Wearable Physiological Monitoring for Human Thermal-Work Strain Optimization.

    PubMed

    Buller, Mark J; Welles, Alexander Pearson; Friedl, Karl E

    2017-08-10

    Safe performance limits of soldiers and athletes have typically relied on predictive work-rest models of ambient conditions, average work intensity, and characteristics of the population. Bioengineering advances in noninvasive sensor technologies including miniaturization, reduced cost, power requirements, and comfort now make it possible to produce individual predictions of safe thermal-work limits. These precision medicine assessments depend on the development of thoughtful algorithms based on physics and physiology. Both physiological telemetry and thermal-strain indices have been available for more than fifty years but greater computing power and better wearable sensors now make it possible to provide actionable information at the individual level. Core temperature can be practically estimated from time series heart rate data, and, using an adaptive physiological strain index, provides meaningful predictions of safe work limits that cannot be predicted from only core temperature or heart rate measurements. Early adopters of this technology include specialized occupations where individuals operate in complete encapsulation such as chemical protective suits. Emerging technologies that focus on heat flux measurements at the skin show even greater potential for estimating thermal-work strain using a parsimonious sensor set. Applications of these wearable technologies include many sports and military training venues where inexperienced individuals can learn effective work pacing strategies and train to safe personal limits. The same strategies can also provide a technologically-based performance edge for experienced workers and athletes faced with novel and non-intuitive physiological challenges, such as health care providers in full protective clothing treating Ebola patients in West Africa in 2014. Copyright © 2017, Journal of Applied Physiology.

  4. Physiological effects of light on the human circadian pacemaker

    NASA Technical Reports Server (NTRS)

    Shanahan, T. L.; Czeisler, C. A.

    2000-01-01

    The physiology of the human circadian pacemaker and its influence and on the daily organization of sleep, endocrine and behavioral processes is an emerging interest in science and medicine. Understanding the development, organization and fundamental properties underlying the circadian timing system may provide insight for the application of circadian principles to the practice of clinical medicine, both diagnostically (interpretation of certain clinical tests are dependent on time of day) and therapeutically (certain pharmacological responses vary with the time of day). The light-dark cycle is the most powerful external influence acting upon the human circadian pacemaker. It has been shown that timed exposure to light can both synchronize and reset the phase of the circadian pacemaker in a predictable manner. The emergence of detectable circadian rhythmicity in the neonatal period is under investigation (as described elsewhere in this issue). Therefore, the pattern of light exposure provided in the neonatal intensive care setting has implications. One recent study identified differences in both amount of sleep time and weight gain in infants maintained in a neonatal intensive care environment that controlled the light-dark cycle. Unfortunately, neither circadian phase nor the time of day has been considered in most clinical investigations. Further studies with knowledge of principles characterizing the human circadian timing system, which governs a wide array of physiological processes, are required to integrate these findings with the practice of clinical medicine.

  5. Evaluation of Interindividual Human Variation in Bioactivation and DNA Adduct Formation of Estragole in Liver Predicted by Physiologically Based Kinetic/Dynamic and Monte Carlo Modeling.

    PubMed

    Punt, Ans; Paini, Alicia; Spenkelink, Albertus; Scholz, Gabriele; Schilter, Benoit; van Bladeren, Peter J; Rietjens, Ivonne M C M

    2016-04-18

    Estragole is a known hepatocarcinogen in rodents at high doses following metabolic conversion to the DNA-reactive metabolite 1'-sulfooxyestragole. The aim of the present study was to model possible levels of DNA adduct formation in (individual) humans upon exposure to estragole. This was done by extending a previously defined PBK model for estragole in humans to include (i) new data on interindividual variation in the kinetics for the major PBK model parameters influencing the formation of 1'-sulfooxyestragole, (ii) an equation describing the relationship between 1'-sulfooxyestragole and DNA adduct formation, (iii) Monte Carlo modeling to simulate interindividual human variation in DNA adduct formation in the population, and (iv) a comparison of the predictions made to human data on DNA adduct formation for the related alkenylbenzene methyleugenol. Adequate model predictions could be made, with the predicted DNA adduct levels at the estimated daily intake of estragole of 0.01 mg/kg bw ranging between 1.6 and 8.8 adducts in 10(8) nucleotides (nts) (50th and 99th percentiles, respectively). This is somewhat lower than values reported in the literature for the related alkenylbenzene methyleugenol in surgical human liver samples. The predicted levels seem to be below DNA adduct levels that are linked with tumor formation by alkenylbenzenes in rodents, which were estimated to amount to 188-500 adducts per 10(8) nts at the BMD10 values of estragole and methyleugenol. Although this does not seem to point to a significant health concern for human dietary exposure, drawing firm conclusions may have to await further validation of the model's predictions.

  6. Characterization of preclinical in vitro and in vivo ADME properties and prediction of human PK using a physiologically based pharmacokinetic model for YQA-14, a new dopamine D3 receptor antagonist candidate for treatment of drug addiction.

    PubMed

    Liu, Fei; Zhuang, Xiaomei; Yang, Cuiping; Li, Zheng; Xiong, Shan; Zhang, Zhiwei; Li, Jin; Lu, Chuang; Zhang, Zhenqing

    2014-07-01

    YQA-14 is a novel and selective dopamine D3 receptor antagonist, with potential for the treatment of drug addiction. However, earlier compounds in its structural class tend to have poor oral bioavailability. The objectives of this study were to characterize the preclinical absorption, distribution, metabolism and excretion (ADME) properties and pharmacokinetics (PK) of YQA-14, then to simulate the clinical PK of YQA-14 using a physiologically based pharmacokinetics (PBPK) model to assess the likelihood of developing YQA-14 as a clinical candidate. For human PK prediction, PBPK models were first built in preclinical species, rats and dogs, for validation purposes. The model was then modified by input of human in vitro ADME data obtained from in vitro studies. The study data showed that YQA-14 is a basic lipophilic compound, with rapid absorption (Tmax ~ 1 h) in both rats and dogs. Liver microsomal clearances and in vivo clearances were moderate in rats and dogs consistent with the moderate bioavailability observed in both species. The PBPK models built for rats and dogs simulated the observed PK data well in both species. The PBPK model refined with human data predicted that YQA-14 would have a clearance of 8.0 ml/min/kg, a volume distribution of 1.7 l/kg and a bioavailability of 16.9%. These acceptable PK properties make YQA-14 an improved candidate for further research and development as a potential dopamine D3R antagonism for the treatment of drug addiction in the clinic.

  7. Physiologically Based Absorption Modeling for Amorphous Solid Dispersion Formulations.

    PubMed

    Mitra, Amitava; Zhu, Wei; Kesisoglou, Filippos

    2016-09-06

    Amorphous solid dispersion (ASD) formulations are routinely used to enable the delivery of poorly soluble compounds. This type of formulations can enhance bioavailability due to higher kinetic solubility of the drug substance and increased dissolution rate of the formulation, by the virtue of the fact that the drug molecule exists in the formulation in a high energy amorphous state. In this article we report the application of physiologically based absorption models to mechanistically understand the clinical pharmacokinetics of solid dispersion formulations. Three case studies are shown here to cover a wide range of ASD bioperformance in human and modeling to retrospectively understand their in vivo behavior. Case study 1 is an example of fairly linear PK observed with dose escalation and the use of amorphous solubility to predict bioperformance. Case study 2 demonstrates the development of a model that was able to accurately predict the decrease in fraction absorbed (%Fa) with dose escalation thus demonstrating that such model can be used to predict the clinical bioperformance in the scenario where saturation of absorption is observed. Finally, case study 3 shows the development of an absorption model with the intent to describe the observed incomplete and low absorption in clinic with dose escalation. These case studies highlight the utility of physiologically based absorption modeling in gaining a thorough understanding of ASD performance and the critical factors impacting performance to drive design of a robust drug product that would deliver the optimal benefit to the patients.

  8. Population Physiology: Leveraging Electronic Health Record Data to Understand Human Endocrine Dynamics

    PubMed Central

    Albers, D. J.; Hripcsak, George; Schmidt, Michael

    2012-01-01

    Studying physiology and pathophysiology over a broad population for long periods of time is difficult primarily because collecting human physiologic data can be intrusive, dangerous, and expensive. One solution is to use data that have been collected for a different purpose. Electronic health record (EHR) data promise to support the development and testing of mechanistic physiologic models on diverse populations and allow correlation with clinical outcomes, but limitations in the data have thus far thwarted such use. For example, using uncontrolled population-scale EHR data to verify the outcome of time dependent behavior of mechanistic, constructive models can be difficult because: (i) aggregation of the population can obscure or generate a signal, (ii) there is often no control population with a well understood health state, and (iii) diversity in how the population is measured can make the data difficult to fit into conventional analysis techniques. This paper shows that it is possible to use EHR data to test a physiological model for a population and over long time scales. Specifically, a methodology is developed and demonstrated for testing a mechanistic, time-dependent, physiological model of serum glucose dynamics with uncontrolled, population-scale, physiological patient data extracted from an EHR repository. It is shown that there is no observable daily variation the normalized mean glucose for any EHR subpopulations. In contrast, a derived value, daily variation in nonlinear correlation quantified by the time-delayed mutual information (TDMI), did reveal the intuitively expected diurnal variation in glucose levels amongst a random population of humans. Moreover, in a population of continuously (tube) fed patients, there was no observable TDMI-based diurnal signal. These TDMI-based signals, via a glucose insulin model, were then connected with human feeding patterns. In particular, a constructive physiological model was shown to correctly predict the

  9. A Method of Ground Simulation of Physiological Effects of Hypogravity on Humans.

    PubMed

    Baranov, M V; Katuntsev, V P; Shpakov, A V; Baranov, V M

    2016-01-01

    A novel method of ground simulation in humans of physiological effects induced by the stay on the surface of celestial bodies with hypogravity was developed and successfully tested. This method is based on the change of gravity force angle, which decreases the gravitational component of the blood hydrostatic pressure characteristic of human vertical posture on the Earth and the load-weight onto the locomotor apparatus to the lower values expected at celestial bodies with hypogravity. The methodological requirements for ground simulation of the physiological effects of lunar gravity on human body are specified and substantiated by theoretical calculations. The experimental study revealed redistribution of liquid media in the human organism, functional changes in the cardiorespiratory system, and a decrease in the load-weight applied to the locomotor apparatus.

  10. A PHYSIOLOGICALLY BASED TOXICOKINETIC MODEL FOR LAKE TROUT (SALVELINUS NAMAYCUSH)

    EPA Science Inventory

    A physiologically based toxicokinetic (PB-TK) model for fish, incorporating chemical exchange at the gill and accumulation in five tissue compartments, was used to examine the effect of natural variability in physiological, morphological, and physico-chemical parameters on model ...

  11. Physiological concentrations of leptin do not affect human neutrophils.

    PubMed

    Kamp, Vera M; Langereis, Jeroen D; van Aalst, Corneli W; van der Linden, Jan A; Ulfman, Laurien H; Koenderman, Leo

    2013-01-01

    Leptin is an adipokine that is thought to be important in many inflammatory diseases, and is known to influence the function of several leukocyte types. However, no clear consensus is present regarding the responsiveness of neutrophils for this adipokine. In this study a 2D DIGE proteomics approach was used as an unbiased approach to identify leptin-induced effects on neutrophils. Additionally chemotaxis and survival experiments were performed to reproduce results from literature showing putative effects of leptin on these neutrophil responses. Leptin did not induce any significant changes in the proteome provided leptin was added at physiologically relevant concentrations (250 ng). Our leptin batches were biologically active as they induced proliferation in LeptinR expressing Ba/F3 cells. At high concentrations (25000 ng) leptin induced a change in neutrophil proteome. Seventeen differently regulated spots were identified of which twelve could be characterized by mass spectrometry. Two of these identified proteins, SerpinB1 and p40 phox, were chosen for further analysis but leptin-induced expression analyzed by western blot were highly variable. Additionally leptin also induced neutrophil survival at these high concentrations. No leptin-induced chemotaxis of human neutrophils was detected at any concentration. In conclusion, physiological concentrations of leptin do not affect neutrophils. High leptin concentrations induced survival and changes in the neutrophils proteome, but this was most likely mediated by an indirect effect. However, it cannot be ruled out that the effects were mediated by a yet not-identified leptin receptor on human neutrophils.

  12. Coupling of the Models of Human Physiology and Thermal Comfort

    NASA Astrophysics Data System (ADS)

    Pokorny, J.; Jicha, M.

    2013-04-01

    A coupled model of human physiology and thermal comfort was developed in Dymola/Modelica. A coupling combines a modified Tanabe model of human physiology and thermal comfort model developed by Zhang. The Coupled model allows predicting the thermal sensation and comfort of both local and overall from local boundary conditions representing ambient and personal factors. The aim of this study was to compare prediction of the Coupled model with the Fiala model prediction and experimental data. Validation data were taken from the literature, mainly from the validation manual of software Theseus-FE [1]. In the paper validation of the model for very light physical activities (1 met) indoor environment with temperatures from 12 °C up to 48 °C is presented. The Coupled model predicts mean skin temperature for cold, neutral and warm environment well. However prediction of core temperature in cold environment is inaccurate and very affected by ambient temperature. Evaluation of thermal comfort in warm environment is supplemented by skin wettedness prediction. The Coupled model is designed for non-uniform and transient environmental conditions; it is also suitable simulation of thermal comfort in vehicles cabins. The usage of the model is limited for very light physical activities up to 1.2 met only.

  13. Human Factors Evaluation of the Hidalgo Equivital EQ-02 Physiological Status Monitoring System

    DTIC Science & Technology

    2013-10-11

    Equivital™ EQ-02 physiological status monitoring ( PSM ) system. The usability and acceptability of this system has been tested previously and generally...under CBRNE- PPE provided utility and was comfortable to wear. Thermal strain; CBRNE; PPE; physiological status monitoring; PSM ; human factors; chem...real-time physiological monitoring. The Hidalgo, Ltd. (Cambridge, UK) Equivital™ EQ-02 physiological status monitoring ( PSM ) system is a typical

  14. Human Physiology and the Environment in Health and Disease: Readings from Scientific American.

    ERIC Educational Resources Information Center

    1976

    This anthology of articles is designed to supplement standard texts for courses in human physiology, environmental physiology, anatomy and physiology, pathobiology, general biology, and environmental medicine. It focuses on the influences of the external environment on the body, the physiological responses to environmental challenges, and the ways…

  15. Human Physiology and the Environment in Health and Disease: Readings from Scientific American.

    ERIC Educational Resources Information Center

    1976

    This anthology of articles is designed to supplement standard texts for courses in human physiology, environmental physiology, anatomy and physiology, pathobiology, general biology, and environmental medicine. It focuses on the influences of the external environment on the body, the physiological responses to environmental challenges, and the ways…

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

    PubMed

    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. Characterizing uncertainty and population variability in the toxicokinetics of trichloroethylene and metabolites in mice, rats, and humans using an updated database, physiologically based pharmacokinetic (PBPK) model, and Bayesian approach

    SciTech Connect

    Chiu, Weihsueh A.; Okino, Miles S.; Evans, Marina V.

    2009-11-15

    We have developed a comprehensive, Bayesian, PBPK model-based analysis of the population toxicokinetics of trichloroethylene (TCE) and its metabolites in mice, rats, and humans, considering a wider range of physiological, chemical, in vitro, and in vivo data than any previously published analysis of TCE. The toxicokinetics of the 'population average,' its population variability, and their uncertainties are characterized in an approach that strives to be maximally transparent and objective. Estimates of experimental variability and uncertainty were also included in this analysis. The experimental database was expanded to include virtually all available in vivo toxicokinetic data, which permitted, in rats and humans, the specification of separate datasets for model calibration and evaluation. The total combination of these approaches and PBPK analysis provides substantial support for the model predictions. In addition, we feel confident that the approach employed also yields an accurate characterization of the uncertainty in metabolic pathways for which available data were sparse or relatively indirect, such as GSH conjugation and respiratory tract metabolism. Key conclusions from the model predictions include the following: (1) as expected, TCE is substantially metabolized, primarily by oxidation at doses below saturation; (2) GSH conjugation and subsequent bioactivation in humans appear to be 10- to 100-fold greater than previously estimated; and (3) mice had the greatest rate of respiratory tract oxidative metabolism as compared to rats and humans. In a situation such as TCE in which there is large database of studies coupled with complex toxicokinetics, the Bayesian approach provides a systematic method of simultaneously estimating model parameters and characterizing their uncertainty and variability. However, care needs to be taken in its implementation to ensure biological consistency, transparency, and objectivity.

  18. Interaction of 5-fluoro-5'-deoxyuridine with human serum albumin under physiological and non-physiological condition: a biophysical investigation.

    PubMed

    Ishtikhar, Mohd; Rabbani, Gulam; Khan, Rizwan Hasan

    2014-11-01

    Uridine analogs 5'dFUrd (a cytotoxic metabolite of a prodrug capecitabine that enzymatically converted into 5'dFUrd) commonly used in the treatment of advanced human cancers, especially gastrointestinal tract, ovary, colorectal, breast cancers etc. Drugs/metabolites are transported in the blood by transporter proteins like human serum albumin (HSA). Here we investigate the interaction of 5'dFUrd to HSA by spectroscopic and calorimetric techniques at physiological (pH 7.4) and non-physiological (pH 9.0) conditions. The binding constant (Kb), enthalpy change (ΔH°), entropy change (ΔS°) and Gibbs free energy change (ΔG°) were also calculated under both conditions. The secondary structure of HSA showed greater alteration in helicity at physiological pH. ITC measurement reveals that HSA have high binding affinity at physiological pH as compares to non-physiological conditions. The thermostability of HSA alone as well of the HSA-drug complex was found to be higher at physiological pH. The binding study was also explored through molecular docking studies which revealed that 5'dFUrd was bound to subdomain IIA of Sudlow's site I through multiple mode of interaction. These results suggest that 5'dFUrd have high binding affinity at physiological condition or "N" isoform so lower drug concentrations are required in compare to non-physiological or "B" isoform of HSA to completely occupied the binding site of the protein.

  19. Physiological and Biomechanical Mechanisms of Distance Specific Human Running Performance.

    PubMed

    Thompson, M A

    2017-08-01

    Running events range from 60-m sprints to ultra-marathons covering 100 miles or more, which presents an interesting diversity in terms of the parameters for successful performance. Here, we review the physiological and biomechanical variations underlying elite human running performance in sprint to ultramarathon distances. Maximal running speeds observed in sprint disciplines are achieved by high vertical ground reaction forces applied over short contact times. To create this high force output, sprint events rely heavily on anaerobic metabolism, as well as a high number and large cross-sectional area of type II fibers in the leg muscles. Middle distance running performance is characterized by intermediates of biomechanical and physiological parameters, with the possibility of unique combinations of each leading to high-level performance. The relatively fast velocities in mid-distance events require a high mechanical power output, though ground reaction forces are less than in sprinting. Elite mid-distance runners exhibit local muscle adaptations that, along with a large anaerobic capacity, provide the ability to generate a high power output. Aerobic capacity starts to become an important aspect of performance in middle distance events, especially as distance increases. In distance running events, V˙O2max is an important determinant of performance, but is relatively homogeneous in elite runners. V˙O2 and velocity at lactate threshold have been shown to be superior predictors of elite distance running performance. Ultramarathons are relatively new running events, as such, less is known about physiological and biomechanical parameters that underlie ultra-marathon performance. However, it is clear that performance in these events is related to aerobic capacity, fuel utilization, and fatigue resistance. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology 2017. This work is written by US Government employees and is in

  20. Bayesian analysis of physiologically based toxicokinetic and toxicodynamic models.

    PubMed

    Hack, C Eric

    2006-04-17

    Physiologically based toxicokinetic (PBTK) and toxicodynamic (TD) models of bromate in animals and humans would improve our ability to accurately estimate the toxic doses in humans based on available animal studies. These mathematical models are often highly parameterized and must be calibrated in order for the model predictions of internal dose to adequately fit the experimentally measured doses. Highly parameterized models are difficult to calibrate and it is difficult to obtain accurate estimates of uncertainty or variability in model parameters with commonly used frequentist calibration methods, such as maximum likelihood estimation (MLE) or least squared error approaches. The Bayesian approach called Markov chain Monte Carlo (MCMC) analysis can be used to successfully calibrate these complex models. Prior knowledge about the biological system and associated model parameters is easily incorporated in this approach in the form of prior parameter distributions, and the distributions are refined or updated using experimental data to generate posterior distributions of parameter estimates. The goal of this paper is to give the non-mathematician a brief description of the Bayesian approach and Markov chain Monte Carlo analysis, how this technique is used in risk assessment, and the issues associated with this approach.

  1. Relationship between sociability toward humans and physiological stress in dogs.

    PubMed

    Shin, Yoon-Joo; Shin, Nam-Shik

    2017-07-28

    Sociability is an essential trait for dogs to successfully interact with humans. In this study, the relationship between sociability and physiological stress was examined. Additionally, whether differences exist between companion dogs (C group) and shelter dogs (S group) was examined. Overall, healthy 37 dogs (C group=21 and S group=16) were examined. After 5 min of walking, the dog and the owner (or the chief manager) rested freely in the experimental location for 5 min. The behavioral test with 6 categories was conducted to evaluate sociability over 4 min. The establishment of two groups (H group=dogs with high sociability; L group=dogs with low sociability) was supported by the statistical results of the behavioral tests. Saliva was collected before (P1) and after the test period (P2), and salivary cortisol levels were determined and statistically analyzed. The cortisol concentrations at P2 and the differences in concentrations between P1 and P2 (P2-P1) in the groups with high sociability were significantly lower than those in the groups with low sociability. These results may demonstrate that sociable dogs adapt more comfortably to strangers and unfamiliar situations. Meanwhile, there were significant differences in hormonal results between the C and S groups. For this reason, their sociability should be evaluated using behavioral and physiological assessments before re-adoption to ensure their successful adaptation.

  2. Examination of Duct Physiology in the Human Mammary Gland

    PubMed Central

    Mills, Dixie; Gomberawalla, Ameer; Gordon, Eva J.; Tondre, Julie; Nejad, Mitra; Nguyen, Tinh; Pogoda, Janice M.; Rao, Jianyu; Chatterton, Robert; Henning, Susanne; Love, Susan M.

    2016-01-01

    Background The human breast comprise several ductal systems, or lobes, which contain a small amount of fluid containing cells, hormones, proteins and metabolites. The complex physiology of these ducts is likely a contributing factor to the development of breast cancer, especially given that the vast majority of breast cancers begin in a single lobular unit. Methods We examined the levels of total protein, progesterone, estradiol, estrone sulfate, dehydroepiandrosterone sulfate, and macrophages in ductal fluid samples obtained from 3 ducts each in 78 women, sampled twice over a 6 month period. Samples were processed for both cytological and molecular analysis. Intraclass correlation coefficients and mixed models were utilized to identify significant data. Results We found that the levels of these ductal fluid components were generally uncorrelated among ducts within a single breast and over time, suggesting that each lobe within the breast has a distinct physiology. However, we also found that estradiol was more correlated in women who were nulliparous or produced nipple aspirate fluid. Conclusions Our results provide evidence that the microenvironment of any given lobular unit is unique to that individual unit, findings that may provide clues about the initiation and development of ductal carcinomas. PMID:27073976

  3. An overview of artificial gravity. [effects on human performance and physiology

    NASA Technical Reports Server (NTRS)

    Stone, R. W., Jr.

    1973-01-01

    The unique characteristics of artificial gravity that affect human performance and physiology in an artificial gravity environment are reviewed. The rate at which these unique characteristics change decreases very rapidly with increasing radius of a rotating vehicle used to produce artificial gravity. Reducing their influence on human performance or physiology by increasing radius becomes a situation of very rapidly diminishing returns. A review of several elements of human performance has developed criteria relative to the sundry characteristics of artificial gravity. A compilation of these criteria indicates that the maximum acceptable rate of rotation, leg heaviness while walking, and material handling are the factors that define the minimum acceptable radius. The ratio of Coriolis force to artificial weight may also be significant. Based on current knowledge and assumptions for the various criteria, a minimum radius between 15.2 and 16.8 m seems desirable.

  4. An overview of artificial gravity. [effects on human performance and physiology

    NASA Technical Reports Server (NTRS)

    Stone, R. W., Jr.

    1973-01-01

    The unique characteristics of artificial gravity that affect human performance and physiology in an artificial gravity environment are reviewed. The rate at which these unique characteristics change decreases very rapidly with increasing radius of a rotating vehicle used to produce artificial gravity. Reducing their influence on human performance or physiology by increasing radius becomes a situation of very rapidly diminishing returns. A review of several elements of human performance has developed criteria relative to the sundry characteristics of artificial gravity. A compilation of these criteria indicates that the maximum acceptable rate of rotation, leg heaviness while walking, and material handling are the factors that define the minimum acceptable radius. The ratio of Coriolis force to artificial weight may also be significant. Based on current knowledge and assumptions for the various criteria, a minimum radius between 15.2 and 16.8 m seems desirable.

  5. Human physiological reaction to geomagnetic disturbances of solar origin

    NASA Astrophysics Data System (ADS)

    Dimitrova, Sv.; Stoilova, I.

    2002-12-01

    During the last two decades publications about the influence of geomagnetic activity on human health increase but there are not still strong evidences for this relationship. We performed measurements and observations of 86 working volunteers during the period of autumn and spring equinox. We examined systolic, diastolic blood pressure and pulse rate. We also collected data for some personal health condition complaints. Four-way analyses of variance (MANOVA method) were employed and the influence of factors geomagnetic activity level, sequence of the days of measurements with respect to the increased geomagnetic activity, medicaments and sex was investigated. We also performed three-way analyses of variance and investigated influence of atmospheric pressure, medicaments and sex on the physiological parameters under consideration. Our investigations indicate that most of the persons examined irrespectively to their health status could be sensitive to the geomagnetic changes, which influence directly self-confidence and working ability.

  6. Integrating an Interprofessional Education Experience Into a Human Physiology Course.

    PubMed

    Edwards, Scott; Molina, Patricia E; McDonough, Kathleen H; Mercante, Donald E; Gunaldo, Tina P

    2017-09-01

    To obtain physician assistant (PA) student perceptions about an interprofessional education (IPE) training experience embedded in a multidisciplinary science course. An IPE training experience was integrated into a graduate human physiology course offered to PA, physical therapy, and graduate studies students. The focus of the activity related to the Interprofessional Education Collaborative (IPEC) competency domains of (1) roles and responsibilities and (2) teams and teamwork. Effectiveness was assessed in pretraining and posttraining surveys, which included questions addressing student self-perceptions of IPEC competency domains, student assessment of the learning activity, and student reflection. We observed a statistically significant positive change in PA student perceptions of IPEC competency domains. Students also provided a positive evaluation of the IPE activity and communicated personal improvements in IPE perspectives. Incorporating planned IPE experiences into multidisciplinary health science courses represents an appropriate venue for PA students to learn and apply interprofessional competencies, which may benefit future interprofessional practice.

  7. The role of leptin in human physiology and pathophysiology.

    PubMed

    Janeckova, R

    2001-01-01

    This review focuses on current knowledge of leptin biology and the role of leptin in various physiological and pathophysiological states. Leptin is involved in the regulation of body weight. Serum leptin can probably be considered as one of the best biological markers reflecting total body fat in both animals and humans. Obesity in man is accompanied by increased circulating leptin concentrations. Gender differences clearly exist. Leptin is not only correlated to a series of endocrine parameters such as insulin, glucocorticoids, thyroid hormones, testosterone, but it also seems to be involved in mediating some endocrine mechanisms (onset of puberty, insulin secretion) and diseases (obesity, polycystic ovary syndrome). It has also been suggested that leptin can act as a growth factor in the fetus and the neonate.

  8. Physiological and Biomechanical Considerations for a Human Mars Mission

    NASA Astrophysics Data System (ADS)

    Hawkey, A.

    Evolving on Earth has made humans perfectly adapted, both physiologically and biomechanically, to its gravity and atmospheric conditions. Leaving the Earth and its protective environment, therefore, results in the degradation of a number of human systems. Long-duration stays on the International Space Station (ISS) are accompanied by significant effects on crew's cardiovascular, vestibular and musculoskeletal systems. Bone loss and muscle atrophy are experienced at a rate of 1-3% and 5% per month respectively, while VO2 (oxygen consumption) measurements are reduced by approximately 25% after a few weeks in space. If these figures are simply extrapolated, a future human mission to Mars will be seriously jeopardised and crews may find they cross the threshold of bone and muscle loss and aerobic fitness - ultimately with them being unable to return to Earth. When arriving on Mars, considerable biomechanical alterations will also occur. Optimum walking speeds will be approximately 30% lower and transitioning from a walk to a run will occur at a speed 25% slower. Peak vertical forces will be reduced by as much as 50%, while stride length, stride time and airborne time will all increase. On Mars, half as much energy will be required to travel the equivalent distance on Earth and it will be 65% more economical to run rather than to walk.

  9. Physiological and biomechanical considerations for a human Mars mission.

    PubMed

    Hawkey, Adam

    2005-01-01

    Evolving on Earth has made humans perfectly adapted, both physiologically and biomechanically, to its gravity and atmospheric conditions. Leaving the Earth and its protective environment, therefore, results in the degradation of a number of human systems. Long-duration stays on the International Space Station (ISS) are accompanied by significant effects on crew's cardiovascular, vestibular and musculoskeletal systems. Bone loss and muscle atrophy are experienced at a rate of 1-3% and 5% per month respectively, while VO2 (oxygen consumption) measurements are reduced by approximately 25% after a few weeks in space. If these figures are simply extrapolated, a future human mission to Mars will be seriously jeopardised and crews may find they cross the threshold of bone and muscle loss and aerobic fitness--ultimately with them being unable to return to Earth. When arriving on Mars, considerable biomechanical alterations will also occur. Optimum walking speeds will be approximately 30% lower and transitioning from a walk to a run will occur at a speed 25% slower. Peak vertical forces will be reduced by as much as 50%, while stride length, stride time and airborne time will all increase. On Mars, half as much energy will be required to travel the equivalent distance on Earth and it will be 65% more economical to run rather than to walk.

  10. Physiological Concentrations of Leptin Do Not Affect Human Neutrophils

    PubMed Central

    Kamp, Vera M.; Langereis, Jeroen D.; van Aalst, Corneli W.; van der Linden, Jan A.; Ulfman, Laurien H.; Koenderman, Leo

    2013-01-01

    Leptin is an adipokine that is thought to be important in many inflammatory diseases, and is known to influence the function of several leukocyte types. However, no clear consensus is present regarding the responsiveness of neutrophils for this adipokine. In this study a 2D DIGE proteomics approach was used as an unbiased approach to identify leptin-induced effects on neutrophils. Additionally chemotaxis and survival experiments were performed to reproduce results from literature showing putative effects of leptin on these neutrophil responses. Leptin did not induce any significant changes in the proteome provided leptin was added at physiologically relevant concentrations (250 ng). Our leptin batches were biologically active as they induced proliferation in LeptinR expressing Ba/F3 cells. At high concentrations (25000 ng) leptin induced a change in neutrophil proteome. Seventeen differently regulated spots were identified of which twelve could be characterized by mass spectrometry. Two of these identified proteins, SerpinB1 and p40 phox, were chosen for further analysis but leptin-induced expression analyzed by western blot were highly variable. Additionally leptin also induced neutrophil survival at these high concentrations. No leptin-induced chemotaxis of human neutrophils was detected at any concentration. In conclusion, physiological concentrations of leptin do not affect neutrophils. High leptin concentrations induced survival and changes in the neutrophils proteome, but this was most likely mediated by an indirect effect. However, it cannot be ruled out that the effects were mediated by a yet not-identified leptin receptor on human neutrophils. PMID:24066032

  11. Physiological Health Challenges for Human Missions to Mars

    NASA Technical Reports Server (NTRS)

    Norsk, Peter

    2015-01-01

    During the next decades, manned space missions are expected to be aiming at the Lagrange points, near Earth asteroids, and Mars flyby and/or landing. The question is therefore: Are we ready to go? To answer this with a yes, we are currently using the International Space Station to develop an integrated human physiological countermeasure suite. The integrated countermeasure suite will most likely encounter: 1) Exercise devices for aerobic, dynamic and resistive exercise training; 2) sensory-motor computer training programs and anti-motion sickness medication for preparing EVAs and G-transitions; 3) lower limb bracelets for preventing and/or treating the VIIP (vision impairment and intracranial pressure) syndrome; 4) nutritional components for maintenance of bone, muscle, the cardiovascular system and preventing oxidative stress and damage and immune deficiencies (e. g. omega-3 fatty acids, PRO/K, anti-oxidants and less salt and iron); 5) bisphosphonates for preventing bone degradation.; 6) lower body compression garment and oral salt and fluid loading for landing on a planetary surface to combat orthostatic intolerance; 7) laboratory analysis equipment for individualized monitoring of biomarkers in blood, urine and saliva for estimation of health status in; 8) advanced ultrasound techniques for monitoring bone and cardiovascular health; and 9) computer modeling programs for individual health status assessments of efficiency and subsequent adjustments of countermeasures. In particular for future missions into deep space, we are concerned with the synergistic effects of weightlessness, radiation, operational constraints and other spaceflight environmental factors. Therefore, increased collaboration between physiological, behavioral, radiation and space vehicle design disciplines are strongly warranted. Another venue we are exploring in NASA's Human Research Program is the usefulness of artificial gravity for mitigating the health risks of long duration weightlessness.

  12. Potential applications of gut microbiota to control human physiology.

    PubMed

    Umu, Ozgün Candan Onarman; Oostindjer, Marije; Pope, Phillip B; Svihus, Birger; Egelandsdal, Bjørg; Nes, Ingolf F; Diep, Dzung B

    2013-11-01

    The microorganisms living in our gut have been a black box to us for a long time. However, with the recent advances in high throughput DNA sequencing technologies, it is now possible to assess virtually all microorganisms in our gut including non-culturable ones. With the use of powerful bioinformatics tools to deal with multivariate analyses of huge amounts of data from metagenomics, metatranscriptomics, metabolomics, we now start to gain some important insights into these tiny gut inhabitants. Our knowledge is increasing about who they are, to some extent, what they do and how they affect our health. Gut microbiota have a broad spectrum of possible effects on health, from preventing serious diseases, improving immune system and gut health to stimulating the brain centers responsible for appetite and food intake control. Further, we may be on the verge of being capable of manipulating the gut microbiota by diet control to possibly improve our health. Diets consisting of different components that are fermentable by microbiota are substrates for different kinds of microbes in the gut. Thus, diet control can be used to favor the growth of some selected gut inhabitants. Nowadays, the gut microbiota is taken into account as a separate organ in human body and their activities and metabolites in gut have many physiological and neurological effects. In this mini-review, we discuss the diversity of gut microbiota, the technologies used to assess them, factors that affect microbial composition and metabolites that affect human physiology, and their potential applications in satiety control via the gut-brain axis.

  13. Prediction of the physiological response of humans wearing protective clothing using a thermophysiological human simulator.

    PubMed

    Psikuta, Agnes; Wang, Li-Chu; Rossi, René M

    2013-01-01

    Most standards and devices for determining clothing properties ignore the physiological state of the wearer and are inadequate to evaluate the transient thermal properties of clothing ensembles. This study evaluated the physiological burden of different types of protective clothing and environmental conditions using the recently developed single-sector thermo-physiological human simulator and compared its performance with a thermal cylinder (without the physiological control model) and with an advanced physiological model (with a simple clothing model). A single-sector physiological simulator developed to simulate the dynamic thermal and perceptual behavior of humans over a wide range of environmental and personal conditions was successfully validated in this study through tests with clothed individuals exposed to hot and cold conditions. In comparative tests on water vapor permeable and impermeable clothing samples, the simulator provided a much more complete picture of actual clothing performance, for example, in terms of moisture retention within the clothing and the additional cooling due to the "heat pipe" effect in impermeable clothing.

  14. Interfacing Physiologically-Based Pharmacokinetic Modeling and Simulation Systems

    DTIC Science & Technology

    1992-01-01

    8217: a simulation of drug dispo- sition in the human body : applications in clinical pharmacokinctics. Br. J. Clin. Pharmacol. 10, 591--602. D’Souza, R.D...physiological processes which can model (tissues) and the anatomical struture of each tissue; affect the distribution and flux of a substance: transport 2... humans the investigator must rely on in vitro or animal properties of the substance (tissue partition coefficients). studies. The graphical user

  15. A hybrid computational fluid dynamics and physiologically based pharmacokinetic model for comparison of predicted tissue concentrations of acrylic acid and other vapors in the rat and human nasal cavities following inhalation exposure.

    PubMed

    Frederick, C B; Gentry, P R; Bush, M L; Lomax, L G; Black, K A; Finch, L; Kimbell, J S; Morgan, K T; Subramaniam, R P; Morris, J B; Ultman, J S

    2001-05-01

    To assist in interspecies dosimetry comparisons for risk assessment of the nasal effects of organic acids, a hybrid computational fluid dynamics (CFD) and physiologically based pharmacokinetic (PBPK) dosimetry model was constructed to estimate the regional tissue dose of inhaled vapors in the rat and human nasal cavity. Application to a specific vapor would involve the incorporation of the chemical-specific reactivity, metabolism, partition coefficients, and diffusivity (in both air and tissue phases) of the vapor. This report describes the structure of the CFD-PBPK model and its application to a representative acidic vapor, acrylic acid, for interspecies tissue concentration comparisons to assist in risk assessment. By using the results from a series of short-term in vivo studies combined with computer modeling, regional nasal tissue dose estimates were developed and comparisons of tissue doses between species were conducted. To make these comparisons, the assumption was made that the susceptibilities of human and rat olfactory epithelium to the cytotoxic effects of organic acids were similar, based on similar histological structure and common mode of action considerations. Interspecies differences in response were therefore assumed to be driven primarily by differences in nasal tissue concentrations that result from regional differences in nasal air flow patterns relative to the species-specific distribution of olfactory epithelium in the nasal cavity. The results of simulations with the seven-compartment CFD-PBPK model suggested that the olfactory epithelium of the human nasal cavity would be exposed to tissue concentrations of acrylic acid similar to that of the rat nasal cavity when the exposure conditions are the same. Similar analysis of CFD data and CFD-PBPK model simulations with a simpler one-compartment model of the whole nasal cavities of rats and humans provides comparable results to averaging over the compartments of the seven-compartment model. These

  16. Neurobehavioral and physiologic effects of trifluoromethane in humans.

    PubMed

    Fagan, S C; Rahill, A A; Balakrishnan, G; Ewing, J R; Branch, C A; Brown, G G

    1995-06-01

    Nuclear magnetic resonance (NMR) imaging shows promise in the measurement of human cerebral blood flow (CBF) in that nonradioactive indicators may be used. Our earlier investigations with trifluoromethane (FC-23) gas have shown that this compound can be used to safely and effectively measure CBF in anesthetized animal models. In this Phase I dose-escalation study we set out to determine the maximal tolerated concentration (MTC) of FC-23 in normal healthy male volunteers and to assess its feasibility as an NMR indicator. Five subjects were exposed in a blinded fashion to escalating concentrations of FC-23 between 10% and 60%, randomly interleaved with exposures to both room air and 40% nitrous oxide. On each study day, the subjects breathed the test gas for eight pulses of 3 min each with 2-min clearance periods between the pulses. The subjects underwent intensive physiologic and neurobehavioral monitoring throughout the study period. The first subject experienced an anesthetic response to 60% FC-23, and the second subject experienced "discomfort" and requested discontinuation at the initiation of 40% FC-23. The MTC was subsequently determined to be 30% FC-23 (all subjects tolerated the gas), although a small (37.6 vs. 40.5) but statistically significant retention of carbon dioxide was found (p = .003). When one subject received 30% FC-23 during an NMR imaging study, a pronounced anesthetic effect with intolerable hyperacusis was demonstrated. Human studies of FC-23 have been discontinued in our laboratory.

  17. Effects of Neuregulin 3 Genotype on Human Prefrontal Cortex Physiology

    PubMed Central

    Tost, Heike; Callicott, Joseph H.; Rasetti, Roberta; Vakkalanka, Radhakrishna; Mattay, Venkata S.; Weinberger, Daniel R.

    2014-01-01

    The neuregulin 3 gene (NRG3) plays pleiotropic roles in neurodevelopment and is a putative susceptibility locus for schizophrenia. Specifically, the T allele of NRG3 rs10748842 has been associated with illness risk, altered cognitive function, and the expression of a novel splice isoform in prefrontal cortex (PFC), but the neural system effects are unexplored. Here, we report an association between rs10748842 and PFC physiology as measured by functional magnetic resonance imaging of human working memory performance, where a convincing link between increased genetic risk for schizophrenia and increased activation in some PFC areas has been established. In 410 control individuals (195 males, 215 females), we detected a highly significant effect of NRG3 genotype manifesting as an unanticipated increase in ventrolateral PFC activation in nonrisk-associated C allele carriers. An additional analysis including 78 patients with schizophrenia spectrum disorders (64 males, 14 females) and 123 unaffected siblings (53 males, 70 females) revealed a whole-brain significant genotype by group interaction in right dorsolateral PFC (DLPFC), manifesting as a relative activation increase in healthy controls and siblings (C > T/T) and as a hypoactivation in patients (T/T > C). These observed genotype-dependent effects in PFC were not explained by task performance and did not conform to established locales of prefrontal inefficiency linked to genetic risk for schizophrenia. Our data indicate a complex modulation of brain physiology by rs10748842, which does not fit the simple inefficiency model of risk association in DLPFC and suggests that other neurobiological mechanisms are involved. PMID:24431462

  18. The physiology and pathophysiology of human breath-hold diving.

    PubMed

    Lindholm, Peter; Lundgren, Claes E G

    2009-01-01

    This is a brief overview of physiological reactions, limitations, and pathophysiological mechanisms associated with human breath-hold diving. Breath-hold duration and ability to withstand compression at depth are the two main challenges that have been overcome to an amazing degree as evidenced by the current world records in breath-hold duration at 10:12 min and depth of 214 m. The quest for even further performance enhancements continues among competitive breath-hold divers, even if absolute physiological limits are being approached as indicated by findings of pulmonary edema and alveolar hemorrhage postdive. However, a remarkable, and so far poorly understood, variation in individual disposition for such problems exists. Mortality connected with breath-hold diving is primarily concentrated to less well-trained recreational divers and competitive spearfishermen who fall victim to hypoxia. Particularly vulnerable are probably also individuals with preexisting cardiac problems and possibly, essentially healthy divers who may have suffered severe alternobaric vertigo as a complication to inadequate pressure equilibration of the middle ears. The specific topics discussed include the diving response and its expression by the cardiovascular system, which exhibits hypertension, bradycardia, oxygen conservation, arrhythmias, and contraction of the spleen. The respiratory system is challenged by compression of the lungs with barotrauma of descent, intrapulmonary hemorrhage, edema, and the effects of glossopharyngeal insufflation and exsufflation. Various mechanisms associated with hypoxia and loss of consciousness are discussed, including hyperventilation, ascent blackout, fasting, and excessive postexercise O(2) consumption. The potential for high nitrogen pressure in the lungs to cause decompression sickness and N(2) narcosis is also illuminated.

  19. Mathematical modeling of acid-base physiology.

    PubMed

    Occhipinti, Rossana; Boron, Walter F

    2015-01-01

    pH is one of the most important parameters in life, influencing virtually every biological process at the cellular, tissue, and whole-body level. Thus, for cells, it is critical to regulate intracellular pH (pHi) and, for multicellular organisms, to regulate extracellular pH (pHo). pHi regulation depends on the opposing actions of plasma-membrane transporters that tend to increase pHi, and others that tend to decrease pHi. In addition, passive fluxes of uncharged species (e.g., CO2, NH3) and charged species (e.g., HCO3(-), [Formula: see text] ) perturb pHi. These movements not only influence one another, but also perturb the equilibria of a multitude of intracellular and extracellular buffers. Thus, even at the level of a single cell, perturbations in acid-base reactions, diffusion, and transport are so complex that it is impossible to understand them without a quantitative model. Here we summarize some mathematical models developed to shed light onto the complex interconnected events triggered by acids-base movements. We then describe a mathematical model of a spherical cells-which to our knowledge is the first one capable of handling a multitude of buffer reactions-that our team has recently developed to simulate changes in pHi and pHo caused by movements of acid-base equivalents across the plasma membrane of a Xenopus oocyte. Finally, we extend our work to a consideration of the effects of simultaneous CO2 and HCO3(-) influx into a cell, and envision how future models might extend to other cell types (e.g., erythrocytes) or tissues (e.g., renal proximal-tubule epithelium) important for whole-body pH homeostasis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Mathematical modeling of acid-base physiology

    PubMed Central

    Occhipinti, Rossana; Boron, Walter F.

    2015-01-01

    pH is one of the most important parameters in life, influencing virtually every biological process at the cellular, tissue, and whole-body level. Thus, for cells, it is critical to regulate intracellular pH (pHi) and, for multicellular organisms, to regulate extracellular pH (pHo). pHi regulation depends on the opposing actions of plasma-membrane transporters that tend to increase pHi, and others that tend to decrease pHi. In addition, passive fluxes of uncharged species (e.g., CO2, NH3) and charged species (e.g., HCO3− , NH4+) perturb pHi. These movements not only influence one another, but also perturb the equilibria of a multitude of intracellular and extracellular buffers. Thus, even at the level of a single cell, perturbations in acid-base reactions, diffusion, and transport are so complex that it is impossible to understand them without a quantitative model. Here we summarize some mathematical models developed to shed light onto the complex interconnected events triggered by acids-base movements. We then describe a mathematical model of a spherical cell–which to our knowledge is the first one capable of handling a multitude of buffer reaction–that our team has recently developed to simulate changes in pHi and pHo caused by movements of acid-base equivalents across the plasma membrane of a Xenopus oocyte. Finally, we extend our work to a consideration of the effects of simultaneous CO2 and HCO3− influx into a cell, and envision how future models might extend to other cell types (e.g., erythrocytes) or tissues (e.g., renal proximal-tubule epithelium) important for whole-body pH homeostasis. PMID:25617697

  1. Human pathogens in plant biofilms: Formation, physiology, and detection.

    PubMed

    Ximenes, Eduardo; Hoagland, Lori; Ku, Seockmo; Li, Xuan; Ladisch, Michael

    2017-01-09

    Fresh produce, viewed as an essential part of a healthy life style is usually consumed in the form of raw or minimally processed fruits and vegetables, and is a potentially important source of food-borne human pathogenic bacteria and viruses. These are passed on to the consumer since the bacteria can form biofilms or otherwise populate plant tissues, thereby using plants as vectors to infect animal hosts. The life cycle of the bacteria in plants differs from those in animals or humans and results in altered physiochemical and biological properties (e.g., physiology, immunity, native microflora, physical barriers, mobility, and temperature). Mechanisms by which healthy plants may become contaminated by microorganisms, develop biofilms, and then pass on their pathogenic burden to people are explored in the context of hollow fiber microfiltration by which plant-derived microorganisms may be recovered and rapidly concentrated to facilitate study of their properties. Enzymes, when added to macerated plant tissues, hydrolyze or alter macromolecules that would otherwise foul hollow-fiber microfiltration membranes. Hence, microfiltration may be used to quickly increase the concentration of microorganisms to detectable levels. This review discusses microbial colonization of vegetables, formation and properties of biofilms, and how hollow fiber microfiltration may be used to concentrate microbial targets to detectable levels. The use of added enzymes helps to disintegrate biofilms and minimize hollow fiber membrane fouling, thereby providing a new tool for more time effectively elucidating mechanisms by which biofilms develop and plant tissue becomes contaminated with human pathogens. Biotechnol. Bioeng. 2016;9999: 1-16. © 2017 Wiley Periodicals, Inc.

  2. Dissimilarity measure based on ordinal pattern for physiological signals

    NASA Astrophysics Data System (ADS)

    Wang, Jing; Shang, Pengjian; Shi, Wenbin; Cui, Xingran

    2016-08-01

    Complex physiologic signals may carry information of their underlying mechanisms. In this paper, we introduce a dissimilarity measure to capture the features of underlying dynamics from various types of physiologic signals based on rank order statistics of ordinal patterns. Simulated 1/f noise and white noise are used to evaluate the effect of data length, embedding dimension and time delay on this measure. We then apply this measure to different physiologic signals. The method can successfully characterize the unique underlying patterns of subjects at similar physiologic states. It can also serve as a good discriminative tool for the healthy young, healthy elderly, congestive heart failure, atrial fibrilation and white noise groups. Furthermore, when investigated into the details of underlying ordinal patterns for each group, it is found that the distributions of ordinal patterns varies significantly for healthy and pathologic states, as well as aging.

  3. Molecular bases of circadian rhythmicity in renal physiology and pathology

    PubMed Central

    Bonny, Olivier; Vinciguerra, Manlio; Gumz, Michelle L.; Mazzoccoli, Gianluigi

    2013-01-01

    The physiological processes that maintain body homeostasis oscillate during the day. Diurnal changes characterize kidney functions, comprising regulation of hydro-electrolytic and acid-base balance, reabsorption of small solutes and hormone production. Renal physiology is characterized by 24-h periodicity and contributes to circadian variability of blood pressure levels, related as well to nychthemeral changes of sodium sensitivity, physical activity, vascular tone, autonomic function and neurotransmitter release from sympathetic innervations. The circadian rhythmicity of body physiology is driven by central and peripheral biological clockworks and entrained by the geophysical light/dark cycle. Chronodisruption, defined as the mismatch between environmental–social cues and physiological–behavioral patterns, causes internal desynchronization of periodic functions, leading to pathophysiological mechanisms underlying degenerative, immune related, metabolic and neoplastic diseases. In this review we will address the genetic, molecular and anatomical elements that hardwire circadian rhythmicity in renal physiology and subtend disarray of time–dependent changes in renal pathology. PMID:23901050

  4. Filtration of human EEG recordings from physiological artifacts with empirical mode method

    NASA Astrophysics Data System (ADS)

    Grubov, Vadim V.; Runnova, Anastasiya E.; Khramova, Marina V.

    2017-03-01

    In the paper we propose the new method for dealing with noise and physiological artifacts in experimental human EEG recordings. The method is based on analysis of EEG signals with empirical mode decomposition (Hilbert-Huang transform). We consider noises and physiological artifacts on EEG as specific oscillatory patterns that cause problems during EEG analysis and can be detected with additional signals recorded simultaneously with EEG (ECG, EMG, EOG, etc.) We introduce the algorithm of the method with following steps: empirical mode decomposition of EEG signal, choosing of empirical modes with artifacts, removing empirical modes with artifacts, reconstruction of the initial EEG signal. We test the method on filtration of experimental human EEG signals from eye-moving artifacts and show high efficiency of the method.

  5. Matters of Taste: Bridging Molecular Physiology and the Humanities

    ERIC Educational Resources Information Center

    Rangachari, P. K.; Rangachari, Usha

    2015-01-01

    Taste perception was the focus of an undergraduate course in the health sciences that bridged the sciences and humanities. A problem-based learning approach was used to study the biological issues, whereas the cultural transmutations of these molecular mechanisms were explored using a variety of resources (novels, cookbooks, and films). Multiple…

  6. Matters of Taste: Bridging Molecular Physiology and the Humanities

    ERIC Educational Resources Information Center

    Rangachari, P. K.; Rangachari, Usha

    2015-01-01

    Taste perception was the focus of an undergraduate course in the health sciences that bridged the sciences and humanities. A problem-based learning approach was used to study the biological issues, whereas the cultural transmutations of these molecular mechanisms were explored using a variety of resources (novels, cookbooks, and films). Multiple…

  7. Derivation of a human equivalent concentration for n-butanol using a physiologically based pharmacokinetic model for n-butyl acetate and metabolites n-butanol and n-butyric acid

    SciTech Connect

    Teeguarden, Justin G.; Deisinger, P. J.; Poet, Torka S.; English, J C.; Faber, W D.; Barton, H. A.; Corley, Rick A.; Clewell, III, H. J.

    2005-05-01

    The metabolic series (family) approach for risk assessment uses a dosimetry-based analysis to develop toxicity information for a group of metabolically linked compounds using pharmacokinetic (PK) data for each compound and toxicity data for the parent compound. An initial physiologically-based pharmacokinetic (PBPK) model was developed to support the implementation of the metabolic series approach for n-butyl acetate and its subsequent metabolites, n-butanol, and n-butyric acid (the butyl series) (Barton et al. 2000). In conjunction with pilot pharmacokinetic studies, the model was used to design the definitive intravenous (i.v.) PK studies. Rats were implanted with dual indwelling cannulae and administered test compounds by i.v. bolus dose, i.v. infusion, or by inhalation in a recirculating closed chamber. Hepatic, vascular and extravascular metabolic constants for metabolism were estimated by fitting the model to the blood time course data from these experiments. The respiratory bioavailability of n-butyl acetate and n-butanol was estimated from closed chamber inhalation studies and measured ventilation rates. The resulting butyl series PBPK model successfully reproduces the blood time course of these compounds following i.v. administration, and inhalation exposure to n-butyl acetate and n-butanol. A fully scaled human version of the model successfully reproduces arterial blood n-butanol kinetics following inhalation exposure to n-butanol. These validated i.v (rat) and inhalation route models (rat, butyl acetate, n-butanol; human, butanol only) can be used to support species and dose-route extrapolations required for risk assessment of butyl series family of compounds. Further, this work demonstrates the usefulness of i.v. kinetic data for parameterization of systemic metabolism and the value of collaboration between experimentalists and kineticists in the development of PBPK models. The product of this effort, validated rat and human PBPK models for the butyl

  8. Smart Sensors and Virtual Physiology Human Approach as a Basis of Personalized Therapies in Diabetes Mellitus

    PubMed Central

    Fernández Peruchena, Carlos M; Prado-Velasco, Manuel

    2010-01-01

    Diabetes mellitus (DM) has a growing incidence and prevalence in modern societies, pushed by the aging and change of life styles. Despite the huge resources dedicated to improve their quality of life, mortality and morbidity rates, these are still very poor. In this work, DM pathology is revised from clinical and metabolic points of view, as well as mathematical models related to DM, with the aim of justifying an evolution of DM therapies towards the correction of the physiological metabolic loops involved. We analyze the reliability of mathematical models, under the perspective of virtual physiological human (VPH) initiatives, for generating and integrating customized knowledge about patients, which is needed for that evolution. Wearable smart sensors play a key role in this frame, as they provide patient’s information to the models. A telehealthcare computational architecture based on distributed smart sensors (first processing layer) and personalized physiological mathematical models integrated in Human Physiological Images (HPI) computational components (second processing layer), is presented. This technology was designed for a renal disease telehealthcare in earlier works and promotes crossroads between smart sensors and the VPH initiative. We suggest that it is able to support a truly personalized, preventive, and predictive healthcare model for the delivery of evolved DM therapies. PMID:21625646

  9. Smart sensors and virtual physiology human approach as a basis of personalized therapies in diabetes mellitus.

    PubMed

    Fernández Peruchena, Carlos M; Prado-Velasco, Manuel

    2010-01-01

    Diabetes mellitus (DM) has a growing incidence and prevalence in modern societies, pushed by the aging and change of life styles. Despite the huge resources dedicated to improve their quality of life, mortality and morbidity rates, these are still very poor. In this work, DM pathology is revised from clinical and metabolic points of view, as well as mathematical models related to DM, with the aim of justifying an evolution of DM therapies towards the correction of the physiological metabolic loops involved. We analyze the reliability of mathematical models, under the perspective of virtual physiological human (VPH) initiatives, for generating and integrating customized knowledge about patients, which is needed for that evolution. Wearable smart sensors play a key role in this frame, as they provide patient's information to the models.A telehealthcare computational architecture based on distributed smart sensors (first processing layer) and personalized physiological mathematical models integrated in Human Physiological Images (HPI) computational components (second processing layer), is presented. This technology was designed for a renal disease telehealthcare in earlier works and promotes crossroads between smart sensors and the VPH initiative. We suggest that it is able to support a truly personalized, preventive, and predictive healthcare model for the delivery of evolved DM therapies.

  10. Physiological characterization of human muscle acetylcholine receptors from ALS patients.

    PubMed

    Palma, Eleonora; Inghilleri, Maurizio; Conti, Luca; Deflorio, Cristina; Frasca, Vittorio; Manteca, Alessia; Pichiorri, Floriana; Roseti, Cristina; Torchia, Gregorio; Limatola, Cristina; Grassi, Francesca; Miledi, Ricardo

    2011-12-13

    Amyotrophic lateral sclerosis (ALS) is characterized by progressive degeneration of motor neurons leading to muscle paralysis. Research in transgenic mice suggests that the muscle actively contributes to the disease onset, but such studies are difficult to pursue in humans and in vitro models would represent a good starting point. In this work we show that tiny amounts of muscle from ALS or from control denervated muscle, obtained by needle biopsy, are amenable to functional characterization by two different technical approaches: "microtransplantation" of muscle membranes into Xenopus oocytes and culture of myogenic satellite cells. Acetylcholine (ACh)-evoked currents and unitary events were characterized in oocytes and multinucleated myotubes. We found that ALS acetylcholine receptors (AChRs) retain their native physiological characteristics, being activated by ACh and nicotine and blocked by α-bungarotoxin (α-BuTX), d-tubocurarine (dTC), and galantamine. The reversal potential of ACh-evoked currents and the unitary channel behavior were also typical of normal muscle AChRs. Interestingly, in oocytes injected with muscle membranes derived from ALS patients, the AChRs showed a significant decrease in ACh affinity, compared with denervated controls. Finally, riluzole, the only drug currently used against ALS, reduced, in a dose-dependent manner, the ACh-evoked currents, indicating that its action remains to be fully characterized. The two methods described here will be important tools for elucidating the role of muscle in ALS pathogenesis and for developing drugs to counter the effects of this disease.

  11. Effects of Weightlessness on Human Fluid and Electrolyte Physiology

    NASA Technical Reports Server (NTRS)

    Leach, Carolyn S.; Johnson, Philip C., Jr.

    1991-01-01

    The changes that occur in human fluid and electrolyte physiology during the acute and adaptive phases of adaptation to spaceflight are summarized. A number of questions remain to be answered. At a time when plasma volume and extracellular fluid volume are contracted and salt and water intake is unrestricted. ADH does not correct the volume deficit and serum sodium decreases. Change in secretion or activity of a natriuretic factor during spaceflight is one possible explanation. Recent identification of a polypeptide hormone produced in cardiac muscle cells which is natiuretic, is hypotensive, and has an inhibitory effect on renin and aldosterone secretion has renewed interest in the role of a natriuretic factor. The role of this atrial natriuretic factor (ANF) in both long- and short-term variation in extracellular volumes and in the inability of the kidney to bring about an escape from the sodium-retaining state accompanying chronic cardiac dysfunction makes it reasonable to look for a role of ANF in the regulation of sodium during exposure to microgravity. Prostaglandin-E is another hormone that may antagonize the action of ADH. Assays of these hormones will be performed on samples from crew members in the future.

  12. Estrogen receptor polymorphisms: significance to human physiology, disease and therapy.

    PubMed

    Figtree, Gemma A; Noonan, Jonathon E; Bhindi, Ravinay; Collins, Peter

    2009-01-01

    Other than its well-recognized effects on reproductive physiology, estrogen has important actions in a wide variety of other body systems with important examples including bone, blood vessels and the heart. These effects are seen in both females and males. Investigators have hypothesized those genetic variants in the genes coding for estrogen signaling proteins may cause variable sensitivity to the hormone and influence an individual's estrogen-sensitive phenotypes. The most obvious candidate genes are the estrogen receptors alpha and (ERalpha and beta). However, the regulation of these genes is complex and not well understood. Furthermore, their coding exons, and regulatory sequences are dispersed across large segments of the genome. A number of common polymorphisms have been identified in both ERalpha and ERbeta, with variable degrees of evidence of their direct biological significance and their association with human disease. The identification of genetic variations associated with altered estrogen response is of potential public health importance. Insights may be gained into the pathogenesis of estrogen sensitive diseases such as osteoporosis, breast cancer and cardiovascular disease contributing to the development and application of newer therapies for these disorders. Furthermore, genetic variants that alter sensitivity to estrogen may affect both therapeutic and harmful responses to exogenous estrogen administered in the form of the oral contraceptive pill or hormone replacement therapy. This clinical significance has led to the publication of a number of patents which will be reviewed.

  13. How consumer physical activity monitors could transform human physiology research.

    PubMed

    Wright, Stephen P; Hall Brown, Tyish S; Collier, Scott R; Sandberg, Kathryn

    2017-03-01

    A sedentary lifestyle and lack of physical activity are well-established risk factors for chronic disease and adverse health outcomes. Thus, there is enormous interest in measuring physical activity in biomedical research. Many consumer physical activity monitors, including Basis Health Tracker, BodyMedia Fit, DirectLife, Fitbit Flex, Fitbit One, Fitbit Zip, Garmin Vivofit, Jawbone UP, MisFit Shine, Nike FuelBand, Polar Loop, Withings Pulse O2, and others have accuracies similar to that of research-grade physical activity monitors for measuring steps. This review focuses on the unprecedented opportunities that consumer physical activity monitors offer for human physiology and pathophysiology research because of their ability to measure activity continuously under real-life conditions and because they are already widely used by consumers. We examine current and potential uses of consumer physical activity monitors as a measuring or monitoring device, or as an intervention in strategies to change behavior and predict health outcomes. The accuracy, reliability, reproducibility, and validity of consumer physical activity monitors are reviewed, as are limitations and challenges associated with using these devices in research. Other topics covered include how smartphone apps and platforms, such as the Apple ResearchKit, can be used in conjunction with consumer physical activity monitors for research. Lastly, the future of consumer physical activity monitors and related technology is considered: pattern recognition, integration of sleep monitors, and other biosensors in combination with new forms of information processing.

  14. Physiological Role of Gut Microbiota for Maintaining Human Health.

    PubMed

    Andoh, Akira

    2016-01-01

    The human body is colonized by an extremely complex and abundant aggregation of microbes, collectively referred to as the gut microbiota. Recent studies have focused on the link between these microbes and our health. Diet contributes to shaping the gut microbial structure and influences metabolic functions of the host. Alteration of the microbial structure and function (dysbiosis) is associated with the pathogenesis of various disorders. Fermentation is the process by which anaerobic bacteria (Firmicutes and Bacteroidetes) break down indigestible carbohydrates to short-chain fatty acids (SCFAs; acetate, propionate and butyrate), collaborating with species specialized in oligosaccharide fermentation (e.g. Bifidobacteria). Butyrate and propionate can regulate intestinal physiology and immune function, while acetate acts as a substrate for lipogenesis and gluconeogenesis. The gut microbiota regulates immune homeostasis via the induction of regulatory T cells and Th17 cells. In addition, butyrate has strong anti-inflammatory effects possibly through the inhibition of histone deacetylase activity. Metabolic products generated by the gut microbiota, such as SCFAs, GABA, tryptophan, serotonin and catecholamine, transmit a signal to resident cells in the gut. Advances made in the DNA sequencing technology and bioinformatics have revolutionized our understanding of the microbes in the gut. © 2016 S. Karger AG, Basel.

  15. Physiological Characterisation of Human iPS-Derived Dopaminergic Neurons

    PubMed Central

    Ribeiro Fernandes, Hugo J.; Vowles, Jane; James, William S.; Cowley, Sally A.; Wade-Martins, Richard

    2014-01-01

    Human induced pluripotent stem cells (hiPSCs) offer the potential to study otherwise inaccessible cell types. Critical to this is the directed differentiation of hiPSCs into functional cell lineages. This is of particular relevance to research into neurological disease, such as Parkinson’s disease (PD), in which midbrain dopaminergic neurons degenerate during disease progression but are unobtainable until post-mortem. Here we report a detailed study into the physiological maturation over time of human dopaminergic neurons in vitro. We first generated and differentiated hiPSC lines into midbrain dopaminergic neurons and performed a comprehensive characterisation to confirm dopaminergic functionality by demonstrating dopamine synthesis, release, and re-uptake. The neuronal cultures include cells positive for both tyrosine hydroxylase (TH) and G protein-activated inward rectifier potassium channel 2 (Kir3.2, henceforth referred to as GIRK2), representative of the A9 population of substantia nigra pars compacta (SNc) neurons vulnerable in PD. We observed for the first time the maturation of the slow autonomous pace-making (<10 Hz) and spontaneous synaptic activity typical of mature SNc dopaminergic neurons using a combination of calcium imaging and electrophysiology. hiPSC-derived neurons exhibited inositol tri-phosphate (IP3) receptor-dependent release of intracellular calcium from the endoplasmic reticulum in neuronal processes as calcium waves propagating from apical and distal dendrites, and in the soma. Finally, neurons were susceptible to the dopamine neuron-specific toxin 1-methyl-4-phenylpyridinium (MPP+) which reduced mitochondrial membrane potential and altered mitochondrial morphology. Mature hiPSC-derived dopaminergic neurons provide a neurophysiologically-defined model of previously inaccessible vulnerable SNc dopaminergic neurons to bridge the gap between clinical PD and animal models. PMID:24586273

  16. Functional Neuroimaging Insights into the Physiology of Human Sleep

    PubMed Central

    Dang-Vu, Thien Thanh; Schabus, Manuel; Desseilles, Martin; Sterpenich, Virginie; Bonjean, Maxime; Maquet, Pierre

    2010-01-01

    -Vu TT; Schabus M; Desseilles M; Sterpenich V; Bonjean M; Maquet P. Functional neuroimaging insights into the physiology of human sleep. SLEEP 2010;33(12):1589-1603. PMID:21120121

  17. Application of physiologically based pharmacokinetic models in chemical risk assessment.

    PubMed

    Mumtaz, Moiz; Fisher, Jeffrey; Blount, Benjamin; Ruiz, Patricia

    2012-01-01

    Post-exposure risk assessment of chemical and environmental stressors is a public health challenge. Linking exposure to health outcomes is a 4-step process: exposure assessment, hazard identification, dose response assessment, and risk characterization. This process is increasingly adopting "in silico" tools such as physiologically based pharmacokinetic (PBPK) models to fine-tune exposure assessments and determine internal doses in target organs/tissues. Many excellent PBPK models have been developed. But most, because of their scientific sophistication, have found limited field application-health assessors rarely use them. Over the years, government agencies, stakeholders/partners, and the scientific community have attempted to use these models or their underlying principles in combination with other practical procedures. During the past two decades, through cooperative agreements and contracts at several research and higher education institutions, ATSDR funded translational research has encouraged the use of various types of models. Such collaborative efforts have led to the development and use of transparent and user-friendly models. The "human PBPK model toolkit" is one such project. While not necessarily state of the art, this toolkit is sufficiently accurate for screening purposes. Highlighted in this paper are some selected examples of environmental and occupational exposure assessments of chemicals and their mixtures.

  18. Application of Physiologically Based Pharmacokinetic Models in Chemical Risk Assessment

    PubMed Central

    Mumtaz, Moiz; Fisher, Jeffrey; Blount, Benjamin; Ruiz, Patricia

    2012-01-01

    Post-exposure risk assessment of chemical and environmental stressors is a public health challenge. Linking exposure to health outcomes is a 4-step process: exposure assessment, hazard identification, dose response assessment, and risk characterization. This process is increasingly adopting “in silico” tools such as physiologically based pharmacokinetic (PBPK) models to fine-tune exposure assessments and determine internal doses in target organs/tissues. Many excellent PBPK models have been developed. But most, because of their scientific sophistication, have found limited field application—health assessors rarely use them. Over the years, government agencies, stakeholders/partners, and the scientific community have attempted to use these models or their underlying principles in combination with other practical procedures. During the past two decades, through cooperative agreements and contracts at several research and higher education institutions, ATSDR funded translational research has encouraged the use of various types of models. Such collaborative efforts have led to the development and use of transparent and user-friendly models. The “human PBPK model toolkit” is one such project. While not necessarily state of the art, this toolkit is sufficiently accurate for screening purposes. Highlighted in this paper are some selected examples of environmental and occupational exposure assessments of chemicals and their mixtures. PMID:22523493

  19. Optimizing nanomedicine pharmacokinetics using physiologically based pharmacokinetics modelling.

    PubMed

    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. © 2014 The British Pharmacological Society.

  20. Identifying Blood Biomarkers and Physiological Processes That Distinguish Humans with Superior Performance under Psychological Stress

    PubMed Central

    Cooksey, Amanda M.; Momen, Nausheen; Stocker, Russell; Burgess, Shane C.

    2009-01-01

    Background Attrition of students from aviation training is a serious financial and operational concern for the U.S. Navy. Each late stage navy aviator training failure costs the taxpayer over $1,000,000 and ultimately results in decreased operational readiness of the fleet. Currently, potential aviators are selected based on the Aviation Selection Test Battery (ASTB), which is a series of multiple-choice tests that evaluate basic and aviation-related knowledge and ability. However, the ASTB does not evaluate a person's response to stress. This is important because operating sophisticated aircraft demands exceptional performance and causes high psychological stress. Some people are more resistant to this type of stress, and consequently better able to cope with the demands of naval aviation, than others. Methodology/Principal Findings Although many psychological studies have examined psychological stress resistance none have taken advantage of the human genome sequence. Here we use high-throughput -omic biology methods and a novel statistical data normalization method to identify plasma proteins associated with human performance under psychological stress. We identified proteins involved in four basic physiological processes: innate immunity, cardiac function, coagulation and plasma lipid physiology. Conclusions/Significance The proteins identified here further elucidate the physiological response to psychological stress and suggest a hypothesis that stress-susceptible pilots may be more prone to shock. This work also provides potential biomarkers for screening humans for capability of superior performance under stress. PMID:20020041

  1. Identifying blood biomarkers and physiological processes that distinguish humans with superior performance under psychological stress.

    PubMed

    Cooksey, Amanda M; Momen, Nausheen; Stocker, Russell; Burgess, Shane C

    2009-12-18

    Attrition of students from aviation training is a serious financial and operational concern for the U.S. Navy. Each late stage navy aviator training failure costs the taxpayer over $1,000,000 and ultimately results in decreased operational readiness of the fleet. Currently, potential aviators are selected based on the Aviation Selection Test Battery (ASTB), which is a series of multiple-choice tests that evaluate basic and aviation-related knowledge and ability. However, the ASTB does not evaluate a person's response to stress. This is important because operating sophisticated aircraft demands exceptional performance and causes high psychological stress. Some people are more resistant to this type of stress, and consequently better able to cope with the demands of naval aviation, than others. Although many psychological studies have examined psychological stress resistance none have taken advantage of the human genome sequence. Here we use high-throughput -omic biology methods and a novel statistical data normalization method to identify plasma proteins associated with human performance under psychological stress. We identified proteins involved in four basic physiological processes: innate immunity, cardiac function, coagulation and plasma lipid physiology. The proteins identified here further elucidate the physiological response to psychological stress and suggest a hypothesis that stress-susceptible pilots may be more prone to shock. This work also provides potential biomarkers for screening humans for capability of superior performance under stress.

  2. Oxygen modulates growth of human cells at physiologic partial pressures

    PubMed Central

    1984-01-01

    We have examined the growth of human diploid fibroblasts (WI-38 and IMR90) as a function of initial seeding density and oxygen tension. Cells at young and mid-passage levels were subcultivated in Dulbecco's modified Eagle's medium with 10% fetal bovine serum at 0.005, 0.01, 0.03, 0.1, 0.3, 1, and 2 X 10(4) cells/cm2. Flasks were equilibrated before and after seeding with 1 of 10 gas mixtures containing the desired oxygen tension (9-591 mm Hg) and placed in incubators that measure and maintain a preset oxygen tension. The partial pressure of oxygen (PO2) in media of all flasks was determined at harvest. Cells were shielded from light of wavelength less than 500 nm. Cell growth varied inversely with oxygen tension and seeding density. At 50 cells/cm2, growth was maximal at PO2 9 and 16 mm Hg. Growth was progressively inhibited as the oxygen tension was increased. The population doubling increase at 14 d was 8.6 for PO2 9 and 16 mm Hg, 5.8 for PO2 42 mm Hg, 3.8 for PO2 78 mm Hg, 3.8 for PO2 104 mm Hg, and 3 for PO2 138 mm Hg. As the seeding density was increased, the differences in growth at PO2 less than 140 mm Hg were progressively minimized, such that at seeding densities of 10(4) cells/cm2 there was little difference in the rate of exponential growth or the final saturation density of cells cultivated between PO2 9 and 96 mm Hg. At all seeding densities tested, growth was progressively inhibited when the PO2 was increased greater than 140 mm Hg. The seeding density dependence of oxygen's influence on cellular growth is not explained by oxygen consumption of higher density cultures. Oxygen acts directly on the cells and not by destroying some essential medium component. We have found that oxygen regulates the growth of human cells under pressures of oxygen physiologic to humans, and that oxygen toxicity contributes to the seeding density dependence of cellular growth commonly seen in cell culture. PMID:6736869

  3. A probabilistic model of human variability in physiology for future application to dose reconstruction and QIVIVE.

    PubMed

    McNally, Kevin; Loizou, George D

    2015-01-01

    The risk assessment of environmental chemicals and drugs is undergoing a paradigm shift in approach which seeks the full replacement of animal testing with high throughput, mechanistic, in vitro systems. This new approach will be reliant on the measurement in vitro, of concentration-dependent responses where prolonged excessive perturbations of specific biochemical pathways are likely to lead to adverse health effects in an intact organism. Such an approach requires a framework, into which disparate data generated by in vitro, in silico, and in chemico systems can be integrated and utilized for quantitative in vitro-to-in vivo extrapolation (QIVIVE), ultimately to the human population level. Physiologically based pharmacokinetic (PBPK) models are ideally suited to this and are needed to translate in vitro concentration- response relationships to an exposure or dose, route and duration regime in human populations. Thus, a realistic description of the variation in the physiology of the human population being modeled is critical. Whilst various studies in the past decade have made progress in describing human variability, the algorithms are typically coded in computer programs and as such are unsuitable for reverse dosimetry. In this report we overcome this limitation by developing a hierarchical statistical model using standard probability distributions for the specification of a virtual US and UK human population. The work draws on information from both population databases and cadaver studies.

  4. A Physiologically Based Model for Methylmercury in Female American Kestrels

    EPA Science Inventory

    A physiologically based toxicokinetic (PBTK) model was developed to describe the uptake, distribution, and elimination of methylmercury (CH3Hg) in female American kestrels. The model consists of six tissue compartments corresponding to the brain, liver, kidney, gut, red blood cel...

  5. A Physiologically Based Model for Methylmercury in Female American Kestrels

    EPA Science Inventory

    A physiologically based toxicokinetic (PBTK) model was developed to describe the uptake, distribution, and elimination of methylmercury (CH3Hg) in female American kestrels. The model consists of six tissue compartments corresponding to the brain, liver, kidney, gut, red blood cel...

  6. Physiological characterization of human muscle acetylcholine receptors from ALS patients

    PubMed Central

    Palma, Eleonora; Inghilleri, Maurizio; Conti, Luca; Deflorio, Cristina; Frasca, Vittorio; Manteca, Alessia; Pichiorri, Floriana; Roseti, Cristina; Torchia, Gregorio; Limatola, Cristina; Grassi, Francesca; Miledi, Ricardo

    2011-01-01

    Amyotrophic lateral sclerosis (ALS) is characterized by progressive degeneration of motor neurons leading to muscle paralysis. Research in transgenic mice suggests that the muscle actively contributes to the disease onset, but such studies are difficult to pursue in humans and in vitro models would represent a good starting point. In this work we show that tiny amounts of muscle from ALS or from control denervated muscle, obtained by needle biopsy, are amenable to functional characterization by two different technical approaches: “microtransplantation” of muscle membranes into Xenopus oocytes and culture of myogenic satellite cells. Acetylcholine (ACh)-evoked currents and unitary events were characterized in oocytes and multinucleated myotubes. We found that ALS acetylcholine receptors (AChRs) retain their native physiological characteristics, being activated by ACh and nicotine and blocked by α-bungarotoxin (α-BuTX), d-tubocurarine (dTC), and galantamine. The reversal potential of ACh-evoked currents and the unitary channel behavior were also typical of normal muscle AChRs. Interestingly, in oocytes injected with muscle membranes derived from ALS patients, the AChRs showed a significant decrease in ACh affinity, compared with denervated controls. Finally, riluzole, the only drug currently used against ALS, reduced, in a dose-dependent manner, the ACh-evoked currents, indicating that its action remains to be fully characterized. The two methods described here will be important tools for elucidating the role of muscle in ALS pathogenesis and for developing drugs to counter the effects of this disease. PMID:22128328

  7. Human thermal physiological and psychological responses under different heating environments.

    PubMed

    Wang, Zhaojun; Ning, Haoran; Ji, Yuchen; Hou, Juan; He, Yanan

    2015-08-01

    Anecdotal evidence suggests that many residents of severely cold areas of China who use floor heating (FH) systems feel warmer but drier compared to those using radiant heating (RH) systems. However, this phenomenon has not been verified experimentally. In order to validate the empirical hypothesis, and research the differences of human physiological and psychological responses in these two asymmetrical heating environments, an experiment was designed to mimic FH and RH systems. The subjects participating in the experiment were volunteer college-students. During the experiment, the indoor air temperature, air speed, relative humidity, globe temperature, and inner surface temperatures were measured, and subjects' heart rate, blood pressure and skin temperatures were recorded. The subjects were required to fill in questionnaires about their thermal responses during testing. The results showed that the subjects' skin temperatures, heart rate and blood pressure were significantly affected by the type of heating environment. Ankle temperature had greatest impact on overall thermal comfort relative to other body parts, and a slightly cool FH condition was the most pleasurable environment for sedentary subjects. The overall thermal sensation, comfort and acceptability of FH were higher than that of RH. However, the subjects of FH felt drier than that of RH, although the relative humidity in FH environments was higher than that of the RH environment. In future environmental design, the thermal comfort of the ankles should be scrutinized, and a FH cool condition is recommended as the most comfortable thermal environment for office workers. Consequently, large amounts of heating energy could be saved in this area in the winter. The results of this study may lead to more efficient energy use for office or home heating systems.

  8. Human plasma kallikrein-kinin system: Physiological and biochemical parameters

    PubMed Central

    Bryant, J.W.; Shariat-Madar, z

    2016-01-01

    The plasma kallikrein-kinin system (KKS) plays a critical role in human physiology. The KKS encompasses coagulation factor XII (FXII), the complex of prekallikrein (PK) and high molecular weight kininogen (HK). The conversion of plasma to kallikrein by the activated FXII and in response to numerous different stimuli leads to the generation of bradykinin (BK) and activated HK (HKa, an antiangiogenic peptide). BK is a proinflammatory peptide, a pain mediator and potent vasodilator, leading to robust accumulation of fluid in the interstitium. Systemic production of BK, HKa with the interplay between BK bound-BK receptors and the soluble form of HKa are key to angiogenesis and hemodynamics. KKS has been implicated in the pathogenesis of inflammation, hypertension, endotoxemia, and coagulopathy. In all these cases increased BK levels is the hallmark. In some cases, the persistent production of BK due to the deficiency of the blood protein C1-inhibitor, which controls FXII, is detrimental to the survival of the patients with hereditary angioedema (HAE). In others, the inability of angiotensin converting enzyme (ACE) to degrade BK leads to elevated BK levels and edema in patients on ACE inhibitors. Thus, the mechanisms that interfere with BK liberation or degradation would lead to blood pressure dysfunction. In contrast, anti-kallikrein treatment could have adverse effects in hemodynamic changes induced by vasoconstrictor agents. Genetic models of kallikrein deficiency are needed to evaluate the quantitative role of kallikrein and to validate whether strategies designed to activate or inhibit kallikrein may be important for regulating whole-body BK sensitivity. PMID:19689262

  9. Designing a socio-economic assessment method for integrative biomedical research: the Osteoporotic Virtual Physiological Human project.

    PubMed

    Thiel, Rainer; Stroetmann, Karl A; Stroetmann, Veli N; Viceconti, Marco

    2009-01-01

    In integrative biomedical research, methods assessing the clinical or even socio-economic impact of more complex technologies such as Information and Communication Technology (ICT)-based tools for modelling and simulation of human physiology have rarely been applied. The EU funded Osteoporotic Virtual Physiological Human (VPHOP) research project, part of the Virtual Physiological Human (VPH) European initiative, will create a patient-specific hypermodel to predict the absolute risk of bone fracture much more accurately than predictions based on current clinical practice. The project has developed an innovative, multilevel generic methodological framework to assess the clinical and socio-economic impact of biocomputational models. The assessment framework consists of three components: a socio-economic cost benefit analysis, health economic analysis of care pathways, and disease cost simulation models. Through its holistic perspective, the method provides a tool to appraise the overall value of biocomputational models for society.

  10. Estimating psycho-physiological state of a human by speech analysis

    NASA Astrophysics Data System (ADS)

    Ronzhin, A. L.

    2005-05-01

    Adverse effects of intoxication, fatigue and boredom could degrade performance of highly trained operators of complex technical systems with potentially catastrophic consequences. Existing physiological fitness for duty tests are time consuming, costly, invasive, and highly unpopular. Known non-physiological tests constitute a secondary task and interfere with the busy workload of the tested operator. Various attempts to assess the current status of the operator by processing of "normal operational data" often lead to excessive amount of computations, poorly justified metrics, and ambiguity of results. At the same time, speech analysis presents a natural, non-invasive approach based upon well-established efficient data processing. In addition, it supports both behavioral and physiological biometric. This paper presents an approach facilitating robust speech analysis/understanding process in spite of natural speech variability and background noise. Automatic speech recognition is suggested as a technique for the detection of changes in the psycho-physiological state of a human that typically manifest themselves by changes of characteristics of voice tract and semantic-syntactic connectivity of conversation. Preliminary tests have confirmed that the statistically significant correlation between the error rate of automatic speech recognition and the extent of alcohol intoxication does exist. In addition, the obtained data allowed exploring some interesting correlations and establishing some quantitative models. It is proposed to utilize this approach as a part of fitness for duty test and compare its efficiency with analyses of iris, face geometry, thermography and other popular non-invasive biometric techniques.

  11. A Web-based course of lectures in respiratory physiology.

    PubMed

    West, John B

    2011-09-01

    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 lectures, reading texts, iPod downloads, and surfing the internet. This Web-based course is another option that may be preferable for some students. A second reason is that it is becoming increasingly difficult for some medical schools to find faculty members who are willing and able to teach the principles of respiratory physiology. This is a potentially serious problem because a sound knowledge of respiratory physiology will always be necessary for the intelligent practice of medicine. Schools with limited faculty may find it useful to use these Web-based lectures followed by a discussion session with students. Another reason is that some schools have moved away from systematic lectures to case-based discussions, with the possibility that students will not be exposed to some of the principles of respiratory physiology. The hope is that this comprehensive course of lectures will help students to assimilate this important material as the medical school curriculum continues to expand at a rapid rate.

  12. Teaching acid/base physiology in the laboratory.

    PubMed

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

    2010-12-01

    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 students that had participated in this laboratory exercise. The acquired data showed very consistent and solid findings after the development of both metabolic acidosis and respiratory alkalosis. All results were consistent with the appropriate diagnosis of the acid/base disorder. Not one single group failed to obtain data that were compatible with the diagnosis; it was only the degree of acidosis/alkalosis and compensation that varied.

  13. Physiologically Based Pharmacokinetic Model for Long-Circulating Inorganic Nanoparticles.

    PubMed

    Liang, Xiaowen; Wang, Haolu; Grice, Jeffrey E; Li, Li; Liu, Xin; Xu, Zhi Ping; Roberts, Michael S

    2016-02-10

    A physiologically based pharmacokinetic model was developed for accurately characterizing and predicting the in vivo fate of long-circulating inorganic nanoparticles (NPs). This model is built based on direct visualization of NP disposition details at the organ and cellular level. It was validated with multiple data sets, indicating robust inter-route and interspecies predictive capability. We suggest that the biodistribution of long-circulating inorganic NPs is determined by the uptake and release of NPs by phagocytic cells in target organs.

  14. Molecular clocks and the human condition: approaching their characterization in human physiology and disease.

    PubMed

    Fitzgerald, G A; Yang, G; Paschos, G K; Liang, X; Skarke, C

    2015-09-01

    Molecular clockworks knit together diverse biological networks and compelling evidence from model systems infers their importance in metabolism, immunological and cardiovascular function. Despite this and the diurnal variation in many aspects of human physiology and the phenotypic expression of disease, our understanding of the role and importance of clock function and dysfunction in humans is modest. There are tantalizing hints of connection across the translational divide and some correlative evidence of gene variation and human disease but most of what we know derives from forced desynchrony protocols in controlled environments. We now have the ability to monitor quantitatively ex vivo or in vivo the genome, metabolome, proteome and microbiome of humans in the wild. Combining this capability, with the power of mobile telephony and the evolution of remote sensing, affords a new opportunity for deep phenotyping, including the characterization of diurnal behaviour and the assessment of the impact of the clock on approved drug function.

  15. An Earth-Based Model of Microgravity Pulmonary Physiology

    NASA Technical Reports Server (NTRS)

    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.

  16. An Earth-Based Model of Microgravity Pulmonary Physiology

    NASA Technical Reports Server (NTRS)

    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.

  17. Physiologically based pharmacokinetic modeling of POPs in Greenlanders.

    PubMed

    Sonne, Christian; Gustavson, Kim; Rigét, Frank F; Dietz, Rune; Krüger, Tanja; Bonefeld-Jørgensen, Eva C

    2014-03-01

    Human exposure to persistent organic pollutants (POPs) and the potential health impact in the Arctic far from the emission sources have been highlighted in numerous studies. As a supplement to human POP biomonitoring studies, a physiologically based pharmacokinetic (PBPK) model was set up to estimate the fate of POPs in Greenlandic Inuit's liver, blood, muscle and adipose tissue following long-term exposure to traditional Greenlandic diet. The PBPK model described metabolism, excretion and POP accumulation on the basis of their physicochemical properties and metabolic rates in the organisms. Basic correlations between chemically analyzed blood POP concentrations and calculated daily POP intake from food questionnaire of 118 middle age (18-35years) Greenlandic Inuits from four cities in West Greenland (Qaanaaq: n=40; Qeqertarsuaq: n=36; Nuuk: n=20; Narsaq: n=22) taken during 2003 to 2006 were analyzed. The dietary items included were polar bear, caribou, musk oxen, several marine species such as whales, seals, bird and fish as well as imported food. The contaminant concentrations of the dietary items as well as their chemical properties, uptake, biotransformation and excretion allowed us to estimate the POP concentration in liver, blood, muscle and adipose tissue following long-term exposure to the traditional Greenlandic diet using the PBPK model. Significant correlations were found between chemically analyzed POP blood concentrations and calculated daily intake of POPs for Qeqertarsuaq, Nuuk and Narsaq Inuit but not for the northernmost settlement Qaanaaq, probably because the highest blood POP level was found in this district which might mask the interview-based POP calculations. Despite the large variation in circulating blood POP concentrations, the PBPK model predicted blood concentrations of a factor 2-3 within the actual measured values. Moreover, the PBPK model showed that estimated blood POP concentration increased significantly after consumption of meals

  18. Optimizing nanomedicine pharmacokinetics using physiologically based pharmacokinetics modelling

    PubMed Central

    Moss, Darren Michael; Siccardi, Marco

    2014-01-01

    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. Linked Articles This article is part of a themed section on Nanomedicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-17 PMID:24467481

  19. History of nutrition and acid-base physiology.

    PubMed

    Manz, F

    2001-10-01

    In the 17th century the notion of nutrition and diet changed in northern European countries. First chemical experiments fostered the idea that salts resulted from a union of acids and bases. Digestion was no more regarded as a process of cooking but a succession of fermentations controlled by a balanced production of acids and alkali. Life seemed to depend on the equilibrium of acids and alkalis. In the 19th century food was systematically analysed for the content of energy and macronutrients and first scientifically based nutritional standards were formulated. The preferred use of processed food from the new food industry resulted in epidemics of nutritional disorders. Acidosis seemed to be a plausible pathogenic factor. Practitioners (S Ishizuka, H Hay, FX Mayr) formulated holistic doctrines integrating the concept of balance of acids and bases and recommending food with an excess of alkali. New micromethods to determine the concentration of electrolytes and blood acid-base status promoted physiological and clinical research into acid-base metabolism in the 1960s. In the new physiologically based terminology of systemic acid-base status, the relationship between blood acid-base status and net acid intake or excretion was, however, incorrectly simplified. In the 1970s metabolic acidosis was observed in patients on chemically defined diets and parenteral nutrition. Based on the data of comprehensive acid-base balance studies, calculation models were used to estimate renal net acid excretion from nutrient intake and to predict the potential renal acid load of single foods. Extrapolating current trends to the future, one can say that acid-base physiology will probably remain a challenge in nutrition and functional medicine over the next few years. The challenge will include new concepts for the manipulation of nutritional acid load in sports, dietetics and preventive medicine as well as new definitions of the upper intake level of potential renal acid load in

  20. On making nursing undergraduate human reproductive physiology content meaningful and relevant: discussion of human pleasure in its biological context.

    PubMed

    McClusky, Leon Mendel

    2012-01-01

    The traditional presentation of the Reproductive Physiology component in an Anatomy and Physiology course to nursing undergraduates focuses on the broad aspects of hormonal regulation of reproduction and gonadal anatomy, with the role of the higher centres of the brain omitted. An introductory discussion is proposed which could precede the lectures on the reproductive organs. The discussion gives an overview of the biological significance of human pleasure, the involvement of the neurotransmitter dopamine, and the role of pleasure in the survival of the individual and even species. Pleasure stimuli (positive and negative) and the biological significance of naturally-induced pleasurable experiences are briefly discussed in the context of reproduction and the preservation of genetic material with an aim to foster relevancy between subject material and human behaviour in any type of society. The tenderness of this aspect of the human existence is well-understood because of its invariable association with soul-revealing human expressions such as love, infatuation, sexual flirtations, all of which are underpinned by arousal, desire and/or pleasure. Assuming that increased knowledge correlates with increased confidence, the proposed approach may provide the nurse with an adequate knowledge base to overcome well-known barriers in communicating with their patients about matters of sexual health and intimacy.

  1. Physiologically based boundary conditions in finite element modelling.

    PubMed

    Speirs, Andrew D; Heller, Markus O; Duda, Georg N; Taylor, William R

    2007-01-01

    Finite element analysis has been used extensively in the study of bone loading and implant performance, such as in the femur. The boundary conditions applied vary widely, generally producing excessive femoral deformation, and although it has been shown that the muscle forces influence femoral deflections and loading, little consideration has been given to the displacement constraints. It is hypothesised that careful application of physiologically based constraints can produce physiological deformation, and therefore straining, of the femur. Joint contact forces and a complete set of muscle forces were calculated based on the geometry of the Standardised Femur using previously validated musculoskeletal models. Five boundary condition cases were applied to a finite element model of the Standardised Femur: (A) diaphyseally constrained with hip contact and abductor forces; (B) case A plus vasti forces; (C) case A with complete set of muscle forces; (D) distally constrained with all muscle forces; (E) physiological constraints with all muscle forces. It was seen that only the physiological boundary conditions, case E, produced physiological deflections (< 2.0mm) of the femoral head in both the coronal and sagittal planes, which resulted in minimal reaction forces at the constrained nodes. Strains in the mid-diaphysis varied by up to 600 micro-strain under walking loads and 1000 micro-strain under stair climbing loads. The mode of loading, as indicated by the strain profiles on the cortex also varied substantially under these boundary conditions, which has important consequences for studies that examine localised bone loading such as fracture or bone remodelling simulations.

  2. Toward Scalable Trustworthy Computing Using the Human-Physiology-Immunity Metaphor

    SciTech Connect

    Hively, Lee M; Sheldon, Frederick T

    2011-01-01

    The cybersecurity landscape consists of an ad hoc patchwork of solutions. Optimal cybersecurity is difficult for various reasons: complexity, immense data and processing requirements, resource-agnostic cloud computing, practical time-space-energy constraints, inherent flaws in 'Maginot Line' defenses, and the growing number and sophistication of cyberattacks. This article defines the high-priority problems and examines the potential solution space. In that space, achieving scalable trustworthy computing and communications is possible through real-time knowledge-based decisions about cyber trust. This vision is based on the human-physiology-immunity metaphor and the human brain's ability to extract knowledge from data and information. The article outlines future steps toward scalable trustworthy systems requiring a long-term commitment to solve the well-known challenges.

  3. New dimensions in tissue engineering: possible models for human physiology.

    PubMed

    Baar, Keith

    2005-11-01

    Tissue engineering is a discipline of great promise. In some areas, such as the cornea, tissues engineered in the laboratory are already in clinical use. In other areas, where the tissue architecture is more complex, there are a number of obstacles to manoeuvre before clinically relevant tissues can be produced. However, even in areas where clinically relevant tissues are decades away, the tissues being produced at the moment provide powerful new models to aid the understanding of complex physiological processes. This article provides a personal view of the role of tissue engineering in advancing our understanding of physiology, with specific attention being paid to musculoskeletal tissues.

  4. Use of physiologically based pharmacokinetic modeling for assessment of drug-drug interactions.

    PubMed

    Baneyx, Guillaume; Fukushima, Yumi; Parrott, Neil

    2012-04-01

    Interactions between co-administered medicines can reduce efficacy or lead to adverse effects. Understanding and managing such interactions is essential in bringing safe and effective medicines to the market. Ideally, interaction potential should be recognized early and minimized in compounds that reach late stages of drug development. Physiologically based pharmacokinetic models combine knowledge of physiological factors with compound-specific properties to simulate how a drug behaves in the human body. These software tools are increasingly used during drug discovery and development and, when integrating relevant in vitro data, can simulate drug interaction potential. This article provides some background and presents illustrative examples. Physiologically based models are an integral tool in the discovery and development of drugs, and can significantly aid our understanding and prediction of drug interactions.

  5. 'Systems biology' in human exercise physiology: is it something different from integrative physiology?

    PubMed

    Greenhaff, Paul L; Hargreaves, Mark

    2011-03-01

    On first impression the 'whole-istic approach to understanding biology' that has been used to describe Systems Biology bears a striking resemblance to what many of us know as Integrative Physiology. However, closer scrutiny reveals that at the present time Systems Biology is rooted in processes operating at a cellular level ('the study of an organism, viewed as an integrated and interacting network of genes, proteins and biochemical reactions which give rise to life ultimately responsible for an organism's form and functions'; http://www.systemsbiology.org), and appears to have evolved as a direct result of advances in high throughput molecular biology platforms (and associated bioinformatics) over the past decade. The Systems Biology approach is in many ways laudable, but it will be immediately apparent to most exercise or integrative physiologists that the challenge of understanding the whole-animal response to exercise as a network of integrated and interacting genes, proteins and biochemical reactions is unlikely to be realized in the near future. This short review will attempt to clarify conceptual inconsistencies between the fields of Systems Biology and Integrative Physiology in the context of exercise science, and will attempt to identify the challenges to whole-body physiologists wishing to harness the tools of Systems Biology.

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

    PubMed

    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.

  7. Physiology and biochemistry of human subjects during entrapment.

    PubMed

    Agapiou, A; Mikedi, K; Karma, S; Giotaki, Z K; Kolostoumbis, D; Papageorgiou, C; Zorba, E; Spiliopoulou, C; Amann, A; Statheropoulos, M

    2013-03-01

    A classification of various categories of entrapped people under the ruins of collapsed buildings after earthquakes, technical failures or explosions is proposed. Type and degree of injury at the moment of building collapse and duration of entrapment are the two basic parameters in this classification. The aim is to provide sources and types of volatile organic compounds (VOCs) that can be used for establishing a new method for locating entrapped victims based on human chemical signatures. Potential target compounds, among others, are ammonia, acetone, isoprene, dimethylsulfide, dimethyldisulfide and trimethylamine. In this context, the possible neuroendocrine, metabolic and physical responses of potential victims during the different types of entrapment are correlated with the sources of VOCs such as expired air, urine, blood and sweat. The proposed classification scheme was developed as part of an integrated research project which investigates the use of combined audio, video and chemical methods for the early location of entrapped people under the ruins of collapsed buildings.

  8. Do Targeted Written Comments and the Rubric Method of Delivery Affect Performance on Future Human Physiology Laboratory Reports?

    ERIC Educational Resources Information Center

    Clayton, Zachary S.; Wilds, Gabriel P.; Mangum, Joshua E.; Hocker, Austin D.; Dawson, Sierra M.

    2016-01-01

    We investigated how students performed on weekly two-page laboratory reports based on whether the grading rubric was provided to the student electronically or in paper form and the inclusion of one- to two-sentence targeted comments. Subjects were registered for a 289-student, third-year human physiology class with laboratory and were randomized…

  9. Do Targeted Written Comments and the Rubric Method of Delivery Affect Performance on Future Human Physiology Laboratory Reports?

    ERIC Educational Resources Information Center

    Clayton, Zachary S.; Wilds, Gabriel P.; Mangum, Joshua E.; Hocker, Austin D.; Dawson, Sierra M.

    2016-01-01

    We investigated how students performed on weekly two-page laboratory reports based on whether the grading rubric was provided to the student electronically or in paper form and the inclusion of one- to two-sentence targeted comments. Subjects were registered for a 289-student, third-year human physiology class with laboratory and were randomized…

  10. Selected physiologic compatibilities and incompatibilities between human and porcine organ systems.

    PubMed

    Ibrahim, Zuhaib; Busch, Jamie; Awwad, Michel; Wagner, Robert; Wells, Kevin; Cooper, David K C

    2006-11-01

    The shortage of donor organs is a major barrier to clinical organ transplantation. Although xenotransplantation is considered one of the alternatives to human organ transplantation, there are immunologic and physiologic incompatibilities between humans and pigs. With the exception of coagulation, the major potential physiologic incompatibilities relating to function of the kidney, heart, liver, lungs, pancreatic islets, and hormones are reviewed. Some of these physiologic differences can be overcome by producing genetically altered pigs to improve compatibility with humans. The possibility of producing such pigs for organ transplantation is considered.

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

    PubMed

    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.

  12. Inferring Nonlinear Neuronal Computation Based on Physiologically Plausible Inputs

    PubMed Central

    McFarland, James M.; Cui, Yuwei; Butts, Daniel A.

    2013-01-01

    The computation represented by a sensory neuron's response to stimuli is constructed from an array of physiological processes both belonging to that neuron and inherited from its inputs. Although many of these physiological processes are known to be nonlinear, linear approximations are commonly used to describe the stimulus selectivity of sensory neurons (i.e., linear receptive fields). Here we present an approach for modeling sensory processing, termed the Nonlinear Input Model (NIM), which is based on the hypothesis that the dominant nonlinearities imposed by physiological mechanisms arise from rectification of a neuron's inputs. Incorporating such ‘upstream nonlinearities’ within the standard linear-nonlinear (LN) cascade modeling structure implicitly allows for the identification of multiple stimulus features driving a neuron's response, which become directly interpretable as either excitatory or inhibitory. Because its form is analogous to an integrate-and-fire neuron receiving excitatory and inhibitory inputs, model fitting can be guided by prior knowledge about the inputs to a given neuron, and elements of the resulting model can often result in specific physiological predictions. Furthermore, by providing an explicit probabilistic model with a relatively simple nonlinear structure, its parameters can be efficiently optimized and appropriately regularized. Parameter estimation is robust and efficient even with large numbers of model components and in the context of high-dimensional stimuli with complex statistical structure (e.g. natural stimuli). We describe detailed methods for estimating the model parameters, and illustrate the advantages of the NIM using a range of example sensory neurons in the visual and auditory systems. We thus present a modeling framework that can capture a broad range of nonlinear response functions while providing physiologically interpretable descriptions of neural computation. PMID:23874185

  13. The Virtual Physiological Human - a European initiative for in silico human modelling -.

    PubMed

    Viceconti, Marco; Clapworthy, Gordon; Van Sint Jan, Serge

    2008-12-01

    The Virtual Physiological Human (VPH) is an initiative, strongly supported by the European Commission (EC), that seeks to develop an integrated model of human physiology at multiple scales from the whole body through the organ, tissue, cell and molecular levels to the genomic level. VPH had its beginnings in 2005 with informal discussions amongst like-minded scientists which led to the STEP project, a Coordination Action funded by the EC that began in early 2006. The STEP project greatly accelerated the progress of the VPH and proved to be a catalyst for wide-ranging discussions within Europe and for outreach activities designed to develop a broad international approach to the huge scientific and technological challenges involved in this area. This paper provides an overview of the VPH and the developments it has engendered in the rapidly expanding worldwide activities associated with the physiome. It then uses one particular project, the Living Human Project, to illustrate the type of advances that are taking place to further the aims of the VPH and similar initiatives worldwide.

  14. Physiological cognitive state assessment: applications for designing effective human-machine systems.

    PubMed

    Estepp, Justin R; Christensen, James C

    2011-01-01

    Significant growth in the field of neuroscience has occurred over the last decade such that new application areas for basic research techniques are opening up to practitioners in many other areas. Of particular interest to many is the principle of neuroergonomics, by which the traditional work in neuroscience and its related topics can be applied to non-traditional areas such as human-machine system design. While work in neuroergonomics certainly predates the use of the term in the literature (previously identified by others as applied neuroscience, operational neuroscience, etc.), there is great promise in the larger framework that is represented by the general context of the terminology. Here, we focus on the very specific concept that principles in brain-computer interfaces, neural prosthetics and the larger realm of machine learning using physiological inputs can be applied directly to the design and implementation of augmented human-machine systems. Indeed, work in this area has been ongoing for more than 25 years with very little cross-talk and collaboration between clinical and applied researchers. We propose that, given increased interest in augmented human-machine systems based on cognitive state, further progress will require research in the same vein as that being done in the aforementioned communities, and that all researchers with a vested interest in physiologically-based machine learning techniques can benefit from increased collaboration. We thereby seek to describe the current state of cognitive state assessment in human-machine systems, the problems and challenges faced, and the tightly-coupled relationship with other research areas. This supports the larger work of the Cognitive State Assessment 2011 Competition by setting the stage for the purpose of the session by showing the need to increase research in the machine learning techniques used by practitioners of augmented human-machine system design.

  15. An investigative laboratory course in human physiology using computer technology and collaborative writing.

    PubMed

    FitzPatrick, Kathleen A

    2004-12-01

    Active investigative student-directed experiences in laboratory science are being encouraged by national science organizations. A growing body of evidence from classroom assessment supports their effectiveness. This study describes four years of implementation and assessment of an investigative laboratory course in human physiology for 65 second-year students in sports medicine and biology at a small private comprehensive college. The course builds on skills and abilities first introduced in an introductory investigations course and introduces additional higher-level skills and more complex human experimental models. In four multiweek experimental modules, involving neuromuscular, reflex, and cardiovascular physiology, by use of computerized hardware/software with a variety of transducers, students carry out self-designed experiments with human subjects and perform data collection and analysis, collaborative writing, and peer editing. In assessments, including standard course evaluations and the Salgains Web-based evaluation, student responses to this approach are enthusiastic, and gains in their skills and abilities are evident in their comments and in improved performance.

  16. Building an experimental model of the human body with non-physiological parameters.

    PubMed

    Labuz, Joseph M; Moraes, Christopher; Mertz, David R; Leung, Brendan M; Takayama, Shuichi

    2017-03-01

    New advances in engineering and biomedical technology have enabled recent efforts to capture essential aspects of human physiology in microscale, in-vitro systems. The application of these advances to experimentally model complex processes in an integrated platform - commonly called a 'human-on-a-chip (HOC)' - requires that relevant compartments and parameters be sized correctly relative to each other and to the system as a whole. Empirical observation, theoretical treatments of resource distribution systems and natural experiments can all be used to inform rational design of such a system, but technical and fundamental challenges (e.g. small system blood volumes and context-dependent cell metabolism, respectively) pose substantial, unaddressed obstacles. Here, we put forth two fundamental principles for HOC design: inducing in-vivo-like cellular metabolic rates is necessary and may be accomplished in-vitro by limiting O2 availability and that the effects of increased blood volumes on drug concentration can be mitigated through pharmacokinetics-based treatments of solute distribution. Combining these principles with natural observation and engineering workarounds, we derive a complete set of design criteria for a practically realizable, physiologically faithful, five-organ millionth-scale (× 10(-6)) microfluidic model of the human body.

  17. Applying systems biology methods to the study of human physiology in extreme environments.

    PubMed

    Edwards, Lindsay M; Thiele, Ines

    2013-03-22

    Systems biology is defined in this review as 'an iterative process of computational model building and experimental model revision with the aim of understanding or simulating complex biological systems'. We propose that, in practice, systems biology rests on three pillars: computation, the omics disciplines and repeated experimental perturbation of the system of interest. The number of ethical and physiologically relevant perturbations that can be used in experiments on healthy humans is extremely limited and principally comprises exercise, nutrition, infusions (e.g. Intralipid), some drugs and altered environment. Thus, we argue that systems biology and environmental physiology are natural symbionts for those interested in a system-level understanding of human biology. However, despite excellent progress in high-altitude genetics and several proteomics studies, systems biology research into human adaptation to extreme environments is in its infancy. A brief description and overview of systems biology in its current guise is given, followed by a mini review of computational methods used for modelling biological systems. Special attention is given to high-altitude research, metabolic network reconstruction and constraint-based modelling.

  18. Dynamic OCT for physiological functions of micro organs in human fingers

    NASA Astrophysics Data System (ADS)

    Haruna, Masamitsu; Ohmi, Masato; Ueda, Yoshihiro; Fuji, Toshie; Yamada, Akihiro; Saigusa, Hiroyuki; Kuwabara, Mitsuo

    2007-11-01

    OCT is a powerful tool for detection of physiological functions of micro organs underneath the human skin surface, besides the clinical application to ophthalmology, as recently demonstrated by the authors' group. In particular, dynamics of peripheral vessels and eccrin sweat glands can be observed clearly in the time-sequential OCT images. The physiological functions of these micro organs, sweating and blood circulation, are controlled by the skin sympathetic nerve in response to externally applied stress. In this paper, we present microscopically analytical results based on the dynamic OCT of the micro organs in human fingers. In sweating dynamics, it is found that a spiral sweat duct is expanded by abrupt increase of sweat due to application of stress to a volunteer, resulting in remarkable increase of the reflection light intensity of the spiral duct in OCT. Mental-stress-induced sweating in each eccrin sweat gland, therefore, is analyzed quantitatively. Furthermore, dynamic OCT observation of peripheral vessels is interesting. A small vein of a human finger is observed clearly by the TD-OCT, where the vein expands and contracts repeatedly even in the resting state for temperature control on the fingertip. A change in the cross-sectional area of the vein exceeds 80 % for a young volunteer. The dynamic OCT will allow us to propose novel diagnoses of excessive sweating and diseases related to the sympathetic nerve.

  19. Applying systems biology methods to the study of human physiology in extreme environments

    PubMed Central

    2013-01-01

    Systems biology is defined in this review as ‘an iterative process of computational model building and experimental model revision with the aim of understanding or simulating complex biological systems’. We propose that, in practice, systems biology rests on three pillars: computation, the omics disciplines and repeated experimental perturbation of the system of interest. The number of ethical and physiologically relevant perturbations that can be used in experiments on healthy humans is extremely limited and principally comprises exercise, nutrition, infusions (e.g. Intralipid), some drugs and altered environment. Thus, we argue that systems biology and environmental physiology are natural symbionts for those interested in a system-level understanding of human biology. However, despite excellent progress in high-altitude genetics and several proteomics studies, systems biology research into human adaptation to extreme environments is in its infancy. A brief description and overview of systems biology in its current guise is given, followed by a mini review of computational methods used for modelling biological systems. Special attention is given to high-altitude research, metabolic network reconstruction and constraint-based modelling. PMID:23849719

  20. Singular value decomposition based feature extraction technique for physiological signal analysis.

    PubMed

    Chang, Cheng-Ding; Wang, Chien-Chih; Jiang, Bernard C

    2012-06-01

    Multiscale entropy (MSE) is one of the popular techniques to calculate and describe the complexity of the physiological signal. Many studies use this approach to detect changes in the physiological conditions in the human body. However, MSE results are easily affected by noise and trends, leading to incorrect estimation of MSE values. In this paper, singular value decomposition (SVD) is adopted to replace MSE to extract the features of physiological signals, and adopt the support vector machine (SVM) to classify the different physiological states. A test data set based on the PhysioNet website was used, and the classification results showed that using SVD to extract features of the physiological signal could attain a classification accuracy rate of 89.157%, which is higher than that using the MSE value (71.084%). The results show the proposed analysis procedure is effective and appropriate for distinguishing different physiological states. This promising result could be used as a reference for doctors in diagnosis of congestive heart failure (CHF) disease.

  1. Assessing Acid-Base Status: Physiologic Versus Physicochemical Approach.

    PubMed

    Adrogué, Horacio J; Madias, Nicolaos E

    2016-11-01

    The physiologic approach has long been used in assessing acid-base status. This approach considers acids as hydrogen ion donors and bases as hydrogen ion acceptors and the acid-base status of the organism as reflecting the interaction of net hydrogen ion balance with body buffers. In the physiologic approach, the carbonic acid/bicarbonate buffer pair is used for assessing acid-base status and blood pH is determined by carbonic acid (ie, Paco2) and serum bicarbonate levels. More recently, the physicochemical approach was introduced, which has gained popularity, particularly among intensivists and anesthesiologists. This approach posits that the acid-base status of body fluids is determined by changes in the dissociation of water that are driven by the interplay of 3 independent variables: the sum of strong (fully dissociated) cation concentrations minus the sum of strong anion concentrations (strong ion difference); the total concentration of weak acids; and Paco2. These 3 independent variables mechanistically determine both hydrogen ion concentration and bicarbonate concentration of body fluids, which are considered as dependent variables. Our experience indicates that the average practitioner is familiar with only one of these approaches and knows very little, if any, about the other approach. In the present Acid-Base and Electrolyte Teaching Case, we attempt to bridge this knowledge gap by contrasting the physiologic and physicochemical approaches to assessing acid-base status. We first outline the essential features, advantages, and limitations of each of the 2 approaches and then apply each approach to the same patient presentation. We conclude with our view about the optimal approach. Copyright © 2016 National Kidney Foundation, Inc. All rights reserved.

  2. Matters of taste: bridging molecular physiology and the humanities.

    PubMed

    Rangachari, P K; Rangachari, Usha

    2015-12-01

    Taste perception was the focus of an undergraduate course in the health sciences that bridged the sciences and humanities. A problem-based learning approach was used to study the biological issues, whereas the cultural transmutations of these molecular mechanisms were explored using a variety of resources (novels, cookbooks, and films). Multiple evaluation procedures were used: problem summaries and problem-solving exercises (tripartite problem-solving exercise) for the problem-based learning component and group tasks and individual exercises for the cultural issues. Self-selected groups chose specific tasks from a prescribed list of options (setting up a journal in molecular gastronomy, developing an electronic tongue, designing a restaurant for synesthetes, organizing a farmers' market, marketing a culinary tour, framing hedonic scales, exploring changing tastes through works of art or recipe books, and crafting beers for space travel). Individual tasks were selected from a menu of options (book reviews, film reviews, conversations, creative writing, and oral exams). A few guest lecturers (wine making, cultural anthropology, film analysis, and nutritional epidemiology) added more flavor. The course was rated highly for its learning value (8.5 ± 1.2, n = 62) and helped students relate biological mechanisms to cultural issues (9.0 ± 0.9, n = 62).

  3. The role of VEGF pathways in human physiologic and pathologic angiogenesis.

    USDA-ARS?s Scientific Manuscript database

    In pre-clinical models VEGF is a potent stimulant of both physiologic and pathologic angiogenesis. Conversely, anti-VEGF regimens have successfully inhibited angiogenesis both in vitro and in vivo. We hypothesized that VEGF would stimulate both physiologic and pathologic angiogenesis in a human-ba...

  4. [Foods and drinks in a 19th century human physiology textbook].

    PubMed

    Chiancone, Francesco M

    2004-01-01

    The Author reports on the chapter of "Nutrition" in the Human Physiology textbook by P. Albertoni and A. Stefani published in the first half of the 19th century. This is one of the first textbooks that treats Physiology as an experimental science in contrast with the thinking of the previous century which was still dominated by Galen and Dioscorides.

  5. An Earth-based Model of Microgravity Pulmonary Physiology

    NASA Technical Reports Server (NTRS)

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

    2004-01-01

    There are currently only two practical methods of achieving microgravity 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 microgravity. We propose to develop an earth-based animal model of microgravity 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 mechanics, to previous space flight and parabolic flight measurements. After validating the model, we will investigate the impact of microgravity on aspects of lung physiology that have not been previously measured. These will include pulmonary blood flow distribution, ventillation distribution, pulmonary capillary wedge pressure, ventilation-perfusion matching and pleural pressures and flows. We expect that this earth-based model of microgravity will enhance our knowledge and understanding of lung physiology in space which will increase in importance as space flights increase in time and distance.

  6. An Earth-based Model of Microgravity Pulmonary Physiology

    NASA Technical Reports Server (NTRS)

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

    2004-01-01

    There are currently only two practical methods of achieving microgravity 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 microgravity. We propose to develop an earth-based animal model of microgravity 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 mechanics, to previous space flight and parabolic flight measurements. After validating the model, we will investigate the impact of microgravity on aspects of lung physiology that have not been previously measured. These will include pulmonary blood flow distribution, ventillation distribution, pulmonary capillary wedge pressure, ventilation-perfusion matching and pleural pressures and flows. We expect that this earth-based model of microgravity will enhance our knowledge and understanding of lung physiology in space which will increase in importance as space flights increase in time and distance.

  7. Driver's mental workload prediction model based on physiological indices.

    PubMed

    Yan, Shengyuan; Tran, Cong Chi; Wei, Yingying; Habiyaremye, Jean Luc

    2017-09-15

    Developing an early warning model to predict the driver's mental workload (MWL) is critical and helpful, especially for new or less experienced drivers. The present study aims to investigate the correlation between new drivers' MWL and their work performance, regarding the number of errors. Additionally, the group method of data handling is used to establish the driver's MWL predictive model based on subjective rating (NASA task load index [NASA-TLX]) and six physiological indices. The results indicate that the NASA-TLX and the number of errors are positively correlated, and the predictive model shows the validity of the proposed model with an R(2) value of 0.745. The proposed model is expected to provide a reference value for the new drivers of their MWL by providing the physiological indices, and the driving lesson plans can be proposed to sustain an appropriate MWL as well as improve the driver's work performance.

  8. Negative air ion effects on human performance and physiological condition.

    PubMed

    Buckalew, L W; Rizzuto, A P

    1984-08-01

    Beneficial effects of exposure to negative air ions have been suggested, to include improved performance, mood, attention, and physiological condition. Existing support is clouded by methodological problems of control and standardization in treatment and equipment. This study investigated effects of negative ions produced by a commercially marketed air purification device on grip magnitude, coding, motor dexterity, reaction time, tracking, pulse, blood pressure, and temperature. Two groups of 12 males were exposed to 6 continuous h of either negative or "normal" ion environments under a double blind condition. Repeated measures (0,3,6 h) on each variable were obtained. MANOVA applied to change scores revealed no differences between groups, and 0 vs. 3 and 0 vs. 6-h group differences showed no significant alteration in any measure. Negative ions generated by an air purification device were concluded to produce no general or specific alteration of cognitive or psychomotor performance or physiological condition.

  9. Translational applications of evaluating physiologic variability in human endotoxemia.

    PubMed

    Scheff, Jeremy D; Mavroudis, Panteleimon D; Calvano, Steve E; Androulakis, Ioannis P

    2013-08-01

    Dysregulation of the inflammatory response is a critical component of many clinically challenging disorders such as sepsis. Inflammation is a biological process designed to lead to healing and recovery, ultimately restoring homeostasis; however, the failure to fully achieve those beneficial results can leave a patient in a dangerous persistent inflammatory state. One of the primary challenges in developing novel therapies in this area is that inflammation is comprised of a complex network of interacting pathways. Here, we discuss our approaches towards addressing this problem through computational systems biology, with a particular focus on how the presence of biological rhythms and the disruption of these rhythms in inflammation may be applied in a translational context. By leveraging the information content embedded in physiologic variability, ranging in scale from oscillations in autonomic activity driving short-term heart rate variability to circadian rhythms in immunomodulatory hormones, there is significant potential to gain insight into the underlying physiology.

  10. Predicting physiological capacity of human load carriage - a review.

    PubMed

    Drain, Jace; Billing, Daniel; Neesham-Smith, Daniel; Aisbett, Brad

    2016-01-01

    This review article aims to evaluate a proposed maximum acceptable work duration model for load carriage tasks. It is contended that this concept has particular relevance to physically demanding occupations such as military and firefighting. Personnel in these occupations are often required to perform very physically demanding tasks, over varying time periods, often involving load carriage. Previous research has investigated concepts related to physiological workload limits in occupational settings (e.g. industrial). Evidence suggests however, that existing (unloaded) workload guidelines are not appropriate for load carriage tasks. The utility of this model warrants further work to enable prediction of load carriage durations across a range of functional workloads for physically demanding occupations. If the maximum duration for which personnel can physiologically sustain a load carriage task could be accurately predicted, commanders and supervisors could better plan for and manage tasks to ensure operational imperatives were met whilst minimising health risks for their workers.

  11. Geo-Effective Heliophysical Variations and Human Physiological State

    NASA Astrophysics Data System (ADS)

    Dimitrova, S.

    2006-03-01

    A group of 86 volunteers was examined on each working day in autumn 2001 and in spring 2002. These periods were chosen because of maximal expected geomagnetic activity. There were 26 persons in the group on a drug treatment, mainly because of hypertension. Systolic and diastolic blood pressure and heart rate were registered. Pulse pressure was calculated. Data about subjective psycho-physiological complaints of the persons examined were also gathered. Altogether 2799 recordings were obtained and analyzed. MANOVA was employed to check the significance of the influence of three factors on the physiological parameters under consideration. The factors were as follows: 1) geomagnetic activity estimated by H-component of the local geomagnetic field and divided into five levels; 2) gender - males and females; 3) presence of medication. Post hoc analysis was performed to elicit the significance of differences in the factors' levels. The average arterial blood pressure, pulse pressure and the percentage of the persons in the group with subjective psycho-physiological complaints were found to increase significantly with the increase of geomagnetic activity. The maximal increment of systolic and diastolic blood pressure was 10-11% and for pulse pressure 13.6%. Analyses revealed that females and persons on a medication were more sensitive to the increase of geomagnetic activity than respectively males and persons with no medication.

  12. Overshoot Measured Physiologically and Psychophysically in the Same Human Ears

    PubMed Central

    Walsh, Kyle P.; Pasanen, Edward G.; McFadden, Dennis

    2010-01-01

    A nonlinear version of the stimulus-frequency otoacoustic emission (SFOAE) was measured using stimulus waveforms similar to those used for behavioral overshoot. Behaviorally, the seven listeners were as much as 11 dB worse at detecting a brief tonal signal (4.0 kHz, 10 ms in duration) when it occurred soon after the onset of a wideband masking noise (0.1 – 6.0 kHz; 400 ms in duration) than when it was delayed by about 200 ms, and the nonlinear SFOAE measure exhibited a similar effect. When either lowpass (0.1 – 3.8 kHz) or bandpass noise (3.8 – 4.2 kHz) was used instead of the wideband noise, the physiological and behavioral measures again were similar. When a highpass noise (4.2 – 6.0 kHz) was used, the physiological and behavioral measures both showed no overshoot-like effect for five of the subjects. The physiological response to the tone decayed slowly after the termination of the noise, much like the time course of resetting for behavioral overshoot. One subject exhibited no overshoot behaviorally even though his cochlear responses were like those of the other subjects. Overall, the evidence suggests that some basic characteristics of overshoot are obligatory consequences of cochlear function, as modulated by the olivocochlear efferent system. PMID:20430072

  13. Physiological origin of biogenic magnetic nanoparticles in health and disease: from bacteria to humans

    PubMed Central

    Gorobets, Oksana; Gorobets, Svitlana; Koralewski, Marceli

    2017-01-01

    The discovery of biogenic magnetic nanoparticles (BMNPs) in the human brain gives a strong impulse to study and understand their origin. Although knowledge of the subject is increasing continuously, much remains to be done for further development to help our society fight a number of pathologies related to BMNPs. This review provides an insight into the puzzle of the physiological origin of BMNPs in organisms of all three domains of life: prokaryotes, archaea, and eukaryotes, including humans. Predictions based on comparative genomic studies are presented along with experimental data obtained by physical methods. State-of-the-art understanding of the genetic control of biomineralization of BMNPs and their properties are discussed in detail. We present data on the differences in BMNP levels in health and disease (cancer, neurodegenerative disorders, and atherosclerosis), and discuss the existing hypotheses on the biological functions of BMNPs, with special attention paid to the role of the ferritin core and apoferritin. PMID:28652739

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

    PubMed

    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.

  15. A Kernel Machine-based fMRI Physiological Noise Removal Method

    PubMed Central

    Song, Xiaomu; Chen, Nan-kuei; Gaur, Pooja

    2013-01-01

    Functional magnetic resonance imaging (fMRI) technique with blood oxygenation level dependent (BOLD) contrast is a powerful tool for noninvasive mapping of brain function under task and resting states. The removal of cardiac- and respiration-induced physiological noise in fMRI data has been a significant challenge as fMRI studies seek to achieve higher spatial resolutions and characterize more subtle neuronal changes. The low temporal sampling rate of most multi-slice fMRI experiments often causes aliasing of physiological noise into the frequency range of BOLD activation signal. In addition, changes of heartbeat and respiration patterns also generate physiological fluctuations that have similar frequencies with BOLD activation. Most existing physiological noise-removal methods either place restrictive limitations on image acquisition or utilize filtering or regression based post-processing algorithms, which cannot distinguish the frequency-overlapping BOLD activation and the physiological noise. In this work, we address the challenge of physiological noise removal via the kernel machine technique, where a nonlinear kernel machine technique, kernel principal component analysis, is used with a specifically identified kernel function to differentiate BOLD signal from the physiological noise of the frequency. The proposed method was evaluated in human fMRI data acquired from multiple task-related and resting state fMRI experiments. A comparison study was also performed with an existing adaptive filtering method. The results indicate that the proposed method can effectively identify and reduce the physiological noise in fMRI data. The comparison study shows that the proposed method can provide comparable or better noise removal performance than the adaptive filtering approach. PMID:24321306

  16. A kernel machine-based fMRI physiological noise removal method.

    PubMed

    Song, Xiaomu; Chen, Nan-kuei; Gaur, Pooja

    2014-02-01

    Functional magnetic resonance imaging (fMRI) technique with blood oxygenation level dependent (BOLD) contrast is a powerful tool for noninvasive mapping of brain function under task and resting states. The removal of cardiac- and respiration-induced physiological noise in fMRI data has been a significant challenge as fMRI studies seek to achieve higher spatial resolutions and characterize more subtle neuronal changes. The low temporal sampling rate of most multi-slice fMRI experiments often causes aliasing of physiological noise into the frequency range of BOLD activation signal. In addition, changes of heartbeat and respiration patterns also generate physiological fluctuations that have similar frequencies with BOLD activation. Most existing physiological noise-removal methods either place restrictive limitations on image acquisition or utilize filtering or regression based post-processing algorithms, which cannot distinguish the frequency-overlapping BOLD activation and the physiological noise. In this work, we address the challenge of physiological noise removal via the kernel machine technique, where a nonlinear kernel machine technique, kernel principal component analysis, is used with a specifically identified kernel function to differentiate BOLD signal from the physiological noise of the frequency. The proposed method was evaluated in human fMRI data acquired from multiple task-related and resting state fMRI experiments. A comparison study was also performed with an existing adaptive filtering method. The results indicate that the proposed method can effectively identify and reduce the physiological noise in fMRI data. The comparison study shows that the proposed method can provide comparable or better noise removal performance than the adaptive filtering approach.

  17. An integrated digital microfluidic lab-on-a-chip for clinical diagnostics on human physiological fluids.

    PubMed

    Srinivasan, Vijay; Pamula, Vamsee K; Fair, Richard B

    2004-08-01

    Clinical diagnostics is one of the most promising applications for microfluidic lab-on-a-chip systems, especially in a point-of-care setting. Conventional microfluidic devices are usually based on continuous-flow in microchannels, and offer little flexibility in terms of reconfigurability and scalability. Handling of real physiological samples has also been a major challenge in these devices. We present an alternative paradigm--a fully integrated and reconfigurable droplet-based "digital" microfluidic lab-on-a-chip for clinical diagnostics on human physiological fluids. The microdroplets, which act as solution-phase reaction chambers, are manipulated using the electrowetting effect. Reliable and repeatable high-speed transport of microdroplets of human whole blood, serum, plasma, urine, saliva, sweat and tear, is demonstrated to establish the basic compatibility of these physiological fluids with the electrowetting platform. We further performed a colorimetric enzymatic glucose assay on serum, plasma, urine, and saliva, to show the feasibility of performing bioassays on real samples in our system. The concentrations obtained compare well with those obtained using a reference method, except for urine, where there is a significant difference due to interference by uric acid. A lab-on-a-chip architecture, integrating previously developed digital microfluidic components, is proposed for integrated and automated analysis of multiple analytes on a monolithic device. The lab-on-a-chip integrates sample injection, on-chip reservoirs, droplet formation structures, fluidic pathways, mixing areas and optical detection sites, on the same substrate. The pipelined operation of two glucose assays is shown on a prototype digital microfluidic lab-on-chip, as a proof-of-concept.

  18. Trait-based approaches to conservation physiology: forecasting environmental change risks from the bottom up

    PubMed Central

    Chown, Steven L.

    2012-01-01

    Trait-based approaches have long been a feature of physiology and of ecology. While the latter fields drifted apart in the twentieth century, they are converging owing at least partly to growing similarities in their trait-based approaches, which have much to offer conservation biology. The convergence of spatially explicit approaches to understanding trait variation and its ecological implications, such as encapsulated in community assembly and macrophysiology, provides a significant illustration of the similarity of these areas. Both adopt trait-based informatics approaches which are not only providing fundamental biological insights, but are also delivering new information on how environmental change is affecting diversity and how such change may perhaps be mitigated. Such trait-based conservation physiology is illustrated here for each of the major environmental change drivers, specifically: the consequences of overexploitation for body size and physiological variation; the impacts of vegetation change on thermal safety margins; the consequences of changing net primary productivity and human use thereof for physiological variation and ecosystem functioning; the impacts of rising temperatures on water loss in ectotherms; how hemisphere-related variation in traits may affect responses to changing rainfall regimes and pollution; and how trait-based approaches may enable interactions between climate change and biological invasions to be elucidated. PMID:22566671

  19. Trait-based approaches to conservation physiology: forecasting environmental change risks from the bottom up.

    PubMed

    Chown, Steven L

    2012-06-19

    Trait-based approaches have long been a feature of physiology and of ecology. While the latter fields drifted apart in the twentieth century, they are converging owing at least partly to growing similarities in their trait-based approaches, which have much to offer conservation biology. The convergence of spatially explicit approaches to understanding trait variation and its ecological implications, such as encapsulated in community assembly and macrophysiology, provides a significant illustration of the similarity of these areas. Both adopt trait-based informatics approaches which are not only providing fundamental biological insights, but are also delivering new information on how environmental change is affecting diversity and how such change may perhaps be mitigated. Such trait-based conservation physiology is illustrated here for each of the major environmental change drivers, specifically: the consequences of overexploitation for body size and physiological variation; the impacts of vegetation change on thermal safety margins; the consequences of changing net primary productivity and human use thereof for physiological variation and ecosystem functioning; the impacts of rising temperatures on water loss in ectotherms; how hemisphere-related variation in traits may affect responses to changing rainfall regimes and pollution; and how trait-based approaches may enable interactions between climate change and biological invasions to be elucidated.

  20. Variability in cardiac electrophysiology: Using experimentally-calibrated populations of models to move beyond the single virtual physiological human paradigm.

    PubMed

    Muszkiewicz, Anna; Britton, Oliver J; Gemmell, Philip; Passini, Elisa; Sánchez, Carlos; Zhou, Xin; Carusi, Annamaria; Quinn, T Alexander; Burrage, Kevin; Bueno-Orovio, Alfonso; Rodriguez, Blanca

    2016-01-01

    Physiological variability manifests itself via differences in physiological function between individuals of the same species, and has crucial implications in disease progression and treatment. Despite its importance, physiological variability has traditionally been ignored in experimental and computational investigations due to averaging over samples from multiple individuals. Recently, modelling frameworks have been devised for studying mechanisms underlying physiological variability in cardiac electrophysiology and pro-arrhythmic risk under a variety of conditions and for several animal species as well as human. One such methodology exploits populations of cardiac cell models constrained with experimental data, or experimentally-calibrated populations of models. In this review, we outline the considerations behind constructing an experimentally-calibrated population of models and review the studies that have employed this approach to investigate variability in cardiac electrophysiology in physiological and pathological conditions, as well as under drug action. We also describe the methodology and compare it with alternative approaches for studying variability in cardiac electrophysiology, including cell-specific modelling approaches, sensitivity-analysis based methods, and populations-of-models frameworks that do not consider the experimental calibration step. We conclude with an outlook for the future, predicting the potential of new methodologies for patient-specific modelling extending beyond the single virtual physiological human paradigm.

  1. The human cerebellum: a review of physiologic neuroanatomy.

    PubMed

    Roostaei, Tina; Nazeri, Arash; Sahraian, Mohammad Ali; Minagar, Alireza

    2014-11-01

    The cerebellum resides in the posterior cranial fossa dorsal to the brainstem and has diverse connections to the cerebrum, brain stem, and spinal cord. It is anatomically and physiologically divided into distinct functional compartments and is composed of highly regular arrays of neuronal units, each sharing the same basic cerebellar microcircuitry. Its circuitry is critically involved in motor control and motor learning, and its role in nonmotor cognitive and affective functions is becoming increasingly recognized. This article describes the cerebellar gross and histologic neuroanatomy in relation to its function, and the relevance of cerebellar circuitry and firing patterns to motor learning.

  2. Advancements in remote physiological measurement and applications in human-computer interaction

    NASA Astrophysics Data System (ADS)

    McDuff, Daniel

    2017-04-01

    Physiological signals are important for tracking health and emotional states. Imaging photoplethysmography (iPPG) is a set of techniques for remotely recovering cardio-pulmonary signals from video of the human body. Advances in iPPG methods over the past decade combined with the ubiquity of digital cameras presents the possibility for many new, lowcost applications of physiological monitoring. This talk will highlight methods for recovering physiological signals, work characterizing the impact of video parameters and hardware on these measurements, and applications of this technology in human-computer interfaces.

  3. A physiologically based toxicokinetic model for lake trout (Salvelinus namaycush).

    PubMed

    Lien, G J; McKim, J M; Hoffman, A D; Jenson, C T

    2001-01-01

    A physiologically based toxicokinetic (PB-TK) model for fish, incorporating chemical exchange at the gill and accumulation in five tissue compartments, was parameterized and evaluated for lake trout (Salvelinus namaycush). Individual-based model parameterization was used to examine the effect of natural variability in physiological, morphological, and physico-chemical parameters on model predictions. The PB-TK model was used to predict uptake of organic chemicals across the gill and accumulation in blood and tissues in lake trout. To evaluate the accuracy of the model, a total of 13 adult lake trout were exposed to waterborne 1,1,2,2-tetrachloroethane (TCE), pentachloroethane (PCE), and hexachloroethane (HCE), concurrently, for periods of 6, 12, 24 or 48 h. The measured and predicted concentrations of TCE, PCE and HCE in expired water, dorsal aortic blood and tissues were generally within a factor of two, and in most instances much closer. Variability noted in model predictions, based on the individual-based model parameterization used in this study, reproduced variability observed in measured concentrations. The inference is made that parameters influencing variability in measured blood and tissue concentrations of xenobiotics are included and accurately represented in the model. This model contributes to a better understanding of the fundamental processes that regulate the uptake and disposition of xenobiotic chemicals in the lake trout. This information is crucial to developing a better understanding of the dynamic relationships between contaminant exposure and hazard to the lake trout.

  4. Physiological stress links parasites to carotenoid-based colour signals.

    PubMed

    Mougeot, F; Martínez-Padilla, J; Bortolotti, G R; Webster, L M I; Piertney, S B

    2010-03-01

    Vertebrates commonly use carotenoid-based traits as social signals. These can reliably advertise current nutritional status and health because carotenoids must be acquired through the diet and their allocation to ornaments is traded-off against other self-maintenance needs. We propose that the coloration more generally reveals an individual's ability to cope with stressful conditions. We tested this idea by manipulating the nematode parasite infection in free-living red grouse (Lagopus lagopus scoticus) and examining the effects on body mass, carotenoid-based coloration of a main social signal and the amount of corticosterone deposited in feathers grown during the experiment. We show that parasites increase stress and reduce carotenoid-based coloration, and that the impact of parasites on coloration was associated with changes in corticosterone, more than changes in body mass. Carotenoid-based coloration appears linked to physiological stress and could therefore reveal an individual's ability to cope with stressors.

  5. The role of adiponectin in human vascular physiology.

    PubMed

    Vaiopoulos, Aristeidis G; Marinou, Kyriakoula; Christodoulides, Constantinos; Koutsilieris, Michael

    2012-03-08

    Adiponectin (ApN) is an adipose tissue-derived hormone which is involved in a wide variety of physiological processes including energy metabolism, inflammation, and vascular physiology via actions on a broad spectrum of target organs including liver, skeletal muscle, and vascular endothelium. Besides possessing insulin sensitizing and anti-inflammatory properties ApN also exerts a pivotal role in vascular protection through activation of multiple intracellular signaling cascades. Enhancement of nitric oxide generation and attenuation of reactive oxygen species production in endothelial cells along with reduced vascular smooth muscle cell proliferation and migration constitute some of ApN's vasoprotective actions. Additionally, recent data indicate that ApN has direct myocardio-protective effects. Decreased plasma ApN levels are implicated in the pathogenesis of the metabolic syndrome and atherosclerosis and may serve as a diagnostic and prognostic biomarker as well as a rational pharmaco-therapeutic target to treat these disorders. This review article summarizes recent work on the cardiovascular actions of ApN.

  6. Gastrointestinal Physiology During Head Down Tilt Bedrest in Human Subjects

    NASA Technical Reports Server (NTRS)

    Vaksman, Z.; Guthienz, J.; Putcha, L.

    2008-01-01

    Introduction: Gastrointestinal (GI) motility plays a key role in the physiology and function of the GI tract. It directly affects absorption of medications and nutrients taken by mouth, in addition to indirectly altering GI physiology by way of changes in the microfloral composition and biochemistry of the GI tract. Astronauts have reported nausea, loss of appetite and constipation during space flight all of which indicate a reduction in GI motility and function similar to the one seen in chronic bed rest patients. The purpose of this study is to determine GI motility and bacterial proliferation during -6 degree head down tilt bed rest (HTD). Methods: Healthy male and female subjects between the ages of 25-40 participated in a 60 day HTD study protocol. GI transit time (GITT) was determined using lactulose breath hydrogen test and bacterial overgrowth was measured using glucose breath hydrogen test. H. Pylori colonization was determined using C13-urea breath test (UBIT#). All three tests were conducted on 9 days before HDT, and repeated on HDT days 2, 28, 58, and again on day 7 after HDT. Results: GITT increased during HTD compared to the respective ambulatory control values; GITT was significantly lower on day 7 after HTD. A concomitant increase in bacterial colonization was also noticed during HDT starting after approximately 28 days of HDT. However, H. Pylori proliferation was not recorded during HDT as indicated by UBIT#. Conclusion: GITT significantly decreased during HDT with a concomitant increase in the proliferation of GI bacterial flora but not H. pylori.

  7. Gastrointestinal Physiology During Head Down Tilt Bedrest in Human Subjects

    NASA Technical Reports Server (NTRS)

    Vaksman, Z.; Guthienz, J.; Putcha, L.

    2008-01-01

    Introduction: Gastrointestinal (GI) motility plays a key role in the physiology and function of the GI tract. It directly affects absorption of medications and nutrients taken by mouth, in addition to indirectly altering GI physiology by way of changes in the microfloral composition and biochemistry of the GI tract. Astronauts have reported nausea, loss of appetite and constipation during space flight all of which indicate a reduction in GI motility and function similar to the one seen in chronic bed rest patients. The purpose of this study is to determine GI motility and bacterial proliferation during -6 degree head down tilt bed rest (HTD). Methods: Healthy male and female subjects between the ages of 25-40 participated in a 60 day HTD study protocol. GI transit time (GITT) was determined using lactulose breath hydrogen test and bacterial overgrowth was measured using glucose breath hydrogen test. H. Pylori colonization was determined using C13-urea breath test (UBIT#). All three tests were conducted on 9 days before HDT, and repeated on HDT days 2, 28, 58, and again on day 7 after HDT. Results: GITT increased during HTD compared to the respective ambulatory control values; GITT was significantly lower on day 7 after HTD. A concomitant increase in bacterial colonization was also noticed during HDT starting after approximately 28 days of HDT. However, H. Pylori proliferation was not recorded during HDT as indicated by UBIT#. Conclusion: GITT significantly decreased during HDT with a concomitant increase in the proliferation of GI bacterial flora but not H. pylori.

  8. Acute Physiological and Behavioral Effects of Intranasal Methamphetamine in Humans

    PubMed Central

    Hart, Carl L; Gunderson, Erik W; Perez, Audrey; Kirkpatrick, Matthew G; Thurmond, Andrew; Comer, Sandra D; Foltin, Richard W

    2016-01-01

    Intranasal methamphetamine abuse has increased dramatically in the past decade, yet only one published study has investigated its acute effects under controlled laboratory conditions. Thus, the current study examined the effects of single-dose intranasal methamphetamine administration on a broad range of behavioral and physiological measures. Eleven nontreatment-seeking methamphetamine abusers (two females, nine males) completed this four-session, in-patient, within-participant, double-blind study. During each session, one of four intranasal methamphetamine doses (0, 12, 25, and 50 mg/70 kg) was administered and methamphetamine plasma concentrations, cardiovascular, subjective, and psychomotor/cognitive performance effects were assessed before drug administration and repeatedly thereafter. Following drug administration, methamphetamine plasma concentrations systematically increased for 4 h postdrug administration then declined. Methamphetamine dose dependently increased cardiovascular measures and ‘positive’ subjective effects, with peaks occurring approximately 5–15 min after drug administration, when plasma levels were still ascending. In addition, cognitive performance on less complicated tasks was improved by all active methamphetamine doses, whereas performance on more complicated tasks was improved only by the intermediate doses (12 and 25 mg). These results show that intranasal methamphetamine produced predictable effects on multiple behavioral and physiological measures before peak plasma levels were observed. Of interest is the dissociation between methamphetamine plasma concentrations with cardiovascular measures and positive subjective effects, which might have important implications for potential toxicity after repeated doses. PMID:17851535

  9. Thermal imaging to detect physiological indicators of stress in humans

    NASA Astrophysics Data System (ADS)

    Cross, Carl B.; Skipper, Julie A.; Petkie, Douglas T.

    2013-05-01

    Real-time, stand-off sensing of human subjects to detect emotional state would be valuable in many defense, security and medical scenarios. We are developing a multimodal sensor platform that incorporates high-resolution electro-optical and mid-wave infrared (MWIR) cameras and a millimeter-wave radar system to identify individuals who are psychologically stressed. Recent experiments have aimed to: 1) assess responses to physical versus psychological stressors; 2) examine the impact of topical skin products on thermal signatures; and 3) evaluate the fidelity of vital signs extracted from thermal imagery and radar signatures. Registered image and sensor data were collected as subjects (n=32) performed mental and physical tasks. In each image, the face was segmented into 29 non-overlapping segments based on fiducial points automatically output by our facial feature tracker. Image features were defined that facilitated discrimination between psychological and physical stress states. To test the ability to intentionally mask thermal responses indicative of anxiety or fear, subjects applied one of four topical skin products to one half of their face before performing tasks. Finally, we evaluated the performance of two non-contact techniques to detect respiration and heart rate: chest displacement extracted from the radar signal and temperature fluctuations at the nose tip and regions near superficial arteries to detect respiration and heart rates, respectively, extracted from the MWIR imagery. Our results are very satisfactory: classification of physical versus psychological stressors is repeatedly greater than 90%, thermal masking was almost always ineffective, and accurate heart and respiration rates are detectable in both thermal and radar signatures.

  10. Carbon-based ocean productivity and phytoplankton physiology from space

    NASA Astrophysics Data System (ADS)

    Behrenfeld, Michael J.; Boss, Emmanuel; Siegel, David A.; Shea, Donald M.

    2005-03-01

    Ocean biogeochemical and ecosystem processes are linked by net primary production (NPP) in the ocean's surface layer, where inorganic carbon is fixed by photosynthetic processes. Determinations of NPP are necessarily a function of phytoplankton biomass and its physiological status, but the estimation of these two terms from space has remained an elusive target. Here we present new satellite ocean color observations of phytoplankton carbon (C) and chlorophyll (Chl) biomass and show that derived Chl:C ratios closely follow anticipated physiological dependencies on light, nutrients, and temperature. With this new information, global estimates of phytoplankton growth rates (μ) and carbon-based NPP are made for the first time. Compared to an earlier chlorophyll-based approach, our carbon-based values are considerably higher in tropical oceans, show greater seasonality at middle and high latitudes, and illustrate important differences in the formation and demise of regional algal blooms. This fusion of emerging concepts from the phycological and remote sensing disciplines has the potential to fundamentally change how we model and observe carbon cycling in the global oceans.

  11. Audited credential delegation: a usable security solution for the virtual physiological human toolkit.

    PubMed

    Haidar, Ali N; Zasada, Stefan J; Coveney, Peter V; Abdallah, Ali E; Beckles, Bruce; Jones, Mike A S

    2011-06-06

    We present applications of audited credential delegation (ACD), a usable security solution for authentication, authorization and auditing in distributed virtual physiological human (VPH) project environments that removes the use of digital certificates from end-users' experience. Current security solutions are based on public key infrastructure (PKI). While PKI offers strong security for VPH projects, it suffers from serious usability shortcomings in terms of end-user acquisition and management of credentials which deter scientists from exploiting distributed VPH environments. By contrast, ACD supports the use of local credentials. Currently, a local ACD username-password combination can be used to access grid-based resources while Shibboleth support is underway. Moreover, ACD provides seamless and secure access to shared patient data, tools and infrastructure, thus supporting the provision of personalized medicine for patients, scientists and clinicians participating in e-health projects from a local to the widest international scale.

  12. Audited credential delegation: a usable security solution for the virtual physiological human toolkit

    PubMed Central

    Haidar, Ali N.; Zasada, Stefan J.; Coveney, Peter V.; Abdallah, Ali E.; Beckles, Bruce; Jones, Mike A. S.

    2011-01-01

    We present applications of audited credential delegation (ACD), a usable security solution for authentication, authorization and auditing in distributed virtual physiological human (VPH) project environments that removes the use of digital certificates from end-users' experience. Current security solutions are based on public key infrastructure (PKI). While PKI offers strong security for VPH projects, it suffers from serious usability shortcomings in terms of end-user acquisition and management of credentials which deter scientists from exploiting distributed VPH environments. By contrast, ACD supports the use of local credentials. Currently, a local ACD username–password combination can be used to access grid-based resources while Shibboleth support is underway. Moreover, ACD provides seamless and secure access to shared patient data, tools and infrastructure, thus supporting the provision of personalized medicine for patients, scientists and clinicians participating in e-health projects from a local to the widest international scale. PMID:22670214

  13. Singularity now: using the ventricular assist device as a model for future human-robotic physiology

    PubMed Central

    Martin, Archer K.

    2016-01-01

    In our 21st century world, human-robotic interactions are far more complicated than Asimov predicted in 1942. The future of human-robotic interactions includes human-robotic machine hybrids with an integrated physiology, working together to achieve an enhanced level of baseline human physiological performance. This achievement can be described as a biological Singularity. I argue that this time of Singularity cannot be met by current biological technologies, and that human-robotic physiology must be integrated for the Singularity to occur. In order to conquer the challenges we face regarding human-robotic physiology, we first need to identify a working model in today’s world. Once identified, this model can form the basis for the study, creation, expansion, and optimization of human-robotic hybrid physiology. In this paper, I present and defend the line of argument that currently this kind of model (proposed to be named “IshBot”) can best be studied in ventricular assist devices – VAD. PMID:28913480

  14. Physiologically-based modeling of sleep-wake regulatory networks.

    PubMed

    Booth, Victoria; Diniz Behn, Cecilia G

    2014-04-01

    Mathematical modeling has played a significant role in building our understanding of sleep-wake and circadian behavior. Over the past 40 years, phenomenological models, including the two-process model and oscillator models, helped frame experimental results and guide progress in understanding the interaction of homeostatic and circadian influences on sleep and understanding the generation of rapid eye movement sleep cycling. Recent advances in the clarification of the neural anatomy and physiology involved in the regulation of sleep and circadian rhythms have motivated the development of more detailed and physiologically-based mathematical models that extend the approach introduced by the classical reciprocal-interaction model. Using mathematical formalisms developed in the field of computational neuroscience to model neuronal population activity, these models investigate the dynamics of proposed conceptual models of sleep-wake regulatory networks with a focus on generating appropriate sleep and wake state transition patterns as well as simulating disease states and experimental protocols. In this review, we discuss several recent physiologically-based mathematical models of sleep-wake regulatory networks. We identify common features among these models in their network structures, model dynamics and approaches for model validation. We describe how the model analysis technique of fast-slow decomposition, which exploits the naturally occurring multiple timescales of sleep-wake behavior, can be applied to understand model dynamics in these networks. Our purpose in identifying commonalities among these models is to propel understanding of both the mathematical models and their underlying conceptual models, and focus directions for future experimental and theoretical work. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Field-based physiological testing of wheelchair athletes.

    PubMed

    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. Physiological bases of bone regeneration I. Histology and physiology of bone tissue.

    PubMed

    Fernández-Tresguerres-Hernández-Gil, Isabel; Alobera-Gracia, Miguel Angel; del-Canto-Pingarrón, Mariano; Blanco-Jerez, Luis

    2006-01-01

    Bone is the only body tissue capable of regeneration, allowing the restitutio ad integrum following trauma. In the event of a fracture or bone graft, new bone is formed, which following the remodeling process is identical to the pre-existing. Bone is a dynamic tissue in constant formation and resorption. This balanced phenomena, known as the remodeling process, allows the renovation of 5-15% of the total bone mass per year under normal conditions. Bone remodeling consists of the resorption of a certain amount of bone by osteoclasts, likewise the formation of osteoid matrix by osteoblasts, and its subsequent mineralization. This phenomenon occurs in small areas of the cortical bone or the trabecular surface, called Basic Multicellular Units (BMU). Treatment in Traumatology, Orthopedics, Implantology, and Maxillofacial and Oral Surgery, is based on the biologic principals of bone regeneration, in which cells, extracellular matrix, and osteoinductive signals are involved. The aim of this paper is to provide an up date on current knowledge on the biochemical and physiological mechanisms of bone regeneration, paying particular attention to the role played by the cells and proteins of the bone matrix.

  17. Nutrition and human physiological adaptations to space flight

    NASA Technical Reports Server (NTRS)

    Lane, H. W.; LeBlanc, A. D.; Putcha, L.; Whitson, P. A.

    1993-01-01

    Space flight provides a model for the study of healthy individuals undergoing unique stresses. This review focuses on how physiological adaptations to weightlessness may affect nutrient and food requirements in space. These adaptations include reductions in body water and plasma volume, which affect the renal and cardiovascular systems and thereby fluid and electrolyte requirements. Changes in muscle mass and function may affect requirements for energy, protein and amino acids. Changes in bone mass lead to increased urinary calcium concentrations, which may increase the risk of forming renal stones. Space motion sickness may influence putative changes in gastro-intestinal-hepatic function; neurosensory alterations may affect smell and taste. Some or all of these effects may be ameliorated through the use of specially designed dietary countermeasures.

  18. [Human orgasm from the physiological perspective--part I].

    PubMed

    Gałecki, Piotr; Depko, Andrzej; Jedrzejewska, Sylwia; Talarowska, Monika

    2012-07-01

    Physiological phenomenon of sexuality occurring in both sexes that brings physical and mental satisfaction, and often affects the quality of life is an orgasm. The ability to experience regular orgasms affects relationship with partner. The definition of orgasm is not an easy task. The way of experiencing it is subjective, and the possibility of observing significantly reduced. Contemporary works on the phenomenon of orgasm are concentrated on several aspects: biological perspective (neurophysiological and biochemical determinants of orgasm), psychological perspective and on the differences in its course in both sexes. In sexology are two models of sexual response: a linear model of sexual response (by W. Masters and V. Johnson, and H. S. Kaplan) and the circular model of sexual response (created by R. Basson). The ability to experiencing an orgasm is inherent in men. In women, that phenomenon is acquired, is the consequence of further experience.

  19. Trace elements in human physiology and pathology. Copper.

    PubMed

    Tapiero, H; Townsend, D M; Tew, K D

    2003-11-01

    Copper is a trace element, important for the function of many cellular enzymes. Copper ions can adopt distinct redox states oxidized Cu(II) or reduced (I), allowing the metal to play a pivotal role in cell physiology as a catalytic cofactor in the redox chemistry of enzymes, mitochondrial respiration, iron absorption, free radical scavenging and elastin cross-linking. If present in excess, free copper ions can cause damage to cellular components and a delicate balance between the uptake and efflux of copper ions determines the amount of cellular copper. In biological systems, copper homeostasis has been characterized at the molecular level. It is coordinated by several proteins such as glutathione, metallothionein, Cu-transporting P-type ATPases, Menkes and Wilson proteins and by cytoplasmic transport proteins called copper chaperones to ensure that it is delivered to specific subcellular compartments and thereby to copper-requiring proteins.

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

    PubMed

    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. Copyright © 2017 the American Physiological Society.

  1. Potent cough suppression by physiologically active substance in human plasma.

    PubMed

    Akaike, Norio; Ito, Yushi; Ogawa, Sachie K; Maeda, Megumi; Wakita, Masahito; Takahama, Kazuo; Noguchi, Tetsuro; Kamei, Shintaro; Hamamoto, Takayoshi; Umehashi, Misako; Maeda, Hiroaki

    2014-01-01

    Human plasma contains wide variety of bioactive proteins that have proved essential in therapeutic discovery. However many human plasma proteins remain orphans with unknown biological functions. Evidences suggest that some plasma components target the respiratory system. In the present study we adapted heparin affinity chromatography to fractionate human plasma for functional bioassay. Fractions from pooled human plasma yielded particular plasma fractions with strong cough suppressing effects. Purification yielded a fraction that was finally identified as an activated blood coagulation factor fXIa using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI/TOF-MS). The fraction almost completely suppressed coughs induced by either chemical or mechanical stimulation applied to larynx or bifurcation of guinea-pig trachea. Cough suppressing effect of the fraction and commercially available fXIa were one million times stronger than codeine and codeine only partially suppressed the mechanically triggered coughing in animal model. Recent reviews highlighted prominent shortcomings of current available antitussives, including narcotic opioids such as codeine and their unpleasant or intolerable side effects. Therefore, safer and more effective cough suppressants would be welcome, and present findings indicate that fXIa in human plasma as a very promising, new therapeutic candidate for effective antitussive action.

  2. The effect of active learning on student characteristics in a human physiology course for nonmajors.

    PubMed

    Wilke, R Russell

    2003-12-01

    This study investigated the effect of active-learning strategies on college students' achievement, motivation, and self-efficacy in a human physiology course for nonmajors. Variables were studied via a quasi-experimental, Solomon four-group design on 141 students at a small west-Texas university. Treatment groups were taught using a continuum-based, active-learning model implemented over the course of a semester. Control groups were taught using traditional didactic lecture methods. To assess the effects of the continuum-based active learning strategies, students were administered a comprehensive physiology content exam, the Motivated Strategies for Learning Questionnaire, and attitude surveys. Factorial analyses indicated that the treatment groups acquired significantly more content knowledge and were significantly more self-efficacious than students in the control groups. There were no significant differences in motivation. Attitude surveys indicated that students in both the treatment and control groups demonstrated a positive attitude toward active learning, believed it helped (or would help) them to learn the material, and would choose an active learning course in the future.

  3. Human mini-guts: new insights into intestinal physiology and host-pathogen interactions.

    PubMed

    In, Julie G; Foulke-Abel, Jennifer; Estes, Mary K; Zachos, Nicholas C; Kovbasnjuk, Olga; Donowitz, Mark

    2016-11-01

    The development of indefinitely propagating human 'mini-guts' has led to a rapid advance in gastrointestinal research related to transport physiology, developmental biology, pharmacology, and pathophysiology. These mini-guts, also called enteroids or colonoids, are derived from LGR5(+) intestinal stem cells isolated from the small intestine or colon. Addition of WNT3A and other growth factors promotes stemness and results in viable, physiologically functional human intestinal or colonic cultures that develop a crypt-villus axis and can be differentiated into all intestinal epithelial cell types. The success of research using human enteroids has highlighted the limitations of using animals or in vitro, cancer-derived cell lines to model transport physiology and pathophysiology. For example, curative or preventive therapies for acute enteric infections have been limited, mostly due to the lack of a physiological human intestinal model. However, the human enteroid model enables specific functional studies of secretion and absorption in each intestinal segment as well as observations of the earliest molecular events that occur during enteric infections. This Review describes studies characterizing these human mini-guts as a physiological model to investigate intestinal transport and host-pathogen interactions.

  4. Human mini-guts: new insights into intestinal physiology and host–pathogen interactions

    PubMed Central

    In, Julie G.; Foulke-Abel, Jennifer; Estes, Mary K.; Zachos, Nicholas C.; Kovbasnjuk, Olga; Donowitz, Mark

    2016-01-01

    The development of indefinitely propagating human ‘mini-guts’ has led to a rapid advance in gastrointestinal research related to transport physiology, developmental biology, pharmacology, and pathophysiology. These mini-guts, also called enteroids or colonoids, are derived from LGR5+ intestinal stem cells isolated from the small intestine or colon. Addition of WNT3A and other growth factors promotes stemness and results in viable, physiologically functional human intestinal or colonic cultures that develop a crypt–villus axis and can be differentiated into all intestinal epithelial cell types. The success of research using human enteroids has highlighted the limitations of using animals or in vitro, cancer-derived cell lines to model transport physiology and pathophysiology. For example, curative or preventive therapies for acute enteric infections have been limited, mostly due to the lack of a physiological human intestinal model. However, the human enteroid model enables specific functional studies of secretion and absorption in each intestinal segment as well as observations of the earliest molecular events that occur during enteric infections. This Review describes studies characterizing these human mini-guts as a physiological model to investigate intestinal transport and host pathogen interactions. PMID:27677718

  5. Physiological tonicity improves human chondrogenic marker expression through nuclear factor of activated T-cells 5 in vitro.

    PubMed

    van der Windt, Anna E; Haak, Esther; Das, Ruud H J; Kops, Nicole; Welting, Tim J M; Caron, Marjolein M J; van Til, Niek P; Verhaar, Jan A N; Weinans, Harrie; Jahr, Holger

    2010-01-01

    Chondrocytes experience a hypertonic environment compared with plasma (280 mOsm) due to the high fixed negative charge density of cartilage. Standard isolation of chondrocytes removes their hypertonic matrix, exposing them to nonphysiological conditions. During in vitro expansion, chondrocytes quickly lose their specialized phenotype, making them inappropriate for cell-based regenerative strategies. We aimed to elucidate the effects of tonicity during isolation and in vitro expansion on chondrocyte phenotype. Human articular chondrocytes were isolated and subsequently expanded at control tonicity (280 mOsm) or at moderately elevated, physiological tonicity (380 mOsm). The effects of physiological tonicity on chondrocyte proliferation and chondrogenic marker expression were evaluated. The role of Tonicity-responsive Enhancer Binding Protein in response to physiological tonicity was investigated using nuclear factor of activated T-cells 5 (NFAT5) RNA interference. Moderately elevated, physiological tonicity (380 mOsm) did not affect chondrocyte proliferation, while higher tonicities inhibited proliferation and diminished cell viability. Physiological tonicity improved expression of chondrogenic markers and NFAT5 and its target genes, while suppressing dedifferentiation marker collagen type I and improving type II/type I expression ratios >100-fold. Effects of physiological tonicity were similar in osteoarthritic and normal (nonosteoarthritic) chondrocytes, indicating a disease-independent mechanism. NFAT5 RNA interference abolished tonicity-mediated effects and revealed that NFAT5 positively regulates collagen type II expression, while suppressing type I. Physiological tonicity provides a simple, yet effective, means to improve phenotypical characteristics during cytokine-free isolation and in vitro expansion of human articular chondrocytes. Our findings will lead to the development of improved cell-based repair strategies for chondral lesions and provides important

  6. Physiological tonicity improves human chondrogenic marker expression through nuclear factor of activated T-cells 5 in vitro

    PubMed Central

    2010-01-01

    Introduction Chondrocytes experience a hypertonic environment compared with plasma (280 mOsm) due to the high fixed negative charge density of cartilage. Standard isolation of chondrocytes removes their hypertonic matrix, exposing them to nonphysiological conditions. During in vitro expansion, chondrocytes quickly lose their specialized phenotype, making them inappropriate for cell-based regenerative strategies. We aimed to elucidate the effects of tonicity during isolation and in vitro expansion on chondrocyte phenotype. Methods Human articular chondrocytes were isolated and subsequently expanded at control tonicity (280 mOsm) or at moderately elevated, physiological tonicity (380 mOsm). The effects of physiological tonicity on chondrocyte proliferation and chondrogenic marker expression were evaluated. The role of Tonicity-responsive Enhancer Binding Protein in response to physiological tonicity was investigated using nuclear factor of activated T-cells 5 (NFAT5) RNA interference. Results Moderately elevated, physiological tonicity (380 mOsm) did not affect chondrocyte proliferation, while higher tonicities inhibited proliferation and diminished cell viability. Physiological tonicity improved expression of chondrogenic markers and NFAT5 and its target genes, while suppressing dedifferentiation marker collagen type I and improving type II/type I expression ratios >100-fold. Effects of physiological tonicity were similar in osteoarthritic and normal (nonosteoarthritic) chondrocytes, indicating a disease-independent mechanism. NFAT5 RNA interference abolished tonicity-mediated effects and revealed that NFAT5 positively regulates collagen type II expression, while suppressing type I. Conclusions Physiological tonicity provides a simple, yet effective, means to improve phenotypical characteristics during cytokine-free isolation and in vitro expansion of human articular chondrocytes. Our findings will lead to the development of improved cell-based repair strategies for

  7. Selected human physiological responses during extreme heat: the Badwater Ultramarathon.

    PubMed

    Brown, Jacqueline S; Connolly, Declan A

    2015-06-01

    The purpose of this article was to examine various physiological responses during an ultramarathon held in extreme heat. Our investigation was conducted at The Badwater Ultramarathon, a nonstop 217-km run across Death Valley, CA, USA. This study recruited 4 male athletes, average age of 43 (±SD) (±7.35), (range) 39-54 years. All 4 subjects successfully completed the race with a mean finish time of 36:20:23 hours (±SD) (±3:08:38) (range) 34:05:25-40:51:46 hours, and a mean running speed of 6.03 km·h(-1) (±SD) (±0.05), (range) 5.3-6.4 km·h(-1). The anthropometric variables measured were (mean, ±SD) mass 79.33 kg (±6.43), height 1.80 m (±0.09), body surface area 1.93 m2 (±0.16), body mass index 24.38 kg·m(-2) (±1.25), fat mass 13.88% (±2.29), and body water 62.08% (±1.56). Selected physiological variables measured were core body temperature, skin temperature, heart rate, breathing rate, and blood pressure. Rate of perceived intensity, rate of thermal sensation, and environmental factors were also monitored. Our study found (mean and ±SD) core body temperature 37.49° C (±0.88); skin temperature 31.13° C (±3.06); heart rate 106.79 b·min(-1) (±5.11); breathing rate 36.55 b·min(-1) (±0.60); blood pressure 128/86 mm Hg (±9.24/4.62); rate of perceived intensity 5.49 (±1.26); rate of thermal sensation 4.69 (±0.37); daytime high temperature of 46.6° C, and a mean temperature of 28.35° C. Our fastest finisher demonstrated a lower overall core body temperature (36.91° C) when compared with the group mean (37.49° C). In contrast to previous findings, our data show that the fastest finisher demonstrates a lower overall core body temperature. We conclude that it may be possible that a time threshold exists whereby success in longer duration events requires an ability to maintain a lower core body temperature vs. tolerating a higher core body temperature.

  8. Human pathogens in plant biofilms: Formation, physiology, and detection

    USDA-ARS?s Scientific Manuscript database

    Fresh produce, viewed as an essential part of a healthy life style is usually consumed in the form of raw or minimally processed fruits and vegetables, and is a potentially important source of food-borne human pathogenic bacteria and viruses. These are passed on to the consumer since the bacteria ca...

  9. Study of Physiological Responses to Acute Carbon Monoxide Exposure with a Human Patient Simulator

    ERIC Educational Resources Information Center

    Cesari, Whitney A.; Caruso, Dominique M.; Zyka, Enela L.; Schroff, Stuart T.; Evans, Charles H., Jr.; Hyatt, Jon-Philippe K.

    2006-01-01

    Human patient simulators are widely used to train health professionals and students in a clinical setting, but they also can be used to enhance physiology education in a laboratory setting. Our course incorporates the human patient simulator for experiential learning in which undergraduate university juniors and seniors are instructed to design,…

  10. Study of Physiological Responses to Acute Carbon Monoxide Exposure with a Human Patient Simulator

    ERIC Educational Resources Information Center

    Cesari, Whitney A.; Caruso, Dominique M.; Zyka, Enela L.; Schroff, Stuart T.; Evans, Charles H., Jr.; Hyatt, Jon-Philippe K.

    2006-01-01

    Human patient simulators are widely used to train health professionals and students in a clinical setting, but they also can be used to enhance physiology education in a laboratory setting. Our course incorporates the human patient simulator for experiential learning in which undergraduate university juniors and seniors are instructed to design,…

  11. Hypohydration and Human Performance: Impact of Environment and Physiological Mechanisms.

    PubMed

    Sawka, Michael N; Cheuvront, Samuel N; Kenefick, Robert W

    2015-11-01

    Body water losses of >2 % of body mass are defined as hypohydration and can occur from sweat loss and/or diuresis from both cold and altitude exposure. Hypohydration elicits intracellular and extracellular water loss proportionate to water and solute deficits. Iso-osmotic hypovolemia (from cold and high-altitude exposure) results in greater plasma loss for a given water deficit than hypertonic hypovolemia from sweat loss. Hypohydration does not impair submaximal intensity aerobic performance in cold-cool environments, sometimes impairs aerobic performance in temperate environments, and usually impairs aerobic performance in warm-hot environments. Hypohydration begins to impair aerobic performance when skin temperatures exceed 27 °C, and with each additional 1 °C elevation in skin temperature there is a further 1.5 % impairment. Hypohydration has an additive effect on impairing aerobic performance in warm-hot high-altitude environments. A commonality of absolute hypovolemia (from plasma volume loss) combined with relative hypovolemia (from tissue vasodilation) is present when aerobic performance is impaired. The decrement in aerobic exercise performance due to hypohydration is likely due to multiple physiological mechanisms, including cardiovascular strain acting as the 'lynchpin', elevated tissue temperatures, and metabolic changes which are all integrated through the CNS to reduce motor drive to skeletal muscles.

  12. Development of a physiologically based pharmacokinetic model for bisphenol A in pregnant mice

    SciTech Connect

    Kawamoto, Yuko; Matsuyama, Wakoto; Wada, Masahiro; Hishikawa, Junko; Chan, Melissa Pui Ling; Nakayama, Aki; Morisawa, Shinsuke

    2007-10-15

    Bisphenol A (BPA) is a weakly estrogenic monomer used to produce polymers for food contact and other applications, so there is potential for oral exposure of humans to trace amounts via ingestion. To date, no physiologically based pharmacokinetic (PBPK) model has been located for BPA in pregnant mice with or without fetuses. An estimate by a mathematical model is essential since information on humans is difficult to obtain experimentally. The PBPK model was constructed based on the pharmacokinetic data of our experiment following single oral administration of BPA to pregnant mice. The risk assessment of bisphenol A (BPA) on the development of human offspring is an important issue. There have been limited data on the exposure level of human fetuses to BPA (e.g. BPA concentration in cord blood) and no information is available on the pharmacokinetics of BPA in humans with or without fetuses. In the present study, we developed a physiologically based pharmacokinetic (PBPK) model describing the pharmacokinetics of BPA in a pregnant mouse with the prospect of future extrapolation to humans. The PBPK model was constructed based on the pharmacokinetic data of an experiment we executed on pregnant mice following single oral administration of BPA. The model could describe the rapid transfer of BPA through the placenta to the fetus and the slow disappearance from fetuses. The simulated time courses after three-time repeated oral administrations of BPA by the constructed model fitted well with the experimental data, and the simulation for the 10 times lower dose was also consistent with the experiment. This suggested that the PBPK model for BPA in pregnant mice was successfully verified and is highly promising for extrapolation to humans who are expected to be exposed more chronically to lower doses.

  13. High Level Impulse Sounds and Human Hearing: Standards, Physiology, Quantification

    DTIC Science & Technology

    2012-05-01

    1976; Dancer , 2004). 3.1.2.2 Warned and Unwarned Response of the Ear The role of the AR in protecting hearing against impulse sounds has been...1974; Dancer , 2004). Price (2007a) refers to human reaction to unexpected and expected sounds as the unwarned response and warned response. The...Henderson et al., 2001; Maison and Liberman, 2000). This system has been referred to by Dancer (2004) as the inner ear acoustic reflex. Although

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

    PubMed

    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.

  15. Neuroanatomy and physiology of colorectal function and defaecation: from basic science to human clinical studies.

    PubMed

    Brookes, S J; Dinning, P G; Gladman, M A

    2009-12-01

    Colorectal physiology is complex and involves programmed, coordinated interaction between muscular and neuronal elements. Whilst a detailed understanding remains elusive, novel information has emerged from recent basic science and human clinical studies concerning normal sensorimotor mechanisms and the organization and function of the key elements involved in the control of motility. This chapter summarizes these observations to provide a contemporary review of the neuroanatomy and physiology of colorectal function and defaecation.

  16. Changing undergraduate human anatomy and physiology laboratories: perspectives from a large-enrollment course.

    PubMed

    Griff, Edwin R

    2016-09-01

    In the present article, a veteran lecturer of human anatomy and physiology taught several sections of the laboratory component for the first time and shares his observations and analysis from this unique perspective. The article discusses a large-enrollment, content-heavy anatomy and physiology course in relationship to published studies on learning and student self-efficacy. Changes in the laboratory component that could increase student learning are proposed. The author also points out the need for research to assess whether selective curricular changes could increase the depth of understanding and retention of learned material. Copyright © 2016 The American Physiological Society.

  17. The Contributions of Human Mini-Intestines to the Study of Intestinal Physiology and Pathophysiology.

    PubMed

    Yu, Huimin; Hasan, Nesrin M; In, Julie G; Estes, Mary K; Kovbasnjuk, Olga; Zachos, Nicholas C; Donowitz, Mark

    2017-02-10

    The lack of accessibility to normal and diseased human intestine and the inability to separate the different functional compartments of the intestine even when tissue could be obtained have held back the understanding of human intestinal physiology. Clevers and his associates identified intestinal stem cells and established conditions to grow "mini-intestines" ex vivo in differentiated and undifferentiated conditions. This pioneering work has made a new model of the human intestine available and has begun making contributions to the understanding of human intestinal transport in normal physiologic conditions and the pathophysiology of intestinal diseases. However, this model is reductionist and lacks many of the complexities of normal intestine. Consequently, it is not yet possible to predict how great the advances using this model will be for understanding human physiology and pathophysiology, nor how the model will be modified to include multiple other intestinal cell types and physical forces necessary to more closely approximate normal intestine. This review describes recent studies using mini-intestines, which have readdressed previously established models of normal intestinal transport physiology and newly examined intestinal pathophysiology. The emphasis is on studies with human enteroids grown either as three-dimensional spheroids or two-dimensional monolayers. In addition, comments are provided on mouse studies in cases when human studies have not yet been described.

  18. Physiological and subjective evaluation of a human-robot object hand-over task.

    PubMed

    Dehais, Frédéric; Sisbot, Emrah Akin; Alami, Rachid; Causse, Mickaël

    2011-11-01

    In the context of task sharing between a robot companion and its human partners, the notions of safe and compliant hardware are not enough. It is necessary to guarantee ergonomic robot motions. Therefore, we have developed Human Aware Manipulation Planner (Sisbot et al., 2010), a motion planner specifically designed for human-robot object transfer by explicitly taking into account the legibility, the safety and the physical comfort of robot motions. The main objective of this research was to define precise subjective metrics to assess our planner when a human interacts with a robot in an object hand-over task. A second objective was to obtain quantitative data to evaluate the effect of this interaction. Given the short duration, the "relative ease" of the object hand-over task and its qualitative component, classical behavioral measures based on accuracy or reaction time were unsuitable to compare our gestures. In this perspective, we selected three measurements based on the galvanic skin conductance response, the deltoid muscle activity and the ocular activity. To test our assumptions and validate our planner, an experimental set-up involving Jido, a mobile manipulator robot, and a seated human was proposed. For the purpose of the experiment, we have defined three motions that combine different levels of legibility, safety and physical comfort values. After each robot gesture the participants were asked to rate them on a three dimensional subjective scale. It has appeared that the subjective data were in favor of our reference motion. Eventually the three motions elicited different physiological and ocular responses that could be used to partially discriminate them. Copyright © 2011 Elsevier Ltd and the Ergonomics Society. All rights reserved.

  19. The application of DIGE-based proteomics to renal physiology.

    PubMed

    Hoorn, Ewout J; Hoffert, Jason D; Knepper, Mark A

    2006-01-01

    Proteomics is seeing increasing use as a means of identifying new mechanistic hypotheses in physiology. Proteomics based on two-dimensional electrophoresis (2-DE) has recently been optimized with the development of Difference Gel Electrophoresis (DIGE). In DIGE-based proteomics, the experimental and control samples are derivatized with different fluorophores and are run in the same gel, thereby minimizing technical variation. DIGE is currently one of the few techniques to perform quantitative proteomics, generating a statistical output to differences in protein abundances. In this review, we discuss the principles of DIGE-based proteomics, including sample preparation, 2-DE, statistical analysis of 2D-gels, and mass spectrometry. Strengths and weaknesses of DIGE are discussed, including possible solutions to overcome certain limitations, such as the identification of low abundance and integral membrane proteins. In addition, we provide a brief synopsis of our recent experiments in which DIGE-based proteomics was applied to study vasopressin signaling in the renal collecting duct. Finally, we illustrate how quantification based on the DIGE approach combined with bioinformatics may facilitate the study of systems biology of the kidney.

  20. Ordinary differential equation models for ethanol pharmacokinetic based on anatomy and physiology.

    PubMed

    Han, Jae-Joon; Plawecki, Martin H; Doerschuk, Peter C; Ramchandani, Vijay A; O'Connor, Sean

    2006-01-01

    Physiologically-based pharmacokinetic (PBPK) models have been used to describe the distribution and elimination characteristics of intravenous ethanol administration. Further, these models have been used to estimate the ethanol infusion profile required to prescribe a specific breath ethanol concentration time course in a specific human being, providing a platform upon which other pharmacokinetic and pharmacodynamic investigations are based. In these PBPK models, the equivalence of two different peripheral tissue models are shown and issues concerning the mass flow into the liver in comparison with ethanol metabolism in the liver are explained.

  1. Synthesis of nitric oxide in human osteoblasts in response to physiologic stimulation of electrotherapy.

    PubMed

    Hamed, Ayman; Kim, Paul; Cho, Michael

    2006-12-01

    Electrotherapy for bone healing, remodeling and wound healing may be mediated by modulation of nitric oxide (NO). Using NO-specific fluorophore (DAF-2), we report here that application of non-invasive, physiologic electrical stimulation induces NO synthesis in human osteoblasts, and that such NO generation is comparable to that induced by estrogen treatment. For example, application of a sinusoidal 1 Hz, 2 V/cm (peak to peak) electrical stimulation (ES) increases NO-bound DAF-2 fluorescence intensity by a 2-fold within 60 min exposure by activating nitric oxide synthase (NOS). Increase in the NO level is found to depend critically on the frequency and strength of ES. While the frequency of 1 Hz ES seems optimal, the ES strength >0.5 V/cm is required to induce significant NO increase, however. Nitric oxide synthesis in response to ES is completely prevented by blocking estrogen receptors using a competitive inhibitor, suggesting that NO generation is likely initiated by activation of estrogen receptors at the cell surface. Based on these findings, physiologic stimulation of electrotherapy appears to represent a potential non-invasive, non-genomic, and novel physical technique that could be used to regulate NO-mediated bone density and facilitate bone remodeling without adverse effects associated with hormone therapy.

  2. Effects of lighting on human physiology and behavior

    SciTech Connect

    Brainard, G.C.

    1996-01-01

    It has been demonstrated and published in the biomedical literature that light in the environment can regulate human biology and behavior. In addition, light is now routinely utilized as a therapeutic tool for various clinical disorders. Studies also suggest that light can be used to improve the health and productivity of shift workers. Finally, the data are beginning to look very promising for the fact that light may be used to improve the health and performance of day workers in addition to shift workers.

  3. Modeling alterations in sinonasal physiology after skull base surgery.

    PubMed

    Frank-Ito, Dennis O; Sajisevi, Mirabelle; Solares, C Arturo; Jang, David W

    2015-01-01

    Endonasal endoscopic skull base surgery (EESBS) often requires significant alterations in intranasal anatomy. For example, posterior septectomy (PS) with middle turbinate resection (MTR) is frequently performed to provide access to large sellar and clival tumors. However, little is known about the alterations that occur in sinonasal physiology. This study was designed to assess changes in sinonasal physiology after virtually performed endoscopic skull base surgery. Three-dimensional models of the sinonasal passage were created from computed tomography scans in three subjects with varying anatomy: no SD (SD), right anterior SD, and left anterior SD, respectively. Four additional surgery types were performed virtually on each model: endoscopic transsphenoidal approach (ETSA) with small (1 cm) PS (smPS), ETSA with complete (2 cm) PS, ETSA with smPS and right MTR, and ETSA with complete PS and right MTR. Computational fluid dynamics (CFD) simulations were performed on the 3 presurgery and 12 virtual surgery models to assess changes from surgery types. Increased nasal airflow corresponded to amount of tissue removed. Effects of MTR on unilateral airflow allocation were unchanged in subject with no SD, worsened in leftward SD, and reversed in rightward SD. Severity of airflow and mucosal wall interactions trended with amount of tissue removed. MTR hindered flow interactions with the olfactory mucosa in subjects with SD. CFD simulations on virtual surgery models are able to reasonably detect changes in airflow patterns in the computer-generated nasal models. In addition, each patient's unique anatomy influences the magnitude and direction of these changes after virtual EESBS. Once future studies can reliably correlate CFD parameters with patient symptoms, CFD will be a useful clinical tool in surgical planning and maximizing patient outcomes.

  4. Adipose circadian rhythms: translating cellular and animal studies to human physiology.

    PubMed

    Johnston, Jonathan D

    2012-02-05

    Emerging links between circadian rhythms and metabolism promise much for the understanding of metabolic physiology and pathophysiology, in which white adipose tissue (WAT) plays a prominent role. Many WAT endocrine molecules, termed adipokines, display rhythmic plasma concentration. Moreover, similar to most other tissues, WAT exhibits widespread 24-h variation in gene expression, with approximately 20% of the murine adipose transcriptome estimated to undergo daily variation. A major limitation to human chronobiology research is the availability of physiologically defined peripheral tissues. To date most analyses of in vivo human peripheral clocks has been limited to blood leucocytes. However, subcutaneous adipose tissue represents a novel opportunity to study peripheral molecular rhythms that are of clearly defined metabolic relevance. This review summarises basic concepts of circadian and metabolic physiology before then comparing alternative protocols used to analyse the rhythmic properties of human adipose tissue.

  5. Trace elements in human physiology and pathology: zinc and metallothioneins.

    PubMed

    Tapiero, Haim; Tew, Kenneth D

    2003-11-01

    Zinc is one of the most abundant nutritionally essential elements in the human body. It is found in all body tissues with 85% of the whole body zinc in muscle and bone, 11% in the skin and the liver and the remaining in all the other tissues. In multicellular organisms, virtually all zinc is intracellular, 30-40% is located in the nucleus, 50% in the cytoplasm, organelles and specialized vesicles (for digestive enzymes or hormone storage) and the remainder in the cell membrane. Zinc intake ranges from 107 to 231 micromol/d depending on the source, and human zinc requirement is estimated at 15 mg/d. Zinc has been shown to be essential to the structure and function of a large number of macromolecules and for over 300 enzymic reactions. It has both catalytic and structural roles in enzymes, while in zinc finger motifs, it provides a scaffold that organizes protein sub-domains for the interaction with either DNA or other proteins. It is critical for the function of a number of metalloproteins, inducing members of oxido-reductase, hydrolase ligase, lyase family and has co-activating functions with copper in superoxide dismutase or phospholipase C. The zinc ion (Zn(++)) does not participate in redox reactions, which makes it a stable ion in a biological medium whose potential is in constant flux. Zinc ions are hydrophilic and do not cross cell membranes by passive diffusion. In general, transport has been described as having both saturable and non-saturable components, depending on the Zn(II) concentrations involved. Zinc ions exist primarily in the form of complexes with proteins and nucleic acids and participate in all aspects of intermediary metabolism, transmission and regulation of the expression of genetic information, storage, synthesis and action of peptide hormones and structural maintenance of chromatin and biomembranes.

  6. Selenoproteins and Their Impact on Human Health Through Diverse Physiological Pathways

    PubMed Central

    Moghadaszadeh, Behzad; Beggs, Alan H.

    2012-01-01

    In the last few decades, the importance of selenium in human health has been the subject of numerous studies. It is believed that the physiological effects of selenium occur mainly through the function of selenoproteins, which incorporate selenium in the form of one or more selenocysteine residues. Recent advances in understanding the complex regulation of selenoprotein synthesis and functional characterization of several members of the selenoprotein family have contributed to an improved comprehension of the role(s) of selenium in human health and the great diversity of physiological pathways influenced by this trace element. PMID:16990451

  7. Cholesterol sulfate in human physiology: what's it all about?

    PubMed

    Strott, Charles A; Higashi, Yuko

    2003-07-01

    Cholesterol sulfate is quantitatively the most important known sterol sulfate in human plasma, where it is present in a concentration that overlaps that of the other abundant circulating steroid sulfate, dehydroepiandrosterone (DHEA) sulfate. Although these sulfolipids have similar production and metabolic clearance rates, they arise from distinct sources and are metabolized by different pathways. While the function of DHEA sulfate remains an enigma, cholesterol sulfate has emerged as an important regulatory molecule. Cholesterol sulfate is a component of cell membranes where it has a stabilizing role, e.g., protecting erythrocytes from osmotic lysis and regulating sperm capacitation. It is present in platelet membranes where it supports platelet adhesion. Cholesterol sulfate can regulate the activity of serine proteases, e.g., those involved in blood clotting, fibrinolysis, and epidermal cell adhesion. As a result of its ability to regulate the activity of selective protein kinase C isoforms and modulate the specificity of phosphatidylinositol 3-kinase, cholesterol sulfate is involved in signal transduction. Cholesterol sulfate functions in keratinocyte differentiation, inducing genes that encode for key components involved in development of the barrier. The accumulating evidence demonstrating a regulatory function for cholesterol sulfate appears solid; the challenge now is to work out the molecular mechanisms whereby this interesting molecule carries out its various roles.

  8. Synchronization Analysis of Language and Physiology in Human Dyads.

    PubMed

    Orsucci, Franco F; Musmeci, Nicolò; Aas, Benjamin; Schiepek, Günter; Reda, Mario A; Canestri, Luca; Giuliani, Alessandro; de Felice, Giulio

    2016-04-01

    We studied the synchronization dynamics of a therapist and patient during a psychotherapy session. This investigation was developed in order to explore a new possible perspective and methodology for studying the expression of emotions. More specifically, literature concerning synchronization of in-session non-verbal variables emphasises its positive correlation with empathy and therapeutic outcomes. We compared the dynamics of galvanic skin response (GSR) and linguistic prosody, chosen as indicators of emotional expression in different domains. We studied their synchronization through complementary methodologies: Recurrence Quantification Analysis (RQA) and Principal Component Analysis (PCA), Markov Transition Matrix (MTM) and Cross-Recurrence Quantification Analysis (CRQA). We investigated the nonlinearity of GSR in terms of self-similarity and power-law, as emerged in autocorrelation functions and signal variations. We considered time-lagged correlations as a measure of dynamical systems' memory. This article concludes by highlighting the importance of a deeper study of all variables related to the psychotherapeutic process and their synchronization in order to extend our knowledge of general human dynamics.

  9. Genetic, molecular and physiological insights into human obesity.

    PubMed

    Farooqi, I Sadaf

    2011-04-01

    Obesity and its associated co-morbidities represent one of the biggest public health challenges facing the western world today. Although environmental factors have driven the recent rise in the prevalence of obesity, the heritability of body weight is high and there is evidence that genetic variation plays a major role in determining the susceptibility to weight gain. Genetic approaches can be used to investigate the mechanisms underlying the regulation of weight and the development of obesity. The discovery that leptin, a hormone that is secreted by adipocytes, could regulate weight through effects on food intake and energy expenditure represented a major breakthrough in our understanding of the molecular components of the systems involved in energy homeostasis. I discuss how the identification of humans with mutations in the genes encoding leptin and its downstream targets has provided insights into the role of leptin responsive pathways in the regulation of body weight, neuroendocrine axes and immunity. © 2011 The Author. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation.

  10. A physiologically based model for spirometric reference equations in adults.

    PubMed

    Brisman, Jonas; Kim, Jeong-Lim; Olin, Anna-Carin; Torén, Kjell; Bake, Björn

    2016-01-01

    A spirometric reference equation consists of a mathematical model with constants and coefficients optimized to fit a specific data set from healthy individuals. Commonly applied models are selected on statistical rather than physiological considerations. A predetermined model with constants and coefficients optimized to various populations would enable interpretable and interesting comparisons between populations. Lubiński and Gólczewski recently presented a piecewise linear model with constants and coefficients claimed to be physiologically interpretable (Lubiński model). Three questions were addressed: Is the Lubiński model as useful clinically as other models: multiple linear, piecewise polynomial and exponential with splines? Will reference equations based on the Lubiński model and optimized to a Swedish and to a Polish population allow for interpretable comparisons? Are three well-known reference equations clinically useful in the Swedish adult population? A recent Swedish random population sample with high-quality spirometric measurements enabled the present analyses. When optimized to fit the Swedish population sample, the Lubiński model and two other models provided accurate predictive normal values. Interesting differences were demonstrated between the Polish and Swedish populations. The proportion of subjects below lower limit normal was adequate for the piecewise polynomial equations but too low and not clinically useful for the advocated exponential equations with splines. It is concluded that the Lubiński model is clinically as useful as other models, and it adds important value and is recommended for future spirometric reference equations for adults. The advocated exponential equations with splines are not recommended for Swedish adults because of too wide normal limits.

  11. Functional neuroimaging insights into the physiology of human sleep.

    PubMed

    Dang-Vu, Thien Thanh; Schabus, Manuel; Desseilles, Martin; Sterpenich, Virginie; Bonjean, Maxime; Maquet, Pierre

    2010-12-01

    Functional brain imaging has been used in humans to noninvasively investigate the neural mechanisms underlying the generation of sleep stages. On the one hand, REM sleep has been associated with the activation of the pons, thalamus, limbic areas, and temporo-occipital cortices, and the deactivation of prefrontal areas, in line with theories of REM sleep generation and dreaming properties. On the other hand, during non-REM (NREM) sleep, decreases in brain activity have been consistently found in the brainstem, thalamus, and in several cortical areas including the medial prefrontal cortex (MPFC), in agreement with a homeostatic need for brain energy recovery. Benefiting from a better temporal resolution, more recent studies have characterized the brain activations related to phasic events within specific sleep stages. In particular, they have demonstrated that NREM sleep oscillations (spindles and slow waves) are indeed associated with increases in brain activity in specific subcortical and cortical areas involved in the generation or modulation of these waves. These data highlight that, even during NREM sleep, brain activity is increased, yet regionally specific and transient. Besides refining the understanding of sleep mechanisms, functional brain imaging has also advanced the description of the functional properties of sleep. For instance, it has been shown that the sleeping brain is still able to process external information and even detect the pertinence of its content. The relationship between sleep and memory has also been refined using neuroimaging, demonstrating post-learning reactivation during sleep, as well as the reorganization of memory representation on the systems level, sometimes with long-lasting effects on subsequent memory performance. Further imaging studies should focus on clarifying the role of specific sleep patterns for the processing of external stimuli, as well as the consolidation of freshly encoded information during sleep.

  12. Human physiological responses to cold exposure: Acute responses and acclimatization to prolonged exposure.

    PubMed

    Castellani, John W; Young, Andrew J

    2016-04-01

    Cold exposure in humans causes specific acute and chronic physiological responses. This paper will review both the acute and long-term physiological responses and external factors that impact these physiological responses. Acute physiological responses to cold exposure include cutaneous vasoconstriction and shivering thermogenesis which, respectively, decrease heat loss and increase metabolic heat production. Vasoconstriction is elicited through reflex and local cooling. In combination, vasoconstriction and shivering operate to maintain thermal balance when the body is losing heat. Factors (anthropometry, sex, race, fitness, thermoregulatory fatigue) that influence the acute physiological responses to cold exposure are also reviewed. The physiological responses to chronic cold exposure, also known as cold acclimation/acclimatization, are also presented. Three primary patterns of cold acclimatization have been observed, a) habituation, b) metabolic adjustment, and c) insulative adjustment. Habituation is characterized by physiological adjustments in which the response is attenuated compared to an unacclimatized state. Metabolic acclimatization is characterized by an increased thermogenesis, whereas insulative acclimatization is characterized by enhancing the mechanisms that conserve body heat. The pattern of acclimatization is dependent on changes in skin and core temperature and the exposure duration. Published by Elsevier B.V.

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

    PubMed

    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.

  14. Animal Farm: Considerations in Animal Gastrointestinal Physiology and Relevance to Drug Delivery in Humans.

    PubMed

    Hatton, Grace B; Yadav, Vipul; Basit, Abdul W; Merchant, Hamid A

    2015-09-01

    "All animals are equal, but some are more equal than others" was the illustrious quote derived from British writer George Orwell's famed work, Animal Farm. Extending beyond the remit of political allegory, however, this statement would appear to hold true for the selection of appropriate animal models to simulate human physiology in preclinical studies. There remain definite gaps in our current knowledge with respect to animal physiology, notably those of intra- and inter-species differences in gastrointestinal (GI) function, which may affect oral drug delivery and absorption. Factors such as cost and availability have often influenced the choice of animal species without clear justification for their similarity to humans, and lack of standardization in techniques employed in past studies using various animals may also have contributed to the generation of contradictory results. As it stands, attempts to identify a single animal species as appropriately representative of human physiology and which may able to adequately simulate human in vivo conditions are limited. In this review, we have compiled and critically reviewed data from numerous studies of GI anatomy and physiology of various animal species commonly used in drug delivery modeling, commenting on the appropriateness of these animals for in vivo comparison and extrapolation to humans.

  15. Thermoregulatory responses in exercising rats: methodological aspects and relevance to human physiology

    PubMed Central

    Wanner, Samuel Penna; Prímola-Gomes, Thales Nicolau; Pires, Washington; Guimarães, Juliana Bohnen; Hudson, Alexandre Sérvulo Ribeiro; Kunstetter, Ana Cançado; Fonseca, Cletiana Gonçalves; Drummond, Lucas Rios; Damasceno, William Coutinho; Teixeira-Coelho, Francisco

    2015-01-01

    Rats are used worldwide in experiments that aim to investigate the physiological responses induced by a physical exercise session. Changes in body temperature regulation, which may affect both the performance and the health of exercising rats, are evident among these physiological responses. Despite the universal use of rats in biomedical research involving exercise, investigators often overlook important methodological issues that hamper the accurate measurement of clear thermoregulatory responses. Moreover, much debate exists regarding whether the outcome of rat experiments can be extrapolated to human physiology, including thermal physiology. Herein, we described the impact of different exercise intensities, durations and protocols and environmental conditions on running-induced thermoregulatory changes. We focused on treadmill running because this type of exercise allows for precise control of the exercise intensity and the measurement of autonomic thermoeffectors associated with heat production and loss. Some methodological issues regarding rat experiments, such as the sites for body temperature measurements and the time of day at which experiments are performed, were also discussed. In addition, we analyzed the influence of a high body surface area-to-mass ratio and limited evaporative cooling on the exercise-induced thermoregulatory responses of running rats and then compared these responses in rats to those observed in humans. Collectively, the data presented in this review represent a reference source for investigators interested in studying exercise thermoregulation in rats. In addition, the present data indicate that the thermoregulatory responses of exercising rats can be extrapolated, with some important limitations, to human thermal physiology. PMID:27227066

  16. Human colorectal mucosal microbiota correlates with its host niche physiology revealed by endomicroscopy

    PubMed Central

    Wang, Ai-Hua; Li, Ming; Li, Chang-Qing; Kou, Guan-Jun; Zuo, Xiu-Li; Li, Yan-Qing

    2016-01-01

    The human gut microbiota plays a pivotal role in the maintenance of health, but how the microbiota interacts with the host at the colorectal mucosa is poorly understood. We proposed that confocal laser endomicroscopy (CLE) might help to untangle this relationship by providing in vivo physiological information of the mucosa. We used CLE to evaluate the in vivo physiology of human colorectal mucosa, and the mucosal microbiota was quantified using 16 s rDNA pyrosequencing. The human mucosal microbiota agglomerated to three major clusters dominated by Prevotella, Bacteroides and Lactococcus. The mucosal microbiota clusters did not significantly correlate with the disease status or biopsy sites but closely correlated with the mucosal niche physiology, which was non-invasively revealed by CLE. Inflammation tilted two subnetworks within the mucosal microbiota. Infiltration of inflammatory cells significantly correlated with multiple components in the predicted metagenome, such as the VirD2 component of the type IV secretory pathway. Our data suggest that a close correlation exists between the mucosal microbiota and the colorectal mucosal physiology, and CLE is a clinically available tool that can be used to facilitate the study of the in vivo correlation between colorectal mucosal physiology and the mucosal microbiota. PMID:26916597

  17. Thermoregulatory responses in exercising rats: methodological aspects and relevance to human physiology.

    PubMed

    Wanner, Samuel Penna; Prímola-Gomes, Thales Nicolau; Pires, Washington; Guimarães, Juliana Bohnen; Hudson, Alexandre Sérvulo Ribeiro; Kunstetter, Ana Cançado; Fonseca, Cletiana Gonçalves; Drummond, Lucas Rios; Damasceno, William Coutinho; Teixeira-Coelho, Francisco

    2015-01-01

    Rats are used worldwide in experiments that aim to investigate the physiological responses induced by a physical exercise session. Changes in body temperature regulation, which may affect both the performance and the health of exercising rats, are evident among these physiological responses. Despite the universal use of rats in biomedical research involving exercise, investigators often overlook important methodological issues that hamper the accurate measurement of clear thermoregulatory responses. Moreover, much debate exists regarding whether the outcome of rat experiments can be extrapolated to human physiology, including thermal physiology. Herein, we described the impact of different exercise intensities, durations and protocols and environmental conditions on running-induced thermoregulatory changes. We focused on treadmill running because this type of exercise allows for precise control of the exercise intensity and the measurement of autonomic thermoeffectors associated with heat production and loss. Some methodological issues regarding rat experiments, such as the sites for body temperature measurements and the time of day at which experiments are performed, were also discussed. In addition, we analyzed the influence of a high body surface area-to-mass ratio and limited evaporative cooling on the exercise-induced thermoregulatory responses of running rats and then compared these responses in rats to those observed in humans. Collectively, the data presented in this review represent a reference source for investigators interested in studying exercise thermoregulation in rats. In addition, the present data indicate that the thermoregulatory responses of exercising rats can be extrapolated, with some important limitations, to human thermal physiology.

  18. Physiologically based computational approach to camouflage and masking patterns

    NASA Astrophysics Data System (ADS)

    Irvin, Gregg E.; Dowler, Michael G.

    1992-09-01

    A computational system was developed to integrate both Fourier image processing techniques and biologically based image processing techniques. The Fourier techniques allow the spatially global manipulation of phase and amplitude spectra. The biologically based techniques allow for spatially localized manipulation of phase, amplitude and orientation independently on multiple spatial frequency scales. These techniques combined with a large variety of basic image processing functions allow for a versatile and systematic approach to be taken toward the development of specialized patterning and visual textures. Current applications involve research for the development of 2-dimensional spatial patterning that can function as effective camouflage patterns and masking patterns for the human visual system.

  19. Investigating the state of physiologically based kinetic modelling practices and challenges associated with gaining regulatory acceptance of model applications

    EPA Science Inventory

    Physiologically based kinetic (PBK) models are used widely throughout a number of working sectors, including academia and industry, to provide insight into the dosimetry related to observed adverse health effects in humans and other species. Use of these models has increased over...

  20. Development of a Physiologically-Based Pharmacokinetic Model of Trichloroethylene and Its Metabolites for Use in Risk Assessment

    DTIC Science & Technology

    2004-09-01

    trichloroethanol (TCOH), and trichloroacetic acid (TCA), in the mouse, rat, and human, for both oral and inhalation exposure. The model includes...vi ABBREVIATIONS ACSL Advanced Continuous Simulation Language ADH Alcohol Dehydrogenase AUC Area Under the Concentration Curve BSA Body Surface Area...Trichloroethylene TCOH Trichloroethanol UGT UDP Glucuronosyl Transferase vii THIS PAGE INTENTIONALLY LEFT BLANK. viii DEVELOPMENT OF A PHYSIOLOGICALLY-BASED

  1. Use of Physiologically Based Kinetic Modeling-Based Reverse Dosimetry to Predict in Vivo Toxicity from in Vitro Data.

    PubMed

    Louisse, Jochem; Beekmann, Karsten; Rietjens, Ivonne M C M

    2017-01-17

    The development of reliable nonanimal based testing strategies, such as in vitro bioassays, is the holy grail in current human safety testing of chemicals. However, the use of in vitro toxicity data in risk assessment is not straightforward. One of the main issues is that concentration-response curves from in vitro models need to be converted to in vivo dose-response curves. These dose-response curves are needed in toxicological risk assessment to obtain a point of departure to determine safe exposure levels for humans. Recent scientific developments enable this translation of in vitro concentration-response curves to in vivo dose-response curves using physiologically based kinetic (PBK) modeling-based reverse dosimetry. The present review provides an overview of the examples available in the literature on the prediction of in vivo toxicity using PBK modeling-based reverse dosimetry of in vitro toxicity data, showing that proofs-of-principle are available for toxicity end points ranging from developmental toxicity, nephrotoxicity, hepatotoxicity, and neurotoxicity to DNA adduct formation. This review also discusses the promises and pitfalls, and the future perspectives of the approach. Since proofs-of-principle available so far have been provided for the prediction of toxicity in experimental animals, future research should focus on the use of in vitro toxicity data obtained in human models to predict the human situation using human PBK models. This would facilitate human- instead of experimental animal-based approaches in risk assessment.

  2. Multifractal parameters as an indication of different physiological and pathological states of the human brain

    NASA Astrophysics Data System (ADS)

    Dutta, Srimonti; Ghosh, Dipak; Samanta, Shukla; Dey, Santanu

    2014-02-01

    This paper presents a study on multifractal parameters of EEG patterns on the human brain. Multifractal detrended fluctuation analysis was applied to human EEG for normal and epileptic patients in different states. The results show that the degree of multifractality of EEG for patients in an epileptic seizure are much higher compared to normal healthy people. The degree of multifractality for normal humans with eyes open and closed was also significantly different. Thus the multifractal parameters can be used to distinguish between different physiological and pathological states of the human brain. The results are discussed in detail.

  3. Audio-Tutorial Project: An Audio-Tutorial Approach to Human Anatomy and Physiology.

    ERIC Educational Resources Information Center

    Muzio, Joseph N.; And Others

    A two course sequence on human anatomy and physiology using the audiotutorial method of instruction was developed for use by nursing students and other students in the health or medical fields at the Kingsborough Community College in New York. The project was motivated by the problems of often underprepared students coming to learn a new field and…

  4. Understanding Protein Synthesis: A Role-Play Approach in Large Undergraduate Human Anatomy and Physiology Classes

    ERIC Educational Resources Information Center

    Sturges, Diana; Maurer, Trent W.; Cole, Oladipo

    2009-01-01

    This study investigated the effectiveness of role play in a large undergraduate science class. The targeted population consisted of 298 students enrolled in 2 sections of an undergraduate Human Anatomy and Physiology course taught by the same instructor. The section engaged in the role-play activity served as the study group, whereas the section…

  5. Physiological responses to prolonged bed rest in humans: A compendium of research, 1981-1988

    NASA Technical Reports Server (NTRS)

    Luu, Phuong B.; Ortiz, Vanessa; Barnes, Paul R.; Greenleaf, John E.

    1990-01-01

    Clinical observations and results form more basic studies that help to elucidate the physiological mechanisms of the adaptation of humans to prolonged bed rest. If the authors' abstract or summary was appropriate, it was included. In some cases a more detailed synopsis was provided under the subheadings of purpose, methods, results, and conclusions.

  6. An Investigative Laboratory Course in Human Physiology Using Computer Technology and Collaborative Writing

    ERIC Educational Resources Information Center

    FitzPatrick, Kathleen A.

    2004-01-01

    Active investigative student-directed experiences in laboratory science are being encouraged by national science organizations. A growing body of evidence from classroom assessment supports their effectiveness. This study describes four years of implementation and assessment of an investigative laboratory course in human physiology for 65…

  7. Understanding Protein Synthesis: A Role-Play Approach in Large Undergraduate Human Anatomy and Physiology Classes

    ERIC Educational Resources Information Center

    Sturges, Diana; Maurer, Trent W.; Cole, Oladipo

    2009-01-01

    This study investigated the effectiveness of role play in a large undergraduate science class. The targeted population consisted of 298 students enrolled in 2 sections of an undergraduate Human Anatomy and Physiology course taught by the same instructor. The section engaged in the role-play activity served as the study group, whereas the section…

  8. An Investigative Laboratory Course in Human Physiology Using Computer Technology and Collaborative Writing

    ERIC Educational Resources Information Center

    FitzPatrick, Kathleen A.

    2004-01-01

    Active investigative student-directed experiences in laboratory science are being encouraged by national science organizations. A growing body of evidence from classroom assessment supports their effectiveness. This study describes four years of implementation and assessment of an investigative laboratory course in human physiology for 65…

  9. Coursera's Introductory Human Physiology Course: Factors That Characterize Successful Completion of a MOOC

    ERIC Educational Resources Information Center

    Engle, Deborah; Mankoff, Chris; Carbrey, Jennifer

    2015-01-01

    Since Massive Open Online Courses (MOOCs) are accessible by anyone in the world at no cost, they have large enrollments that are conducive to educational research. This study examines students in the Coursera MOOC, Introductory Human Physiology. Of the 33,378 students who accessed the course, around 15,000 students responded to items on the…

  10. Human physiological benefits of viewing nature: EEG responses to exact and statistical fractal patterns.

    PubMed

    Hagerhall, C M; Laike, T; Küller, M; Marcheschi, E; Boydston, C; Taylor, R P

    2015-01-01

    Psychological and physiological benefits of viewing nature have been extensively studied for some time. More recently it has been suggested that some of these positive effects can be explained by nature's fractal properties. Virtually all studies on human responses to fractals have used stimuli that represent the specific form of fractal geometry found in nature, i.e. statistical fractals, as opposed to fractal patterns which repeat exactly at different scales. This raises the question of whether human responses like preference and relaxation are being driven by fractal geometry in general or by the specific form of fractal geometry found in nature. In this study we consider both types of fractals (statistical and exact) and morph one type into the other. Based on the Koch curve, nine visual stimuli were produced in which curves of three different fractal dimensions evolve gradually from an exact to a statistical fractal. The patterns were shown for one minute each to thirty-five subjects while qEEG was continuously recorded. The results showed that the responses to statistical and exact fractals differ, and that the natural form of the fractal is important for inducing alpha responses, an indicator of a wakefully relaxed state and internalized attention.

  11. A wireless capsule system with ASIC for monitoring the physiological signals of the human gastrointestinal tract.

    PubMed

    Xu, Fei; Yan, Guozheng; Zhao, Kai; Lu, Li; Gao, Jinyang; Liu, Gang

    2014-12-01

    This paper presents the design of a wireless capsule system for monitoring the physiological signals of the human gastrointestinal (GI) tract. The primary components of the system include a wireless capsule, a portable data recorder, and a workstation. Temperature, pH, and pressure sensors; an RF transceiver; a controlling and processing application specific integrated circuit (ASIC); and batteries were applied in a wireless capsule. Decreasing capsule size, improving sensor precision, and reducing power needs were the primary challenges; these were resolved by employing micro sensors, optimized architecture, and an ASIC design that include power management, clock management, a programmable gain amplifier (PGA), an A/D converter (ADC), and a serial peripheral interface (SPI) communication unit. The ASIC has been fabricated in 0.18- μm CMOS technology with a die area of 5.0 mm × 5.0 mm. The wireless capsule integrating the ASIC controller measures Φ 11 mm × 26 mm. A data recorder and a workstation were developed, and 20 cases of human experiments were conducted in hospitals. Preprocessing in the workstation can significantly improve the quality of the data, and 76 original features were determined by mathematical statistics. Based on the 13 optimal features achieved in the evaluation of the features, the clustering algorithm can identify the patients who lack GI motility with a recognition rate reaching 83.3%.

  12. Evidence for a physiological role of intracellularly occurring photolabile nitrogen oxides in human skin fibroblasts.

    PubMed

    Opländer, Christian; Wetzel, Wiebke; Cortese, Miriam M; Pallua, Norbert; Suschek, Christoph V

    2008-05-01

    Nitric oxide (NO) plays a pivotal role in human skin biology. Cutaneous NO can be produced enzymatically by NO synthases (NOS) as well as enzyme independently via photodecomposition of photolabile nitrogen oxides (PNOs) such as nitrite or nitroso compounds, both found in human skin tissue in comparably high concentrations. Although the physiological role of NOS-produced NO in human skin is well defined, nothing is known about the biological relevance or the chemical origin of intracellularly occurring PNOs. We here, for the first time, give evidence that in human skin fibroblasts (FB) PNOs represent the oxidation products of NOS-produced NO and that in human skin fibroblasts intracellularly occurring PNOs effectively protect against the injurious effects of UVA radiation by a NO-dependent mechanism. In contrast, in PNO-depleted FB cultures an increased susceptibility to UVA-induced lipid peroxidation and cell death is observed, whereas supplementation of PNO-depleted FB cultures with physiological nitrite concentrations (10 microM) or with exogenously applied NO completely restores UVA-increased injuries. Thus, intracellular PNOs are biologically relevant and represent an important initial shield functioning in human skin physiology against UVA radiation. Consequently, nonphysiological low PNO concentrations might promote known UVA-related skin injuries such as premature aging and carcinogenesis.

  13. Beyond diet reconstruction: stable isotope applications to human physiology, health, and nutrition.

    PubMed

    Reitsema, Laurie J

    2013-01-01

    Analysis of stable carbon and nitrogen isotopes from soft or mineralized tissues is a direct and widely-used technique for modeling diets. In addition to its continued role in paleodiet analysis, stable isotope analysis is now contributing to studies of physiology, disease, and nutrition in archaeological and living human populations. In humans and other animals, dietary uptake and distribution of carbon and nitrogen among mineralized and soft tissue is carried out with varying efficiency due to factors of internal biology. Human pathophysiologies may lead to pathology-influenced isotopic fractionation that can be exploited to understand not just skeletal health and diet, but physiological health and nutrition. This study reviews examples from human biology, non-human animal ecology, biomedicine, and bioarchaeology demonstrating how stable isotope analyses are usefully applied to the study of physiological adaptation and adaptability. Suggestions are made for future directions in applying stable isotope analysis to the study of nutritional stress, disease, and growth and development in living and past human populations. Copyright © 2013 Wiley Periodicals, Inc.

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

    PubMed Central

    2010-01-01

    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-to-dose-to-effect" framework for modeling

  15. Physiological evidence for a human-induced landscape of fear in brown bears (Ursus arctos).

    PubMed

    Støen, Ole-Gunnar; Ordiz, Andres; Evans, Alina L; Laske, Timothy G; Kindberg, Jonas; Fröbert, Ole; Swenson, Jon E; Arnemo, Jon M

    2015-12-01

    Human persecution is a major cause of mortality for large carnivores. Consequently, large carnivores avoid humans, but may use human-dominated landscapes by being nocturnal and elusive. Behavioral studies indicate that certain ecological systems are "landscapes of fear", driven by antipredator behavior. Because behavior and physiology are closely interrelated, physiological assessments may provide insight into the behavioral response of large carnivores to human activity. To elucidate changes in brown bears' (Ursus arctos) behavior associated with human activity, we evaluated stress as changes in heart rate (HR) and heart rate variability (HRV) in 12 GPS-collared, free-ranging bears, 7 males and 5 females, 3-11 years old, using cardiac-monitoring devices. We applied generalized linear regression models with HR and HRV as response variables and chest activity, time of day, season, distance traveled, and distance to human settlements from GPS positions recorded every 30 min as potential explanatory variables. Bears exhibited lower HRV, an indication of stress, when they were close to human settlements and especially during the berry season, when humans were more often in the forest, picking berries and hunting. Our findings provide evidence of a human-induced landscape of fear in this hunted population of brown bears.

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

    PubMed

    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.

  17. Physiologically-Based Pharmacokinetic/Toxicokinetic Modeling in Risk Assessment

    DTIC Science & Technology

    2005-03-01

    physiology due to development, pregnancy or aging (life-stage modeling); and interactions between more than one chemical. It may also be necessary to...liver and fat; changes in physiology due to development, pregnancy or aging (life-stage modeling); and interactions between more than one chemical. In...initial pre- pregnancy body weight. Likewise, the temporal changes in maternal cardiac output during gestation and lactation can be described as the sum of

  18. Human Enteroids/Colonoids and Intestinal Organoids Functionally Recapitulate Normal Intestinal Physiology and Pathophysiology.

    PubMed

    Zachos, Nicholas C; Kovbasnjuk, Olga; Foulke-Abel, Jennifer; In, Julie; Blutt, Sarah E; de Jonge, Hugo R; Estes, Mary K; Donowitz, Mark

    2016-02-19

    Identification of Lgr5 as the intestinal stem cell marker as well as the growth factors necessary to replicate adult intestinal stem cell division has led to the establishment of the methods to generate "indefinite" ex vivo primary intestinal epithelial cultures, termed "mini-intestines." Primary cultures developed from isolated intestinal crypts or stem cells (termed enteroids/colonoids) and from inducible pluripotent stem cells (termed intestinal organoids) are being applied to study human intestinal physiology and pathophysiology with great expectations for translational applications, including regenerative medicine. Here we discuss the physiologic properties of these cultures, their current use in understanding diarrhea-causing host-pathogen interactions, and potential future applications.

  19. Perspective on the consequences of short- and long-duration space flight on human physiology.

    PubMed

    Holick, M F

    1999-01-01

    During the past three decades, humans have made significant progress in accomplishing their aspirations for exploring the Moon and the planets. It is now appreciated that humans undergo a remarkable number of physiologic adaptations in microgravity that affect most physiologic systems. Space motion sickness was one of the first adaptations that humans experienced in microgravity. However, it is self-limiting and, most of the time, is effectively treated pharmacologically. Of particular concern is that, in microgravity, there is marked wasting of the skeletal musculature and skeleton that appears to be unrelenting and could impact on the health and welfare of space travelers during prolonged space flights and on return to earth. Microgravity also has a significant impact on the cardiovascular system that could have potentially serious consequences in terms of cardiovascular health during long-duration space flights. Other adaptations such as decreased T-cell responsiveness and changes in circadian rhythms is only now being explored. We need to understand the role that microgravity has on human physiologic systems in order to develop strategies for permitting humans to experience prolonged microgravity without having significant impact on their health and welfare. Engineering some gravitational force as a component of long-duration space vehicles should be given a high priority.

  20. Policy needs and options for a common approach towards modelling and simulation of human physiology and diseases with a focus on the virtual physiological human.

    PubMed

    Viceconti, Marco; McCulloch, Andrew D

    2011-01-01

    Life is the result of an intricate systemic interaction between many processes occurring at radically different spatial and temporal scales. Every day, worldwide biomedical research and clinical practice produce a huge amount of information on such processes. However, this information being highly fragmented, its integration is largely left to the human actors who find this task increasingly and ever more demanding in a context where the information available continues to increase exponentially. Investments in the Virtual Physiological Human (VPH) research are largely motivated by the need for integration in healthcare. As all health information becomes digital, the complexity of health care will continue to evolve, translating into an ever increasing pressure which will result from a growing demand in parallel to limited budgets. Hence, the best way to achieve the dream of personalised, preventive, and participative medicine at sustainable costs will be through the integration of all available data, information and knowledge.

  1. Human physiologic factors in respiratory uptake of 1,3-butadiene.

    PubMed Central

    Lin, Y S; Smith, T J; Kelsey, K T; Wypij, D

    2001-01-01

    1,3-Butadiene (BD), a suspected human carcinogen, is used as the raw material in industries to make synthetic butyl rubber and plastics. Simulation models using experimental animal data have shown that physiologic factors play an important role in the kinetic behavior of BD. However, human data are limited. The aim of this inhalation study was to identify influential human physiologic factors in the respiratory uptake of BD. We recruited 133 healthy volunteers in Boston, Massachusetts, into this study and tested them under an approved human subjects protocol. Each subject was exposed to 2 ppm (4.42 mg/m3) BD for 20 min, followed by purified air for another 40 min. Five exhaled breath samples collected during exposure were used to determine the respiratory uptake of BD, which was defined as absorbed BD (micrograms) per kilogram of body weight during exposure. Although subjects were given identical administered doses (40 ppm x min), there was a wide range of uptake, 0.6-4.9 microg/kg. Of the studied physiologic factors, the blood:air partition coefficient and alveolar ventilation were most significant in determining the respiratory uptake (p < 0.001 for each). In addition, in the multiple regression analysis, females had significantly higher respiratory uptake of BD than males on a weight basis. For all subjects, increasing age and cigarette smoking led to significantly decreased respiratory uptake of BD. The results of this human study are consistent with previous kinetic simulations and animal studies. The findings also suggest that interindividual variation in human physiologic factors that affect the exposure-internal dose relationship should be considered while also exploring exposure-disease associations in future epidemiologic research. PMID:11673121

  2. Innovations and Improvements in Pharmacokinetic Models Based on Physiology.

    PubMed

    Abbiati, Roberto Andrea; Manca, Davide

    2017-01-01

    Accompanied by significant improvements of modeling techniques and computational methods in medical sciences, the last thirty years saw the flourishing of pharmacokinetic models for applications in the pharmacometric field. In particular, physiologically based pharmacokinetic (PBPK) models, grounded on a mechanistic foundation, have been applied to explore a multiplicity of aspects with possible applications in patient care and new drugs development, as in the case of siRNA therapies. This article summarizes the features we recently introduced in PBPK modeling within a threeyear research project funded by Italian Research Ministry. Four major points are detailed: (i) the mathematical formulation of the model, which allows modulating its complexity as a function of the administration route and active principle; (ii) a dedicated parameter of the PBPK model quantifies the drugprotein binding, which affects the active principle distribution; (iii) the gall bladder compartment and the bile enterohepatic circulation process; (iv) the coupling of the pharmacokinetic and pharmacodynamic models to produce an overall understanding of the drug effects on mammalian body. The proposed model is applied to two separate endovenous (remifentanil) and oral (sorafenib) drug administrations. The resulting PBPK simulations are consistent with the literature experimental data. Blood concentration predictability is confirmed in multiple reference subjects. Furthermore, in case of sorafenib administration in mice, it is possible to evaluate the drug concentration in the liver and reproduce the effects of the enterohepatic circulation. Finally, a preliminary application of the coupling of the pharmacokinetic/pharmacodynamic models is presented and discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Physiological conditions can be reflected in human urine proteome and metabolome.

    PubMed

    Wu, Jianqiang; Gao, Youhe

    2015-01-01

    Biomarkers are the measurable changes associated with physiological or pathophysiological processes. Urine, unlike blood, lacks mechanisms for maintaining homeostasis: it is therefore an ideal source of biomarkers that can reflect systemic changes. Urinary proteome and metabolome have been studied for their diagnostic capabilities, ability to monitor disease and prognostic utility. In this review, the effects of common physiological conditions such as gender, age, diet, daily rhythms, exercise, hormone status, lifestyle and extreme environments on human urine are discussed. These effects should be considered when biomarker studies of diseases are conducted. More importantly, if physiological changes can be reflected in urine, we have reason to expect that urine will become widely used to detect small and early changes in pathological and/or pharmacological conditions.

  4. Identification of differences in human and great ape phytanic acid metabolism that could influence gene expression profiles and physiological functions.

    PubMed

    Watkins, Paul A; Moser, Ann B; Toomer, Cicely B; Steinberg, Steven J; Moser, Hugo W; Karaman, Mazen W; Ramaswamy, Krishna; Siegmund, Kimberly D; Lee, D Rick; Ely, John J; Ryder, Oliver A; Hacia, Joseph G

    2010-10-08

    It has been proposed that anatomical differences in human and great ape guts arose in response to species-specific diets and energy demands. To investigate functional genomic consequences of these differences, we compared their physiological levels of phytanic acid, a branched chain fatty acid that can be derived from the microbial degradation of chlorophyll in ruminant guts. Humans who accumulate large stores of phytanic acid commonly develop cerebellar ataxia, peripheral polyneuropathy, and retinitis pigmentosa in addition to other medical conditions. Furthermore, phytanic acid is an activator of the PPAR-alpha transcription factor that influences the expression of genes relevant to lipid metabolism. Despite their trace dietary phytanic acid intake, all great ape species had elevated red blood cell (RBC) phytanic acid levels relative to humans on diverse diets. Unlike humans, chimpanzees showed sexual dimorphism in RBC phytanic acid levels, which were higher in males relative to females. Cultured skin fibroblasts from all species had a robust capacity to degrade phytanic acid. We provide indirect evidence that great apes, in contrast to humans, derive significant amounts of phytanic acid from the hindgut fermentation of plant materials. This would represent a novel reduction of metabolic activity in humans relative to the great apes. We identified differences in the physiological levels of phytanic acid in humans and great apes and propose this is causally related to their gut anatomies and microbiomes. Phytanic acid levels could contribute to cross-species and sex-specific differences in human and great ape transcriptomes, especially those related to lipid metabolism. Based on the medical conditions caused by phytanic acid accumulation, we suggest that differences in phytanic acid metabolism could influence the functions of human and great ape nervous, cardiovascular, and skeletal systems.

  5. Identification of differences in human and great ape phytanic acid metabolism that could influence gene expression profiles and physiological functions

    PubMed Central

    2010-01-01

    Background It has been proposed that anatomical differences in human and great ape guts arose in response to species-specific diets and energy demands. To investigate functional genomic consequences of these differences, we compared their physiological levels of phytanic acid, a branched chain fatty acid that can be derived from the microbial degradation of chlorophyll in ruminant guts. Humans who accumulate large stores of phytanic acid commonly develop cerebellar ataxia, peripheral polyneuropathy, and retinitis pigmentosa in addition to other medical conditions. Furthermore, phytanic acid is an activator of the PPAR-alpha transcription factor that influences the expression of genes relevant to lipid metabolism. Results Despite their trace dietary phytanic acid intake, all great ape species had elevated red blood cell (RBC) phytanic acid levels relative to humans on diverse diets. Unlike humans, chimpanzees showed sexual dimorphism in RBC phytanic acid levels, which were higher in males relative to females. Cultured skin fibroblasts from all species had a robust capacity to degrade phytanic acid. We provide indirect evidence that great apes, in contrast to humans, derive significant amounts of phytanic acid from the hindgut fermentation of plant materials. This would represent a novel reduction of metabolic activity in humans relative to the great apes. Conclusion We identified differences in the physiological levels of phytanic acid in humans and great apes and propose this is causally related to their gut anatomies and microbiomes. Phytanic acid levels could contribute to cross-species and sex-specific differences in human and great ape transcriptomes, especially those related to lipid metabolism. Based on the medical conditions caused by phytanic acid accumulation, we suggest that differences in phytanic acid metabolism could influence the functions of human and great ape nervous, cardiovascular, and skeletal systems. PMID:20932325

  6. Physiological Effects Associated with Quinoa Consumption and Implications for Research Involving Humans: a Review.

    PubMed

    Simnadis, Thomas George; Tapsell, Linda C; Beck, Eleanor J

    2015-09-01

    Quinoa is a pseudo-grain consumed as a dietary staple in South America. In recent years, consumer demand for quinoa in the developed world has grown steadily. Its perceived health benefits have been cited as a driving force behind this trend, but there are very few human studies investigating the impact of quinoa consumption. The aim of this review was to identify physiological effects of quinoa consumption with potential for human health. A critical evaluation of animal model studies was conducted. The quality of identified studies was assessed using a methodological quality assessment tool and summative conclusions were drawn to guide the direction of future human research. The majority of studies were of fair quality. Purported physiological effects of quinoa consumption included decreased weight gain, improved lipid profile and improved capacity to respond to oxidative stress. These physiological effects were attributed to the presence of saponins, protein and 20-hydroxyecdysone in the quinoa seed. The implications of these findings are that human studies should investigate the impact of quinoa consumption on weight gain and lipid levels. The role of quinoa as an antioxidant is still unclear and requires further elucidation in animal models.

  7. Ultrasensitive, passive and wearable sensors for monitoring human muscle motion and physiological signals.

    PubMed

    Cai, Feng; Yi, Changrui; Liu, Shichang; Wang, Yan; Liu, Lacheng; Liu, Xiaoqing; Xu, Xuming; Wang, Li

    2016-03-15

    Flexible sensors have attracted more and more attention as a fundamental part of anthropomorphic robot research, medical diagnosis and physical health monitoring. Here, we constructed an ultrasensitive and passive flexible sensor with the advantages of low cost, lightness and wearability, electric safety and reliability. The fundamental mechanism of the sensor is based on triboelectric effect inducing electrostatic charges on the surfaces between two different materials. Just like a plate capacitor, current will be generated while the distance or size of the parallel capacitors changes caused by the small mechanical disturbance upon it and therefore the output current/voltage will be produced. Typically, the passive sensor unambiguously monitors muscle motions including hand motion from stretch-clench-stretch, mouth motion from open-bite-open, blink and respiration. Moreover, this sensor records the details of the consecutive phases in a cardiac cycle of the apex cardiogram, and identify the peaks including percussion wave, tidal wave and diastolic wave of the radial pulse wave. To record subtle human physiological signals including radial pulsilogram and apex cardiogram with excellent signal/noise ratio, stability and reproducibility, the sensor shows great potential in the applications of medical diagnosis and daily health monitoring. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Assessment of flow-mediated dilation in humans: a methodological and physiological guideline

    PubMed Central

    Black, Mark A.; Pyke, Kyra E.; Padilla, Jaume; Atkinson, Greg; Harris, Ryan A.; Parker, Beth; Widlansky, Michael E.; Tschakovsky, Michael E.; Green, Daniel J.

    2011-01-01

    Endothelial dysfunction is now considered an important early event in the development of atherosclerosis, which precedes gross morphological signs and clinical symptoms. The assessment of flow-mediated dilation (FMD) was introduced almost 20 years ago as a noninvasive approach to examine vasodilator function in vivo. FMD is widely believed to reflect endothelium-dependent and largely nitric oxide-mediated arterial function and has been used as a surrogate marker of vascular health. This noninvasive technique has been used to compare groups of subjects and to evaluate the impact of interventions within individuals. Despite its widespread adoption, there is considerable variability between studies with respect to the protocols applied, methods of analysis, and interpretation of results. Moreover, differences in methodological approaches have important impacts on the response magnitude, can result in spurious data interpretation, and limit the comparability of outcomes between studies. This review results from a collegial discussion between physiologists with the purpose of developing considered guidelines. The contributors represent several distinct research groups that have independently worked to advance the evidence base for improvement of the technical approaches to FMD measurement and analysis. The outcome is a series of recommendations on the basis of review and critical appraisal of recent physiological studies, pertaining to the most appropriate methods to assess FMD in humans. PMID:20952670

  9. Understanding protein synthesis: a role-play approach in large undergraduate human anatomy and physiology classes.

    PubMed

    Sturges, Diana; Maurer, Trent W; Cole, Oladipo

    2009-06-01

    This study investigated the effectiveness of role play in a large undergraduate science class. The targeted population consisted of 298 students enrolled in 2 sections of an undergraduate Human Anatomy and Physiology course taught by the same instructor. The section engaged in the role-play activity served as the study group, whereas the section presented with a traditional lecture served as the control group. A pretest/posttest assessment and a survey were administered to both sections and used in data analysis. In addition, overall test scores and item analysis were examined. The analysis revealed that participants in both groups improved significantly from pretest to posttest, but there were no significant differences between the groups in posttest scores. Neither group showed a significant change from posttest to the exam. However, there was a moderate positive effect on engagement and satisfaction survey questions from being in the study group (based on 255 total surveys returned by both groups). The role-play activity was at least as effective as the lecture in terms of student performance on the above-mentioned assessments. In addition, it proved successful in engaging students in the learning process and increasing their satisfaction.

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

    ERIC Educational Resources Information Center

    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. A Web-Based Course of Lectures in Respiratory Physiology

    ERIC Educational Resources Information Center

    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…

  12. Towards a Physiologically Based HUD (Head-Up Display) Symbology

    DTIC Science & Technology

    1989-01-01

    diplopia , and other types of visual degradation. Much perceptual and physiological evidence links global form perception to near vision, and it has been...perceived as much closer to the optical distance of the outside world, thereby reducing the amount of diplopia and defocus), it does resemble the reaching

  13. Physiologically Based Pharmacokinetic (PBPK) Modeling of Interstrain Variability in Trichloroethylene Metabolism in the Mouse

    PubMed Central

    Campbell, Jerry L.; Clewell, Harvey J.; Zhou, Yi-Hui; Wright, Fred A.; Guyton, Kathryn Z.

    2014-01-01

    Background: Quantitative estimation of toxicokinetic variability in the human population is a persistent challenge in risk assessment of environmental chemicals. Traditionally, interindividual differences in the population are accounted for by default assumptions or, in rare cases, are based on human toxicokinetic data. Objectives: We evaluated 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 1 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). We used a Bayesian population analysis of interstrain variability 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 were less variable (5-fold range) than that through glutathione conjugation (10-fold range). For oxidative metabolites, median predictions of trichloroacetic acid production were less variable (2-fold range) than DCA production (5-fold range), although the uncertainty bounds for DCA exceeded the predicted variability. Conclusions: Population PBPK modeling of genetically diverse mouse strains can provide useful quantitative estimates of toxicokinetic population variability. When extrapolated to lower doses more relevant to environmental exposures, mouse population-derived variability estimates for TCE metabolism closely matched population variability estimates previously derived from human toxicokinetic studies with TCE, highlighting the utility of mouse interstrain metabolism studies for addressing toxicokinetic variability

  14. Widespread seasonal gene expression reveals annual differences in human immunity and physiology

    PubMed Central

    Dopico, Xaquin Castro; Evangelou, Marina; Ferreira, Ricardo C.; Guo, Hui; Pekalski, Marcin L.; Smyth, Deborah J.; Cooper, Nicholas; Burren, Oliver S.; Fulford, Anthony J.; Hennig, Branwen J.; Prentice, Andrew M.; Ziegler, Anette-G.; Bonifacio, Ezio; Wallace, Chris; Todd, John A.

    2015-01-01

    Seasonal variations are rarely considered a contributing component to human tissue function or health, although many diseases and physiological process display annual periodicities. Here we find more than 4,000 protein-coding mRNAs in white blood cells and adipose tissue to have seasonal expression profiles, with inverted patterns observed between Europe and Oceania. We also find the cellular composition of blood to vary by season, and these changes, which differ between the United Kingdom and The Gambia, could explain the gene expression periodicity. With regards to tissue function, the immune system has a profound pro-inflammatory transcriptomic profile during European winter, with increased levels of soluble IL-6 receptor and C-reactive protein, risk biomarkers for cardiovascular, psychiatric and autoimmune diseases that have peak incidences in winter. Circannual rhythms thus require further exploration as contributors to various aspects of human physiology and disease. PMID:25965853

  15. High-Throughput Physiologically Based Toxicokinetic Models for ToxCast Chemicals

    EPA Science Inventory

    Physiologically based toxicokinetic (PBTK) models aid in predicting exposure doses needed to create tissue concentrations equivalent to those identified as bioactive by ToxCast. We have implemented four empirical and physiologically-based toxicokinetic (TK) models within a new R ...

  16. High-Throughput Physiologically Based Toxicokinetic Models for ToxCast Chemicals

    EPA Science Inventory

    Physiologically based toxicokinetic (PBTK) models aid in predicting exposure doses needed to create tissue concentrations equivalent to those identified as bioactive by ToxCast. We have implemented four empirical and physiologically-based toxicokinetic (TK) models within a new R ...

  17. Physiological modes of action of fluoxetine and its human metabolites in algae.

    PubMed

    Neuwoehner, Judith; Fenner, Kathrin; Escher, Beate I

    2009-09-01

    Fluoxetine, the active ingredient of many antidepressants, was identified as specifically toxic toward algae in a quantitative structure-activity relationship (QSAR) analysis with literature data for algae, daphnia, and fish. The goal of this study was to elucidate the mode of action in algae and to evaluate the toxicity of the major human metabolites of fluoxetine using two different algae tests. The time dependence and sensitivity of thedifferenteffectendpointsyield information on the physiological mode of action. Baseline toxicity was predicted with QSARs based on measured liposome-water partition coefficients. The ratio of predicted baseline toxicity to experimental toxicity (toxic ratio TR) gives information on the intrinsic potency (extent of specificity of effect). The metabolite p-trifluoromethylphenol was classified to act as baseline toxicant Fluoxetine (TR 60-150) and its pharmacologically active metabolite norfluoxetine (TR 10-80) exhibited specific toxicity. By comparison with reference compounds we conclude that fluoxetine and norfluoxetine have an effect on the energy budget of algal cells since the time pattern of these two compounds is most similar to that observed for norflurazon, but they act less specifically as indicated by lower TR values and the similarity of the effect pattern to baseline toxicants. The mixture toxicity of fluoxetine and its human metabolites norfluoxetine and p-TFMP can be predicted using the model of concentration addition for practical purposes of risk assessment despite small deviations from this model for the specific endpoints like PSII inhibition because the integrative endpoints like growth rate and reproduction in all cases gave agreement with the predictions for concentration addition.

  18. Human and rodent aryl hydrocarbon receptor (AHR): from mediator of dioxin toxicity to physiologic AHR functions and therapeutic options.

    PubMed

    Bock, Karl Walter

    2017-04-01

    Metabolism of aryl hydrocarbons and toxicity of dioxins led to the discovery of the aryl hydrocarbon receptor (AHR). Tremendous advances have been made on multiplicity of AHR signaling and identification of endogenous ligands including the tryptophan metabolites FICZ and kynurenine. However, human AHR functions are still poorly understood due to marked species differences as well as cell-type- and cell context-dependent AHR functions. Observations in dioxin-poisoned individuals may provide hints to physiologic AHR functions in humans. Based on these observations three human AHR functions are discussed: (1) Chemical defence and homeostasis of endobiotics. The AHR variant Val381 in modern humans leads to reduced AHR affinity to aryl hydrocarbons in comparison with Neanderthals and primates expressing the Ala381 variant while affinity to indoles remains unimpaired. (2) Homeostasis of stem/progenitor cells. Dioxins dysregulate homeostasis in sebocyte stem cells. (3) Modulation of immunity. In addition to microbial defence, AHR may be involved in a 'disease tolerance defence pathway'. Further characterization of physiologic AHR functions may lead to therapeutic options.

  19. The physiology of blood loss and shock: New insights from a human laboratory model of hemorrhage.

    PubMed

    Schiller, Alicia M; Howard, Jeffrey T; Convertino, Victor A

    2017-04-01

    The ability to quickly diagnose hemorrhagic shock is critical for favorable patient outcomes. Therefore, it is important to understand the time course and involvement of the various physiological mechanisms that are active during volume loss and that have the ability to stave off hemodynamic collapse. This review provides new insights about the physiology that underlies blood loss and shock in humans through the development of a simulated model of hemorrhage using lower body negative pressure. In this review, we present controlled experimental results through utilization of the lower body negative pressure human hemorrhage model that provide novel insights on the integration of physiological mechanisms critical to the compensation for volume loss. We provide data obtained from more than 250 human experiments to classify human subjects into two distinct groups: those who have a high tolerance and can compensate well for reduced central blood volume (e.g. hemorrhage) and those with low tolerance with poor capacity to compensate.We include the conceptual introduction of arterial pressure and cerebral blood flow oscillations, reflex-mediated autonomic and neuroendocrine responses, and respiration that function to protect adequate tissue oxygenation through adjustments in cardiac output and peripheral vascular resistance. Finally, unique time course data are presented that describe mechanistic events associated with the rapid onset of hemodynamic failure (i.e. decompensatory shock). Impact Statement Hemorrhage is the leading cause of death in both civilian and military trauma. The work submitted in this review is important because it advances the understanding of mechanisms that contribute to the total integrated physiological compensations for inadequate tissue oxygenation (i.e. shock) that arise from hemorrhage. Unlike an animal model, we introduce the utilization of lower body negative pressure as a noninvasive model that allows for the study of progressive

  20. The lunar cycle: effects on human and animal behavior and physiology.

    PubMed

    Zimecki, Michał

    2006-01-01

    Human and animal physiology are subject to seasonal, lunar, and circadian rhythms. Although the seasonal and circadian rhythms have been fairly well described, little is known about the effects of the lunar cycle on the behavior and physiology of humans and animals. The lunar cycle has an impact on human reproduction, in particular fertility, menstruation, and birth rate. Melatonin levels appear to correlate with the menstrual cycle. Admittance to hospitals and emergency units because of various causes (cardiovascular and acute coronary events, variceal hemorrhage, diarrhea, urinary retention) correlated with moon phases. In addition, other events associated with human behavior, such as traffic accidents, crimes, and suicides, appeared to be influenced by the lunar cycle. However, a number of reports find no correlation between the lunar cycle and human reproduction and admittance to clinics and emergency units. Animal studies revealed that the lunar cycle may affect hormonal changes early in phylogenesis (insects). In fish the lunar clock influences reproduction and involves the hypothalamus-pituitary-gonadal axis. In birds, the daily variations in melatonin and corticosterone disappear during full-moon days. The lunar cycle also exerts effects on laboratory rats with regard to taste sensitivity and the ultrastructure of pineal gland cells. Cyclic variations related to the moon's phases in the magnitude of the humoral immune response of mice to polivinylpyrrolidone and sheep erythrocytes were also described. It is suggested that melatonin and endogenous steroids may mediate the described cyclic alterations of physiological processes. The release of neurohormones may be triggered by the electromagnetic radiation and/or the gravitational pull of the moon. Although the exact mechanism of the moon's influence on humans and animals awaits further exploration, knowledge of this kind of biorhythm may be helpful in police surveillance, medical practice, and investigations

  1. A physiologically-based model for simulation of color vision deficiency.

    PubMed

    Machado, Gustavo M; Oliveira, Manuel M; Fernandes, Leandro A F

    2009-01-01

    Color vision deficiency (CVD) affects approximately 200 million people worldwide, compromising the ability of these individuals to effectively perform color and visualization-related tasks. This has a significant impact on their private and professional lives. We present a physiologically-based model for simulating color vision. Our model is based on the stage theory of human color vision and is derived from data reported in electrophysiological studies. It is the first model to consistently handle normal color vision, anomalous trichromacy, and dichromacy in a unified way. We have validated the proposed model through an experimental evaluation involving groups of color vision deficient individuals and normal color vision ones. Our model can provide insights and feedback on how to improve visualization experiences for individuals with CVD. It also provides a framework for testing hypotheses about some aspects of the retinal photoreceptors in color vision deficient individuals.

  2. DNA hydrogel-based supercapacitors operating in physiological fluids

    PubMed Central

    Hur, Jaehyun; Im, Kyuhyun; Hwang, Sekyu; Choi, ByoungLyong; Kim, Sungjee; Hwang, Sungwoo; Park, Nokyoung; Kim, Kinam

    2013-01-01

    DNA nanostructures have been attractive due to their structural properties resulting in many important breakthroughs especially in controlled assemblies and many biological applications. Here, we report a unique energy storage device which is a supercapacitor that uses nanostructured DNA hydrogel (Dgel) as a template and layer-by-layer (LBL)-deposited polyelectrolyte multilayers (PEMs) as conductors. Our device, named as PEM-Dgel supercapacitor, showed excellent performance in direct contact with physiological fluids such as artificial urine and phosphate buffered saline without any need of additional electrolytes, and exhibited almost no cytotoxicity during cycling tests in cell culture medium. Moreover, we demonstrated that the PEM-Dgel supercapacitor has greater charge-discharge cycling stability in physiological fluids than highly concentrated acid electrolyte solution which is normally used for supercapacitor operation. These conceptually new supercapacitors have the potential to be a platform technology for the creation of implantable energy storage devices for packageless applications directly utilizing biofluids. PMID:23412432

  3. A Physiology-Based Model Describing Heterogeneity in Glucose Metabolism

    PubMed Central

    Maas, Anne H.; Rozendaal, Yvonne J. W.; van Pul, Carola; Hilbers, Peter A. J.; Cottaar, Ward J.; Haak, Harm R.; van Riel, Natal A. W.

    2014-01-01

    Background: Current diabetes education methods are costly, time-consuming, and do not actively engage the patient. Here, we describe the development and verification of the physiological model for healthy subjects that forms the basis of the Eindhoven Diabetes Education Simulator (E-DES). E-DES shall provide diabetes patients with an individualized virtual practice environment incorporating the main factors that influence glycemic control: food, exercise, and medication. Method: The physiological model consists of 4 compartments for which the inflow and outflow of glucose and insulin are calculated using 6 nonlinear coupled differential equations and 14 parameters. These parameters are estimated on 12 sets of oral glucose tolerance test (OGTT) data (226 healthy subjects) obtained from literature. The resulting parameter set is verified on 8 separate literature OGTT data sets (229 subjects). The model is considered verified if 95% of the glucose data points lie within an acceptance range of ±20% of the corresponding model value. Results: All glucose data points of the verification data sets lie within the predefined acceptance range. Physiological processes represented in the model include insulin resistance and β-cell function. Adjusting the corresponding parameters allows to describe heterogeneity in the data and shows the capabilities of this model for individualization. Conclusion: We have verified the physiological model of the E-DES for healthy subjects. Heterogeneity of the data has successfully been modeled by adjusting the 4 parameters describing insulin resistance and β-cell function. Our model will form the basis of a simulator providing individualized education on glucose control. PMID:25526760

  4. Engineering physiologically stiff and stratified human cartilage by fusing condensed mesenchymal stem cells

    PubMed Central

    Bhumiratana, Sarindr; Vunjak-Novakovic, Gordana

    2015-01-01

    For a long time, clinically sized and mechanically functional cartilage could be engineered from young animal chondrocytes, but not from adult human mesenchymal stem cells that are of primary clinical interest. The approaches developed for primary chondrocytes were not successful when used with human mesenchymal cells. The method discussed here was designed to employ a mechanism similar to pre-cartilaginous condensation and fusion of mesenchymal stem cells at a precisely defined time. The formation of cartilage was initiated by press-molding the mesenchymal bodies onto the surface of a bone substrate. By image-guided fabrication of the bone substrate and the molds, the osteochondral constructs were engineered in anatomically precise shapes and sizes. After 5 weeks of cultivation, the cartilage layer assumed physiologically stratified histomorphology, and contained lubricin at the surface, proteoglycans and type II collagen in the bulk phase, collagen type X at the interface with the bone substrate, and collagen type I within the bone phase. For the first time, the Young’s modulus and the friction coefficient of human cartilage engineered from mesenchymal stem cells reached physiological levels for adult human cartilage. We propose that this method can be effective for generating human osteochondral tissue constructs. PMID:25828645

  5. Engineering physiologically stiff and stratified human cartilage by fusing condensed mesenchymal stem cells.

    PubMed

    Bhumiratana, Sarindr; Vunjak-Novakovic, Gordana

    2015-08-01

    For a long time, clinically sized and mechanically functional cartilage could be engineered from young animal chondrocytes, but not from adult human mesenchymal stem cells that are of primary clinical interest. The approaches developed for primary chondrocytes were not successful when used with human mesenchymal cells. The method discussed here was designed to employ a mechanism similar to pre-cartilaginous condensation and fusion of mesenchymal stem cells at a precisely defined time. The formation of cartilage was initiated by press-molding the mesenchymal bodies onto the surface of a bone substrate. By image-guided fabrication of the bone substrate and the molds, the osteochondral constructs were engineered in anatomically precise shapes and sizes. After 5 weeks of cultivation, the cartilage layer assumed physiologically stratified histomorphology, and contained lubricin at the surface, proteoglycans and type II collagen in the bulk phase, collagen type X at the interface with the bone substrate, and collagen type I within the bone phase. For the first time, the Young's modulus and the friction coefficient of human cartilage engineered from mesenchymal stem cells reached physiological levels for adult human cartilage. We propose that this method can be effective for generating human osteochondral tissue constructs.

  6. Low physiological levels of prostaglandins E2 and F2α improve human sperm functions.

    PubMed

    Rios, Mariana; Carreño, Daniela V; Oses, Carolina; Barrera, Nelson; Kerr, Bredford; Villalón, Manuel

    2016-03-01

    Prostaglandins (PGs) have been reported to be present in the seminal fluid and cervical mucus, affecting different stages of sperm maturation from spermatogenesis to the acrosome reaction. This study assessed the effects of low physiological PGE2 and PGF2α concentrations on human sperm motility and on the ability of the spermatozoa to bind to the zona pellucida (ZP). Human spermatozoa were isolated from seminal samples with normal concentration and motility parameters and incubated with 1μM PGE2, 1μM PGF2α or control solution to determine sperm motility and the ability to bind to human ZP. The effects of both PGs on intracellular calcium levels were determined. Incubation for 2 or 18h with PGE2 or PGF2α resulted in a significant (P<0.05) increase in the percentage of spermatozoa with progressive motility. In contrast with PGF2α, PGE2 alone induced an increase in sperm intracellular calcium levels; however, the percentage of sperm bound to the human ZP was doubled for both PGs. These results indicate that incubation of human spermatozoa with low physiological levels of PGE2 or PGF2α increases sperm functions and could improve conditions for assisted reproduction protocols.

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

    SciTech Connect

    Takaku, Tomoyuki 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.

  8. Recreating the Cardiac Microenvironment in Pluripotent Stem Cell Models of Human Physiology and Disease.

    PubMed

    Atmanli, Ayhan; Domian, Ibrahim John

    2016-12-19

    The advent of human pluripotent stem cell (hPSC) biology has opened unprecedented opportunities for the use of tissue engineering to generate human cardiac tissue for in vitro study. Engineering cardiac constructs that recapitulate human development and disease requires faithful recreation of the cardiac niche in vitro. Here we discuss recent progress in translating the in vivo cardiac microenvironment into PSC models of the human heart. We review three key physiologic features required to recreate the cardiac niche and facilitate normal cardiac differentiation and maturation: the biochemical, biophysical, and bioelectrical signaling cues. Finally, we discuss key barriers that must be overcome to fulfill the promise of stem cell biology in preclinical applications and ultimately in clinical practice.

  9. A Problem-Based Learning Course in Physiology for Undergraduate and Graduate Basic Science Students.

    ERIC Educational Resources Information Center

    Mierson, Sheella

    1998-01-01

    Describes a two-semester, problem-based learning in organ-systems physiology course. Employs several types of problems including clinical, laboratory research-based, real-life scenarios, and published research articles. Contains 29 references. (DDR)

  10. Physiological time structure of the tibialis anterior motor activity during sleep in mice, rats and humans.

    PubMed

    Silvani, Alessandro; Lo Martire, Viviana; Salvadè, Agnese; Bastianini, Stefano; Ferri, Raffaele; Berteotti, Chiara; Baracchi, Francesca; Pace, Marta; Bassetti, Claudio L; Zoccoli, Giovanna; Manconi, Mauro

    2015-12-01

    The validation of rodent models for restless legs syndrome (Willis-Ekbom disease) and periodic limb movements during sleep requires knowledge of physiological limb motor activity during sleep in rodents. This study aimed to determine the physiological time structure of tibialis anterior activity during sleep in mice and rats, and compare it with that of healthy humans. Wild-type mice (n = 9) and rats (n = 8) were instrumented with electrodes for recording the electroencephalogram and electromyogram of neck muscles and both tibialis anterior muscles. Healthy human subjects (31 ± 1 years, n = 21) underwent overnight polysomnography. An algorithm for automatic scoring of tibialis anterior electromyogram events of mice and rats during non-rapid eye movement sleep was developed and validated. Visual scoring assisted by this algorithm had inter-rater sensitivity of 92-95% and false-positive rates of 13-19% in mice and rats. The distribution of the time intervals between consecutive tibialis anterior electromyogram events during non-rapid eye movement sleep had a single peak extending up to 10 s in mice, rats and human subjects. The tibialis anterior electromyogram events separated by intervals <10 s mainly occurred in series of two-three events, their occurrence rate in humans being lower than in mice and similar to that in rats. In conclusion, this study proposes reliable rules for scoring tibialis anterior electromyogram events during non-rapid eye movement sleep in mice and rats, demonstrating that their physiological time structure is similar to that of healthy young human subjects. These results strengthen the basis for translational rodent models of periodic limb movements during sleep and restless legs syndrome/Willis-Ekbom disease.

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

    PubMed

    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.

  12. Studying permethrin exposure in flight attendants using a physiologically based pharmacokinetic model.

    PubMed

    Wei, Binnian; Isukapalli, Sastry S; Weisel, Clifford P

    2013-07-01

    Assessment of potential health risks to flight attendants from exposure to pyrethroid insecticides, used for aircraft disinsection, is limited because of (a) lack of information on exposures to these insecticides, and (b) lack of tools for linking these exposures to biomarker data. We developed and evaluated a physiologically based pharmacokinetic (PBPK) model to assess the exposure of flight attendants to the pyrethroid insecticide permethrin attributable to aircraft disinsection. The permethrin PBPK model was developed by adapting previous models for pyrethroids, and was parameterized using currently available metabolic parameters for permethrin. The human permethrin model was first evaluated with data from published human studies. Then, it was used to estimate urinary metabolite concentrations of permethrin in flight attendants who worked in aircrafts, which underwent residual and pre-flight spray treatments. The human model was also applied to analyze the toxicokinetics following permethrin exposures attributable to other aircraft disinsection scenarios. Predicted levels of urinary 3-phenoxybenzoic acid (3-PBA), a metabolite of permethrin, following residual disinsection treatment were comparable to the measurements made for flight attendants. Simulations showed that the median contributions of the dermal, oral and inhalation routes to permethrin exposure in flight attendants were 83.5%, 16.1% and 0.4% under residual treatment scenario, respectively, and were 5.3%, 5.0% and 89.7% under pre-flight spray scenario, respectively. The PBPK model provides the capability to simulate the toxicokinetic profiles of permethrin, and can be used in the studies on human exposure to permethrin.

  13. Physiologically-based Pharmacokinetic Modeling of Target-Mediated Drug Disposition of Bortezomib in Mice

    PubMed Central

    Zhang, Li; Mager, Donald E.

    2015-01-01

    Bortezomib is a reversible proteasome inhibitor with potent antineoplastic activity that exhibits dose- and time-dependent pharmacokinetics (PK). Proteasome-mediated bortezomib disposition is proposed as the primary source of its nonlinear and apparent nonstationary PK behavior. Single intravenous (IV) doses of bortezomib (0.25 and 1 mg/kg) were administrated to BALB/c mice, with blood and tissue samples obtained over 144 hours, which were analyzed by LC/MS/MS. A physiologically based pharmacokinetic (PBPK) model incorporating tissue drug-target binding was developed to test the hypothesis of proteasome-mediated bortezomib disposition. The final model reasonably captured bortezomib plasma and tissue PK profiles, and parameters were estimated with good precision. The rank-order of model estimated tissue target density correlated well with experimentally measured proteasome concentrations reported in the literature, supporting the hypothesis that binding to proteasome influences bortezomib disposition. The PBPK model was further scaled-up to humans to assess the similarity of bortezomib disposition among species. Human plasma bortezomib PK profiles following multiple IV dosing (1.3 mg/m2) on days 1, 4, 8, and 11 were simulated by appropriately scaling estimated mouse parameters. Simulated and observed bortezomib concentrations after multiple dosing were in good agreement, suggesting target-mediated bortezomib disposition is likely for both mice and humans. Furthermore, the model predicts that renal impairment should exert minimal influence on bortezomib exposure in humans, confirming that bortezomib dose adjustment is not necessary for patients with renal impairment. PMID:26391023

  14. Physiologically-based pharmacokinetic modeling of target-mediated drug disposition of bortezomib in mice.

    PubMed

    Zhang, Li; Mager, Donald E

    2015-10-01

    Bortezomib is a reversible proteasome inhibitor with potent antineoplastic activity that exhibits dose- and time-dependent pharmacokinetics (PK). Proteasome-mediated bortezomib disposition is proposed as the primary source of its nonlinear and apparent nonstationary PK behavior. Single intravenous (IV) doses of bortezomib (0.25 and 1 mg/kg) were administrated to BALB/c mice, with blood and tissue samples obtained over 144 h, which were analyzed by LC/MS/MS. A physiologically based pharmacokinetic (PBPK) model incorporating tissue drug-target binding was developed to test the hypothesis of proteasome-mediated bortezomib disposition. The final model reasonably captured bortezomib plasma and tissue PK profiles, and parameters were estimated with good precision. The rank-order of model estimated tissue target density correlated well with experimentally measured proteasome concentrations reported in the literature, supporting the hypothesis that binding to proteasome influences bortezomib disposition. The PBPK model was further scaled-up to humans to assess the similarity of bortezomib disposition among species. Human plasma bortezomib PK profiles following multiple IV dosing (1.3 mg/m(2)) on days 1, 4, 8, and 11 were simulated by appropriately scaling estimated mouse parameters. Simulated and observed bortezomib concentrations after multiple dosing were in good agreement, suggesting target-mediated bortezomib disposition is likely for both mice and humans. Furthermore, the model predicts that renal impairment should exert minimal influence on bortezomib exposure in humans, confirming that bortezomib dose adjustment is not necessary for patients with renal impairment.

  15. Studying permethrin exposure in flight attendants using a physiologically based pharmacokinetic model

    PubMed Central

    Wei, Binnian; Isukapalli, Sastry S.; Weisel, Clifford P.

    2014-01-01

    Assessment of potential health risks to flight attendants from exposure to pyrethroid insecticides, used for aircraft disinsection, is limited because of (a) lack of information on exposures to these insecticides, and (b) lack of tools for linking these exposures to biomarker data. We developed and evaluated a physiologically based pharmacokinetic (PBPK) model to assess the exposure of flight attendants to the pyrethroid insecticide permethrin attributable to aircraft disinsection. The permethrin PBPK model was developed by adapting previous models for pyrethroids, and was parameterized using currently available metabolic parameters for permethrin. The human permethrin model was first evaluated with data from published human studies. Then, it was used to estimate urinary metabolite concentrations of permethrin in flight attendants who worked in aircrafts, which underwent residual and pre-flight spray treatments. The human model was also applied to analyze the toxicokinetics following permethrin exposures attributable to other aircraft disinsection scenarios. Predicted levels of urinary 3-phenoxybenzoic acid (3-PBA), a metabolite of permethrin, following residual disinsection treatment were comparable to the measurements made for flight attendants. Simulations showed that the median contributions of the dermal, oral and inhalation routes to permethrin exposure in flight attendants were 83.5%, 16.1% and 0.4% under residual treatment scenario, respectively, and were 5.3%, 5.0% and 89.7% under pre-flight spray scenario, respectively. The PBPK model provides the capability to simulate the toxicokinetic profiles of permethrin, and can be used in the studies on human exposure to permethrin. PMID:23462847

  16. A Mathematical Model of Human Semicircular Canal Geometry: A New Basis for Interpreting Vestibular Physiology

    PubMed Central

    Curthoys, Ian S.; Todd, Michael J.; Magnussen, John S.; Taubman, David S.; Aw, Swee T.; Halmagyi, G. Michael

    2009-01-01

    We report a precise, simple, and accessible method of mathematically measuring and modeling the three-dimensional (3D) geometry of semicircular canals (SCCs) in living humans. Knowledge of this geometry helps understand the development and physiology of SCC stimulation. We developed a framework of robust techniques that automatically and accurately reconstruct SCC geometry from computed tomography (CT) images and are directly validated using micro-CT as ground truth. This framework measures the 3D centroid paths of the bony SCCs allowing direct comparison and analysis between ears within and between subjects. An average set of SCC morphology is calculated from 34 human ears, within which other geometrical attributes such as nonplanarity, radius of curvature, and inter-SCC angle are examined, with a focus on physiological implications. These measurements have also been used to critically evaluate plane fitting techniques that reconcile many of the discrepancies in current SCC plane studies. Finally, we mathematically model SCC geometry using Fourier series equations. This work has the potential to reinterpret physiology and pathophysiology in terms of real individual 3D morphology. Electronic supplementary material The online version of this article (doi:10.1007/s10162-009-0195-6) contains supplementary material, which is available to authorized users. PMID:19949828

  17. Delineating the Impact of Weightlessness on Human Physiology Using Computational Models

    NASA Technical Reports Server (NTRS)

    Kassemi, Mohammad

    2015-01-01

    Microgravity environment has profound effects on several important human physiological systems. The impact of weightlessness is usually indirect as mediated by changes in the biological fluid flow and transport and alterations in the deformation and stress fields of the compliant tissues. In this context, Fluid-Structural and Fluid-Solid Interaction models provide a valuable tool in delineating the physical origins of the physiological changes so that systematic countermeasures can be devised to reduce their adverse effects. In this presentation, impact of gravity on three human physiological systems will be considered. The first case involves prediction of cardiac shape change and altered stress distributions in weightlessness. The second, presents a fluid-structural-interaction (FSI) analysis and assessment of the vestibular system and explores the reasons behind the unexpected microgravity caloric stimulation test results performed aboard the Skylab. The last case investigates renal stone development in microgravity and the possible impact of re-entry into partial gravity on the development and transport of nucleating, growing, and agglomerating renal calculi in the nephron. Finally, the need for model validation and verification and application of the FSI models to assess the effects of Artificial Gravity (AG) are also briefly discussed.

  18. Differences in fuel utilization between trout and human thrombocytes in physiological media.

    PubMed

    Guppy, M; Hill, D J; Arthur, P; Rowley, A F

    1999-10-01

    Cell culture preparations now play a significant and essential role in physiological and biochemical studies of cell biology. However, the fuels offered in cell culture media are only glucose and glutamine, plus whatever might be in the added sera. It is currently difficult to find a rational way forward on this problem, as there are few data on what fuels cells use in vivo or even in an in vitro physiological situation. A recent study on human platelets redressed the situation somewhat by finding that 75% of ATP turnover could be accounted for by aerobic glycolysis, and by the oxidation of glucose, hydroxybutyrate, acetate, glutamine, palmitate and oleate. In the present study we used a similar strategy to investigate fuel choices by trout thymocytes, cells with a similar function but from a different phylogenetic group. When these cells were presented with a physiological medium, we found that aerobic glycolysis accounted for 9% of total ATP turnover, glucose and glutamine oxidation made a combined contribution of 2.3%, oleate and palmitate oxidation accounted for 15%, and 74% was unaccounted for. These patterns of fuel use are very different from that in human platelets. They demonstrate the cell- and animal-specific nature of cellular metabolism and again expose the inadequacy of the fuel component in culture media.

  19. Apoptosis in pulp elimination during physiological root resorption in human primary teeth.

    PubMed

    Rodrigues, Luciana Villela; Vasconcelos, Anilton César; Campos, Pedro Alves; Brant, Juliana Massote Caldeira

    2009-01-01

    Pulp samples of 50 healthy human teeth with indication for extraction were examined to evaluate the role of apoptosis in pulp elimination during physiological root resorption. Two groups were formed: a test group (n=30) composed of pulp samples of primary teeth with physiological root resorption and a control group (n=20) composed of pulp samples of permanent maxillary third molars. Morphological evidence of apoptosis as well as in situ detection of cellular DNA fragmentation by TUNEL assay and detection of internucleosomal pattern of fragmentation of the genomic DNA by electrophoresis were observed. The apoptotic index of the primary tooth group was significantly higher than that of the permanent tooth group (51.01 +/- 0.52 versus 25.32 +/- 0.68) (p<0.001). TUNEL reaction showed intense and diffuse labeling in the pulp samples of primary teeth, which were discrete in the controls. Intense DNA internucleosomal fragmentation, a specific pattern for apoptosis, was observed in primary tooth pulps DNA by electrophoresis, in the permanent tooth pulps this pattern fragmentation of the genomic DNA for apoptosis were not present. These results seem to indicate a role of apoptosis in pulp elimination during the physiological root resorption of human primary teeth.

  20. Physiology-based gap model of forest dynamics

    SciTech Connect

    Friend, A.D.; Schugart, H.H.; Running, S.W.

    1993-01-01

    A computer model of forest growth and ecosystem processes is presented. The model, HYBRID, is derived from a forest gap model, an ecosystem process model, and a photosynthesis model. In HYBRID individual trees fix and respire carbon, and lose water daily; carbon partitioning occurs at the end of each year. HYBRID obviates many of the limitations of both gap models and ecosystem process models. The growth equations of gap models are replaced with functionally realistic equations and processes for carbon fixation and partitioning, resulting in a dynamic model in which competition and physiology play important roles.

  1. In search of physiologically based distribution volume estimates for macromolecules.

    PubMed

    Garzone, P D; Atkinson, A J

    2012-10-01

    In their semimechanistic analysis of trastuzumab emtansine (T-DM1) pharmacokinetics, Chudasama et al., as reported in this issue, modeled the process of T-DM1 deconjugation with a series of transit compartments representing plasma volume and a single peripheral compartment. The implausibility of the two-compartment distribution model used in this study as well as in other recent attempts to analyze the distribution kinetics of trastuzumab and other macromolecules reflects the fact that this modeling has been guided primarily by statistical rather than physiological considerations.

  2. Critical review evaluating the pig as a model for human nutritional physiology.

    PubMed

    Roura, Eugeni; Koopmans, Sietse-Jan; Lallès, Jean-Paul; Le Huerou-Luron, Isabelle; de Jager, Nadia; Schuurman, Teun; Val-Laillet, David

    2016-06-01

    The present review examines the pig as a model for physiological studies in human subjects related to nutrient sensing, appetite regulation, gut barrier function, intestinal microbiota and nutritional neuroscience. The nutrient-sensing mechanisms regarding acids (sour), carbohydrates (sweet), glutamic acid (umami) and fatty acids are conserved between humans and pigs. In contrast, pigs show limited perception of high-intensity sweeteners and NaCl and sense a wider array of amino acids than humans. Differences on bitter taste may reflect the adaptation to ecosystems. In relation to appetite regulation, plasma concentrations of cholecystokinin and glucagon-like peptide-1 are similar in pigs and humans, while peptide YY in pigs is ten to twenty times higher and ghrelin two to five times lower than in humans. Pigs are an excellent model for human studies for vagal nerve function related to the hormonal regulation of food intake. Similarly, the study of gut barrier functions reveals conserved defence mechanisms between the two species particularly in functional permeability. However, human data are scant for some of the defence systems and nutritional programming. The pig model has been valuable for studying the changes in human microbiota following nutritional interventions. In particular, the use of human flora-associated pigs is a useful model for infants, but the long-term stability of the implanted human microbiota in pigs remains to be investigated. The similarity of the pig and human brain anatomy and development is paradigmatic. Brain explorations and therapies described in pig, when compared with available human data, highlight their value in nutritional neuroscience, particularly regarding functional neuroimaging techniques.

  3. Sirtuins: a family of proteins with implications for human performance and exercise physiology.

    PubMed

    Lappalainen, Zekine

    2011-01-01

    The sirtuin family of proteins consists of seven members in mammals (SirT1-T7). Sirtuins share NAD dependency for their enzymatic activity, but some show NAD-dependent deacetylase activity, others exhibit ADP ribosyltransferase activity or both. Sirtuins have gained considerable attention due to their impact as physiological targets for treating diseases associated with aging. Sirtuins interact with metabolic pathways and may serve as entry points for drugs. This review discusses the biology of sirtuins and their potential as mediators of caloric restriction and pharmacological targets. Reduced insulin sensitivity, mitochondrial dysfunction, and others are consequences of aging or secondary to physical inactivity. Moreover, understanding human energy metabolism through sirtuins may provide a novel approach to exercise physiology. Quercetin, a natural polyphenolic flavonoid that has been widely investigated for its other health benefits, may act as an inducer of SirT1. The benefits of quercetin for exercise performance may have implications for athletes and extended to disease prevention.

  4. Measurements, modeling, control and simulation - as applied to the human left ventricle for purposeful physiological monitoring.

    NASA Technical Reports Server (NTRS)

    Ghista, D. N.; Rasmussen, D. N.; Linebarger, R. N.; Sandler, H.

    1971-01-01

    Interdisciplinary engineering research effort in studying the intact human left ventricle has been employed to physiologically monitor the heart and to obtain its 'state-of-health' characteristics. The left ventricle was selected for this purpose because it plays a key role in supplying energy to the body cells. The techniques for measurement of the left ventricular geometry are described; the geometry is effectively displayed to bring out the abnormalities in cardiac function. Methods of mathematical modeling, which make it possible to determine the performance of the intact left ventricular muscle, are also described. Finally, features of a control system for the left ventricle for predicting the effect of certain physiological stress situations on the ventricle performance are discussed.

  5. Role of the liver X receptors in skin physiology: Putative pharmacological targets in human diseases.

    PubMed

    Ouedraogo, Zangbéwendé Guy; Fouache, Allan; Trousson, Amalia; Baron, Silvère; Lobaccaro, Jean-Marc A

    2017-03-01

    Liver X receptors (LXRs) are members of the nuclear receptor superfamily that have been shown to regulate various physiological functions such as lipid metabolism and cholesterol homeostasis. Concordant reports have elicited the possibility to target them to cure many human diseases including arteriosclerosis, cancer, arthritis, and diabetes. The high relevance of modulating LXR activities to treat numerous skin diseases, mainly those with exacerbated inflammation processes, contrasts with the lack of approved therapeutic use. This review makes an assessment to sum up the findings regarding the physiological roles of LXRs in skin and help progress towards the therapeutic and safe management of their activities. It focuses on the possible pharmacological targeting of LXRs to cure or prevent selected skin diseases.

  6. Cortisol as a Biomarker of Stress in Term Human Labor: Physiological and Methodological Issues

    PubMed Central

    Newton, Edward R.; Tanner, Charles J.; Heitkemper, Margaret M.

    2013-01-01

    Literature on the use of plasma cortisol to quantify psychophysiological stress in humans is extensive. However, in parturition at term gestation the use of cortisol as a biomarker of stress is particularly complex. Plasma cortisol levels increase as labor progresses. This increase seems to be important for maintenance of maternal/fetal wellbeing and facilitation of normal labor progress. Unique physiological and methodological issues involved in the use of cortisol as a biomarker of stress in labor present challenges for researchers. This review examines these issues, suggests mixed methods and within-subject repeated measures designs, and offers recommendations for assay procedures for parturient sampling. Documentation of clinical interventions and delivery outcomes may elucidate relationships among psychophysiological stressors, cortisol and normal labor progress. With attention to these methodological issues, analysis of plasma cortisol may lead to clinical interventions that support normal labor physiology. PMID:23338011

  7. The apelinergic system: the role played in human physiology and pathology and potential therapeutic applications.

    PubMed

    Ladeiras-Lopes, Ricardo; Ferreira-Martins, João; Leite-Moreira, Adelino F

    2008-05-01

    Apelin is a recently discovered peptide, identified as an endogenous ligand of receptor APJ. Apelin and receptor APJ are expressed in a wide variety of tissues including heart, brain, kidneys and lungs. Their interaction may have relevant pathophysiologic effects in those tissues. In fact, the last decade has been rich in illustrating the possible roles played by apelin in human physiology, namely as a regulating peptide of cardiovascular, hypothalamus-hypophysis, gastrointestinal, and immune systems. The possible involvement of apelin in the pathogenesis of high prevalence conditions and comorbidities - such as hypertension, heart failure, and Diabetes Mellitus Type 2 (T2DM) - rank it as a likely therapeutic target to be investigated in the future. The present paper is an overview of apelin physiologic effects and presents the possible role played by this peptide in the pathogenesis of a number of conditions as well as the therapeutic implications that might, therefore, be investigated.

  8. Cortisol as a biomarker of stress in term human labor: physiological and methodological issues.

    PubMed

    Benfield, Rebecca D; Newton, Edward R; Tanner, Charles J; Heitkemper, Margaret M

    2014-01-01

    Literature on the use of plasma cortisol to quantify psychophysiological stress in humans is extensive. However, in parturition at term gestation, the use of cortisol as a biomarker of stress is particularly complex. Plasma cortisol levels increase as labor progresses. This increase seems to be important for maintenance of maternal/fetal well-being and facilitation of normal labor progress. Unique physiological and methodological issues involved in the use of cortisol as a biomarker of stress in labor present challenges for researchers. This review examines these issues, suggests mixed methods and within-subject repeated measures designs, and offers recommendations for assay procedures for parturient sampling. Documentation of clinical interventions and delivery outcomes may elucidate relationships among psychophysiological stressors, cortisol, and normal labor progress. With attention to these methodological issues, analysis of plasma cortisol may lead to clinical interventions that support normal labor physiology.

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

    PubMed

    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

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

    PubMed Central

    Levitt, David G

    2009-01-01

    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 . 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_Java, along with the included tutorial

  11. Simulation of differential drug pharmacokinetics under heat and exercise stress using a physiologically based pharmacokinetic modeling approach.

    PubMed

    Sidhu, Pardeep; Peng, Henry T; Cheung, Bob; Edginton, Andrea

    2011-05-01

    Under extreme conditions of heat exposure and exercise stress, the human body undergoes major physiological changes. Perturbations in organ blood flows, gastrointestinal properties, and vascular physiology may impact the body's ability to absorb, distribute, and eliminate drugs. Clinical studies on the effect of these stressors on drug pharmacokinetics demonstrate that the likelihood of pharmacokinetic alteration is dependent on drug properties and the intensity of the stressor. The objectives of this study were to use literature data to quantify the correlation between exercise and heat exposure intensity to changing physiological parameters and further, to use this information for the parameterization of a whole-body, physiologically based pharmacokinetic model for the purposes of determining those drug properties most likely to demonstrate altered drug pharmacokinetics under stress. Cardiac output and most organ blood flows were correlated with heart rate using regression analysis. Other altered parameters included hematocrit and intravascular albumin concentration. Pharmacokinetic simulations of intravenous and oral administration of hypothetical drugs with either a low or high value of lipophilicity, unbound fraction in plasma, and unbound intrinsic hepatic clearance demonstrated that the area under the curve of those drugs with a high unbound intrinsic clearance was most affected (up to a 130% increase) following intravenous administration, whereas following oral administration, pharmacokinetic changes were smaller (<40% increase in area under the curve) for all hypothetical compounds. A midazolam physiologically based pharmacokinetic model was also used to demonstrate that simulated changes in pharmacokinetic parameters under exercise and heat stress were generally consistent with those reported in the literature.

  12. Central respiratory chemosensitivity and cerebrovascular CO2 reactivity: a rebreathing demonstration illustrating integrative