[Critical analysis of reference studies on aluminium-based adjuvants toxicokinetics].

Science.gov (United States)

Masson, J-D; Crépeaux, G; Authier, F-J; Exley, C; Gherardi, R K

2017-07-01

We reviewed the three reference toxicokinetic studies commonly used to suggest innocuity of aluminum (Al)-based adjuvants. A single experimental study was carried out using isotopic 26 Al (Flarend et al., 1997). This study ignored adjuvant cell capture. It was conducted over a short period of time (28 days) and used only two rabbits per adjuvant. At the endpoint, Al retention was 78% for aluminum phosphate and 94% for aluminum hydroxide, both results being incompatible with quick elimination of vaccine-derived Al in urines. Tissue distribution analysis omitted three important retention sites: the injected muscle, the draining lymph node and bone. Two theoretical studies have evaluated the potential risk of vaccine Al in infants, by reference to the oral Minimal Risk Level (MRL) extrapolated from animal studies. Keith et al., 2002 used a too high MRL (2mg/kg/d), an erroneous model of 100% immediate absorption of vaccine Al, and did not consider renal and blood-brain barrier immaturity. Mitkus et al. (2011) only considered absorbed Al, with erroneous calculations of absorption duration. They ignored particulate Al captured by immune cells, which play a role in systemic diffusion and the neuro-inflammatory potential of the adjuvant. MRL they used was both inappropriate (oral Al vs injected adjuvant) and far too high (1mg/kg/d) with regard to experimental studies of Al-induced memory and behavioral changes. Both paucity and serious weaknesses of these studies strongly suggest that novel experimental studies of Al adjuvants toxicokinetics should be performed on the long-term, including post-natal and adult exposures, to ensure innocuity and restore population confidence in Al-containing vaccines. Copyright © 2017 Académie Nationale de Pharmacie. All rights reserved.

Toxicokinetics of the pyrethroid insecticide bifenthrin in blood and brain of the rat

Science.gov (United States)

Bifenthrin is a pyrethroid insecticide and human exposure to it can occur by oral, pulmonary and dermal routes. Pyrethroids are neurotoxic agents and it is generally believed that the parent pyrethroid is the toxic entity. The objective of this study was to assess the toxicokinet...

Toxicokinetics of PFOS in rainbow trout

Data.gov (United States)

U.S. Environmental Protection Agency — This ScienceHub entry was developed for the published paper: Consoer et al., 2016, Toxicokinetics of perfluorooctane sulfonate in rainow trout (Oncorhynchus mykiss),...

Intravenous and inhalation toxicokinetics of sarin stereoisomers in atropinized guinea pigs

NARCIS (Netherlands)

Spruit, W.E.T.; Langenberg, J.P.; Trap, H.C.; Wiel, H.J. van der; Helmich, R.B.; Helden, H.P.M. van; Benschop, H.P.

2000-01-01

We report the first toxicokinetic studies of (±)-sarin. The toxicokinetics of the stereoisomers of this nerve agent were studied in anesthetized, atropinized, and restrained guinea pigs after intravenous bolus administration of a dose corresponding to 0.8 LD50 and after nose-only exposure to vapor

In Silico Prediction of Toxicokinetic Parameters for Environmentally Relevant Chemicals for Risk-Based Prioritization

Science.gov (United States)

Toxicokinetic (TK) models can address an important component of chemical risk assessments by helping bridge the gap between chemical exposure and measured toxicity endpoints. The metabolic clearance rate (CLint) and fraction of a chemical unbound by plasma proteins (Fub) are crit...

Advances in In Vitro and In Silico Tools for Toxicokinetic Dose ...

Science.gov (United States)

Recent advances in vitro assays, in silico tools, and systems biology approaches provide opportunities for refined mechanistic understanding for chemical safety assessment that will ultimately lead to reduced reliance on animal-based methods. With the U.S. commercial chemical landscape encompassing thousands of chemicals with limited data, safety assessment strategies that reliably predict in vivo systemic exposures and subsequent in vivo effects efficiently are a priority. Quantitative in vitro-in vivo extrapolation (QIVIVE) is a methodology that facilitates the explicit and quantitative application of in vitro experimental data and in silico modeling to predict in vivo system behaviors and can be applied to predict chemical toxicokinetics, toxicodynamics and also population variability. Tiered strategies that incorporate sufficient information to reliably inform the relevant decision context will facilitate acceptance of these alternative data streams for safety assessments. This abstract does not necessarily reflect U.S. EPA policy. This talk will provide an update to an international audience on the state of science being conducted within the EPA’s Office of Research and Development to develop and refine approaches that estimate internal chemical concentrations following a given exposure, known as toxicokinetics. Toxicokinetic approaches hold great potential in their ability to link in vitro activities or toxicities identified during high-throughput screen

Interpreting in vitro developmental toxicity test battery results: The consideration of toxicokinetics

NARCIS (Netherlands)

Bosgra, S.; Westerhout, J.

2015-01-01

In the EU collaborative project ChemScreen an alternative, in vitro assay-based test strategy was developed to screen compounds for reproductive toxicity. A toxicokinetic modeling approach was used to allow quantitative comparison between effective concentrations in the in vitro test battery and

Extrapolation of plasma clearance to understand species differences in toxicokinetics of bisphenol A.

Science.gov (United States)

Poet, Torka; Hays, Sean

2017-10-13

1. Understanding species differences in the toxicokinetics of bisphenol A (BPA) is central to setting acceptable exposure limits for human exposures to BPA. BPA toxicokinetics have been well studied, with controlled oral dosing studies in several species and across a wide dose range. 2. We analyzed the available toxicokinetic data for BPA following oral dosing to assess potential species differences and dose dependencies. BPA is rapidly conjugated and detoxified in all species. The toxicokinetics of BPA can be well described using non-compartmental analyses. 3. Several studies measured free (unconjugated) BPA in blood and reported area under the curve (AUC) of free BPA in blood of mice, rats, monkeys, chimpanzees and humans following controlled oral doses. Extrinsic clearance was calculated and analyzed across species and dose using allometric scaling. 4. The results indicate free BPA clearance is well described using allometric scaling with high correlation coefficients across all species and doses up to 10 mg/kg. The results indicate a human equivalent dose factor (HEDf) of 0.9 is appropriate for extrapolating a point of departure from mice and rats to a human equivalent dose (HED), thereby replacing default uncertainty factors for animal to human toxicokinetics.

“httk”: EPA’s Tool for High Throughput Toxicokinetics (CompTox CoP)

Science.gov (United States)

Thousands of chemicals have been pro?led by high-throughput screening programs such as ToxCast and Tox21; these chemicals are tested in part because most of them have limited or no data on hazard, exposure, or toxicokinetics. Toxicokinetic models aid in predicting tissue concentr...

In Silico Prediction of Toxicokinetic Parameters for Environmentally Relevant Chemicals with Application to Risk-Based Prioritization

Science.gov (United States)

Toxicokinetic (TK) models can help bridge the gap between chemical exposure and measured toxicity endpoints, thereby addressing an important component of chemical risk assessments. The fraction of a chemical unbound by plasma proteins (Fub) and metabolic clearance rate (CLint) ar...

HTTK R Package v1.4 - JSS Article on HTTK: R Package for High-Throughput Toxicokinetics

Data.gov (United States)

U.S. Environmental Protection Agency — httk: High-Throughput Toxicokinetics Functions and data tables for simulation and statistical analysis of chemical toxicokinetics ("TK") using data obtained from...

HTTK R Package v1.5 - Identifying populations sensitive to environmental chemicals by simulating toxicokinetic variability

Data.gov (United States)

U.S. Environmental Protection Agency — httk: High-Throughput Toxicokinetics Functions and data tables for simulation and statistical analysis of chemical toxicokinetics ("TK") using data obtained from...

Identifying populations sensitive to environmental chemicals by simulating toxicokinetic variability.

Science.gov (United States)

Ring, Caroline L; Pearce, Robert G; Setzer, R Woodrow; Wetmore, Barbara A; Wambaugh, John F

2017-09-01

The thousands of chemicals present in the environment (USGAO, 2013) must be triaged to identify priority chemicals for human health risk research. Most chemicals have little of the toxicokinetic (TK) data that are necessary for relating exposures to tissue concentrations that are believed to be toxic. Ongoing efforts have collected limited, in vitro TK data for a few hundred chemicals. These data have been combined with biomonitoring data to estimate an approximate margin between potential hazard and exposure. The most "at risk" 95th percentile of adults have been identified from simulated populations that are generated either using standard "average" adult human parameters or very specific cohorts such as Northern Europeans. To better reflect the modern U.S. population, we developed a population simulation using physiologies based on distributions of demographic and anthropometric quantities from the most recent U.S. Centers for Disease Control and Prevention National Health and Nutrition Examination Survey (NHANES) data. This allowed incorporation of inter-individual variability, including variability across relevant demographic subgroups. Variability was analyzed with a Monte Carlo approach that accounted for the correlation structure in physiological parameters. To identify portions of the U.S. population that are more at risk for specific chemicals, physiologic variability was incorporated within an open-source high-throughput (HT) TK modeling framework. We prioritized 50 chemicals based on estimates of both potential hazard and exposure. Potential hazard was estimated from in vitro HT screening assays (i.e., the Tox21 and ToxCast programs). Bioactive in vitro concentrations were extrapolated to doses that produce equivalent concentrations in body tissues using a reverse dosimetry approach in which generic TK models are parameterized with: 1) chemical-specific parameters derived from in vitro measurements and predicted from chemical structure; and 2) with

Fusariotoxins in Avian Species: Toxicokinetics, Metabolism and Persistence in Tissues

Directory of Open Access Journals (Sweden)

Philippe Guerre

2015-06-01

Full Text Available Fusariotoxins are mycotoxins produced by different species of the genus Fusarium whose occurrence and toxicity vary considerably. Despite the fact avian species are highly exposed to fusariotoxins, the avian species are considered as resistant to their toxic effects, partly because of low absorption and rapid elimination, thereby reducing the risk of persistence of residues in tissues destined for human consumption. This review focuses on the main fusariotoxins deoxynivalenol, T-2 and HT-2 toxins, zearalenone and fumonisin B1 and B2. The key parameters used in the toxicokinetic studies are presented along with the factors responsible for their variations. Then, each toxin is analyzed separately. Results of studies conducted with radiolabelled toxins are compared with the more recent data obtained with HPLC/MS-MS detection. The metabolic pathways of deoxynivalenol, T-2 toxin, and zearalenone are described, with attention paid to the differences among the avian species. Although no metabolite of fumonisins has been reported in avian species, some differences in toxicokinetics have been observed. All the data reviewed suggest that the toxicokinetics of fusariotoxins in avian species differs from those in mammals, and that variations among the avian species themselves should be assessed.

An evaluation of in vivo models for toxicokinetics of hexavalent chromium in the stomach

Energy Technology Data Exchange (ETDEWEB)

Sasso, A.F., E-mail: sasso.alan@epa.gov; Schlosser, P.M., E-mail: schlosser.paul@epa.gov

2015-09-15

Hexavalent chromium (Cr6) is a drinking water contaminant that has been detected in most of the water systems throughout the United States. In 2-year drinking water bioassays, the National Toxicology Program (NTP) found clear evidence of carcinogenic activity in male and female rats and mice. Because reduction of Cr6 to trivalent chromium (Cr3) is an important detoxifying step in the gastrointestinal (GI) tract prior to systemic absorption, models have been developed to estimate the extent of reduction in humans and animals. The objective of this work was to use a revised model of ex vivo Cr6 reduction kinetics in gastric juice to analyze the potential reduction kinetics under in vivo conditions for mice, rats and humans. A published physiologically-based pharmacokinetic (PBPK) model was adapted to incorporate the new reduction model. This paper focuses on the toxicokinetics of Cr6 in the stomach compartment, where most of the extracellular Cr6 reduction is believed to occur in humans. Within the range of doses administered by the NTP bioassays, neither the original nor revised models predict saturation of stomach reducing capacity to occur in vivo if applying default parameters. However, both models still indicate that mice exhibit the lowest extent of reduction in the stomach, meaning that a higher percentage of the Cr6 dose may escape stomach reduction in that species. Similarly, both models predict that humans exhibit the highest extent of reduction at low doses. - Highlights: • We outline a new in vivo model for hexavalent chromium reduction in the stomach. • We examine in vivo reduction for mice, rats, and humans under varying conditions. • Species differences in toxicokinetics may explain susceptibility. • We show that a simplified stomach reduction model is adequate for extrapolation. • Internal dose uncertainties still exist.

Toxicity and toxicokinetics of binary combinations of petroleum hydrocarbon distillates with the earthworm Eisenia andrei.

Science.gov (United States)

Cermak, Janet; Stephenson, Gladys; Birkholz, Detlef; Dixon, D George

2013-04-01

Petroleum hydrocarbons (PHCs) act via narcosis and are expected to have additive toxicity. However, previous work has demonstrated less-than-additive toxicity with PHC distillates and earthworms. A study was initiated to investigate this through toxicity and toxicokinetic studies with the earthworm Eisenia andrei. Three petroleum distillate fractions, F2 (>C10-C16), F3a (>C16-C23), and F3b (>C23-C34), were used in two binary combinations, F2F3a and F3aF3b. In the toxicity study, clean soil was spiked with equitoxic combinations of the two distillates ranging from 0.5 to 2.5 toxic units. In the toxicokinetic study, a binary combination consisting of one concentration of each distillate was used. On a soil concentration basis, the toxicity of the binary combinations of distillates was less than additive. Accumulation of the individual distillates, however, was generally reduced when a second distillate was present, resulting in lower body burden. This is thought to be due to the presence of a nonaqueous-phase liquid at the soil concentrations used. On a tissue concentration basis, toxicity was closer to additive. The results demonstrate that tissue concentrations are the preferred metric for toxicity for earthworms. They also demonstrate that the Canada-wide soil standards based on individual distillates are likely protective. Copyright © 2013 SETAC.

Mercury toxicokinetics-dependency on strain and gender

International Nuclear Information System (INIS)

Ekstrand, Jimmy; Nielsen, Jesper B.; Havarinasab, Said; Zalups, Rudolfs K.; Soederkvist, Peter; Hultman, Per

2010-01-01

Mercury (Hg) exposure from dental amalgam fillings and thimerosal in vaccines is not a major health hazard, but adverse health effects cannot be ruled out in a small and more susceptible part of the exposed population. Individual differences in toxicokinetics may explain susceptibility to mercury. Inbred, H-2-congenic A.SW and B10.S mice and their F1- and F2-hybrids were given HgCl 2 with 2.0 mg Hg/L drinking water and traces of 203 Hg. Whole-body retention (WBR) was monitored until steady state after 5 weeks, when the organ Hg content was assessed. Despite similar Hg intake, A.SW males attained a 20-30% significantly higher WBR and 2- to 5-fold higher total renal Hg retention/concentration than A.SW females and B10.S mice. A selective renal Hg accumulation but of lower magnitude was seen also in B10.S males compared with females. Differences in WBR and organ Hg accumulation are therefore regulated by non-H-2 genes and gender. Lymph nodes lacked the strain- and gender-dependent Hg accumulation profile of kidney, liver and spleen. After 15 days without Hg A.SW mice showed a 4-fold higher WBR and liver Hg concentration, but 11-fold higher renal Hg concentration, showing the key role for the kidneys in explaining the slower Hg elimination in A.SW mice. The trait causing higher mercury accumulation was not dominantly inherited in the F1 hybrids. F2 mice showed a large inter-individual variation in Hg accumulation, showing that multiple genetic factors influence the Hg toxicokinetics in the mouse. The genetically heterogeneous human population may therefore show a large variation in mercury toxicokinetics.

Fun with High Throughput Toxicokinetics (CalEPA webinar)

Science.gov (United States)

Thousands of chemicals have been profiled by high-throughput screening (HTS) programs such as ToxCast and Tox21. These chemicals are tested in part because there are limited or no data on hazard, exposure, or toxicokinetics (TK). TK models aid in predicting tissue concentrations ...

Sex differences in the toxicokinetics of inhaled solvent vapors in humans 2. 2-propanol

International Nuclear Information System (INIS)

Ernstgaard, Lena; Sjoegren, Bengt; Warholm, Margareta; Johanson, Gunnar

2003-01-01

The aim of this study was to evaluate possible sex differences in the inhalation toxicokinetics of 2-propanol vapor. Nine women and eight men were exposed on different occasions for 2 h during light physical exercise (50 W) to 2-propanol (350 mg/m 3 ) and to clean air (control exposure). The level corresponds to the Swedish occupational exposure limit. 2-Propanol and its metabolite acetone were monitored up to 24 h after exposure in exhaled air, blood, saliva, and urine by headspace gas chromatography. Body fat and lean body mass were estimated from sex-specific equations using bioelectrical impedance, body weight, height, and age. Genotypes were determined by PCR-based assays for alcohol dehydrogenase and cytochrome P450 2E1 (CYP2E1). The CYP2E1 phenotype was assessed by the 2-h plasma 6-hydroxychlorzoxazone/chlorzoxazone metabolic ratio in vivo. The toxicokinetic profile in blood was analyzed using a one-compartment population model. The following sex differences were significant at the p 0.05 level (Student's t test). The respiratory uptake was lower and the volume of distribution smaller in females. The women had a slightly shorter half-time of 2-propanol in blood and a higher apparent total clearance when corrected for body composition. However, women reached approximately four times higher 2-propanol levels in exhaled air at 10-min postexposure and onward. Acetone in blood was markedly higher in females than in males in the control experiment and slightly higher following exposure to 2-propanol. A marked sex difference was that of a 10-fold higher in vivo blood:breath ratio in men, suggesting sex differences in the lung metabolism of 2-propanol. The most marked sex difference was that of salivary acetone, for which an approximately 100-fold increase was seen in women, but no increase in men, after exposure to 2-propanol compared to clean air. The toxicokinetic analysis revealed no significant differences in toxicokinetics between subjects of different

Simple estimate of the influence of competitive inhibition on PBTK based risk assessment

DEFF Research Database (Denmark)

Reffstrup, Trine Klein; Petersen, Annette; Nielsen, Elsa

2014-01-01

Background: In recent years, increased focus has been on the development of methods for assessing health risks caused by exposure to mixtures of chemicals from food and the environment. It has been recommended by international bodies to consider physiologically based toxicokinetic (PBTK) modellin...

TK Modeler version 1.0, a Microsoft® Excel®-based modeling software for the prediction of diurnal blood/plasma concentration for toxicokinetic use.

Science.gov (United States)

McCoy, Alene T; Bartels, Michael J; Rick, David L; Saghir, Shakil A

2012-07-01

TK Modeler 1.0 is a Microsoft® Excel®-based pharmacokinetic (PK) modeling program created to aid in the design of toxicokinetic (TK) studies. TK Modeler 1.0 predicts the diurnal blood/plasma concentrations of a test material after single, multiple bolus or dietary dosing using known PK information. Fluctuations in blood/plasma concentrations based on test material kinetics are calculated using one- or two-compartment PK model equations and the principle of superposition. This information can be utilized for the determination of appropriate dosing regimens based on reaching a specific desired C(max), maintaining steady-state blood/plasma concentrations, or other exposure target. This program can also aid in the selection of sampling times for accurate calculation of AUC(24h) (diurnal area under the blood concentration time curve) using sparse-sampling methodologies (one, two or three samples). This paper describes the construction, use and validation of TK Modeler. TK Modeler accurately predicted blood/plasma concentrations of test materials and provided optimal sampling times for the calculation of AUC(24h) with improved accuracy using sparse-sampling methods. TK Modeler is therefore a validated, unique and simple modeling program that can aid in the design of toxicokinetic studies. Copyright © 2012 Elsevier Inc. All rights reserved.

Investigation of the toxicokinetics of petroleum hydrocarbon distillates with the earthworm Eisenia andrei.

Science.gov (United States)

Cermak, Janet; Stephenson, Gladys; Birkholz, Detlef; Dixon, D George

2013-04-01

The Canada-wide standards for petroleum hydrocarbons in soils regulate petroleum hydrocarbons based on four distillate ranges: F1 (C6-C10), F2 (>C10-C16), F3 (>C16-C34), and F4 (>C34). Previous toxicity tests with earthworms and F2, as well as two subfractions of F3, F3a (>C16-C23) and F3a (>C23-C34), indicate that test durations might not be sufficiently long to reach threshold effect concentrations, likely because of the differing toxicokinetics for each distillate. A study was conducted to determine the toxicokinetics of both aliphatic and aromatic fractions of F2, F3a, and F3b with the earthworm Eisenia andrei. Peak accumulation curves were observed for F2 aliphatics and aromatics and F3a aromatics, likely as a result of changes in exposure concentration over the test duration via loss or a decrease in the bioavailable fraction. Biota-soil accumulation factors were >1 for total F2 aliphatics and aromatics and F3a aromatics as well as for several individual polyaromatic hydrocarbons for each distillate. Aromatics were disproportionately accumulated over aliphatics and were the main contributors to toxicity; therefore, aromatics and aliphatics should be regulated separately. The toxicokinetics were used to interpret previous toxicity data. Higher molecular weight distillates need longer-than-standard test durations to determine toxicity, so toxicity test results from fixed, standard-duration tests are not strictly comparable for these petroleum distillates. Copyright © 2013 SETAC.

Risk assessment of titanium dioxide nanoparticles via oral exposure, including toxicokinetic considerations.

Science.gov (United States)

Heringa, Minne B; Geraets, Liesbeth; van Eijkeren, Jan C H; Vandebriel, Rob J; de Jong, Wim H; Oomen, Agnes G

2016-12-01

Titanium dioxide white pigment consists of particles of various sizes, from which a fraction is in the nano range (food as additive E 171 as well as in other products, such as food supplements and toothpaste. Here, we assessed whether a human health risk can be expected from oral ingestion of these titanium dioxide nanoparticles (TiO 2 NPs), based on currently available information. Human health risks were assessed using two different approaches: Approach 1, based on intake, i.e. external doses, and Approach 2, based on internal organ concentrations using a kinetic model in order to account for accumulation over time (the preferred approach). Results showed that with Approach 1, a human health risk is not expected for effects in liver and spleen, but a human health risk cannot be excluded for effects on the ovaries. When based on organ concentrations by including the toxicokinetics of TiO 2 NPs (Approach 2), a potential risk for liver, ovaries and testes is found. This difference between the two approaches shows the importance of including toxicokinetic information. The currently estimated risk can be influenced by factors such as absorption, form of TiO 2 , particle fraction, particle size and physico-chemical properties in relation to toxicity, among others. Analysis of actual particle concentrations in human organs, as well as organ concentrations and effects in liver and the reproductive system after chronic exposure to well-characterized TiO 2 (NPs) in animals are recommended to refine this assessment.

Toxicity-based toxicokinetic/toxicodynamic assessment of bioaccumulation and nanotoxicity of zerovalent iron nanoparticles in Caenorhabditis elegans

Directory of Open Access Journals (Sweden)

Yang YF

2017-06-01

Full Text Available Ying-Fei Yang, Yi-Jun Lin, Chung-Min Liao Department of Bioenvironmental Systems Engineering, College of Bioresources and Agriculture, National Taiwan University, Taipei, Taiwan Abstract: Elucidating the relationships between the toxicity-based-toxicokinetic (TBTK/toxicodynamic (TD properties of engineered nanomaterials and their nanotoxicity is crucial for human health-risk analysis. Zerovalent iron (Fe0 nanoparticles (NPs are one of the most prominent NPs applied in remediating contaminated soils and groundwater. However, there are concerns that Fe0NP application contributes to long-term environmental and human health impacts. The nematode Caenorhabditis elegans is a surrogate in vivo model that has been successfully applied to assess the potential nanotoxicity of these nanomaterials. Here we present a TBTK/TD approach to appraise bioaccumulation and nanotoxicity of Fe0NPs in C. elegans. Built on a present C. elegans bioassay with estimated TBTK/TD parameters, we found that average bioconcentration factors in C. elegans exposed to waterborne and food-borne Fe0NPs were ~50 and ~5×10–3, respectively, whereas 10% inhibition concentrations for fertility, locomotion, and development, were 1.26 (95% CI 0.19–5.2, 3.84 (0.38–42, and 6.78 (2.58–21 µg·g–1, respectively, implicating that fertility is the most sensitive endpoint in C. elegans. Our results also showed that biomagnification effects were not observed in waterborne or food-borne Fe0NP-exposed worms. We suggest that the TBTK/TD assessment for predicting NP-induced toxicity at different concentrations and conditions in C. elegans could enable rapid selection of nanomaterials that are more likely to be nontoxic in larger animals. We conclude that the use of the TBTK/TD scheme manipulating C. elegans could be used for rapid evaluation of in vivo toxicity of NPs or for drug screening in the field of nanomedicine. Keywords: zerovalent iron nanoparticles, Caenorhabditis elegans

Sex differences in the toxicokinetics of inhaled solvent vaporsin humans 1. m-Xylene

International Nuclear Information System (INIS)

Ernstgaard, Lena; Sjoegren, Bengt; Warholm, Margareta; Johanson, Gunnar

2003-01-01

The aim of this study was to evaluate possible sex differences in the inhalation toxicokinetics of m-xylene vapor. Seventeen healthy volunteers (nine women and eight men) were exposed to m-xylene (200 mg/m 3 ) and to clean air (control exposure) on different occasions during 2 h of light physical exercise (50 W). The chosen level corresponds to the occupational exposure limit (8-h time weighted average) in Sweden. m-Xylene was monitored up to 24 h after exposure in exhaled air, blood, saliva, and urine by headspace gas chromatography. m-Methylhippuric acid (a metabolite of m-xylene) was analyzed in urine by high-performance liquid chromatography. Body fat and lean body mass (LBM) were estimated from sex-specific equations using bioelectrical impedance, body weight, height, and age. Genotypes and/or phenotypes of cytochromes P450 2E1 and 1A1, glutathione transferases M1 and P1, and epoxide hydrolase were determined. The toxicokinetic profile in blood was analyzed using a two-compartment population model. The area under the concentration-time curve (AUC) of m-xylene in exhaled air postexposure was larger in women than in men. In addition, the excretion via exhaled air was significantly higher in women when correcting for body weight or LBM. In contrast, the men had a significantly higher volume of distribution, excretion of m-methylhippuric acid in urine, and AUC of m-xylene in urine. The toxicokinetic analyses revealed no differences between subjects of different metabolic genotypes or phenotypes. In conclusion, the study indicates small sex differences in the inhalation toxicokinetics of m-xylene, which can be explained by body build

[The rabbit experimental study for toxicokinetics of chlorpyrifos impacted by hemoperfusion].

Science.gov (United States)

Guo, Xiang; Chen, Xiao; Zhang, Hongshun; Long, Xin; He, Qian; Sun, Chengye; Huang, Xianqing; He, Jian

2015-11-01

To investigate toxicokinetic parameters impacted by hemoperfusion after oral chlorpyrifos exposure, to investigate the adsorption effect of hemoperhusion for chlorpyrifos poisoning. 12 rabbits were divided into two groups after oral exposure with chlorpyrifos 300 mg/kg body weight. Control group: without hemoperfusion; hemoperfusion group: hemoperfusion starts 0.5 h after chlorpyrifos exposure and lasts for 2h. Blood samples were collected at different times, concentrations of chlorpyrifos were tested by GC, then, toxicokinetic parameterswere calculated and analysis by DAS3.0. In hemoperfusion group, peak time was (7.19±3.74) h, peak concentrations was (1.37±0.56) mg/L, clearance rate was (13.93±10.27) L/h/kg, apparent volume of distribution was (418.18±147.15) L/kg The difference of these parameter were statistically significant compared with control group (Pchlorpyrifos poisoning.

Toxicokinetics of Microcystin and Dihydro-Microcystin in Swine

Science.gov (United States)

1994-05-14

fate, toxicokinetics, pharmacokinetics , lesions, 16. PRICE CODE toxicity. 17. SECURITY CLASSIFICATION 10. SECURITY C.SAIFICATION 1g. SECURITY...wildlife, sheep, pigs, cattle, dogs , and man (Carmichael et al., 1984, 1985; Sykora and Keliti, 1981; Galey at al., 1987; Carmichael and Falconer 1993...was inserted. A combination of xylazine (0.66 mg/kg) and lidocaine (3.6 mg/kg) was then administered to the pigs by epidural injection. Anesthesia was

Toxicokinetics of the neonicotinoid insecticide imidacloprid in rainbow trout (Oncorhynchus mykiss)

Science.gov (United States)

Imidacloprid (IMI) is the largest selling insecticide internationally. Little is known about the toxicokinetics of IMI in fish, however. In vivo time-course studies were conducted to study the distribution and elimination of IMI in rainbow trout. Animals confined to respiromet...

Serum toxicokinetics after intravenous and oral dosing of larkspur toxins in goats

Science.gov (United States)

Poisoning of cattle by larkspur plants (Delphinium spp.) is a concern for cattle ranchers in western North America. Previous research studies have evaluated the toxicokinetic profile of multiple larkspur toxins in several livestock species. However, those studies were all performed by orally dosing ...

The oral bioavailability and toxicokinetics of methylmercury in common loon (Gavia immer) chicks

Science.gov (United States)

Fournier, F.; Karasov, W.H.; Kenow, K.P.; Meyer, M.W.; Hines, R.K.

2002-01-01

We compared the toxicokinetics of methylmercury in captive common loon chicks during two time intervals to assess the impact of feather growth on the kinetics of mercury. We also determined the oral bioavailability of methylmercury during these trials to test for age-related changes. The blood concentration-time curves for individuals dosed during feather development (initiated 35 days post hatch) were best described by a one-compartment toxicokinetic model with an elimination half-life of 3 days. The data for birds dosed following completion of feather growth (84 days post hatch) were best fitted by a two-compartment elimination model that includes an initial rapid distribution phase with a half-life of 0.9 days, followed by a slow elimination phase with a half-life of 116 days. We determined the oral bioavailability of methylmercury during the first dosing interval by comparing the ratios of the area under the blood concentration-time curves (AUC0→∞) for orally and intravenously dosed chicks. The oral bioavailability of methylmercury during the first dosing period was 0.83. We also determined bioavailability during both dosing periods using a second measure because of irregularities with intravenous results in the second period. This second bioavailability measure estimated the percentage of the dose that was deposited in the blood volume (f), and the results show that there was no difference in bioavailability among dosing periods. The results of this study highlight the importance of feather growth on the toxicokinetics of methylmercury.

Metabolic capacity and interindividual variation in toxicokinetics of styrene in volunteers

NARCIS (Netherlands)

Wenker, M. A.; Kezić, S.; Monster, A. C.; de Wolff, F. A.

2001-01-01

The aim of the present study was to assess the interindividual variation in styrene toxicokinetics and to correlate this variation with the individual metabolic capacity for cytochrome P450 (CYP), CYP2E1, CYP1A2 and CYP2D6. Twenty male volunteers were exposed on separate occasions to 104+/-3 and

Evaluating In Vitro-In Vivo Extrapolation of Toxicokinetics.

Science.gov (United States)

Wambaugh, John F; Hughes, Michael F; Ring, Caroline L; MacMillan, Denise K; Ford, Jermaine; Fennell, Timothy R; Black, Sherry R; Snyder, Rodney W; Sipes, Nisha S; Wetmore, Barbara A; Westerhout, Joost; Setzer, R Woodrow; Pearce, Robert G; Simmons, Jane Ellen; Thomas, Russell S

2018-05-01

Prioritizing the risk posed by thousands of chemicals potentially present in the environment requires exposure, toxicity, and toxicokinetic (TK) data, which are often unavailable. Relatively high throughput, in vitro TK (HTTK) assays and in vitro-to-in vivo extrapolation (IVIVE) methods have been developed to predict TK, but most of the in vivo TK data available to benchmark these methods are from pharmaceuticals. Here we report on new, in vivo rat TK experiments for 26 non-pharmaceutical chemicals with environmental relevance. Both intravenous and oral dosing were used to calculate bioavailability. These chemicals, and an additional 19 chemicals (including some pharmaceuticals) from previously published in vivo rat studies, were systematically analyzed to estimate in vivo TK parameters (e.g., volume of distribution [Vd], elimination rate). For each of the chemicals, rat-specific HTTK data were available and key TK predictions were examined: oral bioavailability, clearance, Vd, and uncertainty. For the non-pharmaceutical chemicals, predictions for bioavailability were not effective. While no pharmaceutical was absorbed at less than 10%, the fraction bioavailable for non-pharmaceutical chemicals was as low as 0.3%. Total clearance was generally more under-estimated for nonpharmaceuticals and Vd methods calibrated to pharmaceuticals may not be appropriate for other chemicals. However, the steady-state, peak, and time-integrated plasma concentrations of nonpharmaceuticals were predicted with reasonable accuracy. The plasma concentration predictions improved when experimental measurements of bioavailability were incorporated. In summary, HTTK and IVIVE methods are adequately robust to be applied to high throughput in vitro toxicity screening data of environmentally relevant chemicals for prioritizing based on human health risks.

Implementing a framework for integrating toxicokinetics into human health risk assessment for agrochemicals.

Science.gov (United States)

Terry, Claire; Hays, Sean; McCoy, Alene T; McFadden, Lisa G; Aggarwal, Manoj; Rasoulpour, Reza J; Juberg, Daland R

2016-03-01

A strategic and comprehensive program in which toxicokinetic (TK) measurements are made for all agrochemicals undergoing toxicity testing (both new compounds and compounds already registered for use) is described. This approach provides the data to more accurately assess the toxicokinetics of agrochemicals and their metabolites in laboratory animals and humans. Having this knowledge provides the ability to conduct more insightful toxicity studies, refine and interpret exposure assessments and reduce uncertainty in risk assessments. By developing a better understanding of TK across species, including humans via in vitro metabolism studies, any differences across species in TK can be identified early and the most relevant species can be selected for toxicity tests. It also provides the ability to identify any non-linearities in TK as a function of dose, which in turn can be used to identify a kinetically derived maximum dose (KMD) and avoid dosing inappropriately outside of the kinetic linear range. Measuring TK in key life stages also helps to identify changes in ADME parameters from in utero to adults. A robust TK database can also be used to set internal concentration based "Reference Concentrations" and Biomonitoring Equivalents (BE), and support selection of Chemical Specific Adjustment Factors (CSAF). All of these factors support the reduction of uncertainty throughout the entire risk assessment process. This paper outlines how a TK research strategy can be integrated into new agrochemical toxicity testing programs, together with a proposed Framework for future use. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparison of the serum toxicokinetics of larkspur toxins in cattle, sheep and goats

Science.gov (United States)

Larkspurs (Delphinium spp.) are a major cause of cattle losses in western North America, whereas sheep are thought to be resistant to larkspur toxicosis. Goats are often used as a small ruminant model to study poisonous plants. In this study, we compared the serum toxicokinetic profile of toxic lark...

Toxicokinetic-toxicodynamic modeling of quantal and graded sublethal endpoints: a brief discussion of concepts

NARCIS (Netherlands)

Ashauer, R.; Agatz, A.; Albert, C.; Ducrot, V.; Galic, N.G.; Hendriks, J.; Jager, T.; Kretschmann, A.; O'Connor, I.; Rubach, M.N.; Nyman, M.; Schmitt, W.; Stadnicka, J.; Brink, van den P.J.

2011-01-01

We report on the advantages and problems of using toxicokinetic-toxicodynamic (TKTD) models for the analysis, understanding, and simulation of sublethal effects. Only a few toxicodynamic approaches for sublethal effects are available. These differ in their effect mechanism and emphasis on linkages

The pH-dependent toxicity of basic pharmaceuticals in the green algae Scenedesmus vacuolatus can be explained with a toxicokinetic ion-trapping model

Energy Technology Data Exchange (ETDEWEB)

Neuwoehner, Judith [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Uberlandstr. 133, 8600 Duebendorf (Switzerland); Institute of Biogeochemistry and Pollutant Dynamics (IBP), ETH Zuerich, 8092 Zuerich (Switzerland); Escher, Beate I., E-mail: b.escher@uq.edu.au [The University of Queensland, National Research Centre for Environmental Toxicology (Entox), 39 Kessels Road, Brisbane, QLD 4108 (Australia); Eawag, Swiss Federal Institute of Aquatic Science and Technology, Uberlandstr. 133, 8600 Duebendorf (Switzerland)

2011-01-17

Several previous studies revealed that pharmaceuticals with aliphatic amine function exhibit a higher toxicity toward algae than toward other aquatic organisms. Here we investigated the pH-dependent toxicity of the five basic pharmaceuticals fluoxetine, its metabolite norfluoxetine, propranolol, lidocaine, and trimipramine. For all of them, the toxicity increased with increasing pH when aqueous effect concentrations were considered. Since these pharmaceuticals contain a basic amine group that is protonated and thus positively charged at physiological pH and because algae are capable of biological homeostasis, i.e., pH inside the algal cell remains virtually independent of variable external pH, the speciation of aliphatic amines can be different inside the algal cell compared to the external medium. Therefore, we hypothesized that the high toxicity of aliphatic amines in algae is a toxicokinetic effect caused by speciation and not a toxicodynamic effect caused by a specific mode of toxic action. This hypothesis also implies that internal effect concentrations are independent on external pH. On this basis we developed a simple toxicokinetic model, which assumes that only the neutral molecule is bioavailable and can pass the plasma membrane. This assumption is likely to be valid at pH values down to two units below the acidity constant (pK{sub a}). For lower pH values a more complex model would have to be evoked that includes, an, albeit smaller, permeability of the charged species. For pH > pK{sub a} - 2, we can safely assume that the outer membrane serves as insulator and that the charged species is formed inside the cell according to the pH in the cytoplasm. Thus this toxicokinetic model is an ion-trapping model. The input parameters of this model are the measured aqueous effect concentrations determined as a function of pH and the membrane-water partitioning, which was modelled by the liposome-water partition coefficients of the neutral and cationic species. They

The pH-dependent toxicity of basic pharmaceuticals in the green algae Scenedesmus vacuolatus can be explained with a toxicokinetic ion-trapping model

International Nuclear Information System (INIS)

Neuwoehner, Judith; Escher, Beate I.

2011-01-01

Several previous studies revealed that pharmaceuticals with aliphatic amine function exhibit a higher toxicity toward algae than toward other aquatic organisms. Here we investigated the pH-dependent toxicity of the five basic pharmaceuticals fluoxetine, its metabolite norfluoxetine, propranolol, lidocaine, and trimipramine. For all of them, the toxicity increased with increasing pH when aqueous effect concentrations were considered. Since these pharmaceuticals contain a basic amine group that is protonated and thus positively charged at physiological pH and because algae are capable of biological homeostasis, i.e., pH inside the algal cell remains virtually independent of variable external pH, the speciation of aliphatic amines can be different inside the algal cell compared to the external medium. Therefore, we hypothesized that the high toxicity of aliphatic amines in algae is a toxicokinetic effect caused by speciation and not a toxicodynamic effect caused by a specific mode of toxic action. This hypothesis also implies that internal effect concentrations are independent on external pH. On this basis we developed a simple toxicokinetic model, which assumes that only the neutral molecule is bioavailable and can pass the plasma membrane. This assumption is likely to be valid at pH values down to two units below the acidity constant (pK a ). For lower pH values a more complex model would have to be evoked that includes, an, albeit smaller, permeability of the charged species. For pH > pK a - 2, we can safely assume that the outer membrane serves as insulator and that the charged species is formed inside the cell according to the pH in the cytoplasm. Thus this toxicokinetic model is an ion-trapping model. The input parameters of this model are the measured aqueous effect concentrations determined as a function of pH and the membrane-water partitioning, which was modelled by the liposome-water partition coefficients of the neutral and cationic species. They were

The toxicokinetics of cadmium in carp under normoxic and hypoxic conditions

International Nuclear Information System (INIS)

Hattink, Jasper; Boeck, Gudrun De; Blust, Ronny

2005-01-01

Temporal depletion of oxygen, i.e. hypoxic events, frequently occurs in natural waters. It has been suggested that accumulation of micro-pollutants increases in aquatic animals as a result of an increased ventilation rate during such occasions. The observed increased toxicity under hypoxia of micro-pollutants may support this hypothesis, but for heavy metals the available uptake studies are contradictory. The present study tests whether accumulation of cadmium in common carp, Cyprinus carpio (L.) is increased under hypoxia and if the toxicokinetics are altered. A cadmium toxicity study was performed in which the cadmium uptake rates were determined using the radiotracer 109 Cd under hypoxia and normoxia. The cadmium toxicokinetics were studied with radiotracer experiments at 100% air saturation, 50%, and 25% saturation from 6.5 nmol/L Cd at 25 deg C. We could confirm the higher sensitivity of carp to cadmium under hypoxia. Hypoxic conditions did not influence the uptake rates or the accumulation dynamics. Therefore, the increased sensitivity of carp for Cd under hypoxia cannot be explained by a higher Cd body burden, initiated by a higher uptake rate or lower elimination rate under hypoxia. Additional, possible indirect effects, such as internal anoxia due to gill damage, could play a role in Cd toxicity under hypoxia

The toxicokinetics of cadmium in carp under normoxic and hypoxic conditions

Energy Technology Data Exchange (ETDEWEB)

Hattink, Jasper [University of Antwerp, Department of Biology, Laboratory of Ecophysiology, Biochemistry, and Toxicology, Groenenborgerlaan 171, 2020 Antwerp (Belgium)]. E-mail: jasper.hattink@ua.ac.be; Boeck, Gudrun De [University of Antwerp, Department of Biology, Laboratory of Ecophysiology, Biochemistry, and Toxicology, Groenenborgerlaan 171, 2020 Antwerp (Belgium); Blust, Ronny [University of Antwerp, Department of Biology, Laboratory of Ecophysiology, Biochemistry, and Toxicology, Groenenborgerlaan 171, 2020 Antwerp (Belgium)

2005-10-05

Temporal depletion of oxygen, i.e. hypoxic events, frequently occurs in natural waters. It has been suggested that accumulation of micro-pollutants increases in aquatic animals as a result of an increased ventilation rate during such occasions. The observed increased toxicity under hypoxia of micro-pollutants may support this hypothesis, but for heavy metals the available uptake studies are contradictory. The present study tests whether accumulation of cadmium in common carp, Cyprinus carpio (L.) is increased under hypoxia and if the toxicokinetics are altered. A cadmium toxicity study was performed in which the cadmium uptake rates were determined using the radiotracer {sup 109}Cd under hypoxia and normoxia. The cadmium toxicokinetics were studied with radiotracer experiments at 100% air saturation, 50%, and 25% saturation from 6.5 nmol/L Cd at 25 deg C. We could confirm the higher sensitivity of carp to cadmium under hypoxia. Hypoxic conditions did not influence the uptake rates or the accumulation dynamics. Therefore, the increased sensitivity of carp for Cd under hypoxia cannot be explained by a higher Cd body burden, initiated by a higher uptake rate or lower elimination rate under hypoxia. Additional, possible indirect effects, such as internal anoxia due to gill damage, could play a role in Cd toxicity under hypoxia.

New psychoactive substances: an overview on recent publications on their toxicodynamics and toxicokinetics.

Science.gov (United States)

Meyer, Markus R

2016-10-01

This review article covers English-written and PubMed-listed review articles and original studies published between January 2015 and April 2016 dealing with the toxicodynamics and toxicokinetics of new psychoactive substances. Compounds covered include stimulants and entactogens, synthetic cannabinoids, tryptamines, NBOMes, phencyclidine-like drugs, benzodiazepines, and opioids. First, an overview and discussion is provided on timely review articles followed by an overview and discussion on recent original studies. Both sections are then concluded by an opinion on these latest developments. This review shows that the NPS market is still highly dynamic and that the data published on their toxicodynamics and toxicokinetics can hardly keep pace with the appearance of new entities. However, data available are very helpful to understand and predict how NPS may behave in severe intoxication. The currently best-documented parameter is the in vitro metabolism of NPS, a prerequisite to allow detection of NPS in biological matrices in cases of acute intoxications or chronic consumption. However, additional data such as their chronic toxicity are still lacking.

Toxicokinetic-toxicodynamic modelling of quantal and graded sub-lethal endpoints - a brief discussion of concepts.

NARCIS (Netherlands)

Ashauer, R.; Agatz, A.; Albert, C.; Ducrot, V.; Galic, N.; Hendriks, A.J.; Jager, T.; Kretschmann, A.; O'Connor, I.; Rubach, M.N.; Nyman, A.M.; Schmitt, W.; Stadnicka, J.; van den Brink, P.; Preuss, T.G.

2011-01-01

We report on the advantages and problems of using toxicokinetic-toxicodynamic (TKTD) models for the analysis, understanding, and simulation of sublethal effects. Only a few toxicodynamic approaches for sublethal effects are available. These differ in their effect mechanism and emphasis on linkages

Generalized INverse imaging (GIN): ultrafast fMRI with physiological noise correction.

Science.gov (United States)

Boyacioğlu, Rasim; Barth, Markus

2013-10-01

An ultrafast functional magnetic resonance imaging (fMRI) technique, called generalized inverse imaging (GIN), is proposed, which combines inverse imaging with a phase constraint-leading to a less underdetermined reconstruction-and physiological noise correction. A single 3D echo planar imaging (EPI) prescan is sufficient to obtain the necessary coil sensitivity information and reference images that are used to reconstruct standard images, so that standard analysis methods are applicable. A moving dots stimulus paradigm was chosen to assess the performance of GIN. We find that the spatial localization of activation for GIN is comparable to an EPI protocol and that maximum z-scores increase significantly. The high temporal resolution of GIN (50 ms) and the acquisition of the phase information enable unaliased sampling and regression of physiological signals. Using the phase time courses obtained from the 32 channels of the receiver coils as nuisance regressors in a general linear model results in significant improvement of the functional activation, rendering the acquisition of external physiological signals unnecessary. The proposed physiological noise correction can in principle be used for other fMRI protocols, such as simultaneous multislice acquisitions, which acquire the phase information sufficiently fast and sample physiological signals unaliased. Copyright © 2012 Wiley Periodicals, Inc.

Physiologically Based Pharmacokinetic (PBPK) Modeling of Interstrain Variability in Trichloroethylene Metabolism in the Mouse

Science.gov (United States)

Background: Quantitative estimation of toxicokinetic variability in the human population is a persistent challenge in risk assessment of environmental chemicals. Traditionally, inter-individual differences in the population are accounted for by default assumptions or, in rare cas...

A toxicokinetic analysis in a patient with acute glufosinate poisoning.

Science.gov (United States)

Hirose, Y; Kobayashi, M; Koyama, K; Kohda, Y; Tanaka, T; Honda, H; Hori, Y; Yoshida, K; Kikuchi, M

1999-05-01

Incidents of poisoning in humans caused by the ingestion of the glufosinate ammonium containing herbicides are gradually increasing in Japan. This poisoning is characterized by various neurological symptoms such as disturbances of consciousness, convulsions and apnea which appear after an asymptomatic interval of several hours. We studied the toxicokinetics of glufosinate in a patient with this poisoning successfully treated without extracorporeal hemopurification. A 65-year-old male ingested BASTA, which contains 20% w/v of glufosinate ammonium, about 300 ml, more than the estimated human toxic dose. Four and a half hours after ingestion, he showed speech ataxia and systemic tremor. He was prophylactically intubated before the occurrence of serious respiratory failure. After 5 days of artificial ventilation he was extubated and discharged without any sequelae. We studied the serial change of serum glufosinate concentration every 3-6 h and assessed the urinary excretion of glufosinate every 24 h. The absorbed amount of glufosinate was estimated from the cumulative excreted in urine. Toxicokinetic analysis was performed using the two-compartment model. The changes in serum glufosinate concentration exhibited T1/2alpha of 1.84 and T1/2beta of 9.59 h. The apparent distribution volume at beta-phase and the total body clearance were 1.44 l/kg and 86.6 ml/min, respectively. Renal clearance was estimated to be 77.9 ml/min. The indication for extracorporeal hemopurification for this poisoning has been discussed.

Fearful imagery in social phobia: generalization, comorbidity, and physiological reactivity.

Science.gov (United States)

McTeague, Lisa M; Lang, Peter J; Laplante, Marie-Claude; Cuthbert, Bruce N; Strauss, Cyd C; Bradley, Margaret M

2009-03-01

Social phobia has been characterized as a disorder of exaggerated fear of social threat and heightened sensitivity to imagery of social failure. To assess the physiological basis of this description, social phobia patients (n=75) and demographically matched control participants (n=75) imagined neutral and fearful events while acoustic startle probes were occasionally presented and eye-blink responses (orbicularis occuli) recorded. Changes in heart rate, skin conductance level, and facial expressivity were also indexed. In addition to comparing control participants and social phobia patients, the influences of diagnostic subtype (circumscribed, generalized), comorbid depression, and chronicity were assessed. Patients exceeded control participants in startle reflex and autonomic responding during imagery of social threat, whereas the groups evinced commensurate reactivity to contents depicting commonly shared fears (survival threat). Individuals with circumscribed performance phobia were similar to control participants, with the exception of more robust reactions to idiographic, performance fear imagery. In contrast, generalized phobic patients were characterized by longer disorder chronicity and demonstrated heightened sensitivity to a broader range of fear contents. Those with generalized phobia plus comorbid depression showed attenuation of fear-potentiated startle and reported the most protracted social anxiety. Subtypes of social phobia can be objectively distinguished in patterns of physiological reactivity. Furthermore, subtypes vary systematically in chronicity and defensive engagement with the shortest disorder duration (circumscribed phobia) associated with the most robust and focal physiological reactivity, followed by broader defensive sensitivity in more chronic generalized phobia, and finally attenuation of the formerly exaggerated fear potentiation in the comorbidly depressed, the most chronic form.

Towards toxicokinetic modelling of aluminium exposure from adjuvants in medicinal products.

Science.gov (United States)

Weisser, Karin; Stübler, Sabine; Matheis, Walter; Huisinga, Wilhelm

2017-08-01

As a potentially toxic agent on nervous system and bone, the safety of aluminium exposure from adjuvants in vaccines and subcutaneous immune therapy (SCIT) products has to be continuously re-evaluated, especially regarding concomitant administrations. For this purpose, knowledge on absorption and disposition of aluminium in plasma and tissues is essential. Pharmacokinetic data after vaccination in humans, however, are not available, and for methodological and ethical reasons difficult to obtain. To overcome these limitations, we discuss the possibility of an in vitro-in silico approach combining a toxicokinetic model for aluminium disposition with biorelevant kinetic absorption parameters from adjuvants. We critically review available kinetic aluminium-26 data for model building and, on the basis of a reparameterized toxicokinetic model (Nolte et al., 2001), we identify main modelling gaps. The potential of in vitro dissolution experiments for the prediction of intramuscular absorption kinetics of aluminium after vaccination is explored. It becomes apparent that there is need for detailed in vitro dissolution and in vivo absorption data to establish an in vitro-in vivo correlation (IVIVC) for aluminium adjuvants. We conclude that a combination of new experimental data and further refinement of the Nolte model has the potential to fill a gap in aluminium risk assessment. Copyright © 2017 Elsevier Inc. All rights reserved.

Using toxicokinetic-toxicodynamic modeling as an acute risk assessment refinement approach in vertebrate ecological risk assessment.

Science.gov (United States)

Ducrot, Virginie; Ashauer, Roman; Bednarska, Agnieszka J; Hinarejos, Silvia; Thorbek, Pernille; Weyman, Gabriel

2016-01-01

Recent guidance identified toxicokinetic-toxicodynamic (TK-TD) modeling as a relevant approach for risk assessment refinement. Yet, its added value compared to other refinement options is not detailed, and how to conduct the modeling appropriately is not explained. This case study addresses these issues through 2 examples of individual-level risk assessment for 2 hypothetical plant protection products: 1) evaluating the risk for small granivorous birds and small omnivorous mammals of a single application, as a seed treatment in winter cereals, and 2) evaluating the risk for fish after a pulsed treatment in the edge-of-field zone. Using acute test data, we conducted the first tier risk assessment as defined in the European Food Safety Authority (EFSA) guidance. When first tier risk assessment highlighted a concern, refinement options were discussed. Cases where the use of models should be preferred over other existing refinement approaches were highlighted. We then practically conducted the risk assessment refinement by using 2 different models as examples. In example 1, a TK model accounting for toxicokinetics and relevant feeding patterns in the skylark and in the wood mouse was used to predict internal doses of the hypothetical active ingredient in individuals, based on relevant feeding patterns in an in-crop situation, and identify the residue levels leading to mortality. In example 2, a TK-TD model accounting for toxicokinetics, toxicodynamics, and relevant exposure patterns in the fathead minnow was used to predict the time-course of fish survival for relevant FOCUS SW exposure scenarios and identify which scenarios might lead to mortality. Models were calibrated using available standard data and implemented to simulate the time-course of internal dose of active ingredient or survival for different exposure scenarios. Simulation results were discussed and used to derive the risk assessment refinement endpoints used for decision. Finally, we compared the

Bioavailability and intravenous toxicokinetic parameters for Pacific ciguatoxin P-CTX-1 in rats.

Science.gov (United States)

Ledreux, Aurélie; Ramsdell, John S

2013-03-15

Ciguatoxins are sodium channel activator toxins responsible for ciguatera fish poisoning. In this study, we determined the toxicokinetic parameters of the Pacific ciguatoxin P-CTX-1 in rats after an intravenous (iv) dose of 0.13 ng P-CTX-1 per g of body weight. The ciguatoxin activity was assessed over time in blood using the sensitive functional Neuro2a assay. The data were analyzed with a two-compartmental model. After exposure, the ciguatoxin activity exhibited a rapid (alpha half-life of 6 min) and extensive distribution into tissues (apparent steady state volume of distribution of 7.8 L). Ciguatoxin elimination from blood was slower with a beta half-life estimated at 35.5 h. The toxicokinetic parameters determined from this study were compared to data previously obtained after oral and intraperitoneal exposure of rats to 0.26 ng P-CTX-1 per g of body weight. Maximal bioavailability was determined by the area under the concentration curve, and was used to calculate the absolute P-CTX-1 bioavailabilities for oral and intraperitoneal routes of exposures of 39% and 75%, respectively. Published by Elsevier Ltd.

Using a toxicokinetics approach to explain the effect of soil pH on cadmium bioavailability to Folsomia candida

International Nuclear Information System (INIS)

Ardestani, Masoud M.; Gestel, Cornelis A.M. van

2013-01-01

The aim of this study was to improve our understanding of metal bioavailability in soil by linking the biotic ligand approach with toxicokinetics modelling. We determined cadmium bioaccumulation kinetics in Folsomia candida (Collembola) as a function of soil pH. Animals were exposed for 21 days to LUFA 2.2 soil at 5 or 20 μg Cd g −1 dry soil followed by 21 days elimination in clean soil. Internal cadmium concentrations were modelled using a first-order one-compartment model, relating uptake rate constants (k 1 ) to total soil, water or 0.01 M CaCl 2 extractable and porewater concentrations. Based on total soil concentrations, k 1 was independent of soil pH while it strongly increased with increasing pH based on porewater concentrations explaining the reduced competition of H + ions making cadmium more bioavailable in pore water at high pH. This shows that the principles of biotic ligand modelling are applicable to predict cadmium accumulation kinetics in soil-living invertebrates. -- Highlights: •Cadmium uptake and elimination in Folsomia candida were investigated. •Animals were exposed to LUFA 2.2 soil at different pH levels. •Langmuir isotherms were used to describe interaction of Ca and protons with Cd. •pH was the main factor affecting Cd toxicokinetics when pore water was considered. -- Integrating bioaccumulation kinetics with a BLM approach provides novel insights into the bioavailability of cadmium to springtails in soil

TOXICOKINETICS OF TREMOROGENIC NATURAL PRODUCTS, HARMANE AND HARMINE, IN MALE SPRAGUE-DAWLEY RATS

OpenAIRE

Guan, Yongbiao; Louis, Elan D.; Zheng, Wei

2001-01-01

Tremorogenic β-carboline alkaloids are present in foodstuffs and beverages. Acute exposure to β-carboline derivatives causes severe tremor; however, the disposition of these dietary contaminants remains unclear. This study was performed to evaluate toxicokinetics of harmane and harmine, two major β-carboline alkaloids, in rats. Blood concentrations of both toxicants were quantified by high-performance liquid chromatography (HPLC). Following an intravenous injection (0.5 mg/ kg), the concentra...

Toxicokinetics and metabolisms of benzophenone-type UV filters in rats

International Nuclear Information System (INIS)

Jeon, Hee-Kyung; Sarma, Sailendra Nath; Kim, Youn-Jung; Ryu, Jae-Chun

2008-01-01

Sunscreens containing UV filters are recommended to reduce damage caused by solar UV radiation. Recently, benzophenone (BP)-type UV filters have become widely used as UV stabilizers in skin-moisturizing products and sunscreen lotions; however, very little information is available regarding the potential harmful effects of prolonged exposure to these compounds. Therefore, we investigated the toxicokinetics and metabolism of BP-type UV filters in rats using gas chromatography-mass spectrometry (GC-MS). To examine the metabolism of BP-type UV filters, we analyzed the parent compounds BP and 2-hydroxy-4-methoxybenzophenone (HMB). In rats, BP was mainly converted to benzhydrol (BH) and 4-hydroxybenzophenone (HBP) (i.e., type A UV filters). In contrast, HMB was converted into at least three intermediates, including 2,4-dihydroxybenzophenone (DHB), which was formed via o-demethylation and subsequently converted into 2,3,4-trihydroxybenzophenone (THB), and 2,2'-dihydroxy-4-methoxybenzophenone (DHMB), which formed via the aromatic hydroxylation of HMB (i.e., type B UV filters). Next, the toxicokinetic curve for BP showed a peak concentration (C max ) of 2.06 ± 0.46 μg/ml at approximately 4 h after BP administration. After a single oral dose of HMB, the C max of HMB reached 21.21 ± 11.61 μg/ml within 3 h (T max ), and then declined rapidly compared to the kinetic curve of BP. The concentration of these metabolites in rat blood decreased much more slowly over time compared to the parent compounds. Thus, our results indicate that such metabolites might have more significant adverse effects than the parent compounds over the long term

Teaching Acid/Base Physiology in the Laboratory

Science.gov (United States)

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

2010-01-01

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

The influence of microplastics and halogenated contaminants in feed on toxicokinetics and gene expression in European seabass (Dicentrarchus labrax)

NARCIS (Netherlands)

Granby, Kit; Rainieri, Sandra; Rasmussen, Rie Romme; Kotterman, Michiel J.J.; Sloth, Jens Jørgen; Cederberg, Tommy Licht; Barranco, Alex; Marques, António; Larsen, Bodil Katrine

2018-01-01

When microplastics pollute fish habitats, it may be ingested by fish, thereby contaminating fish with sorbed contaminants. The present study investigates how combinations of halogenated contaminants and microplastics associated with feed are able to alter toxicokinetics in European seabass and

AN IN VIVO MICRODIALYSIS METHOD FOR THE QUALITATIVE ANALYSIS OF HEPATIC PHASE I METABOLITES OF PHENOL IN RAINBOW TROUT (ONCORHYNCHUS MYKISS)

Science.gov (United States)

Development of reliable and accurate methodologies for determination of xenobiotic hepatic biotransformation rate and capacity parameters is important to the derivation of precise physiologically-based toxicokinetic (PB-TK) models. Biotransformation data incorporated into PB-TK m...

Emerging Fusarium and Alternaria Mycotoxins: Occurrence, Toxicity and Toxicokinetics

Directory of Open Access Journals (Sweden)

Sophie Fraeyman

2017-07-01

Full Text Available Emerging Fusarium and Alternaria mycotoxins gain more and more interest due to their frequent contamination of food and feed, although in vivo toxicity and toxicokinetic data are limited. Whereas the Fusarium mycotoxins beauvericin, moniliformin and enniatins particularly contaminate grain and grain-based products, Alternaria mycotoxins are also detected in fruits, vegetables and wines. Although contamination levels are usually low (µg/kg range, higher contamination levels of enniatins and tenuazonic acid may occasionally occur. In vitro studies suggest genotoxic effects of enniatins A, A1 and B1, beauvericin, moniliformin, alternariol, alternariol monomethyl ether, altertoxins and stemphyltoxin-III. Furthermore, in vitro studies suggest immunomodulating effects of most emerging toxins and a reproductive health hazard of alternariol, beauvericin and enniatin B. More in vivo toxicity data on the individual and combined effects of these contaminants on reproductive and immune system in both humans and animals is needed to update the risk evaluation by the European Food Safety Authority. Taking into account new occurrence data for tenuazonic acid, the complete oral bioavailability, the low total body clearance in pigs and broiler chickens and the limited toxicity data, a health risk cannot be completely excluded. Besides, some less known Alternaria toxins, especially the genotoxic altertoxins and stemphyltoxin III, should be incorporated in risk evaluation as well.

Toxicokinetics of the food-toxin IQ in human placental perfusion is not affected by ABCG2 or xenobiotic metabolism

DEFF Research Database (Denmark)

Immonen, E; Kummu, M; Petsalo, A

2010-01-01

Metabolizing enzymes and transporters affect toxicokinetics of foreign compounds (e.g. drugs and carcinogens) in human placenta. The heterocyclic amine, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) is a food-borne carcinogen being metabolically activated by cytochrome P450 (CYP) enzymes, especial...

Epithelial transport in The Journal of General Physiology.

Science.gov (United States)

Palmer, Lawrence G

2017-10-02

Epithelia define the boundaries of the body and often transfer solutes and water from outside to inside (absorption) or from inside to outside (secretion). Those processes involve dual plasma membranes with different transport components that interact with each other. Understanding those functions has entailed breaking down the problem to analyze properties of individual membranes (apical vs. basolateral) and individual transport proteins. It also requires understanding of how those components interact and how they are regulated. This article outlines the modern history of this research as reflected by publications in The Journal of General Physiology . © 2017 Palmer.

DBS-platform for biomonitoring and toxicokinetics of toxicants: proof of concept using LC-MS/MS analysis of fipronil and its metabolites in blood

Science.gov (United States)

Raju, Kanumuri Siva Rama; Taneja, Isha; Rashid, Mamunur; Sonkar, Ashish Kumar; Wahajuddin, Muhammad; Singh, Sheelendra Pratap

2016-03-01

A simple, sensitive and high throughput LC-MS/MS method was developed and validated for quantification of fipronil, fipronil sulfone and fipronil desulfinyl in rat and human dried blood spots (DBS). DBS samples were prepared by spiking 10 μl blood on DMPK-C cards followed by drying at room temperature. The whole blood spots were then punched from the card and extracted using acetonitrile. The total chromatographic run time of the method was only 2 min. The lower limit of quantification of the method was 0.1 ng/ml for all the analytes. The method was successfully applied to determine fipronil desulfinyl in DBS samples obtained from its toxicokinetic study in rats following intravenous dose (1 mg/kg). In conclusion, the proposed DBS methodology has significant potential in toxicokinetics and biomonitoring studies of environmental toxicants. This microvolume DBS technique will be an ideal tool for biomonitoring studies, particularly in paediatric population. Small volume requirements, minimally invasive blood sampling method, easier storage and shipping procedure make DBS a suitable technique for such studies. Further, DBS technique contributes towards the principles of 3Rs resulting in significant reduction in the number of rodents used and refinement in sample collection for toxicokinetic studies.

Development of an on-line solid phase extraction ultra-high-performance liquid chromatography technique coupled to tandem mass spectrometry for quantification of bisphenol S and bisphenol S glucuronide: Applicability to toxicokinetic investigations.

Science.gov (United States)

Grandin, Flore; Picard-Hagen, Nicole; Gayrard, Véronique; Puel, Sylvie; Viguié, Catherine; Toutain, Pierre-Louis; Debrauwer, Laurent; Lacroix, Marlène Z

2017-12-01

Regulatory measures and public concerns regarding bisphenol A (BPA) have led to its replacement by structural analogues, such as Bisphenol S (BPS), in consumer products. At present, no toxicokinetic investigations have been conducted to assess the factors determining human internal exposure to BPS for subsequent risk assessment. Toxicokinetic studies require reliable analytical methods to measure the plasma concentrations of BPS and its main conjugated metabolite, BPS-glucuronide (BPS-G). An efficient on-line SPE-UPLC-MS/MS method for the simultaneous quantification of BPS and BPS-G in ovine plasma was therefore developed and validated in accordance with the European Medicines Agency guidelines for bioanalytical method validation. This method has a limit of quantification of 3ngmL -1 for BPS and 10ngmL -1 for BPS-G, an analytical capacity of 200 samples per day, and is particularly well suited to toxicokinetic studies. Use of this method in toxicokinetic studies in sheep showed that BPS, like BPA, is efficiently metabolized into its glucuronide form. However, the clearances and distributions of BPS and BPS-G were lower than those of the corresponding unconjugated and glucuroconjugated forms of BPA. Copyright © 2017 Elsevier B.V. All rights reserved.

PHYSIOLOGY OF ACID BASE BALANCE

Directory of Open Access Journals (Sweden)

Awati

2014-12-01

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

Using physiologically based pharmacokinetic (PBPK) modeling for dietary risk assessment of titanium dioxide (TiO2) nanoparticles.

Science.gov (United States)

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

2015-05-01

Nano-sized titanium dioxide particles (nano-TiO2) can be found in a large number of foods and consumer products, such as cosmetics and toothpaste, thus, consumer exposure occurs via multiple sources, possibly involving different exposure routes. In order to determine the disposition of nano-TiO2 particles that are taken up, a physiologically based pharmacokinetic (PBPK) model was developed. High priority was placed on limiting the number of parameters to match the number of underlying data points (hence to avoid overparameterization), but still reflecting available mechanistic information on the toxicokinetics of nano-TiO2. To this end, the biodistribution of nano-TiO2 was modeled based on their ability to cross the capillary wall of the organs and to be phagocytosed in the mononuclear phagocyte system (MPS). The model's predictive power was evaluated by comparing simulated organ levels to experimentally assessed organ levels of independent in vivo studies. The results of our PBPK model indicate that: (1) within the application domain of the PBPK model from 15 to 150 nm, the size and crystalline structure of the particles had a minor influence on the biodistribution; and (2) at high internal exposure the particles agglomerate in vivo and are subsequently taken up by macrophages in the MPS. Furthermore, we also give an example on how the PBPK model may be used for risk assessment. For this purpose, the daily dietary intake of nano-TiO2 was calculated for the German population. The PBPK model was then used to convert this chronic external exposure into internal titanium levels for each organ.

Inhalation and Percutaneous Toxicokinetics of Sulfur Mustard and Its adducts in Hairless Guinea Pigs and Marmosets. Efficacy of Nasal Scavengers

National Research Council Canada - National Science Library

Langenberg, Jan P

2004-01-01

As a follow-up to DAMDl7-94-V-4OO9, the inhalation toxicokinetics of sulfur mustard are studied in more detail in the hairless guinea pig as well as in a species more relevant for man, i.e., the marmoset...

NITRO MUSK ADDUCTS OF RAINBOW TROUT HEMOGLOBIN: DOSE-RESPONSE AND TOXICOKINETICS DETERMINATION BY GC-NICI-MS FOR A SENTINEL SPECIES

Science.gov (United States)

Rainbow trout and other fish species can serve as 'sentinel' species for the assessment of ecological status and the presence of certain environmental contaminants. As such they act as bioindicators of exposure. Here we present seminal data regarding dose-response and toxicokinet...

Domoic acid toxicokinetics in Dungeness crabs: New insights into mechanisms that regulate bioaccumulation

Energy Technology Data Exchange (ETDEWEB)

Schultz, Irvin R., E-mail: ir_schultz@pnl.gov; Skillman, Ann; Sloan-Evans, Siobhan; Woodruff, Dana

2013-09-15

Highlights: •Domoic acid is retained in the hepatopancreas after oral dosing but not after intravascular dosing. •Localization of domoic acid in the hepatopancreas is extracellular, likely in the lumen of tubules. •Isolated hepatopancreas cells do not absorb domoic acid from culture media. •Domoic acid is eliminated through urinary excretion. -- Abstract: Domoic acid (DA) is an excitatory neurotoxic amino acid produced by several marine algal species and is the causative agent of amnesic shellfish poisoning. Profound differences in the toxicokinetics of DA have been identified in a wide variety of shellfish. We characterized the toxicokinetics of DA in Dungeness crabs (Metacarcinus magister) after oral and intravascular dosing (IV) using a variety of doses ranging from 0.1 to 20 mg/kg. After a 1 mg/kg oral dose, DA disappeared from the foregut within 2 h and largely accumulated in the hepatopancreas, with hemolymph and other tissues having 100–1000 times lower concentrations. After IV dosing, hemolymph concentrations of DA were unexpectedly high and toxicokinetic analysis indicated the steady-state volume of distribution (V{sub ss}) was 123–197 ml/kg, which is well below the hemolymph volume of 350 ml/kg for crabs. This indicated only limited extravascular distribution of DA was occurring after IV injection, which is surprising considering the capacity of the hepatopancreas to sequester DA after oral dosing. Additional studies measured the partitioning of DA in hepatopancreas cellular and subcellular fractions. The subcellular distribution of DA was primarily associated with the S8 fraction and could be filtered through a 30,000 MW cut-off filter, indicating DA was not appreciably bound to macromolecules. Interestingly, very little (<0.4%) of the total hepatopancreas DA tissue content was associated with the cellular fraction isolated after dissociation and separation from tissue fragments. The in vivo and in vitro results led us to hypothesize that DA

Evaluation of semi-generic PBTK modeling for emergency risk assessment after acute inhalation exposure to volatile hazardous chemicals

NARCIS (Netherlands)

Olie, J Daniël N; Bessems, Jos G; Clewell, Harvey J; Meulenbelt, Jan; Hunault, Claudine C

BACKGROUND: Physiologically Based Toxicokinetic Models (PBTK) may facilitate emergency risk assessment after chemical incidents with inhalation exposure, but they are rarely used due to their relative complexity and skill requirements. We aimed to tackle this problem by evaluating a semi-generic

Evaluation of semi-generic PBTK modeling for emergency risk assessment after acute inhalation exposure to volatile hazardous chemicals

NARCIS (Netherlands)

Olie, J. Daniël N; Bessems, Jos G.; Clewell, Harvey J.; Meulenbelt, Jan; Hunault, Claudine C.

2015-01-01

BACKGROUND: Physiologically Based Toxicokinetic Models (PBTK) may facilitate emergency risk assessment after chemical incidents with inhalation exposure, but they are rarely used due to their relative complexity and skill requirements. We aimed to tackle this problem by evaluating a semi-generic

Toxicokinetics of ibogaine and noribogaine in a patient with prolonged multiple cardiac arrhythmias after ingestion of internet purchased ibogaine

NARCIS (Netherlands)

Henstra, Marieke; Wong, Liza; Chahbouni, Abdel; Swart, Noortje; Allaart, Cor; Sombogaard, Ferdi

2017-01-01

Ibogaine is an agent that has been evaluated as an unapproved anti-addictive agent for the management of drug dependence. Sudden cardiac death has been described to occur secondary to its use. We describe the clinical effects and toxicokinetics of ibogaine and noribogaine in a single patient. For

Toxicity-based toxicokinetic/toxicodynamic assessment of bioaccumulation and nanotoxicity of zerovalent iron nanoparticles in Caenorhabditis elegans.

Science.gov (United States)

Yang, Ying-Fei; Lin, Yi-Jun; Liao, Chung-Min

2017-01-01

Elucidating the relationships between the toxicity-based-toxicokinetic (TBTK)/toxicodynamic (TD) properties of engineered nanomaterials and their nanotoxicity is crucial for human health-risk analysis. Zerovalent iron (Fe 0 ) nanoparticles (NPs) are one of the most prominent NPs applied in remediating contaminated soils and groundwater. However, there are concerns that Fe 0 NP application contributes to long-term environmental and human health impacts. The nematode Caenorhabditis elegans is a surrogate in vivo model that has been successfully applied to assess the potential nanotoxicity of these nanomaterials. Here we present a TBTK/TD approach to appraise bioaccumulation and nanotoxicity of Fe 0 NPs in C. elegans . Built on a present C. elegans bioassay with estimated TBTK/TD parameters, we found that average bioconcentration factors in C. elegans exposed to waterborne and food-borne Fe 0 NPs were ~50 and ~5×10 -3 , respectively, whereas 10% inhibition concentrations for fertility, locomotion, and development, were 1.26 (95% CI 0.19-5.2), 3.84 (0.38-42), and 6.78 (2.58-21) μg·g -1 , respectively, implicating that fertility is the most sensitive endpoint in C. elegans . Our results also showed that biomagnification effects were not observed in waterborne or food-borne Fe 0 NP-exposed worms. We suggest that the TBTK/TD assessment for predicting NP-induced toxicity at different concentrations and conditions in C. elegans could enable rapid selection of nanomaterials that are more likely to be nontoxic in larger animals. We conclude that the use of the TBTK/TD scheme manipulating C. elegans could be used for rapid evaluation of in vivo toxicity of NPs or for drug screening in the field of nanomedicine.

Proper knowledge on toxicokinetics improves human hazard testing and subsequent health risk characterisation. A case study approach.

Science.gov (United States)

Bessems, Jos G M; Geraets, Liesbeth

2013-12-01

In the current EU legislative frameworks on chemicals safety, the requirements with respect to information on general kinetic parameters (absorption, distribution, metabolism and excretion or ADME) or integrated toxicokinetic parameters (TK, i.e. plasma concentration-time curve, area under the curve etcetera) in humans and experimental animals vary widely. For agrochemicals and cosmetics, there are regulatory requirements whereas for other frameworks, such as food ingredients, biocides, consumer products and high production volume chemicals (REACH) there are very little or no requirements. This paper presents case studies that illustrate the importance of ADME and TK data in regulatory risk characterisations. The examples were collected by interviewing regulatory risk assessors from various chemicals (non-pharmaceutical) frameworks. The case studies illustrate how (1) applying ADME/TK in an early phase of toxicity testing can be used to improve study design and support the 3R-goals and how (2) increased use of ADME/TK data can improve the final risk assessment. Copyright © 2013 Elsevier Inc. All rights reserved.

Toxicokinetics and toxicodynamics of differently coated silver nanoparticles and silver nitrate in Enchytraeus crypticus upon aqueous exposure in an inert sand medium.

Science.gov (United States)

Topuz, Emel; van Gestel, Cornelis A M

2015-12-01

The aim of the present study was to evaluate the effect of silver nanoparticles (AgNPs) on Enchytraeus crypticus, applying a combined toxicokinetics and toxicodynamics approach to understand the relationship between survival and the development of internal Ag concentrations in the animals over time. Toxicity tests were conducted in medium composed of well-defined aqueous solutions added to inert quartz sand to avoid the complexity of soil conditions. Citrate-coated AgNPs (AgNP-Cit) and polyvinylpyrrolidone-coated AgNPs (AgNP-PVP) were tested and compared with silver nitrate (AgNO3), which was used as a positive control for Ag ion effects. The median lethal concentration (LC50) values based on Ag concentrations in the solution phase of the test medium decreased over time and reached steady state after 7 d, with AgNO3 and AgNP-PVP being more toxic than AgNP-Cit. Slow dissolution may explain the low uptake kinetics and lower toxicity of AgNP-Cit compared with the other 2 Ag forms. The LC50 values based on internal Ag concentrations in the animals were almost stable over time, highlighting the importance of integrating toxicokinetics and toxicodynamics and relating survival with internal Ag concentrations. Neither survival-based elimination rates nor internal LC50s in the organisms showed any significant evidence of nano-specific effects for both AgNPs, although they suggested some uptake of particulate Ag for AgNP-Cit. The authors conclude that the toxicity of both types of AgNP probably is mainly attributable to the release of Ag ions. © 2015 SETAC.

Effects of diethyldithiocarbamate on the toxicokinetics of cadmium chloride in mice

DEFF Research Database (Denmark)

Andersen, O; Nielsen, J B

1989-01-01

Diethyldithiocarbamate (DDC) efficiently alleviates the acute toxicity of injected cadmium chloride, but enhances the acute toxicity of orally administered cadmium chloride. Further, DDC induces extensive changes in organ distribution of cadmium, and mobilizes aged cadmium depots. The present study...... investigates effects of DDC on the toxicokinetics of cadmium at lower doses of cadmium than those used in previous studies. During single exposure to subtoxic oral doses of cadmium chloride DDC enhanced intestinal cadmium absorption, both after intraperitoneal and oral administration of DDC. In such acute...... exposure experiments orally administered DDC only slightly changed the relative organ distribution of absorbed cadmium, while intraperitoneal administration of DDC induced extensive changes in organ preference of absorbed cadmium. The relative hepatic and testicular deposition was reduced, while...

Toxicokinetische modellering van nitraat en nitriet I. Modeldefinitie en toepassing bij de normering van nitraat

NARCIS (Netherlands)

Zeilmaker MJ

1992-01-01

This report describes the development of a human physiologically based toxicokinetic model for nitrate and nitrite and its application in setting dietary standards (Acceptable Daily Intake). On the basis of a literature survey a concept of human PBPK-model was defined. This model contains the

Optimization of the cumulative risk assessment of pesticides and biocides using computational techniques: Pilot project

DEFF Research Database (Denmark)

Jonsdottir, Svava Osk; Reffstrup, Trine Klein; Petersen, Annette

This pilot project is intended as the first step in developing a computational strategy to assist in refining methods for higher tier cumulative and aggregate risk assessment of exposure to mixture of pesticides and biocides. For this purpose, physiologically based toxicokinetic (PBTK) models were...

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

Science.gov (United States)

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

2013-06-01

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

Improved inhalation technology for setting safe exposure levels for workplace chemicals

Science.gov (United States)

Stuart, Bruce O.

1993-01-01

Threshold Limit Values recommended as allowable air concentrations of a chemical in the workplace are often based upon a no-observable-effect-level (NOEL) determined by experimental inhalation studies using rodents. A 'safe level' for human exposure must then be estimated by the use of generalized safety factors in attempts to extrapolate from experimental rodents to man. The recent development of chemical-specific physiologically-based toxicokinetics makes use of measured physiological, biochemical, and metabolic parameters to construct a validated model that is able to 'scale-up' rodent response data to predict the behavior of the chemical in man. This procedure is made possible by recent advances in personal computer software and the emergence of appropriate biological data, and provides an analytical tool for much more reliable risk evaluation and airborne chemical exposure level setting for humans.

Activities of xenobiotic metabolizing enzymes in rat placenta and liver in vitro

NARCIS (Netherlands)

Fabian, Eric; Wang, Xinyi; Engel, Franziska; Li, Hequn; Landsiedel, Robert; Ravenzwaay, van Bennard

2016-01-01

In order to assess whether the placental metabolism of xenobiotic compounds should be taken into consideration for physiologically-based toxicokinetic (PBTK) modelling, the activities of seven phase I and phase II enzymes have been quantified in the 18-day placenta of untreated Wistar rats. To

Compartmental analysis of benzo[a]pyrene toxicokinetics

International Nuclear Information System (INIS)

Bevan, D.R.; Weyand, E.H.

1986-01-01

A multicompartmental model to describe quantitatively the toxicokinetics of benzo[a]pyrene (B[a]P) was developed using SAAM (Simulation, Analysis and Modeling). [ 3 H]-B[a]P dissolved in triethylene glycol was administered intratracheally to male Sprague-Dawley rats, and amounts of [ 3 H] were quantified in various tissues at selected times up to 6 hr after administration. Elimination of [ 3 H]-B[a]P and/or metabolites from lungs was biphasic, with half-times of 5.3 min. and 116 min. [ 3 H]-B[a]P and/or metabolites were subsequently distributed primarily to liver and carcass (muscle, bones, fat, skin and associated blood). Carcass contained about 20% of administered [ 3 H] at 6 hr after administration, and agreement between the model and experimental data required that the carcass be modeled as two compartments, one with rapid and one with slow exchange. Approximately 50% of the administered dose was excreted in feces in 6 hr and only 2% appeared in urine. Enterohepatic circulation was accounted for in the model. The model was then used to predict amounts of [ 3 H]-B[a]P and/or metabolites which would be excreted into bile in animals with bile duct cannulas, and good agreement between the model and data was observed

Daily rhythms in blood and milk lead toxicokinetics following intravenous administration of lead acetate to dairy cows in summer

Science.gov (United States)

Valtorta, S. E.; Scaglione, M. C.; Acosta, P.; Coronel, J. E.; Beldomenico, H. R.; Boggio, J. C.

2006-01-01

The objective of this study was to investigate circadian variations of blood and milk lead toxicokinetics in dairy cows in summer. Twenty lactating Holstein animals were randomly assigned to four treatments corresponding to different hours after onset of light (HALO): 2, 8, 14, and 20. Cows received a single intravenous administration of 2.5 mg/kg lead as lead acetate. Blood and milk samples were taken and analyzed by atomic absorption spectrophotometry. For each toxicokinetic parameter, a one-way analysis of variance (ANOVA) was performed to outline the existence of daily variations. Significant blood differences as a function of HALO were found for the hybrid constant of distribution (α), hybrid constant of elimination (β), elimination half-life ({text{t}}_{{{text{1/2 β }}}} ), area under the curve (AUC), volume of distribution at steady state (Vss) and clearance (ClB) ( pMilk data showed significant differences for maximum concentration and AUC ( pmilk. It differed significantly throughout the day ( pMilk data for the significant parameters could be fitted to circadian rhythms. No circadian rhythms were detected in blood parameters or in the ratio AUCmilk/AUCblood.

Physiologically-based PK/PD modelling of therapeutic macromolecules.

Science.gov (United States)

Thygesen, Peter; Macheras, Panos; Van Peer, Achiel

2009-12-01

Therapeutic proteins are a diverse class of drugs consisting of naturally occurring or modified proteins, and due to their size and physico-chemical properties, they can pose challenges for the pharmacokinetic and pharmacodynamic studies. Physiologically-based pharmacokinetics (PBPK) modelling has been effective for early in silico prediction of pharmacokinetic properties of new drugs. The aim of the present workshop was to discuss the feasibility of PBPK modelling of macromolecules. The classical PBPK approach was discussed with a presentation of the successful example of PBPK modelling of cyclosporine A. PBPK model was performed with transport of the cyclosporine across cell membranes, affinity to plasma proteins and active membrane transporters included to describe drug transport between physiological compartments. For macromolecules, complex PBPK modelling or permeability-limited and/or target-mediated distribution was discussed. It was generally agreed that PBPK modelling was feasible and desirable. The role of the lymphatic system should be considered when absorption after extravascular administration is modelled. Target-mediated drug disposition was regarded as an important feature for generation of PK models. Complex PK-models may not be necessary when a limited number of organs are affected. More mechanistic PK/PD models will be relevant when adverse events/toxicity are included in the PK/PD modelling.

Physiology-based modelling approaches to characterize fish habitat suitability: Their usefulness and limitations

Science.gov (United States)

Teal, Lorna R.; Marras, Stefano; Peck, Myron A.; Domenici, Paolo

2018-02-01

empirical relationships which can be found consistently within physiological data across the animal kingdom. The advantages of the DEB models are that they make use of the generalities found in terms of animal physiology and can therefore be applied to species for which little data or empirical observations are available. In addition, the limitations as well as useful potential refinements of these and other physiology-based modelling approaches are discussed. Inclusion of the physiological response of various life stages and modelling the patterns of extreme events observed in nature are suggested for future work.

Can toxicokinetic and toxicodynamic modeling be used to understand and predict synergistic interactions between chemicals?

DEFF Research Database (Denmark)

Cedergreen, Nina; Dalhoff, Kristoffer; Li, Dan

2017-01-01

including synergists. The aim of the present study is to develop a mechanistic toxicokinetic (TK) and toxicodynamic (TD) model for the synergistic mixture of the azole fungicide, propiconazole (the synergist), and the insecticide, α-cypermethrin, on the mortality of the crustacean Daphnia magna. The study...... by their effect on the biotransformation rate but that this effect could only partly be explained by the effect of the two azoles on cytochrome P450 activity, measured on D. magna in vivo. TKTD models of interacting mixtures seem to be a promising tool to test mechanisms of interactions between chemicals...

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.

Science.gov (United States)

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.

Physiological Based Simulator Fidelity Design Guidance

Science.gov (United States)

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.

DICHLOROACETATE TOXICOKINETICS AND DISRUPTION OF TYROSINE CATABOLISM IN B6C3F1 MICE: DOSE RESPONSE RELATIONSHIPS AND AGE AS A MODIFYING FACTOR. (R825954)

Science.gov (United States)

Dichloroacetate (DCA) is a rodent carcinogen commonly found in municipal drinking water supplies. Toxicokinetic studies have established that elimination of DCA is controlled by liver metabolism, which occurs by the cytosolic enzyme glutathione-S-transferase-zeta (GST-z...

Toxico-kinetic, chemical and radiological toxicity of uranium on zebra fish (Danio rerio)

International Nuclear Information System (INIS)

Barillet, S.

2007-06-01

This thesis explores the toxico-kinetic and toxicological aspects of uranium in fish. Uranium, appears to be highly bio accumulated and bio concentrated in fish. It spreads all through the whole organism. Nevertheless, its distribution is heterogeneous (gills and liver being the main sites of accumulation).From a toxicological point of view, we notice perturbations of the antioxidant system (inhibitions of hepatic Sod, Cat and G Px activities; depletion of total GSH) and of the cholinergic system (inhibition/over-activation of brain AChE). Genotoxic effects also appear in red blood cells, hepatocytes and gonad cells. The kinetics of these biochemical perturbations depend on the radiological activity of uranium, responses appearing earlier with increasing delivered activity. Histological effects (differing in types depending on delivered radiological activity) are also observed (in gills and muscles). (author)

Using US EPA’s Chemical Safety for Sustainability’s Comptox Chemistry Dashboard and Tools for Bioactivity, Chemical and Toxicokinetic Modeling Analyses (Course at 2017 ISES Annual Meeting)

Science.gov (United States)

Title: Using US EPA’s Chemical Safety for Sustainability’s Comptox Chemistry Dashboard and Tools for Bioactivity, Chemical and Toxicokinetic Modeling Analyses • Class format: half-day (4 hours) • Course leader(s): Barbara A. Wetmore and Antony J. Williams,...

Feasibility Analysis of Incorporating In-Vitro Toxicokinetic Data ...

Science.gov (United States)

The underlying principle of read-across is that biological activity is a function of physical and structural properties of chemicals. Analogs are typically identified on the basis of structural similarity and subsequently evaluated for their use in read-across on the basis of their bioavailability, reactivity and metabolic similarity. While the concept of similarity is the major tenet in grouping chemicals for read-across, a critical consideration is to evaluate if structural differences significantly impact toxicological activity. This is a key source of uncertainty in read-across predictions. We hypothesize that inclusion of toxicokinetic (TK) information will reduce the uncertainty in read-across predictions. TK information can help substantiate whether chemicals within a category have similar ADME properties and, hence, increase the likelihood of exhibiting similar toxicological properties. This current case study is part of a larger study aimed at performing a systematic assessment of the extent to which in-vitro TK data can obviate in-vivo TK data, while maintaining or increasing scientific confidence in read-across predictions. The analysis relied on a dataset of ~7k chemicals with predicted exposure data (chemical inventory), of which 819 chemicals had rat and/or human in-vitro TK data (analog inventory), and 33 chemicals had rat in-vivo TK data (target inventory). The set of chemicals with human in vitro TK data was investigated to determine whether str

Oral Exposure and Absorption of Toxicants

Science.gov (United States)

This chapter provides an overview of the toxicokinetics of orally absorbed xenobiotics. This includes a description of the basic anatomy and physiology of the digestive tract most relevant to the absorption process. In addition, differences in anatomy and physiology between human...

Bioaccumulation, toxicokinetics, and effects of copper from sediment spiked with aqueous Cu, nano-CuO, or micro-CuO in the deposit-feeding snail, Potamopyrgus antipodarum

DEFF Research Database (Denmark)

Pang, Chengfang; Selck, Henriette; Banta, Gary Thomas

2013-01-01

The present study examined the relative importance of copper (aqueous Cu and CuO particles of different sizes) added to sediment to determine the bioaccumulation, toxicokinetics, and effects in the deposit feeder Potamopyrgus antipodarum. In experiment 1, the bioaccumulation of Cu (240 mg Cu/g dr...

Toxicokinetics of zinc oxide nanoparticles in rats

International Nuclear Information System (INIS)

Chung, H E; Yu, J; Baek, M; Lee, J A; Choi, S J; Kim, M S; Kim, S H; Maeng, E H; Lee, J K; Jeong, J

2013-01-01

Zinc oxide (ZnO) nanoparticle have been extensively applied to diverse industrial fields because they possess UV light absorption, catalytic, semi-conducting, and magnetic characteristics as well as antimicrobial property. However, up to date, toxicological effects of ZnO nanoparticles in animal models have not been completely determined. Moreover, little information is available about kinetic behaviors of ZnO nanoparticles in vivo, which will be crucial to predict their potential chronic toxicity after long-term exposure. The aim of this study was, therefore, to evaluate the pharmacokinetics and toxicokinetics of ZnO nanoparticles after single-dose and repeated dose 90-day oral administration in male and female rats, respectively. The blood samples were collected following administration of three different doses (125, 250, and 500 mg/kg) and ZnO concentration was assessed by measuring zinc level with inductively coupled plasma-atomic emission spectroscopy (ICP-AES). The result showed that the plasma ZnO concentration significantly increased in a dose-dependent manner, but decreased within 24 h after single-dose oral administration up to 500 mg/kg, without any significant difference between gender. However, when repeated dose 90-day oral toxicity study was performed, the elevated plasma concentrations did not return to normal control levels in all the cases, indicating their toxicity potential. These findings suggest that repeated oral exposure to ZnO nanoparticles up to the dose of 125 mg/kg could accumulate in the systemic circulation, thereby implying that the NOAEL values could be less than 125 mg/kg via oral intake.

Assessing Acid-Base Status: Physiologic Versus Physicochemical Approach.

Science.gov (United States)

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, Paco 2 ) 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 Paco 2 . 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.

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

Science.gov (United States)

Nybo, Lars; May, Michael

2015-06-01

The present study was conducted to investigate the effects of changing a laboratory physiology course for undergraduate students from a traditional step-by-step guided structure to an inquiry-based approach. With this aim in mind, quantitative and qualitative evaluations of learning outcomes (individual subject-specific tests and group interviews) were performed for a laboratory course in cardiorespiratory exercise physiology that was conducted in one year with a traditional step-by-step guided manual (traditional course) and the next year completed with an inquiry-based structure (I-based course). The I-based course was a guided inquiry course where students had to design the experimental protocol and conduct their own study on the basis of certain predefined criteria (i.e., they should evaluate respiratory responses to submaximal and maximal exercise and provide indirect and direct measures of aerobic exercise capacity). The results indicated that the overall time spent on the experimental course as well as self-evaluated learning outcomes were similar across groups. However, students in the I-based course used more time in preparation (102 ± 5 min) than students in the traditional course (42 ± 3 min, P traditional course. Furthermore, students in the I-based course achieved a higher (P traditional course (31 ± 4%). Although students were unfamiliar with cardiorespiratory exercise physiology and the experimental methods before the course, it appears that an inquiry-based approach rather than one that provides students with step-by-step instructions may benefit learning outcomes in a laboratory physiology course. Copyright © 2015 The American Physiological Society.

Successful implementation of inquiry-based physiology laboratories in undergraduate major and nonmajor courses.

Science.gov (United States)

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

2008-12-01

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 modifications were to improve the teaching of physiological concepts, teach students the scientific approach, and promote creative and critical thinking. We assessed our modifications using formative (laboratory exams, oral presentations, and laboratory reports) and summative evaluations (surveys, laboratory notebook, and an end of semester project). Students appreciated the freedom offered by the new curriculum and the opportunity to engage in the inquiry process. Results from both forms of evaluation showed a marked improvement due to the curricular revisions. Our analyses indicate an increased confidence in students' ability to formulate questions and hypotheses, design experiments, collect and analyze data, and make conclusions. Thus, we have successfully incorporated inquiry-based laboratories in both major and nonmajor courses.

A physiologically informed virtual reality based social communication system for individuals with autism.

Science.gov (United States)

Lahiri, Uttama; Bekele, Esubalew; Dohrmann, Elizabeth; Warren, Zachary; Sarkar, Nilanjan

2015-04-01

Clinical applications of advanced technology may hold promise for addressing impairments associated with autism spectrum disorders (ASD). This project evaluated the application of a novel physiologically responsive virtual reality based technological system for conversation skills in a group of adolescents with ASD. The system altered components of conversation based on (1) performance alone or (2) the composite effect of performance and physiological metrics of predicted engagement (e.g., gaze pattern, pupil dilation, blink rate). Participants showed improved performance and looking pattern within the physiologically sensitive system as compared to the performance based system. This suggests that physiologically informed technologies may have the potential of being an effective tool in the hands of interventionists.

Zebrafish Bone and General Physiology Are Differently Affected by Hormones or Changes in Gravity.

Science.gov (United States)

Aceto, Jessica; Nourizadeh-Lillabadi, Rasoul; Marée, Raphael; Dardenne, Nadia; Jeanray, Nathalie; Wehenkel, Louis; Aleström, Peter; van Loon, Jack J W A; Muller, Marc

2015-01-01

Teleost fish such as zebrafish (Danio rerio) are increasingly used for physiological, genetic and developmental studies. Our understanding of the physiological consequences of altered gravity in an entire organism is still incomplete. We used altered gravity and drug treatment experiments to evaluate their effects specifically on bone formation and more generally on whole genome gene expression. By combining morphometric tools with an objective scoring system for the state of development for each element in the head skeleton and specific gene expression analysis, we confirmed and characterized in detail the decrease or increase of bone formation caused by a 5 day treatment (from 5dpf to 10 dpf) of, respectively parathyroid hormone (PTH) or vitamin D3 (VitD3). Microarray transcriptome analysis after 24 hours treatment reveals a general effect on physiology upon VitD3 treatment, while PTH causes more specifically developmental effects. Hypergravity (3g from 5dpf to 9 dpf) exposure results in a significantly larger head and a significant increase in bone formation for a subset of the cranial bones. Gene expression analysis after 24 hrs at 3g revealed differential expression of genes involved in the development and function of the skeletal, muscular, nervous, endocrine and cardiovascular systems. Finally, we propose a novel type of experimental approach, the "Reduced Gravity Paradigm", by keeping the developing larvae at 3g hypergravity for the first 5 days before returning them to 1g for one additional day. 5 days exposure to 3g during these early stages also caused increased bone formation, while gene expression analysis revealed a central network of regulatory genes (hes5, sox10, lgals3bp, egr1, edn1, fos, fosb, klf2, gadd45ba and socs3a) whose expression was consistently affected by the transition from hyper- to normal gravity.

Zebrafish Bone and General Physiology Are Differently Affected by Hormones or Changes in Gravity.

Directory of Open Access Journals (Sweden)

Jessica Aceto

Full Text Available Teleost fish such as zebrafish (Danio rerio are increasingly used for physiological, genetic and developmental studies. Our understanding of the physiological consequences of altered gravity in an entire organism is still incomplete. We used altered gravity and drug treatment experiments to evaluate their effects specifically on bone formation and more generally on whole genome gene expression. By combining morphometric tools with an objective scoring system for the state of development for each element in the head skeleton and specific gene expression analysis, we confirmed and characterized in detail the decrease or increase of bone formation caused by a 5 day treatment (from 5dpf to 10 dpf of, respectively parathyroid hormone (PTH or vitamin D3 (VitD3. Microarray transcriptome analysis after 24 hours treatment reveals a general effect on physiology upon VitD3 treatment, while PTH causes more specifically developmental effects. Hypergravity (3g from 5dpf to 9 dpf exposure results in a significantly larger head and a significant increase in bone formation for a subset of the cranial bones. Gene expression analysis after 24 hrs at 3g revealed differential expression of genes involved in the development and function of the skeletal, muscular, nervous, endocrine and cardiovascular systems. Finally, we propose a novel type of experimental approach, the "Reduced Gravity Paradigm", by keeping the developing larvae at 3g hypergravity for the first 5 days before returning them to 1g for one additional day. 5 days exposure to 3g during these early stages also caused increased bone formation, while gene expression analysis revealed a central network of regulatory genes (hes5, sox10, lgals3bp, egr1, edn1, fos, fosb, klf2, gadd45ba and socs3a whose expression was consistently affected by the transition from hyper- to normal gravity.

Dose selection based on physiologically based pharmacokinetic (PBPK) approaches.

Science.gov (United States)

Jones, Hannah M; Mayawala, Kapil; Poulin, Patrick

2013-04-01

Physiologically based pharmacokinetic (PBPK) models are built using differential equations to describe the physiology/anatomy of different biological systems. Readily available in vitro and in vivo preclinical data can be incorporated into these models to not only estimate pharmacokinetic (PK) parameters and plasma concentration-time profiles, but also to gain mechanistic insight into compound properties. They provide a mechanistic framework to understand and extrapolate PK and dose across in vitro and in vivo systems and across different species, populations and disease states. Using small molecule and large molecule examples from the literature and our own company, we have shown how PBPK techniques can be utilised for human PK and dose prediction. Such approaches have the potential to increase efficiency, reduce the need for animal studies, replace clinical trials and increase PK understanding. Given the mechanistic nature of these models, the future use of PBPK modelling in drug discovery and development is promising, however some limitations need to be addressed to realise its application and utility more broadly.

Refined generalized multiscale entropy analysis for physiological signals

Science.gov (United States)

Liu, Yunxiao; Lin, Youfang; Wang, Jing; Shang, Pengjian

2018-01-01

Multiscale entropy analysis has become a prevalent complexity measurement and been successfully applied in various fields. However, it only takes into account the information of mean values (first moment) in coarse-graining procedure. Then generalized multiscale entropy (MSEn) considering higher moments to coarse-grain a time series was proposed and MSEσ2 has been implemented. However, the MSEσ2 sometimes may yield an imprecise estimation of entropy or undefined entropy, and reduce statistical reliability of sample entropy estimation as scale factor increases. For this purpose, we developed the refined model, RMSEσ2, to improve MSEσ2. Simulations on both white noise and 1 / f noise show that RMSEσ2 provides higher entropy reliability and reduces the occurrence of undefined entropy, especially suitable for short time series. Besides, we discuss the effect on RMSEσ2 analysis from outliers, data loss and other concepts in signal processing. We apply the proposed model to evaluate the complexity of heartbeat interval time series derived from healthy young and elderly subjects, patients with congestive heart failure and patients with atrial fibrillation respectively, compared to several popular complexity metrics. The results demonstrate that RMSEσ2 measured complexity (a) decreases with aging and diseases, and (b) gives significant discrimination between different physiological/pathological states, which may facilitate clinical application.

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

Science.gov (United States)

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

2015-09-01

Students entering medical college generally show vast diversity in their school education. It becomes the responsibility of teachers to motivate students and meet the needs of all diversities. One such measure is teaching students in their own preferred learning style. The present study was aimed to incorporate a learning style-based teaching-learning program for medical students and to reveal its significance and utility. Learning styles of students were assessed online using the visual-auditory-kinesthetic (VAK) learning style self-assessment questionnaire. When respiratory physiology was taught, students were divided into three groups, namely, visual (n = 34), auditory (n = 44), and kinesthetic (n = 28), based on their learning style. A fourth group (the traditional group; n = 40) was formed by choosing students randomly from the above three groups. Visual, auditory, and kinesthetic groups were taught following the appropriate teaching-learning strategies. The traditional group was taught via the routine didactic lecture method. The effectiveness of this intervention was evaluated by a pretest and two posttests, posttest 1 immediately after the intervention and posttest 2 after a month. In posttest 1, one-way ANOVA showed a significant statistical difference (P=0.005). Post hoc analysis showed significance between the kinesthetic group and traditional group (P=0.002). One-way ANOVA showed a significant difference in posttest 2 scores (P learning style-based groups compared with the traditional group [visual vs. traditional groups (p=0.002), auditory vs. traditional groups (p=0.03), and Kinesthetic vs. traditional groups (p=0.001)]. This study emphasizes that teaching methods tailored to students' style of learning definitely improve their understanding, performance, and retrieval of the subject. Copyright © 2015 The American Physiological Society.

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

Science.gov (United States)

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

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

Science.gov (United States)

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.

Contactless physiological signals extraction based on skin color magnification

Science.gov (United States)

Suh, Kun Ha; Lee, Eui Chul

2017-11-01

Although the human visual system is not sufficiently sensitive to perceive blood circulation, blood flow caused by cardiac activity makes slight changes on human skin surfaces. With advances in imaging technology, it has become possible to capture these changes through digital cameras. However, it is difficult to obtain clear physiological signals from such changes due to its fineness and noise factors, such as motion artifacts and camera sensing disturbances. We propose a method for extracting physiological signals with improved quality from skin colored-videos recorded with a remote RGB camera. The results showed that our skin color magnification method reveals the hidden physiological components remarkably in the time-series signal. A Korea Food and Drug Administration-approved heart rate monitor was used for verifying the resulting signal synchronized with the actual cardiac pulse, and comparisons of signal peaks showed correlation coefficients of almost 1.0. In particular, our method can be an effective preprocessing before applying additional postfiltering techniques to improve accuracy in image-based physiological signal extractions.

General physiology, experimental psychology, and evolutionism. Unicellular organisms as objects of psychophysiological research, 1877-1918.

Science.gov (United States)

Schloegel, Judy Johns; Schmidgen, Henning

2002-12-01

This essay aims to shed new light on the relations between physiology and psychology in the late nineteenth and early twentieth centuries by focusing on the use of unicellular organisms as research objects during that period. Within the frameworks of evolutionism and monism advocated by Ernst Haeckel, protozoa were perceived as objects situated at the borders between organism and cell and individual and society. Scholars such as Max Verworn, Alfred Binet, and Herbert Spencer Jennings were provoked by these organisms to undertake experimental investigations situated between general physiology and psychology that differed from the physiological psychology advocated by Wilhelm Wundt. Some of these investigations sought to locate psychological properties in the molecular structure of protoplasm; others stressed the existence of organic and psychological individuality in protozoa. In the following decades, leading philosophers such as Friedrich Nietzsche, Charles Sanders Peirce, and Henri Bergson, as well as psychological researchers like Sigmund Freud, integrated the results of these investigations into their reflections on such problems as the nature of the will, the structure of the ego, and the holistic nature of the reactions of organisms to their environment.

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

Science.gov (United States)

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

2016-01-01

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

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

DEFF Research Database (Denmark)

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

2010-01-01

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

A comprehensive physiologically based pharmacokinetic ...

Science.gov (United States)

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

Toxicokinetics of mercury in blood compartments and hair of fish-fed sled dogs

Directory of Open Access Journals (Sweden)

Lieske Camilla L

2011-12-01

Full Text Available Abstract Background Understanding mercury (Hg distribution in blood and the importance of hair as an excretory pathway is critical for evaluating risk from long term dietary Hg exposure. The major objective of this study was to characterize changes in total Hg concentrations in specific blood compartments and hair over time due to long term piscivory. Methods Eight sled dogs (Canis lupus familiaris were fed either a fish and kibble diet (n = 4, or a fish-free control diet (n = 4 for 12 weeks. Concentrations of Hg were monitored throughout the exposure period, and for 10 weeks post exposure, until Hg concentrations in all blood compartments of one of the exposed dogs dropped below detection limit. Additionally, foreleg hair was sampled during acclimation and weeks 0 and 12. Results Hg was detected primarily in whole blood and packed cells, although it was sporadically detected at low concentrations in plasma and serum in two of the fish fed dogs. Dogs ingested an estimated average of 13.4 ± 0.58 μg Hg per kg body weight per day. Hg was detectable in whole blood and packed cells within a week of exposure. Detected concentrations continued to rise until plateauing at approximately 3-6 weeks of exposure at a mean of 9.2 ± 1.97 ng/g (ppb in whole blood. Hg concentration decreased post exposure following 1st order elimination. The mean half-life (t1/2 in whole blood for Hg was 7 weeks. Mean Hg in hair for the fish-fed dogs at week 12 was 540 ± 111 ppb and was significantly greater (about 7-fold than the Hg hair concentration for the control dogs. The hair to blood ratio for Hg in fish-fed dogs was 59.0 ± 7.6:1. Conclusions This study found the sled dog model to be an effective method for investigating and characterizing blood Hg distribution (whole blood, serum, plasma, packed cells and toxicokinetics associated with a piscivorous diet, especially for Hg-exposed fur bearing mammals (such as polar bears. Although hair excretion and hair to blood

Comparative toxicokinetics of MMB4 DMS in rats, rabbits, dogs, and monkeys following single and repeated intramuscular administration.

Science.gov (United States)

Hong, S Peter; Gibbs, Seth T; Kobs, Dean J; Hawk, Michael A; Croutch, Claire R; Osheroff, Merrill R; Johnson, Jerry D; Burback, Brian L

2013-01-01

1,1'-Methylenebis[4-[(hydroxyimino)methyl]-pyridinium] (MMB4) dimethanesulfonate (DMS) is a bisquaternary pyridinium aldoxime that reactivates acetylcholinesterase inhibited by organophosphorus nerve agent. Time courses of MMB4 concentrations in plasma were characterized following 7-day repeated intramuscular (IM) administrations of MMB4 DMS to male and female Sprague-Dawley rats, New Zealand White rabbits, beagle dogs (single dose only), and rhesus monkeys at drug dose levels used in earlier toxicology studies. In general, there were no significant differences in MMB4 toxicokinetic (TK) parameters between males and females for all the species tested in these studies. After a single IM administration to rats, rabbits, dogs, and monkeys, MMB4 DMS was rapidly absorbed, resulting in average T max values ranging from 5 to 30 minutes. Although C max values did not increase dose proportionally, the overall exposure to MMB4 in these preclinical species, as indicated by area under the curve (AUC) extrapolated to the infinity (AUC∞) values, increased in an approximately dose-proportional manner. The MMB4 DMS was extensively absorbed into the systemic circulation after IM administration as demonstrated by greater than 80% absolute bioavailability values for rats, rabbits, and dogs. Repeated administrations of MMB4 DMS for 7 days did not overtly alter TK parameters for MMB4 in rats, rabbits, and monkeys (150 and 300 mg/kg/d dose groups only). However, C max and AUC values decreased in monkeys given 450 and 600 mg/kg IM doses of MMB4 DMS following repeated administrations for 7 days. Based on the TK results obtained from the current study and published investigations, it was found that the apparent volume of distribution and clearance values were similar among various preclinical species, except for the rat.

Improving in vitro to in vivo extrapolation by incorporating toxicokinetic measurements: A case study of lindane-induced neurotoxicity

Energy Technology Data Exchange (ETDEWEB)

Croom, Edward L.; Shafer, Timothy J.; Evans, Marina V.; Mundy, William R.; Eklund, Chris R.; Johnstone, Andrew F.M.; Mack, Cina M.; Pegram, Rex A., E-mail: pegram.rex@epa.gov

2015-02-15

Approaches for extrapolating in vitro toxicity testing results for prediction of human in vivo outcomes are needed. The purpose of this case study was to employ in vitro toxicokinetics and PBPK modeling to perform in vitro to in vivo extrapolation (IVIVE) of lindane neurotoxicity. Lindane cell and media concentrations in vitro, together with in vitro concentration-response data for lindane effects on neuronal network firing rates, were compared to in vivo data and model simulations as an exercise in extrapolation for chemical-induced neurotoxicity in rodents and humans. Time- and concentration-dependent lindane dosimetry was determined in primary cultures of rat cortical neurons in vitro using “faux” (without electrodes) microelectrode arrays (MEAs). In vivo data were derived from literature values, and physiologically based pharmacokinetic (PBPK) modeling was used to extrapolate from rat to human. The previously determined EC{sub 50} for increased firing rates in primary cultures of cortical neurons was 0.6 μg/ml. Media and cell lindane concentrations at the EC{sub 50} were 0.4 μg/ml and 7.1 μg/ml, respectively, and cellular lindane accumulation was time- and concentration-dependent. Rat blood and brain lindane levels during seizures were 1.7–1.9 μg/ml and 5–11 μg/ml, respectively. Brain lindane levels associated with seizures in rats and those predicted for humans (average = 7 μg/ml) by PBPK modeling were very similar to in vitro concentrations detected in cortical cells at the EC{sub 50} dose. PBPK model predictions matched literature data and timing. These findings indicate that in vitro MEA results are predictive of in vivo responses to lindane and demonstrate a successful modeling approach for IVIVE of rat and human neurotoxicity. - Highlights: • In vitro to in vivo extrapolation for lindane neurotoxicity was performed. • Dosimetry of lindane in a micro-electrode array (MEA) test system was assessed. • Cell concentrations at the MEA EC

Nasal Physiology

Science.gov (United States)

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

Using measures of single-cell physiology and physiological state to understand organismic aging.

Science.gov (United States)

Mendenhall, Alexander; Driscoll, Monica; Brent, Roger

2016-02-01

Genetically identical organisms in homogeneous environments have different lifespans and healthspans. These differences are often attributed to stochastic events, such as mutations and 'epimutations', changes in DNA methylation and chromatin that change gene function and expression. But work in the last 10 years has revealed differences in lifespan- and health-related phenotypes that are not caused by lasting changes in DNA or identified by modifications to DNA or chromatin. This work has demonstrated persistent differences in single-cell and whole-organism physiological states operationally defined by values of reporter gene signals in living cells. While some single-cell states, for example, responses to oxygen deprivation, were defined previously, others, such as a generally heightened ability to make proteins, were, revealed by direct experiment only recently, and are not well understood. Here, we review technical progress that promises to greatly increase the number of these measurable single-cell physiological variables and measureable states. We discuss concepts that facilitate use of single-cell measurements to provide insight into physiological states and state transitions. We assert that researchers will use this information to relate cell level physiological readouts to whole-organism outcomes, to stratify aging populations into groups based on different physiologies, to define biomarkers predictive of outcomes, and to shed light on the molecular processes that bring about different individual physiologies. For these reasons, quantitative study of single-cell physiological variables and state transitions should provide a valuable complement to genetic and molecular explanations of how organisms age. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

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

International Nuclear Information System (INIS)

Badugu, Ramachandram; Lakowicz, Joseph R.; Geddes, Chris D.

2004-01-01

We characterize six new fluorescent probes that show both intensity and lifetime changes in the presence of free uncomplexed aqueous cyanide, allowing for fluorescence based cyanide sensing up to physiological safeguard levels, i.e. 2 to the anionic R-B - (CN) 3 form, a new cyanide binding mechanism which we have recently reported. The presence of an electron deficient quaternary heterocyclic nitrogen nucleus, and the electron rich cyanide bound form, provides for the intensity changes observed. We have determined the disassociation constants of the probes to be in the range ∼15-84 μM 3 . In addition we have synthesized control compounds which do not contain the boronic acid moiety, allowing for a rationale of the cyanide responses between the probe isomers to be made. The lifetime of the cyanide bound probes are significantly shorter than the free R-B(OH) 2 probe forms, providing for the opportunity of lifetime based cyanide sensing up to physiologically lethal levels. Finally, while fluorescent probes containing the boronic acid moiety have earned a well-deserved reputation for monosaccharide sensing, we show that strong bases such as CN - and OH - preferentially bind as compared to glucose, enabling the potential use of these probes for cyanide safeguard and determination in physiological fluids, especially given that physiologies do not experience any notable changes in pH

The Impact of Deoxynivalenol on Pigeon Health: Occurrence in Feed, Toxicokinetics and Interaction with Salmonellosis.

Science.gov (United States)

Antonissen, Gunther; Haesendonck, Roel; Devreese, Mathias; Broekaert, Nathan; Verbrugghe, Elin; De Saeger, Sarah; Audenaert, Kris; Haesebrouck, Freddy; Pasmans, Frank; Ducatelle, Richard; Croubels, Siska; Martel, An

2016-01-01

Seed-based pigeon diets could be expected to result in exposure of pigeons to mycotoxins such as deoxynivalenol (DON). Ingestion of low to moderate contamination levels of DON may impair intestinal health, immune function and/or pathogen fitness, resulting in altered host-pathogen interactions and thus different outcome of infections. Here we demonstrate that DON was one of the most frequently detected mycotoxins in seed-based racing pigeons feed, contaminating 5 out of 10 samples (range 177-1,466 μg/kg). Subsequently, a toxicokinetic analysis revealed a low absolute oral bioavailability (F) of DON in pigeons (30.4%), which is comparable to other avian species. Furthermore, semi-quantitative analysis using high-resolution mass spectrometry revealed that DON-3α-sulphate is the major metabolite of DON in pigeons after intravenous as well as oral administration. Following ingestion of DON contaminated feed, the intestinal epithelial cells are exposed to significant DON concentrations which eventually may affect intestinal translocation and colonization of bacteria. Feeding pigeons a DON contaminated diet resulted in an increased percentage of pigeons shedding Salmonella compared to birds fed control diet, 87 ± 17% versus 74 ± 13%, respectively. However, no impact of DON was observed on the Salmonella induced disease signs, organ lesions, faecal and organ Salmonella counts. The presented risk assessment indicates that pigeons are frequently exposed to mycotoxins such as DON, which can affect the outcome of a Salmonella infection. The increasing number of pigeons shedding Salmonella suggests that DON can promote the spread of the bacterium within pigeon populations.

The Impact of Deoxynivalenol on Pigeon Health: Occurrence in Feed, Toxicokinetics and Interaction with Salmonellosis.

Directory of Open Access Journals (Sweden)

Gunther Antonissen

Full Text Available Seed-based pigeon diets could be expected to result in exposure of pigeons to mycotoxins such as deoxynivalenol (DON. Ingestion of low to moderate contamination levels of DON may impair intestinal health, immune function and/or pathogen fitness, resulting in altered host-pathogen interactions and thus different outcome of infections. Here we demonstrate that DON was one of the most frequently detected mycotoxins in seed-based racing pigeons feed, contaminating 5 out of 10 samples (range 177-1,466 μg/kg. Subsequently, a toxicokinetic analysis revealed a low absolute oral bioavailability (F of DON in pigeons (30.4%, which is comparable to other avian species. Furthermore, semi-quantitative analysis using high-resolution mass spectrometry revealed that DON-3α-sulphate is the major metabolite of DON in pigeons after intravenous as well as oral administration. Following ingestion of DON contaminated feed, the intestinal epithelial cells are exposed to significant DON concentrations which eventually may affect intestinal translocation and colonization of bacteria. Feeding pigeons a DON contaminated diet resulted in an increased percentage of pigeons shedding Salmonella compared to birds fed control diet, 87 ± 17% versus 74 ± 13%, respectively. However, no impact of DON was observed on the Salmonella induced disease signs, organ lesions, faecal and organ Salmonella counts. The presented risk assessment indicates that pigeons are frequently exposed to mycotoxins such as DON, which can affect the outcome of a Salmonella infection. The increasing number of pigeons shedding Salmonella suggests that DON can promote the spread of the bacterium within pigeon populations.

Genetic approaches in comparative and evolutionary physiology

Science.gov (United States)

Bridgham, Jamie T.; Kelly, Scott A.; Garland, Theodore

2015-01-01

Whole animal physiological performance is highly polygenic and highly plastic, and the same is generally true for the many subordinate traits that underlie performance capacities. Quantitative genetics, therefore, provides an appropriate framework for the analysis of physiological phenotypes and can be used to infer the microevolutionary processes that have shaped patterns of trait variation within and among species. In cases where specific genes are known to contribute to variation in physiological traits, analyses of intraspecific polymorphism and interspecific divergence can reveal molecular mechanisms of functional evolution and can provide insights into the possible adaptive significance of observed sequence changes. In this review, we explain how the tools and theory of quantitative genetics, population genetics, and molecular evolution can inform our understanding of mechanism and process in physiological evolution. For example, lab-based studies of polygenic inheritance can be integrated with field-based studies of trait variation and survivorship to measure selection in the wild, thereby providing direct insights into the adaptive significance of physiological variation. Analyses of quantitative genetic variation in selection experiments can be used to probe interrelationships among traits and the genetic basis of physiological trade-offs and constraints. We review approaches for characterizing the genetic architecture of physiological traits, including linkage mapping and association mapping, and systems approaches for dissecting intermediary steps in the chain of causation between genotype and phenotype. We also discuss the promise and limitations of population genomic approaches for inferring adaptation at specific loci. We end by highlighting the role of organismal physiology in the functional synthesis of evolutionary biology. PMID:26041111

Toxicokinetics of α-thujone following intravenous and gavage administration of α-thujone or α- and β-thujone mixture in male and female F344/N rats and B6C3F1 mice

International Nuclear Information System (INIS)

Waidyanatha, Suramya; Johnson, Jerry D.; Hong, S. Peter; Robinson, Veronica Godfrey; Gibbs, Seth; Graves, Steven W.; Hooth, Michelle J.; Smith, Cynthia S.

2013-01-01

Plants containing thujone have widespread use and hence have significant human exposure. α-Thujone caused seizures in rodents following gavage administration. We investigated the toxicokinetics of α-thujone in male and female F344/N rats and B6C3F1 mice following intravenous and gavage administration of α-thujone or a mixture of α- and β-thujone (which will be referred to as α,β-thujone). Absorption of α-thujone following gavage administration was rapid without any dose-, species-, sex- or test article-related effect. Absolute bioavailability of α-thujone following administration of α-thujone or α,β-thujone was generally higher in rats than in mice. In rats, females had higher bioavailability than males following administration of either test article although a sex difference was not observed in mice. C max and AUC ∞ increased greater than proportional to the dose in female rats following administration of α-thujone and in male and female mice following administration of α,β-thujone suggesting possible saturation of elimination kinetics with increasing dose. Dose-adjusted AUC ∞ for male and female rats was 5- to 15-fold and 3- to 24-fold higher than mice counterparts following administration of α-thujone and α,β-thujone, respectively (p-value < 0.0001 for all comparisons). Following both intravenous and gavage administration, α-thujone was distributed to the brains of rats and mice with females, in general, having higher brain:plasma ratios than males. These data are in support of the observed toxicity of α-thujone and α,β-thujone where females were more sensitive than males of both species to α-thujone-induced neurotoxicity. In general there was no difference in toxicokinetics between test articles when normalized to α-thujone concentration. - Highlights: • Absorption of α-thujone following gavage administration was rapid in rats and mice. • Rats undergo higher exposure to α-thujone than mice. • α-Thujone brain:plasma ratios

Toxicokinetics of α-thujone following intravenous and gavage administration of α-thujone or α- and β-thujone mixture in male and female F344/N rats and B6C3F1 mice

Energy Technology Data Exchange (ETDEWEB)

Waidyanatha, Suramya, E-mail: waidyanathas@niehs.nih.gov [Division of National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States); Johnson, Jerry D.; Hong, S. Peter [Battelle Memorial Institute, Columbus, OH 43201 (United States); Robinson, Veronica Godfrey [Division of National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States); Gibbs, Seth; Graves, Steven W. [Battelle Memorial Institute, Columbus, OH 43201 (United States); Hooth, Michelle J.; Smith, Cynthia S. [Division of National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States)

2013-09-01

Plants containing thujone have widespread use and hence have significant human exposure. α-Thujone caused seizures in rodents following gavage administration. We investigated the toxicokinetics of α-thujone in male and female F344/N rats and B6C3F1 mice following intravenous and gavage administration of α-thujone or a mixture of α- and β-thujone (which will be referred to as α,β-thujone). Absorption of α-thujone following gavage administration was rapid without any dose-, species-, sex- or test article-related effect. Absolute bioavailability of α-thujone following administration of α-thujone or α,β-thujone was generally higher in rats than in mice. In rats, females had higher bioavailability than males following administration of either test article although a sex difference was not observed in mice. C{sub max} and AUC{sub ∞} increased greater than proportional to the dose in female rats following administration of α-thujone and in male and female mice following administration of α,β-thujone suggesting possible saturation of elimination kinetics with increasing dose. Dose-adjusted AUC{sub ∞} for male and female rats was 5- to 15-fold and 3- to 24-fold higher than mice counterparts following administration of α-thujone and α,β-thujone, respectively (p-value < 0.0001 for all comparisons). Following both intravenous and gavage administration, α-thujone was distributed to the brains of rats and mice with females, in general, having higher brain:plasma ratios than males. These data are in support of the observed toxicity of α-thujone and α,β-thujone where females were more sensitive than males of both species to α-thujone-induced neurotoxicity. In general there was no difference in toxicokinetics between test articles when normalized to α-thujone concentration. - Highlights: • Absorption of α-thujone following gavage administration was rapid in rats and mice. • Rats undergo higher exposure to α-thujone than mice. • α-Thujone brain

A physiologically based nonhomogeneous Poisson counter model of visual identification

DEFF Research Database (Denmark)

Christensen, Jeppe H; Markussen, Bo; Bundesen, Claus

2018-01-01

A physiologically based nonhomogeneous Poisson counter model of visual identification is presented. The model was developed in the framework of a Theory of Visual Attention (Bundesen, 1990; Kyllingsbæk, Markussen, & Bundesen, 2012) and meant for modeling visual identification of objects that are ......A physiologically based nonhomogeneous Poisson counter model of visual identification is presented. The model was developed in the framework of a Theory of Visual Attention (Bundesen, 1990; Kyllingsbæk, Markussen, & Bundesen, 2012) and meant for modeling visual identification of objects...... that mimicked the dynamics of receptive field selectivity as found in neurophysiological studies. Furthermore, the initial sensory response yielded theoretical hazard rate functions that closely resembled empirically estimated ones. Finally, supplied with a Naka-Rushton type contrast gain control, the model...

Teaching acid/base physiology in the laboratory

DEFF Research Database (Denmark)

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

2010-01-01

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....

Bioaccumulation of trace metals in the Antarctic amphipod Paramoera walkeri (Stebbing, 1906): comparison of two-compartment and hyperbolic toxicokinetic models

International Nuclear Information System (INIS)

Clason, B.; Duquesne, S.; Liess, M.; Schulz, R.; Zauke, G.-P.

2003-01-01

Bioaccumulation of Cd, Pb, Cu and Zn in the Antarctic gammaridean amphipod Paramoera walkeri (Stebbing, 1906) was investigated at Casey station (Australian Antarctic Territory). The main goals were to provide information on accumulation strategies of the organisms tested and to verify toxicokinetic models as a predictive tool. The organisms accumulated metals upon exposure and it was possible to estimate significant model parameters of two-compartment and hyperbolic models. These models were successfully verified in a second toxicokinetic study. However, the application of hyperbolic models appears to be more promising as a predictive tool for metals in amphipods compared to compartment models, which have failed to adequately predict metal accumulation in experiments with increasing external exposures in previous studies. The following kinetic bioconcentration factors (BCFs) for the theoretical equilibrium were determined: 150-630 (Cd), 1600-7000 (Pb), 1700-3800 (Cu) and 670-2400 (Zn). We find decreasing BCFs with increasing external metal dosing but similar results for treatments with and without natural UV radiation and for the combined effect of different exposure regimes (single versus multiple metal exposure) and/or the amphipod collective involved (Beall versus Denison Island). A tentative estimation showed the following sequence of sensitivity of P. walkeri to an increase of soluble metal exposure: 0.2-3.0 μg Cd l -1 , 0.12-0.25 μg Pb l -1 , 0.9-3.0 μg Cu l -1 and 9-26 μg Zn l -1 . Thus, the amphipod investigated proved to be more sensitive as biomonitor compared to gammarids from German coastal waters (with the exception of Cd) and to copepods from the Weddell Sea inferred from literature data

A physiologically based kinetic model for bacterial sulfide oxidation.

Science.gov (United States)

Klok, Johannes B M; de Graaff, Marco; van den Bosch, Pim L F; Boelee, Nadine C; Keesman, Karel J; Janssen, Albert J H

2013-02-01

In the biotechnological process for hydrogen sulfide removal from gas streams, a variety of oxidation products can be formed. Under natron-alkaline conditions, sulfide is oxidized by haloalkaliphilic sulfide oxidizing bacteria via flavocytochrome c oxidoreductase. From previous studies, it was concluded that the oxidation-reduction state of cytochrome c is a direct measure for the bacterial end-product formation. Given this physiological feature, incorporation of the oxidation state of cytochrome c in a mathematical model for the bacterial oxidation kinetics will yield a physiologically based model structure. This paper presents a physiologically based model, describing the dynamic formation of the various end-products in the biodesulfurization process. It consists of three elements: 1) Michaelis-Menten kinetics combined with 2) a cytochrome c driven mechanism describing 3) the rate determining enzymes of the respiratory system of haloalkaliphilic sulfide oxidizing bacteria. The proposed model is successfully validated against independent data obtained from biological respiration tests and bench scale gas-lift reactor experiments. The results demonstrate that the model is a powerful tool to describe product formation for haloalkaliphilic biomass under dynamic conditions. The model predicts a maximum S⁰ formation of about 98 mol%. A future challenge is the optimization of this bioprocess by improving the dissolved oxygen control strategy and reactor design. Copyright © 2012 Elsevier Ltd. All rights reserved.

Bayesian Population Physiologically-Based Pharmacokinetic (PBPK Approach for a Physiologically Realistic Characterization of Interindividual Variability in Clinically Relevant Populations.

Directory of Open Access Journals (Sweden)

Markus Krauss

Full Text Available Interindividual variability in anatomical and physiological properties results in significant differences in drug pharmacokinetics. The consideration of such pharmacokinetic variability supports optimal drug efficacy and safety for each single individual, e.g. by identification of individual-specific dosings. One clear objective in clinical drug development is therefore a thorough characterization of the physiological sources of interindividual variability. In this work, we present a Bayesian population physiologically-based pharmacokinetic (PBPK approach for the mechanistically and physiologically realistic identification of interindividual variability. The consideration of a generic and highly detailed mechanistic PBPK model structure enables the integration of large amounts of prior physiological knowledge, which is then updated with new experimental data in a Bayesian framework. A covariate model integrates known relationships of physiological parameters to age, gender and body height. We further provide a framework for estimation of the a posteriori parameter dependency structure at the population level. The approach is demonstrated considering a cohort of healthy individuals and theophylline as an application example. The variability and co-variability of physiological parameters are specified within the population; respectively. Significant correlations are identified between population parameters and are applied for individual- and population-specific visual predictive checks of the pharmacokinetic behavior, which leads to improved results compared to present population approaches. In the future, the integration of a generic PBPK model into an hierarchical approach allows for extrapolations to other populations or drugs, while the Bayesian paradigm allows for an iterative application of the approach and thereby a continuous updating of physiological knowledge with new data. This will facilitate decision making e.g. from preclinical to

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

Science.gov (United States)

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.

An overview of the toxicology and toxicokinetics of fusarenon-X, a type B trichothecene mycotoxin.

Science.gov (United States)

Aupanun, Sawinee; Poapolathep, Saranya; Giorgi, Mario; Imsilp, Kanjana; Poapolathep, Amnart

2017-01-20

Fusarenon-X (FX) is a type B trichothecene mycotoxin that is frequently observed along with deoxynivalenol (DON) and nivalenol (NIV) in agricultural commodities. This review aims to give an overview of the literature concerning the toxicology and toxicokinetics of FX. FX is primarily found in cereals grown in temperate regions, but it can also be found worldwide because of the global transport of products. The major toxicity of FX occurs through inhibition of protein synthesis, followed by the disruption of DNA synthesis. Moreover, FX has also been shown to induce apoptosis in in vitro and in vivo studies. The targets of FX are organs containing actively proliferating cells, such as the thymus, spleen, skin, small intestine, testes and bone marrow. FX causes immunosuppression, intestinal malabsorption, developmental toxicity and genotoxicity. In addition, sufficient evidence of carcinogenicity in experimental animals is currently lacking, and the International Agency for Research on Cancer (IARC) classifies it as a group 3 carcinogen.

Three-phase metal kinetics in terrestrial invertebrates exposed to high metal concentrations

Energy Technology Data Exchange (ETDEWEB)

Laskowski, Ryszard, E-mail: ryszard.laskowski@uj.edu.pl [Institute of Environmental Sciences, Jagiellonian University, Gronostajowa 7, 30-387 Krakow (Poland); Bednarska, Agnieszka J. [Institute of Environmental Sciences, Jagiellonian University, Gronostajowa 7, 30-387 Krakow (Poland); Spurgeon, David; Svendsen, Claus [Centre for Ecology and Hydrology, Maclean Building, Benson Lane, Crowmarsh Gifford, Wallingford, Oxon, OX10 8BB (United Kingdom); Gestel, Cornelis A.M. van [Institute of Ecological Science, Vrije Universiteit, De Boelelaan 1085, 1081 HV Amsterdam (Netherlands)

2010-08-15

Models of metal toxicokinetics are critically evaluated using both newly generated data in the NoMiracle project as well as those originating from older studies. The analysis showed that the most frequently used one-compartment two-phase toxicokinetic model, with one assimilation and one elimination rate constant, does not describe correctly certain data sets pertaining particularly to the pattern of assimilation of trace elements. Using nickel toxicokinetics in carabid beetles and earthworms as examples, we showed that Ni in fact exhibits a three-phase kinetics with a short phase of fast metal accumulation immediately after exposure, followed by partial elimination to an equilibrium concentration at a later stage of a metal exposure phase, and by final elimination upon transfer to an uncontaminated food/soil. A similar phenomenon was also found for data on cadmium kinetics in ground beetles and copper kinetics in earthworms in data already published in the literature that was not accounted for in the earlier analysis of the data. The three-phase model suggests that the physiology of controlling body metal concentrations can change shortly after exposure, at least in some cases, by increasing the elimination rate and/or decreasing metal assimilation. Hence, the three-phase model, that allows for different assimilation and/or elimination rates in different phases of exposure to a toxicant, may provide insight into temporal changes in the physiology of metal handling. Consequently, this alternative model should always be tested when describing metal toxicokinetics when temporal patterns of internal metal concentration exhibit an initial 'overshoot' in body metal concentrations.

Three-phase metal kinetics in terrestrial invertebrates exposed to high metal concentrations

International Nuclear Information System (INIS)

Laskowski, Ryszard; Bednarska, Agnieszka J.; Spurgeon, David; Svendsen, Claus; Gestel, Cornelis A.M. van

2010-01-01

Models of metal toxicokinetics are critically evaluated using both newly generated data in the NoMiracle project as well as those originating from older studies. The analysis showed that the most frequently used one-compartment two-phase toxicokinetic model, with one assimilation and one elimination rate constant, does not describe correctly certain data sets pertaining particularly to the pattern of assimilation of trace elements. Using nickel toxicokinetics in carabid beetles and earthworms as examples, we showed that Ni in fact exhibits a three-phase kinetics with a short phase of fast metal accumulation immediately after exposure, followed by partial elimination to an equilibrium concentration at a later stage of a metal exposure phase, and by final elimination upon transfer to an uncontaminated food/soil. A similar phenomenon was also found for data on cadmium kinetics in ground beetles and copper kinetics in earthworms in data already published in the literature that was not accounted for in the earlier analysis of the data. The three-phase model suggests that the physiology of controlling body metal concentrations can change shortly after exposure, at least in some cases, by increasing the elimination rate and/or decreasing metal assimilation. Hence, the three-phase model, that allows for different assimilation and/or elimination rates in different phases of exposure to a toxicant, may provide insight into temporal changes in the physiology of metal handling. Consequently, this alternative model should always be tested when describing metal toxicokinetics when temporal patterns of internal metal concentration exhibit an initial 'overshoot' in body metal concentrations.

Work-based physiological assessment of physically-demanding trades: a methodological overview.

Science.gov (United States)

Taylor, Nigel A S; Groeller, Herb

2003-03-01

Technological advances, modified work practices, altered employment strategies, work-related injuries, and the rise in work-related litigation and compensation claims necessitate ongoing trade analysis research. Such research enables the identification and development of gender- and age-neutral skills, physiological attributes and employment standards required to satisfactorily perform critical trade tasks. This paper overviews a methodological approach which may be adopted when seeking to establish trade-specific physiological competencies for physically-demanding trades (occupations). A general template is presented for conducting a trade analyses within physically-demanding trades, such as those encountered within military or emergency service occupations. Two streams of analysis are recommended: the trade analysis and the task analysis. The former involves a progressive dissection of activities and skills into a series of specific tasks (elements), and results in a broad approximation of the types of trade duties, and the links between trade tasks. The latter, will lead to the determination of how a task is performed within a trade, and the physiological attributes required to satisfactorily perform that task. The approach described within this paper is designed to provide research outcomes which have high content, criterion-related and construct validities.

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

Science.gov (United States)

Kilgas, Matthew A; Elmer, Steven J

2017-03-01

We implemented a team-based activity in our exercise physiology teaching laboratory that was inspired from Abbott et al.'s classic 1952 Journal of Physiology paper titled "The physiological cost of negative work." Abbott et al. connected two bicycles via one chain. One person cycled forward (muscle shortening contractions, positive work) while the other resisted the reverse moving pedals (muscle lengthening contractions, negative work), and the cost of work was compared. This study was the first to link human whole body energetics with isolated muscle force-velocity characteristics. The laboratory activity for our students ( n = 35) was designed to reenact Abbott et al.'s experiment, integrate previously learned techniques, and illustrate differences in physiological responses to muscle shortening and lengthening contractions. Students (11-12 students/laboratory section) were split into two teams (positive work vs. negative work). One student from each team volunteered to cycle against the other for ~10 min. The remaining students in each team were tasked with measuring: 1 ) O 2 consumption, 2 ) heart rate, 3 ) blood lactate, and 4 ) perceived exertion. Students discovered that O 2 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.

A Physiologically Based, Multi-Scale Model of Skeletal Muscle Structure and Function

Science.gov (United States)

Röhrle, O.; Davidson, J. B.; Pullan, A. J.

2012-01-01

Models of skeletal muscle can be classified as phenomenological or biophysical. Phenomenological models predict the muscle’s response to a specified input based on experimental measurements. Prominent phenomenological models are the Hill-type muscle models, which have been incorporated into rigid-body modeling frameworks, and three-dimensional continuum-mechanical models. Biophysically based models attempt to predict the muscle’s response as emerging from the underlying physiology of the system. In this contribution, the conventional biophysically based modeling methodology is extended to include several structural and functional characteristics of skeletal muscle. The result is a physiologically based, multi-scale skeletal muscle finite element model that is capable of representing detailed, geometrical descriptions of skeletal muscle fibers and their grouping. Together with a well-established model of motor-unit recruitment, the electro-physiological behavior of single muscle fibers within motor units is computed and linked to a continuum-mechanical constitutive law. The bridging between the cellular level and the organ level has been achieved via a multi-scale constitutive law and homogenization. The effect of homogenization has been investigated by varying the number of embedded skeletal muscle fibers and/or motor units and computing the resulting exerted muscle forces while applying the same excitatory input. All simulations were conducted using an anatomically realistic finite element model of the tibialis anterior muscle. Given the fact that the underlying electro-physiological cellular muscle model is capable of modeling metabolic fatigue effects such as potassium accumulation in the T-tubular space and inorganic phosphate build-up, the proposed framework provides a novel simulation-based way to investigate muscle behavior ranging from motor-unit recruitment to force generation and fatigue. PMID:22993509

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

Directory of Open Access Journals (Sweden)

Oliver eRöhrle

2012-09-01

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

Doppler radar physiological sensing

CERN Document Server

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

2016-01-01

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

An open-loop, physiologic model-based decision support system can provide appropriate ventilator settings

DEFF Research Database (Denmark)

Karbing, Dan Stieper; Spadaro, Savino; Dey, Nilanjan

2018-01-01

OBJECTIVES: To evaluate the physiologic effects of applying advice on mechanical ventilation by an open-loop, physiologic model-based clinical decision support system. DESIGN: Prospective, observational study. SETTING: University and Regional Hospitals' ICUs. PATIENTS: Varied adult ICU population...

Toxicokinetics of perfluorooctane sulfonate in rabbits under environmentally realistic exposure conditions and comparative assessment between mammals and birds.

Science.gov (United States)

Tarazona, J V; Rodríguez, C; Alonso, E; Sáez, M; González, F; San Andrés, M D; Jiménez, B; San Andrés, M I

2016-01-22

This article describes the toxicokinetics of perfluorooctane sulfonate (PFOS) in rabbits under low repeated dosing, equivalent to 0.085μg/kg per day, and the observed differences between rabbits and chickens. The best fitting for both species was provided by a simple pseudo monocompartmental first-order kinetics model, regulated by two rates, and accounting for real elimination as well as binding of PFOS to non-exchangeable structures. Elimination was more rapid in rabbits, with a pseudo first-order dissipation half-life of 88 days compared to the 230 days observed for chickens. By contrast, the calculated assimilation efficiency for rabbits was almost 1, very close to full absorption, significantly higher than the 0.66 with confidence intervals of 0.64 and 0.68 observed for chickens. The results confirm a very different kinetics than that observed in single-dose experiments confirming clear dose-related differences in apparent elimination rates in rabbits, as previously described for humans and other mammals; suggesting the role of a capacity-limited saturable process resulting in different kinetic behaviours for PFOS in high dose versus environmentally relevant low dose exposure conditions. The model calculations confirmed that the measured maximum concentrations were still far from the steady state situation, and that the different kinetics between birds and mammals should may play a significant role in the biomagnifications assessment and potential exposure for humans and predators. For the same dose regime, the steady state concentration was estimated at about 36μg PFOS/L serum for rabbits, slightly above one-half of the 65μg PFOS/L serum estimated for chickens. The toxicokinetic parameters presented here can be used for higher-tier bioaccumulation estimations of PFOS in rabbits and chickens as starting point for human health exposure assessments and as surrogate values for modeling PFOS kinetics in wild mammals and bird in exposure assessment of predatory

Physiological roles of acid-base sensors.

Science.gov (United States)

Levin, Lonny R; Buck, Jochen

2015-01-01

Acid-base homeostasis is essential for life. The macromolecules upon which living organisms depend are sensitive to pH changes, and physiological systems use the equilibrium between carbon dioxide, bicarbonate, and protons to buffer their pH. Biological processes and environmental insults are constantly challenging an organism's pH; therefore, to maintain a consistent and proper pH, organisms need sensors that measure pH and that elicit appropriate responses. Mammals use multiple sensors for measuring both intracellular and extracellular pH, and although some mammalian pH sensors directly measure protons, it has recently become apparent that many pH-sensing systems measure pH via bicarbonate-sensing soluble adenylyl cyclase.

The influence of microplastics and halogenated contaminants in feed on toxicokinetics and gene expression in European seabass (Dicentrarchus labrax)

DEFF Research Database (Denmark)

Granby, Kit; Rainieri, Sandra; Rasmussen, Rie Romme

2018-01-01

When microplastics pollute fish habitats, it may be ingested by fish, thereby contaminating fish with sorbed contaminants. The present study investigates how combinations of halogenated contaminants and microplastics associated with feed are able to alter toxicokinetics in European seabass...... and affect the fish. Microplastic particles (2%) were added to the feed either with sorbed contaminants or as a mixture of clean microplastics and chemical contaminants, and compared to feed containing contaminants without microplastics. For the contaminated microplastic diet, the accumulation...... days of exposure indicate that microplastics might indeed exacerbate the toxic effects (liver metabolism, immune system, oxidative stress) of some chemical contaminants sorbed to microplastics. Seabass quickly metabolised BDE99 to BDE47 by debromination, probably mediated by deiodinase enzymes...

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

Science.gov (United States)

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.

The interaction of psychological and physiological homeostatic drives and role of general control principles in the regulation of physiological systems, exercise and the fatigue process - The Integrative Governor theory.

Science.gov (United States)

St Clair Gibson, A; Swart, J; Tucker, R

2018-02-01

Either central (brain) or peripheral (body physiological system) control mechanisms, or a combination of these, have been championed in the last few decades in the field of Exercise Sciences as how physiological activity and fatigue processes are regulated. In this review, we suggest that the concept of 'central' or 'peripheral' mechanisms are both artificial constructs that have 'straight-jacketed' research in the field, and rather that competition between psychological and physiological homeostatic drives is central to the regulation of both, and that governing principles, rather than distinct physical processes, underpin all physical system and exercise regulation. As part of the Integrative Governor theory we develop in this review, we suggest that both psychological and physiological drives and requirements are underpinned by homeostatic principles, and that regulation of the relative activity of each is by dynamic negative feedback activity, as the fundamental general operational controller. Because of this competitive, dynamic interplay, we propose that the activity in all systems will oscillate, that these oscillations create information, and comparison of this oscillatory information with either prior information, current activity, or activity templates create efferent responses that change the activity in the different systems in a similarly dynamic manner. Changes in a particular system are always the result of perturbations occurring outside the system itself, the behavioural causative 'history' of this external activity will be evident in the pattern of the oscillations, and awareness of change occurs as a result of unexpected rather than planned change in physiological activity or psychological state.

Physiologically based pharmacokinetics model for estimating urinary excretion of short half-life nuclides in nuclear medicine

International Nuclear Information System (INIS)

Akahane, K.; Kai, M.; Konishi, E.; Kusama, T.; Aoki, Y.

1995-01-01

The biokinetic model in ICRP 53 is used for calculating absorbed dose to each organ of a patient in nuclear medicine. The ICRP model is a simple compartment model based on human data; however, the model cannot produce the biokinetics of radiopharmaceuticals under various physiological conditions. On the other hand, a physiologically based pharmacokinetics model (PBPK model) can describe the flow of radiopharmaceuticals as a compartment model for any physiological conditions theoretically. The PBPK model was applied especially for the kidney-bladder dynamics, and similar results obtained compared with the ICRP model. This suggests the possibility of the PBPK model for predicting the biokinetics of radiopharmaceuticals under various physiological conditions. (Author)

The Contribution of Peroxisome Proliferator-Activated Receptor Alpha to the Relationship Between Toxicokinetics and Toxicodynamics of Trichloroethylene.

Science.gov (United States)

Yoo, Hong Sik; Cichocki, Joseph A; Kim, Sungkyoon; Venkatratnam, Abhishek; Iwata, Yasuhiro; Kosyk, Oksana; Bodnar, Wanda; Sweet, Stephen; Knap, Anthony; Wade, Terry; Campbell, Jerry; Clewell, Harvey J; Melnyk, Stepan B; Chiu, Weihsueh A; Rusyn, Ivan

2015-10-01

Exposure to the ubiquitous environmental contaminant trichloroethylene (TCE) is associated with cancer and non-cancer toxicity in both humans and rodents. Peroxisome proliferator-activated receptor-alpha (PPARα) is thought to be playing a role in liver toxicity in rodents through activation of the receptor by the TCE metabolite trichloroacetic acid (TCA). However, most studies using genetically altered mice have not assessed the potential for PPARα to alter TCE toxicokinetics, which may lead to differences in TCA internal doses and hence confound inferences as to the role of PPARα in TCE toxicity. To address this gap, male and female wild type (129S1/SvImJ), Pparα-null, and humanized PPARα (hPPARα) mice were exposed intragastrically to 400 mg/kg TCE in single-dose (2, 5 and 12 h) and repeat-dose (5 days/week, 4 weeks) studies. Interestingly, following either a single- or repeat-dose exposure to TCE, levels of TCA in liver and kidney were lower in Pparα-null and hPPARα mice as compared with those in wild type mice. Levels of trichloroethanol (TCOH) were similar in all strains. TCE-exposed male mice consistently had higher levels of TCA and TCOH in all tissues compared with females. Additionally, in both single- and repeat-dose studies, a similar degree of induction of PPARα-responsive genes was observed in liver and kidney of hPPARα and wild type mice, despite the difference in hepatic and renal TCA levels. Additional sex- and strain-dependent effects were observed in the liver, including hepatocyte proliferation and oxidative stress, which were not dependent on TCA or TCOH levels. These data demonstrate that PPARα status affects the levels of the putative PPARα agonist TCA following TCE exposure. Therefore, interpretations of studies using Pparα-null and hPPARα mice need to consider the potential contribution of genotype-dependent toxicokinetics to observed differences in toxicity, rather than attributing such differences only to receptor

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

Science.gov (United States)

Marino, Dale J

2005-01-01

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

Tissue distribution and elimination of BDE 47 in mice following a single oral dose

Energy Technology Data Exchange (ETDEWEB)

Staskal, D. [Curriculum in Toxicology, Chapel Hill, NC (United States); Diliberto, J.; DeVito, M.; Birnbaum, L. [US EPA, ORD, NHEERL, ETD, RTP (United States)

2004-09-15

2,2',4,4'-Tetrabromodiphenyl ether (BDE 47) is a polybrominated diphenyl ether (PBDE) congener which is part of a class of brominated flame retardants (BFRs) commonly used in a variety of highly flammable consumer goods. Concern for the effects of PBDEs has increased significantly in recent years as their presence has been detected in environmental samples and in human tissues at steadily increasing concentrations. Despite its small contribution to the PBDE global production and usage, BDE 47 is the major congener found in environmental samples and human tissue. Limited toxicology studies suggest that BDE 47 is a developmental neurotoxicant and an endocrine disruptor however, several data gaps exist and must be investigated in order to evaluate the human health risk of BDE 47. This study investigated basic toxicokinetic properties of BDE 47 in female C57BL/6J mice. Here we report the effect of time on the absorption, distribution, and excretion following a single, oral dose of 14C-labeled BDE 47. Animals were administered 1.0mg BDE 47/kg bw, a dose chosen based on previous studies. Distribution and elimination were monitored at several time points ranging from 1 hour to 21 days following exposure. Data from these basic toxicokinetic studies will be applied to studies investigating the toxicokinetics of BDE 47 in a developmental model as well as in the development of a physiologically-based pharmacokinetic (PBPK) model.

Physiologically Based Pharmacokinetic and Absorption Modeling for Osmotic Pump Products.

Science.gov (United States)

Ni, Zhanglin; Talattof, Arjang; Fan, Jianghong; Tsakalozou, Eleftheria; Sharan, Satish; Sun, Dajun; Wen, Hong; Zhao, Liang; Zhang, Xinyuan

2017-07-01

Physiologically based pharmacokinetic (PBPK) and absorption modeling approaches were employed for oral extended-release (ER) drug products based on an osmotic drug delivery system (osmotic pumps). The purpose was to systemically evaluate the in vivo relevance of in vitro dissolution for this type of formulation. As expected, in vitro dissolution appeared to be generally predictive of in vivo PK profiles, because of the unique feature of this delivery system that the in vitro and in vivo release of osmotic pump drug products is less susceptible to surrounding environment in the gastrointestinal (GI) tract such as pH, hydrodynamic, and food effects. The present study considered BCS (Biopharmaceutics Classification System) class 1, 2, and 3 drug products with half-lives ranging from 2 to greater than 24 h. In some cases, the colonic absorption models needed to be adjusted to account for absorption in the colon. C max (maximum plasma concentration) and AUCt (area under the concentration curve) of the studied drug products were sensitive to changes in colon permeability and segmental GI transit times in a drug product-dependent manner. While improvement of the methodology is still warranted for more precise prediction (e.g., colonic absorption and dynamic movement in the GI tract), the results from the present study further emphasized the advantage of using PBPK modeling in addressing product-specific questions arising from regulatory review and drug development.

Toxicokinetics of drugs of abuse: current knowledge of the isoenzymes involved in the human metabolism of tetrahydrocannabinol, cocaine, heroin, morphine, and codeine.

Science.gov (United States)

Maurer, Hans H; Sauer, Christoph; Theobald, Denis S

2006-06-01

This review summarizes the major metabolic pathways of the drugs of abuse, tetrahydrocannabinol, cocaine, heroin, morphine, and codeine, in humans including the involvement of isoenzymes. This knowledge may be important for predicting their possible interactions with other xenobiotics, understanding pharmaco-/toxicokinetic and pharmacogenetic variations, toxicological risk assessment, developing suitable toxicological analysis procedures, and finally for understanding certain pitfalls in drug testing. The detection times of these drugs and/or their metabolites in biological samples are summarized and the implications of the presented data on the possible interactions of drugs of abuse with other xenobiotics, ie, inhibition or induction of individual polymorphic and nonpolymorphic isoenzymes, discussed.

Measuring the Differences between Traditional Learning and Game-Based Learning Using Electroencephalography (EEG) Physiologically Based Methodology

Science.gov (United States)

Chen, Ching-Huei

2017-01-01

Students' cognitive states can reflect a learning experience that results in engagement in an activity. In this study, we used electroencephalography (EEG) physiologically based methodology to evaluate students' levels of attention and relaxation, as well as their learning performance within a traditional and game-based learning context. While no…

Physiological Bases of Bulimia, and Antidepressant Treatment.

Science.gov (United States)

Getzfeld, Andrew R.

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

Inferring physiological energetics of loggerhead turtle (Caretta caretta) from existing data using a general metabolic theory.

Science.gov (United States)

Marn, Nina; Kooijman, S A L M; Jusup, Marko; Legović, Tarzan; Klanjšček, Tin

2017-05-01

Loggerhead turtle is an endangered sea turtle species with a migratory lifestyle and worldwide distribution, experiencing markedly different habitats throughout its lifetime. Environmental conditions, especially food availability and temperature, constrain the acquisition and the use of available energy, thus affecting physiological processes such as growth, maturation, and reproduction. These physiological processes at the population level determine survival, fecundity, and ultimately the population growth rate-a key indicator of the success of conservation efforts. As a first step towards the comprehensive understanding of how environment shapes the physiology and the life cycle of a loggerhead turtle, we constructed a full life cycle model based on the principles of energy acquisition and utilization embedded in the Dynamic Energy Budget (DEB) theory. We adapted the standard DEB model using data from published and unpublished sources to obtain parameter estimates and model predictions that could be compared with data. The outcome was a successful mathematical description of ontogeny and life history traits of the loggerhead turtle. Some deviations between the model and the data existed (such as an earlier age at sexual maturity and faster growth of the post-hatchlings), yet probable causes for these deviations were found informative and discussed in great detail. Physiological traits such as the capacity to withstand starvation, trade-offs between reproduction and growth, and changes in the energy budget throughout the ontogeny were inferred from the model. The results offer new insights into physiology and ecology of loggerhead turtle with the potential to lead to novel approaches in conservation of this endangered species. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

Directory of Open Access Journals (Sweden)

Patricia Ruiz

2011-10-01

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

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

Science.gov (United States)

Pelaez, Nancy J

2002-12-01

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

Toxicokinetic comparison of 14C-monocrotaline and 14C-senecionine in the rat

International Nuclear Information System (INIS)

Estep, J.E.; Lame', M.W.; Morin, D.; Segall, H.J.; Wilson, D.W.

1990-01-01

Two commonly studied macrocyclic pyrrolizidine alkaloids (PAs) are monocrotaline (MCT) and senecionine (SEN). Both PAs exhibit hepatic, renal and pulmonary toxicity, but SEN primarily causes centrol lobular necrosis of the liver while MCT promotes the development of pulmonary hypertension with decreased liver necrosis. Previous work in our laboratory has shown that MCT (60mg/kg IV) is sequestered in the red blood cell (RBC). To determine if this retention could play a role in MCT pulmonary toxicity, we compared the toxicokinetics of MCT with SEN. Both compounds exhibited a similar decline in plasma concentration (as measured by carbon 14) by the end of seven hours. The decrease in radioactivity associated with RBC's differed significantly with MCT declining from 144.34 to 81.46 nmol MCT-equivalents/gm of RBC's, while SEN decreased from 108.55 to 26.18 nmol SEN-equivalents/gm. Fortyfour versus 12 percent of the radioactivity was excreted in the bile for SEN and MCT dosed rats, respectively. In the absence of bile duct cannulation, plasma and RBC levels of radioactivity were identical to cannulated animals receiving MCT while SEN dosed animals exhibited almost twice the radioactivity associated with the RBC's, suggesting enterohepatic recirculation. The results of these studies suggest that the RBC-MCT complex is involved in MCT pulmonary toxicity

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

Science.gov (United States)

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.

Physiology and biochemistry of honey bees

Science.gov (United States)

Despite their tremendous economic importance, honey bees are not a typical model system for studying general questions of insect physiology. This is primarily due to the fact that honey bees live in complex social settings which impact their physiological and biochemical characteristics. Not surpris...

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

Science.gov (United States)

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

Flight physiology training experiences and perspectives: survey of 117 pilots.

Science.gov (United States)

Patrão, Luís; Zorro, Sara; Silva, Jorge; Castelo-Branco, Miguel; Ribeiro, João

2013-06-01

Human factors and awareness of flight physiology play a crucial role in flight safety. Even so, international legislation is vague relative to training requirements in hypoxia and altitude physiology. Based on a previously developed survey, an adapted questionnaire was formulated and released online for Portuguese pilots. Specific questions regarding the need for pilot attention monitoring systems were added to the original survey. There were 117 pilots, 2 of whom were women, who completed the survey. Most of the pilots had a light aviation license and flew in unpressurized cabins at a maximum ceiling of 10,000 ft (3048 m). The majority of the respondents never experienced hypoxic symptoms. In general, most of the individuals agreed with the importance of an introductory hypoxia course without altitude chamber training (ACT) for all pilot populations, and with a pilot monitoring system in order to increase flight safety. Generally, most of the pilots felt that hypoxia education and training for unpressurized aircraft is not extensive enough. However, almost all the respondents were willing to use a flight physiology monitoring system in order to improve flight safety.

Uptake and elimination kinetics of metals in soil invertebrates: a review.

Science.gov (United States)

Ardestani, Masoud M; van Straalen, Nico M; van Gestel, Cornelis A M

2014-10-01

Uptake and elimination kinetics of metals in soil invertebrates are a function of both soil and organism properties. This study critically reviewed metal toxicokinetics in soil invertebrates and its potential use for assessing bioavailability. Uptake and elimination rate constants of different metals are summarized. Invertebrates have different strategies for essential and non-essential metals. As a consequence, different types of models must be applied to describe metal uptake and elimination kinetics. We discuss model parameters for each metal separately and show how they are influenced by exposure concentrations and by physiological properties of the organisms. Soil pH, cation exchange capacity, clay and organic matter content significantly affect uptake rates of non-essential metals in soil invertebrates. For essential metals, kinetics is hardly influenced by soil properties, but rather prone to physiological regulation mechanisms of the organisms. Our analysis illustrates that toxicokinetics can be a valuable measurement to assess bioavailability of soil-bound metals. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

Science.gov (United States)

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

2017-07-01

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

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

Science.gov (United States)

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

2003-01-01

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

Non-animal approaches for toxicokinetics in risk evaluations of food chemicals.

Science.gov (United States)

Punt, Ans; Peijnenburg, Ad A C M; Hoogenboom, Ron L A P; Bouwmeester, Hans

2017-01-01

The objective of the present work was to review the availability and predictive value of non-animal toxicokinetic approaches and to evaluate their current use in European risk evaluations of food contaminants, additives and food contact materials, as well as pesticides and medicines. Results revealed little use of quantitative animal or human kinetic data in risk evaluations of food chemicals, compared with pesticides and medicines. Risk evaluations of medicines provided sufficient in vivo kinetic data from different species to evaluate the predictive value of animal kinetic data for humans. These data showed a relatively poor correlation between the in vivo bioavailability in rats and dogs versus that in humans. In contrast, in vitro (human) kinetic data have been demonstrated to provide adequate predictions of the fate of compounds in humans, using appropriate in vitro-in vivo scalers and by integration of in vitro kinetic data with in silico kinetic modelling. Even though in vitro kinetic data were found to be occasionally included within risk evaluations of food chemicals, particularly results from Caco-2 absorption experiments and in vitro data on gut-microbial conversions, only minor use of in vitro methods for metabolism and quantitative in vitro-in vivo extrapolation methods was identified. Yet, such quantitative predictions are essential in the development of alternatives to animal testing as well as to increase human relevance of toxicological risk evaluations. Future research should aim at further improving and validating quantitative alternative methods for kinetics, thereby increasing regulatory acceptance of non-animal kinetic data.

A community of practice approach to bioanalysis delivery: the role of the Preclinical Bioanalysis and Toxicokinetics department at AstraZeneca.

Science.gov (United States)

Wilson, Amanda; Silvester, Stephen; Woods, Karen

2014-05-01

Retaining regulated bioanalysis within AstraZeneca (AZ) is important for the effective delivery of nonclinical and clinical bioanalysis. The focus for the in-house team is the delivery of high-throughput bioanalysis and toxicokinetics support for investigational toxicology; however, by retaining GLP compliance, AZ will have an in-house understanding of every candidate drug that is progressed into development by supporting the first rodent GLP study for each project. The majority of nonclinical bioanalysis and all of the clinical bioanalysis are delivered by two external partnership models. This article describes the key benefits of retaining GLP compliance, the partnership interactions, discusses the management of non-GLP support in a GLP environment and how, having practical experience of regulatory facing method development, validation and study execution adds value to the AZ portfolio delivery.

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

Science.gov (United States)

Nádvorník, P; Pogády, J; Bernadic, M

2003-05-01

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

Prediction of paraquat exposure and toxicity in clinically ill poisoned patients: a model based approach.

Science.gov (United States)

Wunnapuk, Klintean; Mohammed, Fahim; Gawarammana, Indika; Liu, Xin; Verbeeck, Roger K; Buckley, Nicholas A; Roberts, Michael S; Musuamba, Flora T

2014-10-01

Paraquat poisoning is a medical problem in many parts of Asia and the Pacific. The mortality rate is extremely high as there is no effective treatment. We analyzed data collected during an ongoing cohort study on self-poisoning and from a randomized controlled trial assessing the efficacy of immunosuppressive therapy in hospitalized paraquat-intoxicated patients. The aim of this analysis was to characterize the toxicokinetics and toxicodynamics of paraquat in this population. A non-linear mixed effects approach was used to perform a toxicokinetic/toxicodynamic population analysis in a cohort of 78 patients. The paraquat plasma concentrations were best fitted by a two compartment toxicokinetic structural model with first order absorption and first order elimination. Changes in renal function were used for the assessment of paraquat toxicodynamics. The estimates of toxicokinetic parameters for the apparent clearance, the apparent volume of distribution and elimination half-life were 1.17 l h(-1) , 2.4 l kg(-1) and 87 h, respectively. Renal function, namely creatinine clearance, was the most significant covariate to explain between patient variability in paraquat clearance.This model suggested that a reduction in paraquat clearance occurred within 24 to 48 h after poison ingestion, and afterwards the clearance was constant over time. The model estimated that a paraquat concentration of 429 μg l(-1) caused 50% of maximum renal toxicity. The immunosuppressive therapy tested during this study was associated with only 8% improvement of renal function. The developed models may be useful as prognostic tools to predict patient outcome based on patient characteristics on admission and to assess drug effectiveness during antidote drug development. © 2014 The British Pharmacological Society.

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

Directory of Open Access Journals (Sweden)

Kai Wang

2016-01-01

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

A bio-inspired glucose controller based on pancreatic β-cell physiology.

Science.gov (United States)

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

2012-05-01

Control algorithms for closed-loop insulin delivery in type 1 diabetes have been mainly based on control engineering or artificial intelligence techniques. These, however, are not based on the physiology of the pancreas but seek to implement engineering solutions to biology. Developments in mathematical models of the β-cell physiology of the pancreas have described the glucose-induced insulin release from pancreatic β cells at a molecular level. This has facilitated development of a new class of bio-inspired glucose control algorithms that replicate the functionality of the biological pancreas. However, technologies for sensing glucose levels and delivering insulin use the subcutaneous route, which is nonphysiological and introduces some challenges. In this article, a novel glucose controller is presented as part of a bio-inspired artificial pancreas. A mathematical model of β-cell physiology was used as the core of the proposed controller. In order to deal with delays and lack of accuracy introduced by the subcutaneous route, insulin feedback and a gain scheduling strategy were employed. A United States Food and Drug Administration-accepted type 1 diabetes mellitus virtual population was used to validate the presented controller. Premeal and postmeal mean ± standard deviation blood glucose levels for the adult and adolescent populations were well within the target range set for the controller [(70, 180) mg/dl], with a percent time in range of 92.8 ± 7.3% for the adults and 83.5 ± 14% for the adolescents. This article shows for the first time very good glucose control in a virtual population with type 1 diabetes mellitus using a controller based on a subcellular β-cell model. © 2012 Diabetes Technology Society.

All individuals are not created equal; accounting for interindividual variation in fitting life-history responses to toxicants.

Science.gov (United States)

Jager, Tjalling

2013-02-05

The individuals of a species are not equal. These differences frustrate experimental biologists and ecotoxicologists who wish to study the response of a species (in general) to a treatment. In the analysis of data, differences between model predictions and observations on individual animals are usually treated as random measurement error around the true response. These deviations, however, are mainly caused by real differences between the individuals (e.g., differences in physiology and in initial conditions). Understanding these intraspecies differences, and accounting for them in the data analysis, will improve our understanding of the response to the treatment we are investigating and allow for a more powerful, less biased, statistical analysis. Here, I explore a basic scheme for statistical inference to estimate parameters governing stress that allows individuals to differ in their basic physiology. This scheme is illustrated using a simple toxicokinetic-toxicodynamic model and a data set for growth of the springtail Folsomia candida exposed to cadmium in food. This article should be seen as proof of concept; a first step in bringing more realism into the statistical inference for process-based models in ecotoxicology.

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

Science.gov (United States)

Nybo, Lars; May, Michael

2015-01-01

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

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

Science.gov (United States)

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...

Phage Therapy: Eco-Physiological Pharmacology

Directory of Open Access Journals (Sweden)

Stephen T. Abedon

2014-01-01

Full Text Available Bacterial virus use as antibacterial agents, in the guise of what is commonly known as phage therapy, is an inherently physiological, ecological, and also pharmacological process. Physiologically we can consider metabolic properties of phage infections of bacteria and variation in those properties as a function of preexisting bacterial states. In addition, there are patient responses to pathogenesis, patient responses to phage infections of pathogens, and also patient responses to phage virions alone. Ecologically, we can consider phage propagation, densities, distribution (within bodies, impact on body-associated microbiota (as ecological communities, and modification of the functioning of body “ecosystems” more generally. These ecological and physiological components in many ways represent different perspectives on otherwise equivalent phenomena. Comparable to drugs, one also can view phages during phage therapy in pharmacological terms. The relatively unique status of phages within the context of phage therapy as essentially replicating antimicrobials can therefore result in a confluence of perspectives, many of which can be useful towards gaining a better mechanistic appreciation of phage therapy, as I consider here. Pharmacology more generally may be viewed as a discipline that lies at an interface between organism-associated phenomena, as considered by physiology, and environmental interactions as considered by ecology.

Baby, you light-up my face: culture-general physiological responses to infants and culture-specific cognitive judgements of adults.

Directory of Open Access Journals (Sweden)

Gianluca Esposito

Full Text Available Infants universally elicit in adults a set of solicitous behaviors that are evolutionarily important for the survival of the species. However, exposure, experience, and prejudice appear to govern adults' social choice and ingroup attitudes towards other adults. In the current study, physiological arousal and behavioral judgments were assessed while adults processed unfamiliar infant and adult faces of ingroup vs. outgroup members in two contrasting cultures, Japan and Italy. Physiological arousal was investigated using the novel technique of infrared thermography and behavioral judgments using ratings. We uncovered a dissociation between physiological and behavioral responses. At the physiological level, both Japanese and Italian adults showed significant activation (increase of facial temperature for both ingroup and outgroup infant faces. At the behavioral level, both Japanese and Italian adults showed significant preferences for ingroup adults. Arousal responses to infants appear to be mediated by the autonomic nervous system and are not dependent on direct caregiving exposure, but behavioral responses appear to be mediated by higher-order cognitive processing based on social acceptance and cultural exposure.

Development of a population-based threshold model of conidial germination for analysing the effects of physiological manipulation on the stress tolerance and infectivity of insect pathogenic fungi.

Science.gov (United States)

Andersen, M; Magan, N; Mead, A; Chandler, D

2006-09-01

Entomopathogenic fungi are being used as biocontrol agents of insect pests, but their efficacy can be poor in environments where water availability is reduced. In this study, the potential to improve biocontrol by physiologically manipulating fungal inoculum was investigated. Cultures of Beauveria bassiana, Lecanicillium muscarium, Lecanicillium longisporum, Metarhizium anisopliae and Paecilomyces fumosoroseus were manipulated by growing them under conditions of water stress, which produced conidia with increased concentrations of erythritol. The time-course of germination of conidia at different water activities (water activity, aw) was described using a generalized linear model, and in most cases reducing the water activity of the germination medium delayed the onset of germination without affecting the distribution of germination times. The germination of M. anisopliae, L. muscarium, L. longisporum and P. fumosoroseus was accelerated over a range of aw levels as a result of physiological manipulation. However, the relationship between the effect of physiological manipulation on germination and the osmolyte content of conidia varied according to fungal species. There was a linear relationship between germination rate, expressed as the reciprocal of germination time, and aw of the germination medium, but there was no significant effect of fungal species or physiological manipulation on the aw threshold for germination. In bioassays with M. anisopliae, physiologically manipulated conidia germinated more rapidly on the surface of an insect host, the melon cotton aphid Aphis gossypii, and fungal virulence was increased even when relative humidity was reduced after an initial high period. It is concluded that physiological manipulation may lead to improvements in biocontrol in the field, but choice of fungal species/isolate will be critical. In addition, the population-based threshold model used in this study, which considered germination in terms of physiological

Prediction of human CNS pharmacokinetics using a physiologically-based pharmacokinetic modeling approach

NARCIS (Netherlands)

Yamamoto, Yumi; Valitalo, Pyry A.; Wong, Yin Cheong; Huntjens, Dymphy R.; Proost, Johannes H.; Vermeulen, An; Krauwinkel, Walter; Beukers, Margot W.; Kokki, Hannu; Kokki, Merja; Danhof, Meindert; van Hasselt, Johan G. C.; de Lange, Elizabeth C. M.

2018-01-01

Knowledge of drug concentration-time profiles at the central nervous system (CNS) target-site is critically important for rational development of CNS targeted drugs. Our aim was to translate a recently published comprehensive CNS physiologically-based pharmacokinetic (PBPK) model from rat to human,

General concepts of ventricular function, Myocardial perfusion, and exercise physiology relevant to nuclear cardiology

International Nuclear Information System (INIS)

Kronenberg, M.W.; Becker, L.C.

1988-01-01

Knowledge of ventricular mechanics, the physiology of the coronary circulation, and exercise physiology is necessary for the accurate interpretation of radionuclide ventriculographic and myocardial perfusion images. This chapter outlines these important basic concepts as applied to the whole heart

Zebrafish Bone and General Physiology Are Differently Affected by Hormones or Changes in Gravity

NARCIS (Netherlands)

Aceto, J.; Nourizadeh-Lillabadi, R.; Maree, R.; Dardenne, N.; Jeanray, N.; Wehenkel, L.; Alestrom, P.; van Loon, J.J.W.A.; Muller, M.

2015-01-01

Teleost fish such as zebrafish (Danio rerio) are increasingly used for physiological, genetic and developmental studies. Our understanding of the physiological consequences of altered gravity in an entire organism is still incomplete. We used altered gravity and drug treatment experiments to

An Individualized, Perception-Based Protocol to Investigate Human Physiological Responses to Cooling

Science.gov (United States)

Coolbaugh, Crystal L.; Bush, Emily C.; Galenti, Elizabeth S.; Welch, E. Brian; Towse, Theodore F.

2018-01-01

Cold exposure, a known stimulant of the thermogenic effects of brown adipose tissue (BAT), is the most widely used method to study BAT physiology in adult humans. Recently, individualized cooling has been recommended to standardize the physiological cold stress applied across participants, but critical experimental details remain unclear. The purpose of this work was to develop a detailed methodology for an individualized, perception-based protocol to investigate human physiological responses to cooling. Participants were wrapped in two water-circulating blankets and fitted with skin temperature probes to estimate BAT activity and peripheral vasoconstriction. We created a thermoesthesia graphical user interface (tGUI) to continuously record the subject's perception of cooling and shivering status during the cooling protocol. The protocol began with a 15 min thermoneutral phase followed by a series of 10 min cooling phases and concluded when sustained shivering (>1 min duration) occurred. Researchers used perception of cooling feedback (tGUI ratings) to manually adjust and personalize the water temperature at each cooling phase. Blanket water temperatures were recorded continuously during the protocol. Twelve volunteers (ages: 26.2 ± 1.4 years; 25% female) completed a feasibility study to evaluate the proposed protocol. Water temperature, perception of cooling, and shivering varied considerably across participants in response to cooling. Mean clavicle skin temperature, a surrogate measure of BAT activity, decreased (−0.99°C, 95% CI: −1.7 to −0.25°C, P = 0.16) after the cooling protocol, but an increase in supraclavicular skin temperature was observed in 4 participants. A strong positive correlation was also found between thermoesthesia and peripheral vasoconstriction (ρ = 0.84, P < 0.001). The proposed individualized, perception-based protocol therefore has potential to investigate the physiological responses to cold stress applied across populations with

From physiological psychology to psychological physiology: Postnonclassical approach to ethnocultural phenomena.

Directory of Open Access Journals (Sweden)

Asmolov, A.G.

2015-07-01

Full Text Available In modern science, along with the “classic” and “non-classical” approach to solving fundamental and applied problems, there is an actively developing “postnonclassical” research paradigm. This renovation of general scientific methodology has been accompanied by the emergence of new experimental technologies and new scientific research directions based on them. “Social psychophysiology” is one such direction. It is formed within the frame of postnonclassical methodology at the intersection of neuroscience and psychology. This work is devoted to the analytical review of the methods, achievements and prospects of contemporary social neuroscience and social psychophysiology studying brain structures that are specifically related to the implementation of social forms of behavior and intercultural communication. Physiological studies of brain activity during social interaction processes, which are simulated using virtual reality environments, are analyzed, and the physiological approach to the study of the brain mechanisms associated with social perception, social cognition and social behavior is used. Along with the analysis of psychophysiological studies of the mechanisms of social perception and social cognition, we discuss the theories of “Brain Reading” and “Theory of Mind” and the underlying data concerning “Gnostic neurons recognition of persons and recognition of emotional facial expressions”, “mirror neurons”, “emotional resonance” and “cognitive resonance”. Particular emphasis is placed on the discussion of a fundamentally new trend in the study of the relationship between the brain and culture (i.e., “cultural neuroscience”. Related to this connection, the following topics are raised: physiological mechanisms protecting the “individual distance” in communication between members of a personified community, psychophysiological approaches to the study of cross-cultural differences, physiological

Generalized eigenvalue based spectrum sensing

KAUST Repository

Shakir, Muhammad

2012-01-01

Spectrum sensing is one of the fundamental components in cognitive radio networks. In this chapter, a generalized spectrum sensing framework which is referred to as Generalized Mean Detector (GMD) has been introduced. In this context, we generalize the detectors based on the eigenvalues of the received signal covariance matrix and transform the eigenvalue based spectrum sensing detectors namely: (i) the Eigenvalue Ratio Detector (ERD) and two newly proposed detectors which are referred to as (ii) the GEometric Mean Detector (GEMD) and (iii) the ARithmetic Mean Detector (ARMD) into an unified framework of generalize spectrum sensing. The foundation of the proposed framework is based on the calculation of exact analytical moments of the random variables of the decision threshold of the respective detectors. The decision threshold has been calculated in a closed form which is based on the approximation of Cumulative Distribution Functions (CDFs) of the respective test statistics. In this context, we exchange the analytical moments of the two random variables of the respective test statistics with the moments of the Gaussian (or Gamma) distribution function. The performance of the eigenvalue based detectors is compared with the several traditional detectors including the energy detector (ED) to validate the importance of the eigenvalue based detectors and the performance of the GEMD and the ARMD particularly in realistic wireless cognitive radio network. Analytical and simulation results show that the newly proposed detectors yields considerable performance advantage in realistic spectrum sensing scenarios. Moreover, the presented results based on proposed approximation approaches are in perfect agreement with the empirical results. © 2012 Springer Science+Business Media Dordrecht.

From in vitro to in vivo: Integration of the virtual cell based assay with physiologically based kinetic modelling.

Science.gov (United States)

Paini, Alicia; Sala Benito, Jose Vicente; Bessems, Jos; Worth, Andrew P

2017-12-01

Physiologically based kinetic (PBK) models and the virtual cell based assay can be linked to form so called physiologically based dynamic (PBD) models. This study illustrates the development and application of a PBK model for prediction of estragole-induced DNA adduct formation and hepatotoxicity in humans. To address the hepatotoxicity, HepaRG cells were used as a surrogate for liver cells, with cell viability being used as the in vitro toxicological endpoint. Information on DNA adduct formation was taken from the literature. Since estragole induced cell damage is not directly caused by the parent compound, but by a reactive metabolite, information on the metabolic pathway was incorporated into the model. In addition, a user-friendly tool was developed by implementing the PBK/D model into a KNIME workflow. This workflow can be used to perform in vitro to in vivo extrapolation and forward as backward dosimetry in support of chemical risk assessment. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

On the existence of physiological age based on functional hierarchy: a formal definition related to time irreversibility.

Science.gov (United States)

Chauvet, Gilbert A

2006-09-01

The present approach of aging and time irreversibility is a consequence of the theory of functional organization that I have developed and presented over recent years (see e.g., Ref. 11). It is based on the effect of physically small and numerous perturbations known as fluctuations, of structural units on the dynamics of the biological system during its adult life. Being a highly regulated biological system, a simple realistic hypothesis, the time-optimum regulation between the levels of organization, leads to the existence of an internal age for the biological system, and time-irreversibility associated with aging. Thus, although specific genes are controlling aging, time-irreversibility of the system may be shown to be due to the degradation of physiological functions. In other words, I suggest that for a biological system, the nature of time is specific and is an expression of the highly regulated integration. An internal physiological age reflects the irreversible course of a living organism towards death because of the irreversible course of physiological functions towards dysfunction, due to the irreversible changes in the regulatory processes. Following the works of Prigogine and his colleagues in physics, and more generally in the field of non-integrable dynamical systems (theorem of Poincaré-Misra), I have stated this problem in terms of the relationship between the macroscopic irreversibility of the functional organization and the basic mechanisms of regulation at the lowest "microscopic" level, i.e., the molecular, lowest level of organization. The neuron-neuron elementary functional interaction is proposed as an illustration of the method to define aging in the nervous system.

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

Science.gov (United States)

Longmuir, Kenneth J.

2014-01-01

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

Complexity and network dynamics in physiological adaptation: An integrated view

OpenAIRE

Baffy, Gyorgy; Loscalzo, Joseph

2014-01-01

Living organisms constantly interact with their surroundings and sustain internal stability against perturbations. This dynamic process follows three fundamental strategies (restore, explore, and abandon) articulated in historical concepts of physiological adaptation such as homeostasis, allostasis, and the general adaptation syndrome. These strategies correspond to elementary forms of behavior (ordered, chaotic, and static) in complex adaptive systems and invite a network-based analysis of t...

Ultrasound-based teaching of cardiac anatomy and physiology to undergraduate medical students.

Science.gov (United States)

Hammoudi, Nadjib; Arangalage, Dimitri; Boubrit, Lila; Renaud, Marie Christine; Isnard, Richard; Collet, Jean-Philippe; Cohen, Ariel; Duguet, Alexandre

2013-10-01

Ultrasonography is a non-invasive imaging modality that offers the opportunity to teach living cardiac anatomy and physiology. The objectives of this study were to assess the feasibility of integrating an ultrasound-based course into the conventional undergraduate medical teaching programme and to analyse student and teacher feedback. An ultrasound-based teaching course was implemented and proposed to all second-year medical students (n=348) at the end of the academic year, after all the conventional modules at our faculty. After a brief theoretical and practical demonstration, students were allowed to take the probe and use the ultrasound machine. Students and teachers were asked to complete a survey and were given the opportunity to provide open feedback. Two months were required to implement the entire module; 330 (95%) students (divided into 39 groups) and 37 teachers participated in the course. Student feedback was very positive: 98% of students agreed that the course was useful; 85% and 74% considered that their understanding of cardiac anatomy and physiology, respectively, was improved. The majority of the teachers (97%) felt that the students were interested, 81% agreed that the course was appropriate for second-year medical students and 84% were willing to participate to future sessions. Cardiac anatomy and physiology teaching using ultrasound is feasible for undergraduate medical students and enhances their motivation to improve their knowledge. Student and teacher feedback on the course was very positive. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

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

NARCIS (Netherlands)

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

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

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

NARCIS (Netherlands)

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

2000-01-01

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

A computer-aided framework for development, identification andmanagement of physiologically-based pharmacokinetic models

DEFF Research Database (Denmark)

Heitzig, Martina; Linninger, Andreas; Sin, Gürkan

2014-01-01

The objective of this work is the development of a generic computer-aided modelling framework to support the development of physiologically-based pharmacokinetic models thereby increasing the efficiency and quality of the modelling process. In particular, the framework systematizes the modelling...

Challenges Associated With Applying Physiologically Based Pharmacokinetic Modeling for Public Health Decision-Making

Science.gov (United States)

The development and application of physiologically based pharmacokinetic (PBPK) models in chemical toxicology have grown steadily since their emergence in the 1980s. However, critical evaluation of PBPK models to support public health decision-making across federal agencies has t...

Video-based lectures: An emerging paradigm for teaching human anatomy and physiology to student nurses

Directory of Open Access Journals (Sweden)

Rabab El-Sayed Hassan El-Sayed

2013-09-01

Full Text Available Video-based teaching material is a rich and powerful medium being used in computer assisted learning. This paper aimed to assess the learning outcomes and student nurses’ acceptance and satisfaction with the video-based lectures versus the traditional method of teaching human anatomy and physiology courses. Data were collected from 27 students in a Bachelor of Nursing program and experimental control was achieved using an alternating-treatments design. Overall, students experienced 10 lectures, which delivered by the teacher as either video-based or PowerPoint-based lectures. Results revealed that video-based lectures offer more successes and reduce failures in the immediate and follow-up measures as compared with the traditional method of teaching human anatomy and physiology that was based on printout illustrations, but these differences were not statistically significant. Moreover, nurse students appeared positive about their learning experiences, as they rated highly all the items assessing their acceptance and satisfaction with the video-based lectures. KEYWORDS: Video-based lecture, Traditional, Print-based illustration

Regulatory Physiology

Science.gov (United States)

Lane, Helen W.; Whitson, Peggy A.; Putcha, Lakshmi; Baker, Ellen; Smith, Scott M.; Stewart, Karen; Gretebeck, Randall; Nimmagudda, R. R.; Schoeller, Dale A.; Davis-Street, Janis

1999-01-01

As noted elsewhere in this report, a central goal of the Extended Duration Orbiter Medical Project (EDOMP) was to ensure that cardiovascular and muscle function were adequate to perform an emergency egress after 16 days of spaceflight. The goals of the Regulatory Physiology component of the EDOMP were to identify and subsequently ameliorate those biochemical and nutritional factors that deplete physiological reserves or increase risk for disease, and to facilitate the development of effective muscle, exercise, and cardiovascular countermeasures. The component investigations designed to meet these goals focused on biochemical and physiological aspects of nutrition and metabolism, the risk of renal (kidney) stone formation, gastrointestinal function, and sleep in space. Investigations involved both ground-based protocols to validate proposed methods and flight studies to test those methods. Two hardware tests were also completed.

High Throughput Determinations of Critical Dosing Parameters (IVIVE workshop)

Science.gov (United States)

High throughput toxicokinetics (HTTK) is an approach that allows for rapid estimations of TK for hundreds of environmental chemicals. HTTK-based reverse dosimetry (i.e, reverse toxicokinetics or RTK) is used in order to convert high throughput in vitro toxicity screening (HTS) da...

A prospective observational study comparing a physiological scoring system with time-based discharge criteria in pediatric ambulatory surgical patients.

Science.gov (United States)

Armstrong, James; Forrest, Helen; Crawford, Mark W

2015-10-01

Discharge criteria based on physiological scoring systems can be used in the postanesthesia care unit (PACU) to fast-track patients after ambulatory surgery; however, studies comparing physiological scoring systems with traditional time-based discharge criteria are lacking. The purpose of this study was to compare PACU discharge readiness times using physiological vs time-based discharge criteria in pediatric ambulatory surgical patients. We recorded physiological observations from consecutive American Society of Anesthesiologists physical status I-III patients aged 1-18 yr who were admitted to the PACU after undergoing ambulatory surgery in a tertiary academic pediatric hospital. The physiological score was a combination of the Aldrete and Chung systems. Scores were recorded every 15 min starting upon arrival in the PACU. Patients were considered fit for discharge once they attained a score ≥12 (maximum score, 14), provided no score was zero, with the time to achieve a score ≥12 defining the criteria-based discharge (CBD) time. Patients were discharged from the PACU when both the CBD and the existing time-based discharge (TBD) criteria were met. The CBD and TBD data were compared using Kaplan-Meier and log-rank analysis. Observations from 506 children are presented. Median (interquartile range [IQR]) age was 5.5 [2.8-9.9] yr. Median [IQR] CBD and TBD PACU discharge readiness times were 30 [15-45] min and 60 [45-60] min, respectively. Analysis of Kaplan-Meier curves indicated a significant difference in discharge times using the different criteria (hazard ratio, 5.43; 95% confidence interval, 4.51 to 6.53; P < 0.001). All patients were discharged home without incident. This prospective study suggests that discharge decisions based on physiological criteria have the potential for significantly speeding the transit of children through the PACU, thereby enhancing PACU efficiency and resource utilization.

Toxicokinetics and correlation of carbamazepine salivary and serum concentrations in acute poisonings

Directory of Open Access Journals (Sweden)

Đorđević Snežana

2012-01-01

Full Text Available Background/Aim. Saliva is a body fluid which, like serum, can be used for determination of concentrations of certain drugs, both in pharmacotherapy as well as in acute poisonings. The aim of this study was to determine carbamazepine concentrations in both saliva and serum in acute poisoning in order to show if there is a correlation between the obtained values, as well as to monitor toxicokinetics of carbamazepine in body fluides. Methods. Saliva and serum samples were obtained from 26 patients treated with carbamazepine and 20 patients acutely poisoned by the drug immediately after their admission in the Emergency Toxicology Unit. Determination of salivary and serum carbamazepine concentrations was performed by the validated high pressure liquid chromatographyultraviolet (HPLC-UV method. Results. A significant correlation of salivary and serum carbamazepine concentrations in both therapeutic application and acute poisoning (r = 0.9481 and 0.9117, respectively was confirmed. In acute poisonings the mean ratio between salivary and serum concentrations of carbamazepine (0.43 was similar to the mean ratio after its administration in therapeutic doses (0.39, but there were high inter-individual variations in carbamazepine concentrations in the acutely poisoned patients, as a consequence of different ingested doses of the drug. In acute poisoning the halftime of carbamazepine in saliva and serum was 12.57 h and 6.76 h, respectively. Conclusion. Our results suggest a possible use of saliva as an alternative biological material for determination of carbamazepine concentrations in therapeutic application and acute poisoning as well, and a possible extrapolation of the results obtained in saliva to serum concentrations of carbamazepine.

Use of Case-Based or Hands-On Laboratory Exercises with Physiology Lectures Improves Knowledge Retention, but Veterinary Medicine Students Prefer Case-Based Activities

Science.gov (United States)

McFee, Renee M.; Cupp, Andrea S.; Wood, Jennifer R.

2018-01-01

Didactic lectures are prevalent in physiology courses within veterinary medicine programs, but more active learning methods have also been utilized. Our goal was to identify the most appropriate learning method to augment the lecture component of our physiology course. We hypothesized that case-based learning would be well received by students and…

Effects of worry on physiological and subjective reactivity to emotional stimuli in generalized anxiety disorder and nonanxious control participants.

Science.gov (United States)

Llera, Sandra J; Newman, Michelle G

2010-10-01

The present study examined the effect of worry versus relaxation and neutral thought activity on both physiological and subjective responding to positive and negative emotional stimuli. Thirty-eight participants with generalized anxiety disorder (GAD) and 35 nonanxious control participants were randomly assigned to engage in worry, relaxation, or neutral inductions prior to sequential exposure to each of four emotion-inducing film clips. The clips were designed to elicit fear, sadness, happiness, and calm emotions. Self reported negative and positive affect was assessed following each induction and exposure, and vagal activity was measured throughout. Results indicate that worry (vs. relaxation) led to reduced vagal tone for the GAD group, as well as higher negative affect levels for both groups. Additionally, prior worry resulted in less physiological and subjective responding to the fearful film clip, and reduced negative affect in response to the sad clip. This suggests that worry may facilitate avoidance of processing negative emotions by way of preventing a negative emotional contrast. Implications for the role of worry in emotion avoidance are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

Physiological Aldosterone Concentrations Are Associated with Alterations of Lipid Metabolism: Observations from the General Population.

Science.gov (United States)

Hannich, M; Wallaschofski, H; Nauck, M; Reincke, M; Adolf, C; Völzke, H; Rettig, R; Hannemann, A

2018-01-01

Aldosterone and high-density lipoprotein cholesterol (HDL-C) are involved in many pathophysiological processes that contribute to the development of cardiovascular diseases. Previously, associations between the concentrations of aldosterone and certain components of the lipid metabolism in the peripheral circulation were suggested, but data from the general population is sparse. We therefore aimed to assess the associations between aldosterone and HDL-C, low-density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides, or non-HDL-C in the general adult population. Data from 793 men and 938 women aged 25-85 years who participated in the first follow-up of the Study of Health in Pomerania were obtained. The associations of aldosterone with serum lipid concentrations were assessed in multivariable linear regression models adjusted for sex, age, body mass index (BMI), estimated glomerular filtration rate (eGFR), and HbA1c. The linear regression models showed statistically significant positive associations of aldosterone with LDL-C ( β -coefficient = 0.022, standard error = 0.010, p = 0.03) and non-HDL-C ( β -coefficient = 0.023, standard error = 0.009, p = 0.01) as well as an inverse association of aldosterone with HDL-C ( β -coefficient = -0.022, standard error = 0.011, p = 0.04). The present data show that plasma aldosterone is positively associated with LDL-C and non-HDL-C and inversely associated with HDL-C in the general population. Our data thus suggests that aldosterone concentrations within the physiological range may be related to alterations of lipid metabolism.

Complexity and network dynamics in physiological adaptation: an integrated view.

Science.gov (United States)

Baffy, György; Loscalzo, Joseph

2014-05-28

Living organisms constantly interact with their surroundings and sustain internal stability against perturbations. This dynamic process follows three fundamental strategies (restore, explore, and abandon) articulated in historical concepts of physiological adaptation such as homeostasis, allostasis, and the general adaptation syndrome. These strategies correspond to elementary forms of behavior (ordered, chaotic, and static) in complex adaptive systems and invite a network-based analysis of the operational characteristics, allowing us to propose an integrated framework of physiological adaptation from a complex network perspective. Applicability of this concept is illustrated by analyzing molecular and cellular mechanisms of adaptation in response to the pervasive challenge of obesity, a chronic condition resulting from sustained nutrient excess that prompts chaotic exploration for system stability associated with tradeoffs and a risk of adverse outcomes such as diabetes, cardiovascular disease, and cancer. Deconstruction of this complexity holds the promise of gaining novel insights into physiological adaptation in health and disease. Published by Elsevier Inc.

Cyanide toxicokinetics: the behavior of cyanide, thiocyanate and 2-amino-2-thiazoline-4-carboxylic acid in multiple animal models.

Science.gov (United States)

Bhandari, Raj K; Oda, Robert P; Petrikovics, Ilona; Thompson, David E; Brenner, Matthew; Mahon, Sari B; Bebarta, Vikhyat S; Rockwood, Gary A; Logue, Brian A

2014-05-01

Cyanide causes toxic effects by inhibiting cytochrome c oxidase, resulting in cellular hypoxia and cytotoxic anoxia, and can eventually lead to death. Cyanide exposure can be verified by direct analysis of cyanide concentrations or analyzing its metabolites, including thiocyanate (SCN(-)) and 2-amino-2-thiazoline-4-carboxylic acid (ATCA) in blood. To determine the behavior of these markers following cyanide exposure, a toxicokinetics study was performed in three animal models: (i) rats (250-300 g), (ii) rabbits (3.5-4.2 kg) and (iii) swine (47-54 kg). Cyanide reached a maximum in blood and declined rapidly in each animal model as it was absorbed, distributed, metabolized and eliminated. Thiocyanate concentrations rose more slowly as cyanide was enzymatically converted to SCN(-). Concentrations of ATCA did not rise significantly above the baseline in the rat model, but rose quickly in rabbits (up to a 40-fold increase) and swine (up to a 3-fold increase) and then fell rapidly, generally following the relative behavior of cyanide. Rats were administered cyanide subcutaneously and the apparent half-life (t1/2) was determined to be 1,510 min. Rabbits were administered cyanide intravenously and the t1/2 was determined to be 177 min. Swine were administered cyanide intravenously and the t1/2 was determined to be 26.9 min. The SCN(-) t1/2 in rats was 3,010 min, but was not calculated in rabbits and swine because SCN(-) concentrations did not reach a maximum. The t1/2 of ATCA was 40.7 and 13.9 min in rabbits and swine, respectively, while it could not be determined in rats with confidence. The current study suggests that cyanide exposure may be verified shortly after exposure by determining significantly elevated cyanide and SCN(-) in each animal model and ATCA may be used when the ATCA detoxification pathway is significant.

A Physiologically Informed Virtual Reality Based Social Communication System for Individuals with Autism

Science.gov (United States)

Lahiri, Uttama; Bekele, Esubalew; Dohrmann, Elizabeth; Warren, Zachary; Sarkar, Nilanjan

2015-01-01

Clinical applications of advanced technology may hold promise for addressing impairments associated with autism spectrum disorders (ASD). This project evaluated the application of a novel physiologically responsive virtual reality based technological system for conversation skills in a group of adolescents with ASD. The system altered components…

A Moodle-based blended learning solution for physiology education in Montenegro: a case study.

Science.gov (United States)

Popovic, Natasa; Popovic, Tomo; Rovcanin Dragovic, Isidora; Cmiljanic, Oleg

2018-03-01

This study evaluates the impact of web-based blended learning in the physiology course at the Faculty of Medicine, University of Montenegro. The two main goals of the study were: to determine the impact of e-learning on student success in mastering the course, and to assess user satisfaction after the introduction of e-learning. The study compared a group of students who attended the physiology course before, with a group of students who attended the physiology course after the Moodle platform was fully implemented as an educational tool. Formative and summative assessment scores were compared between these two groups. The impact of high vs. low Moodle use on the assessment scores was analyzed. The satisfaction among Moodle users was assessed by the survey. The study found that attendance of face-to-face lectures had a positive impact on academic performance. The introduction of Moodle in the presented model of teaching increased interest of students, attendance of face-to-face lectures, as well as formative and summative scores. High frequency of Moodle use was not always associated with better academic performance, suggesting that the introduction of a new method of teaching was most likely equally accepted by low- and high-achieving students. Most of the students agreed that Moodle was easy to use and it complemented traditional teaching very well, but it could not completely replace traditional face-to-face lectures. The study supports continuing the use of web-based learning in a form of blended learning for physiology, as well as for other courses in medical education.

Development of Screening Tools for the Interpretation of Chemical Biomonitoring Data

Directory of Open Access Journals (Sweden)

Richard A. Becker

2012-01-01

Full Text Available Evaluation of a larger number of chemicals in commerce from the perspective of potential human health risk has become a focus of attention in North America and Europe. Screening-level chemical risk assessment evaluations consider both exposure and hazard. Exposures are increasingly being evaluated through biomonitoring studies in humans. Interpreting human biomonitoring results requires comparison to toxicity guidance values. However, conventional chemical-specific risk assessments result in identification of toxicity-based exposure guidance values such as tolerable daily intakes (TDIs as applied doses that cannot directly be used to evaluate exposure information provided by biomonitoring data in a health risk context. This paper describes a variety of approaches for development of screening-level exposure guidance values with translation from an external dose to a biomarker concentration framework for interpreting biomonitoring data in a risk context. Applications of tools and concepts including biomonitoring equivalents (BEs, the threshold of toxicologic concern (TTC, and generic toxicokinetic and physiologically based toxicokinetic models are described. These approaches employ varying levels of existing chemical-specific data, chemical class-specific assessments, and generic modeling tools in response to varying levels of available data in order to allow assessment and prioritization of chemical exposures for refined assessment in a risk management context.

A physiologically based biokinetic model for cesium in the human body

International Nuclear Information System (INIS)

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

2003-01-01

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

[Pregnancy in the context of general adaptation syndrome].

Science.gov (United States)

Gur'ianov, V A; Pyregov, A V; Tolmachev, G N; Volodin, A V

2007-01-01

Based on their own findings and the data available in the literature on pregnancy including that complicated by gestosis, the authors consider these conditions in the context of Selye's general adaptation syndrome. They identify its basic links (the autonomic nervous and cardiovascular systems) the function of which is affected by all the physiological and pathophysiological processes involved in its development. There is a high likelihood of baseline impaired adaption processes in these links, which may lead to an inability to accommodate (dysadaptation) by the moment of delivery. The paper gives the current interpretation of functional disorders, called Zangemeister'a triad in 1913, from the present-day points of view of the evaluation of pregnancy as the systemic inflammatory response syndrome and, probably, adaptation disease. Based on the results of analyzing the data available in the literature, the authors indicate physiologically the basic trends in the modulation of impaired development processes of the general adaptation syndrome towards the completion of pregnancy and surgical delivery.

Physiological pseudomyopia.

Science.gov (United States)

Jones, R

1990-08-01

Objective refraction through plus fogging lenses and base-in prisms revealed that normally accommodation is not completely relaxed when the stimulus to accommodation is zero. The myopic shift in the refractive error due to this focus error of accommodation was defined as physiological pseudomyopia. Two previously established features of accommodation are responsible for this behavior: (1) accommodation acts as a proportional control system for steady-state responses; and (2) the rest focus of accommodation is nonzero. It is proposed that the hyperopic shift in refraction observed in cycloplegia is the result of elimination of physiological pseudomyopia.

Toxicity and efficacy of carbon nanotubes and graphene: the utility of carbon-based nanoparticles in nanomedicine.

Science.gov (United States)

Zhang, Yongbin; Petibone, Dayton; Xu, Yang; Mahmood, Meena; Karmakar, Alokita; Casciano, Dan; Ali, Syed; Biris, Alexandru S

2014-05-01

Carbon-based nanomaterials have attracted great interest in biomedical applications such as advanced imaging, tissue regeneration, and drug or gene delivery. The toxicity of the carbon nanotubes and graphene remains a debated issue although many toxicological studies have been reported in the scientific community. In this review, we summarize the biological effects of carbon nanotubes and graphene in terms of in vitro and in vivo toxicity, genotoxicity and toxicokinetics. The dose, shape, surface chemistry, exposure route and purity play important roles in the metabolism of carbon-based nanomaterials resulting in differential toxicity. Careful examination of the physico-chemical properties of carbon-based nanomaterials is considered a basic approach to correlate the toxicological response with the unique properties of the carbon nanomaterials. The reactive oxygen species-mediated toxic mechanism of carbon nanotubes has been extensively discussed and strategies, such as surface modification, have been proposed to reduce the toxicity of these materials. Carbon-based nanomaterials used in photothermal therapy, drug delivery and tissue regeneration are also discussed in this review. The toxicokinetics, toxicity and efficacy of carbon-based nanotubes and graphene still need to be investigated further to pave a way for biomedical applications and a better understanding of their potential applications to humans.

Determination of Parameters for Development of a Physiologically Based Model for the Toxicokinetics of C(+)P(+)-Soman

Science.gov (United States)

1993-06-01

In conducting research utilizing recombinant DNA technology , the investigator(s) adhered to current guidelines promulgated by the National...zur Rtickstandanalyse), saponin (BDH, Poole, UK), aluminium sulfate.16 H2 0 (BDH Analar, Ž 98%), sodium bicarbonate (Lamens en Indemans, ’s...isopropanol). The mixture was extracted with 3 ml ethyl acetate. Gas chromatographic analysis of the soman stereoisomers in the ethyl acetate phase was

Physiological health parameters among college students to promote chronic disease prevention and health promotion

Directory of Open Access Journals (Sweden)

David R. Black

2017-09-01

Full Text Available This study aimed to provide physiologic health risk parameters by gender and age among college students enrolled in a U.S. Midwestern University to promote chronic disease prevention and ameliorate health. A total of 2615 college students between 18 and 25 years old were recruited annually using a series of cross-sectional designs during the spring semester over an 8-year period. Physiologic parameters measured included body mass index (BMI, percentage body fat (%BF, blood serum cholesterol (BSC, and systolic (SBP and diastolic (DBP blood pressure. These measures were compared to data from NHANES to identify differences in physiologic parameters among 18–25 year olds in the general versus college-enrolled population. A quantitative instrument assessed health behaviors related to physical activity, diet, and licit drug use. Results suggest that average physiologic parameters from 18 to 25 year olds enrolled in college were significantly different from parameters of 18–25 year olds in the general population. Generally, men reported higher percentiles for BMI, SBP, and DBP than women, but lower %BF and BSC percentiles than women at each age. SBP and DBP significantly increased with age and alcohol use. Students in the lowest (5th and highest percentiles (95th and 75th, for most age groups, demonstrated DBP, BMI, and %BF levels potentially problematic for health and future development of chronic disease based on percentiles generated for their peer group. Newly identified physiologic parameters may be useful to practitioners serving college students 18–25 years old from similar institutions in determining whether behavior change or treatment interventions are appropriate.

Dinosaur energetics: setting the bounds on feasible physiologies and ecologies

OpenAIRE

Clarke, Andrew

2013-01-01

The metabolic status of dinosaurs has long been debated but remains unresolved as no consistent picture has emerged from a range of anatomical and isotopic evidence. Quantitative analysis of dinosaur energetics, based on general principles applicable to all vertebrates, shows that many features of dinosaur lifestyle are compatible with a physiology similar to that of extant lizards, scaled up to dinosaur body masses and temperatures. The analysis suggests that sufficient metabolic scope would...

Toxicokinetics of Kava

Directory of Open Access Journals (Sweden)

Anthony Rowe

2011-01-01

Full Text Available Kava is traditionally consumed by South Pacific islanders as a drink and became popular in Western society as a supplement for anxiety and insomnia. Kava extracts are generally well tolerated, but reports of hepatotoxicity necessitated an international reappraisal of its safety. Hepatotoxicity can occur as an acute, severe form or a chronic, mild form. Inflammation appears to be involved in both forms and may result from activation of liver macrophages (Kupffer cells, either directly or via kava metabolites. Pharmacogenomics may influence the severity of this inflammatory response.

Physiological Aldosterone Concentrations Are Associated with Alterations of Lipid Metabolism: Observations from the General Population

Directory of Open Access Journals (Sweden)

M. Hannich

2018-01-01

Full Text Available Objective. Aldosterone and high-density lipoprotein cholesterol (HDL-C are involved in many pathophysiological processes that contribute to the development of cardiovascular diseases. Previously, associations between the concentrations of aldosterone and certain components of the lipid metabolism in the peripheral circulation were suggested, but data from the general population is sparse. We therefore aimed to assess the associations between aldosterone and HDL-C, low-density lipoprotein cholesterol (LDL-C, total cholesterol, triglycerides, or non-HDL-C in the general adult population. Methods. Data from 793 men and 938 women aged 25–85 years who participated in the first follow-up of the Study of Health in Pomerania were obtained. The associations of aldosterone with serum lipid concentrations were assessed in multivariable linear regression models adjusted for sex, age, body mass index (BMI, estimated glomerular filtration rate (eGFR, and HbA1c. Results. The linear regression models showed statistically significant positive associations of aldosterone with LDL-C (β-coefficient = 0.022, standard error = 0.010, p=0.03 and non-HDL-C (β-coefficient = 0.023, standard error = 0.009, p=0.01 as well as an inverse association of aldosterone with HDL-C (β-coefficient = −0.022, standard error = 0.011, p=0.04. Conclusions. The present data show that plasma aldosterone is positively associated with LDL-C and non-HDL-C and inversely associated with HDL-C in the general population. Our data thus suggests that aldosterone concentrations within the physiological range may be related to alterations of lipid metabolism.

Physiology-based face recognition in the thermal infrared spectrum.

Science.gov (United States)

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

2007-04-01

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

Physiological and molecular biochemical mechanisms of bile formation

Science.gov (United States)

Reshetnyak, Vasiliy Ivanovich

2013-01-01

This review considers the physiological and molecular biochemical mechanisms of bile formation. The composition of bile and structure of a bile canaliculus, biosynthesis and conjugation of bile acids, bile phospholipids, formation of bile micellar structures, and enterohepatic circulation of bile acids are described. In general, the review focuses on the molecular physiology of the transporting systems of the hepatocyte sinusoidal and apical membranes. Knowledge of physiological and biochemical basis of bile formation has implications for understanding the mechanisms of development of pathological processes, associated with diseases of the liver and biliary tract. PMID:24259965

Deconstructing the superorganism: social physiology, groundplans, and sociogenomics

DEFF Research Database (Denmark)

Johnson, Brian R; Linksvayer, Timothy A

2010-01-01

changes in the regulation of ancestral gene sets affecting reproductive physiology and behavior, and we argue that this hypothesis is explanatory for the evolution of division of labor (social anatomy) but not for the regulatory systems that ensure group-level coordination of action (social physiology...... to a truly integrative approach remains, as social physiology--the basis of group-level coordination--has generally been neglected by geneticists. In this paper, we begin a synthesis of these fields by first reviewing three classes of social insect organization that mark major transitions in increasing...

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

DEFF Research Database (Denmark)

Nybo, Lars; May, Michael

2015-01-01

(individual subject-specific tests and group interviews) were performed for a laboratory course in cardiorespiratory exercise physiology that was conducted in one year with a traditional step-by-step guided manual (traditional course) and the next year completed with an inquiry-based structure (I-based course......). The I-based course was a guided inquiry course where students had to design the experimental protocol and conduct their own study on the basis of certain predefined criteria (i.e., they should evaluate respiratory responses to submaximal and maximal exercise and provide indirect and direct measures...... of aerobic exercise capacity). The results indicated that the overall time spent on the experimental course as well as self-evaluated learning outcomes were similar across groups. However, students in the I-based course used more time in preparation (102 ± 5 min) than students in the traditional course (42...

[Physiology in Relation to Anesthesia Practice: Preface and Comments].

Science.gov (United States)

Yamada, Yoshitsugu

2016-05-01

It has been long recognized that anesthesia practice is profoundly based in physiology. With the advance of the technology of imaging, measurement and information, a serious gap has emerged between anesthesia mainly handling gross systemic parameters and molecular physiology. One of the main reasons is the lack of establishment of integration approach. This special series of reviews deals with systems physiology covering respiratory, cardiovascular, and nervous systems. It also includes metabolism, and fluid, acid-base, and electrolyte balance. Each review focuses on several physiological concepts in each area, explaining current understanding and limits of the concepts based on the new findings. They reaffirm the importance of applying physiological inference in anesthesia practice and underscore the needs of advancement of systems physiology.

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

Science.gov (United States)

Zhu, Lingyun; Li, Lianjie; Meng, Chunyan

2014-12-01

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

Prediction of acute toxicity of cadmium and lead to zebrafish larvae by using a refined toxicokinetic-toxicodynamic model

International Nuclear Information System (INIS)

Gao, Yongfei; Feng, Jianfeng; Zhu, Lin

2015-01-01

Highlights: • We developed a BLM-aided TK-TD model that considers the effects of H"+. • The time-course metal concentration in larvae was well described by the TK model. • The time-course survival of zebrafish larvae was well simulated by the TD model. - Abstract: The biotic ligand model (BLM) and the toxicokinetic-toxicodynamic (TK-TD) model are essential in predicting the acute toxicity of metals in various species and exposure conditions; however, these models are usually separately utilized. In this study, a mechanistic TK-TD model was developed to predict the acute toxicity of 10"−"6 M Cd and 10"−"6 M Pb to zebrafish (Danio rerio) larvae. The novel approach links the BLM with relevant TK processes to simulate the bioaccumulation processes of Cd or Pb as a function of the maximum uptake rate of each metal, the affinity constants, and the concentrations of free metal ions and H"+ in test solutions. Results showed that the refined TK-TD model can accurately predict the accumulation and acute toxicity of Cd and Pb to zebrafish larvae at pH 5.5, 6.5, and 7.0.

Prediction of acute toxicity of cadmium and lead to zebrafish larvae by using a refined toxicokinetic-toxicodynamic model

Energy Technology Data Exchange (ETDEWEB)

Gao, Yongfei; Feng, Jianfeng, E-mail: fengjf@nankai.edu.cn; Zhu, Lin, E-mail: zhulin@nankai.edu.cn

2015-12-15

Highlights: • We developed a BLM-aided TK-TD model that considers the effects of H{sup +}. • The time-course metal concentration in larvae was well described by the TK model. • The time-course survival of zebrafish larvae was well simulated by the TD model. - Abstract: The biotic ligand model (BLM) and the toxicokinetic-toxicodynamic (TK-TD) model are essential in predicting the acute toxicity of metals in various species and exposure conditions; however, these models are usually separately utilized. In this study, a mechanistic TK-TD model was developed to predict the acute toxicity of 10{sup −6} M Cd and 10{sup −6} M Pb to zebrafish (Danio rerio) larvae. The novel approach links the BLM with relevant TK processes to simulate the bioaccumulation processes of Cd or Pb as a function of the maximum uptake rate of each metal, the affinity constants, and the concentrations of free metal ions and H{sup +} in test solutions. Results showed that the refined TK-TD model can accurately predict the accumulation and acute toxicity of Cd and Pb to zebrafish larvae at pH 5.5, 6.5, and 7.0.

Effect of tetraethylthiuramdisulphide and diethyldithiocarbamate on nickel toxicokinetics in mice

International Nuclear Information System (INIS)

Dalsgaard, G.; Andersen, O.

1994-01-01

A new experimental pharmacokinetic model using the γ-emitting isotope 57 Ni for studying nickel toxicokinetics was employed in a recent investigation in order to quantitatively study, for the first time, the effect of tetraethylthiuram disulphide (disulfiram, Antabuse, TTD) and sodium diethyldithiocarbamate (DDC) on whole-body retention and organ distribution of nickel in mice. TTD or its decomposition product DDC given orally by stomach tube shortly after oral administration of a low dose of nickel chloride labelled with 57 Ni resulted in an approximately ten times higher whole-body retention of nickel compared to the retention in a control group exposed to nickel only. These chelators increased the whole-body retention of nickel also when given by intraperitoneal injection shortly after oral or intraperitoneal administration of nickel. Oral administration of a single dose of TTD or DDC rapidly after an oral dose of nickel chloride also resulted in extensive changes in the organ distribution of nickel, thus the nickel content in the brain was at least 700 times higher than in a control group given the same dose of nickel only. If DDC was given intraperitoneally after nickel given orally, the relative organ distribution of nickel to most organs was the same as if the chelator was given orally, though the contents of the liver and lungs were lower. That TTD and DDC resulted in a transport of nickel to the brain, is underlined by the fact that after 20 hr, approximately 15% and after 45-50 hr, 30% of the total body burden of Ni was found in the brain. Stating the nickel content as concentrations, we found after 19 hr to 23 hr the highest nickel concentration in the brain, kidneys, lungs and liver, in order of decreasing concentration. From 68 hr to 122 hr the order was brain, lungs, kidneys and liver. TTD and DDC are widely used clinically. These results indicate, that long-term simultaneous administration of nickel and TTD or DDC to humans should be avoided, as

Behavior Assessment in Children Following Hospital-Based General Anesthesia versus Office-Based General Anesthesia

Directory of Open Access Journals (Sweden)

LaQuia A. Vinson

2016-08-01

Full Text Available The purpose of this study was to determine if differences in behavior exist following dental treatment under hospital-based general anesthesia (HBGA or office-based general anesthesia (OBGA in the percentage of patients exhibiting positive behavior and in the mean Frankl scores at recall visits. This retrospective study examined records of a pediatric dental office over a 4 year period. Patients presenting before 48 months of age for an initial exam who were diagnosed with early childhood caries were included in the study. Following an initial exam, patients were treated under HBGA or OBGA. Patients were followed to determine their behavior at 6-, 12- and 18-month recall appointments. Fifty-four patients received treatment under HBGA and 26 were treated under OBGA. OBGA patients were significantly more likely to exhibit positive behavior at the 6- and 12-month recall visits p = 0.038 & p = 0.029. Clinicians should consider future behavior when determining general anesthesia treatment modalities in children with early childhood caries presenting to their office.

Toxicokinetics of tremorogenic natural products, harmane and harmine, in male Sprague-Dawley rats.

Science.gov (United States)

Guan, Y; Louis, E D; Zheng, W

2001-12-21

Tremorogenic beta-carboline alkaloids are present in foodstuffs and beverages. Acute exposure to beta-carboline derivatives causes severe tremor; however, the disposition of these dietary contaminants remains unclear. This study was performed to evaluate toxicokinetics of harmane and harmine, two major beta-carboline alkaloids, in rats. Blood concentrations of both toxicants were quantified by high-performance liquid chromatography (HPLC). Following an intravenous injection (0.5 mg/kg), the concentration-time profiles of harmane or harmine fit well with a two-compartment model. While both compounds had comparable elimination t 1/2beta (24 and 26 min for harmane and harmine, respectively), the systemic clearance (CLs) for harmine (103.2 ml/kg/ml) was two times greater than that for harmane (52.2 ml/kg/ml). Accordingly, the area under the blood concentration-time curve (AUC) in harmane-treated rats was 2.7-fold greater than that in harmine-treated rats. Harmine appeared to distribute to tissues better than harmane, with a larger volume of distribution (V,d) (3.9 and 1.6 L/kg for harmine and harmane, respectively). After an oral dose (20 mg/kg), the absolute bioavailability (F) was 19% for harmane and 3% for harmine. Harmane was absorbed more slowly (lower Ka), yet more completely (higher Cmax' AUC, and F) than harmine. An oral administration of harmane resulted in blood harmine whose formation accounted for 13% of the ingested harmane, indicating a biotransformation of harmane to harmine. These results suggest that harmane is absorbed into the systemic circulation more completely than harmine. Upon entering the body, harmane can be metabolized to form harmine; the latter may better distribute to the tissue compartment.

Emotion of Physiological Signals Classification Based on TS Feature Selection

Institute of Scientific and Technical Information of China (English)

Wang Yujing; Mo Jianlin

2015-01-01

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

Toxicological effects of pyrethroids on non-target aquatic insects.

Science.gov (United States)

Antwi, Frank B; Reddy, Gadi V P

2015-11-01

The toxicological effects of pyrethroids on non-target aquatic insects are mediated by several modes of entry of pyrethroids into aquatic ecosystems, as well as the toxicological characteristics of particular pyrethroids under field conditions. Toxicokinetics, movement across the integument of aquatic insects, and the toxicodynamics of pyrethroids are discussed, and their physiological, symptomatic and ecological effects evaluated. The relationship between pyrethroid toxicity and insecticide uptake is not fully defined. Based on laboratory and field data, it is likely that the susceptibility of aquatic insects (vector and non-vector) is related to biochemical and physiological constraints associated with life in aquatic ecosystems. Understanding factors that influence aquatic insects susceptibility to pyrethroids is critical for the effective and safe use of these compounds in areas adjacent to aquatic environments. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Space Physiology within an Exercise Physiology Curriculum

Science.gov (United States)

Carter, Jason R.; West, John B.

2013-01-01

Compare and contrast strategies remain common pedagogical practices within physiological education. With the support of an American Physiological Society Teaching Career Enhancement Award, we have developed a junior- or senior-level undergraduate curriculum for exercise physiology that compares and contrasts the physiological adaptations of…

COMPARISON OF PROBLEM BASED LEARNING WITH TRADITIONAL LECTURES AMONG FIRST YEAR MEDICAL STUDENTS IN PHYSIOLOGY

OpenAIRE

Evelyn

2015-01-01

BACKGROUND: Problem based learning has emerged as an effective teaching learning method. Students taught by the problem based learning method have better problem solving skills and better long-term memory than those taught by traditional lectures. OBJECTIVE: To compare the effectiveness of problem based learning with that of traditional lecture method. METHODOLOGY: First MBBS students (n=127) were divided into two groups. One group was taught a topic from Applied Physiolog...

Micro-patterned graphene-based sensing skins for human physiological monitoring

Science.gov (United States)

Wang, Long; Loh, Kenneth J.; Chiang, Wei-Hung; Manna, Kausik

2018-03-01

Ultrathin, flexible, conformal, and skin-like electronic transducers are emerging as promising candidates for noninvasive and nonintrusive human health monitoring. In this work, a wearable sensing membrane is developed by patterning a graphene-based solution onto ultrathin medical tape, which can then be attached to the skin for monitoring human physiological parameters and physical activity. Here, the sensor is validated for monitoring finger bending/movements and for recognizing hand motion patterns, thereby demonstrating its future potential for evaluating athletic performance, physical therapy, and designing next-generation human-machine interfaces. Furthermore, this study also quantifies the sensor’s ability to monitor eye blinking and radial pulse in real-time, which can find broader applications for the healthcare sector. Overall, the printed graphene-based sensing skin is highly conformable, flexible, lightweight, nonintrusive, mechanically robust, and is characterized by high strain sensitivity.

Jacques Loeb (1859-1924) and His Forgotten Contributions to Electrolyte and Acid-Base Physiology in The Organism as a Whole.

Science.gov (United States)

Sgambato, Francesco; Sgambato, Ester; De Santo, Natale Gaspare

2016-02-01

Jacques Loeb (1859-1924) was the founder of the Journal of General Physiology which he co-directed in association with W.J.V. Osterhout in the years 1918-1924. Having worked (1889-1891)at the Marine Zoological Station of Naples, newly founded by Anton Dohrn, he was imprinted for life. A strong investigator used to perform the experiments personally. Loeb was engaged lifelong in the explanation of life on physico-chemical basis. He touched various fields (being a creative scientist full of ideas), and centered on the exchanges of electrolytes, acids and bases between the body and sea water in fish. He identified two equations: {[K+]+[Na+]}: {[Ca++]+[Mg++]} (Loebs 1st equation) {[K+]+[Na+]}: {[H+]+[Ca++]+[Mg++]} (Loebs final equation) Even nowadays these equations may have applications in a wide list of electrolyte and acid-base disturbances. Unfortunately his heredity has been dissipated.

General herpetological collecting is size-based for five Pacific lizards

Science.gov (United States)

Rodda, Gordon H.; Yackel Adams, Amy A.; Campbell, Earl W.; Fritts, Thomas H.

2015-01-01

Accurate estimation of a species’ size distribution is a key component of characterizing its ecology, evolution, physiology, and demography. We compared the body size distributions of five Pacific lizards (Carlia ailanpalai, Emoia caeruleocauda, Gehyra mutilata, Hemidactylus frenatus, and Lepidodactylus lugubris) from general herpetological collecting (including visual surveys and glue boards) with those from complete censuses obtained by total removal. All species exhibited the same pattern: general herpetological collecting undersampled juveniles and oversampled mid-sized adults. The bias was greatest for the smallest juveniles and was not statistically evident for newly maturing and very large adults. All of the true size distributions of these continuously breeding species were skewed heavily toward juveniles, more so than the detections obtained from general collecting. A strongly skewed size distribution is not well characterized by the mean or maximum, though those are the statistics routinely reported for species’ sizes. We found body mass to be distributed more symmetrically than was snout–vent length, providing an additional rationale for collecting and reporting that size measure.

Physiological effects of diet mixing on consumer fitness: a meta-analysis.

Science.gov (United States)

Lefcheck, Jonathan S; Whalen, Matthew A; Davenport, Theresa M; Stone, Joshua P; Duffy, J Emmett

2013-03-01

The degree of dietary generalism among consumers has important consequences for population, community, and ecosystem processes, yet the effects on consumer fitness of mixing food types have not been examined comprehensively. We conducted a meta-analysis of 161 peer-reviewed studies reporting 493 experimental manipulations of prey diversity to test whether diet mixing enhances consumer fitness based on the intrinsic nutritional quality of foods and consumer physiology. Averaged across studies, mixed diets conferred significantly higher fitness than the average of single-species diets, but not the best single prey species. More than half of individual experiments, however, showed maximal growth and reproduction on mixed diets, consistent with the predicted benefits of a balanced diet. Mixed diets including chemically defended prey were no better than the average prey type, opposing the prediction that a diverse diet dilutes toxins. Finally, mixed-model analysis showed that the effect of diet mixing was stronger for herbivores than for higher trophic levels. The generally weak evidence for the nutritional benefits of diet mixing in these primarily laboratory experiments suggests that diet generalism is not strongly favored by the inherent physiological benefits of mixing food types, but is more likely driven by ecological and environmental influences on consumer foraging.

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

NARCIS (Netherlands)

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

2006-01-01

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

Helmet-based physiological signal monitoring system.

Science.gov (United States)

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.

Using physiologically based models for clinical translation: predictive modelling, data interpretation or something in-between?

Science.gov (United States)

Niederer, Steven A; Smith, Nic P

2016-12-01

Heart disease continues to be a significant clinical problem in Western society. Predictive models and simulations that integrate physiological understanding with patient information derived from clinical data have huge potential to contribute to improving our understanding of both the progression and treatment of heart disease. In particular they provide the potential to improve patient selection and optimisation of cardiovascular interventions across a range of pathologies. Currently a significant proportion of this potential is still to be realised. In this paper we discuss the opportunities and challenges associated with this realisation. Reviewing the successful elements of model translation for biophysically based models and the emerging supporting technologies, we propose three distinct modes of clinical translation. Finally we outline the challenges ahead that will be fundamental to overcome if the ultimate goal of fully personalised clinical cardiac care is to be achieved. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Effects of activity-rest schedules on physiological strain and spinal load in hospital-based porters.

Science.gov (United States)

Beynon, C; Burke, J; Doran, D; Nevill, A

2000-10-01

Workers in physically demanding occupations require rest breaks to recover from physiological stress and biomechanical loading. Physiological stress can increase the risk of developing musculoskeletal disorders and repeated loading of the spine may increase the potential for incurring back pain. The aim of the study was to assess the impact of an altered activity-rest schedule on physiological and spinal loading in hospital-based porters. An existing 4-h activity-rest schedule was obtained from observations on eight male porters. This schedule formed the normal trial, which included two 5- and one 15-min breaks. An alternative 4-h schedule was proposed (experimental condition) that had two breaks each of 12.5 min. It was hypothesized that the experimental trial is more effective in promoting recovery from physiological strain and spinal shrinkage than the normal trial, due to the 5-min breaks being insufficient to allow physiological variables to return to resting levels or the intervertebral discs to reabsorb fluid. Ten males performed both test conditions and oxygen uptake VO2, heart rate, minute ventilation VE, perceived exertion and spinal shrinkage were recorded. There were no significant differences in any of the measured variables between the two trials (p > 0.05). Median heart rates were 78 (range 71-93) and 82 (71-90) beats.min(-1) for the normal trial and the experimental trial respectively, indicating that the activity was of low intensity. The light intensity was corroborated by the oxygen uptakes (0.75, range 0.65-0.94 1.min(-1)). Spinal shrinkage occurred to the same extent in the two trials (2.12 +/- 3.16 mm and 2.88 +/- 2.92 mm in the normal trial and the experimental trial respectively). Varying the length and positioning of the rest breaks did not significantly affect the physiological responses or magnitude of spinal shrinkage between the two trials. More physically demanding work than the porters' schedule should induce greater physiological

Bengt Saltin and exercise physiology: a perspective.

Science.gov (United States)

Joyner, Michael J

2017-01-01

This perspective highlights some of the key contributions of Professor Bengt Saltin (1935-2014) to exercise physiology. The emergence of exercise physiology from work physiology as his career began is discussed as are his contributions in a number of areas. Saltin's open and question-based style of leadership is a model for the future of our field.

Cardiovascular anatomy and physiology in the female.

Science.gov (United States)

Wingate, S

1997-12-01

Important differences in male and female cardiovascular anatomy and physiology may account for many of the gender differences seen in various cardiac disease states. Predominant influences on female disease manifestations include (1) women's smaller body size, hence smaller hearts and smaller coronary vessels and (2) women's fluctuating levels of estrogen throughout their lifespan. Understanding these critical anatomic and physiologic differences allows the clinician to better predict and plan care for women. For example, knowing that women generally have a smaller body surface area than men allows one to better understand why men have higher creatine kinase (CK) values than do women--an important distinction when interpreting these values in the acute care setting. The fact that women's hearts and coronary vessels are generally smaller than men's also helps one understand why women have a higher in-hospital mortality than men post-coronary artery bypass graft surgery (see article by Allen in this issue for more detailed information on revascularization). These are only a few examples of the many opportunities that acute care nurses have to integrate their knowledge of anatomy and physiology into proactive planning for their female cardiac patients.

A framework and case studies for evaluation of enzyme ontogeny in children's health risk evaluation.

Science.gov (United States)

Ginsberg, Gary; Vulimiri, Suryanarayana V; Lin, Yu-Sheng; Kancherla, Jayaram; Foos, Brenda; Sonawane, Babasaheb

2017-01-01

Knowledge of the ontogeny of Phase I and Phase II metabolizing enzymes may be used to inform children's vulnerability based upon likely differences in internal dose from xenobiotic exposure. This might provide a qualitative assessment of toxicokinetic (TK) variability and uncertainty pertinent to early lifestages and help scope a more quantitative physiologically based toxicokinetic (PBTK) assessment. Although much is known regarding the ontogeny of metabolizing systems, this is not commonly utilized in scoping and problem formulation stage of human health risk evaluation. A framework is proposed for introducing this information into problem formulation which combines data on enzyme ontogeny and chemical-specific TK to explore potential child/adult differences in internal dose and whether such metabolic differences may be important factors in risk evaluation. The framework is illustrated with five case study chemicals, including some which are data rich and provide proof of concept, while others are data poor. Case studies for toluene and chlorpyrifos indicate potentially important child/adult TK differences while scoping for acetaminophen suggests enzyme ontogeny is unlikely to increase early-life risks. Scoping for trichloroethylene and aromatic amines indicates numerous ways that enzyme ontogeny may affect internal dose which necessitates further evaluation. PBTK modeling is a critical and feasible next step to further evaluate child-adult differences in internal dose for a number of these chemicals.

Human physiologically based pharmacokinetic model for propofol

Directory of Open Access Journals (Sweden)

Schnider Thomas W

2005-04-01

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

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

Science.gov (United States)

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

2015-01-01

Gait function is traditionally assessed using well-lit, unobstructed walkways with minimal distractions. In patients with subclinical physiological abnormalities, these conditions may not provide enough stress on their ability to adapt to walking. The introduction of challenging walking conditions in gait can induce responses in physiological systems in addition to the locomotor system. There is a need for a device that is capable of monitoring multiple physiological systems in various walking conditions. To address this need, an Android-based gait-monitoring device was developed that enabled the recording of a patient's physiological systems during walking. The gait-monitoring device was tested during self-regulated overground walking sessions of fifteen healthy subjects that included 6 females and 9 males aged 18 to 35 years. The gait-monitoring device measures the patient's stride interval, acceleration, electrocardiogram, skin conductance and respiratory rate. The data is stored on an Android phone and is analyzed offline through the extraction of features in the time, frequency and time-frequency domains. The analysis of the data depicted multisystem physiological interactions during overground walking in healthy subjects. These interactions included locomotion-electrodermal, locomotion-respiratory and cardiolocomotion couplings. The current results depicting strong interactions between the locomotion system and the other considered systems (i.e., electrodermal, respiratory and cardivascular systems) warrant further investigation into multisystem interactions during walking, particularly in challenging walking conditions with older adults. PMID:26390946

Non-self-adjoint Hamiltonians defined by generalized Riesz bases

Energy Technology Data Exchange (ETDEWEB)

Inoue, H., E-mail: h-inoue@math.kyushu-u.ac.jp [Graduate School of Mathematics, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395 (Japan); Takakura, M., E-mail: mayumi@fukuoka-u.ac.jp [Department of Applied Mathematics, Fukuoka University, Fukuoka 814-0180 (Japan)

2016-08-15

Bagarello, Inoue, and Trapani [J. Math. Phys. 55, 033501 (2014)] investigated some operators defined by the Riesz bases. These operators connect with quasi-Hermitian quantum mechanics, and its relatives. In this paper, we introduce a notion of generalized Riesz bases which is a generalization of Riesz bases and investigate some operators defined by the generalized Riesz bases by changing the frameworks of the operators defined in the work of Bagarello, Inoue, and Trapani.

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

Science.gov (United States)

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

2014-11-01

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

Uncertainty and Variability in Physiologically-Based Pharmacokinetic (PBPK) Models: Key Issues and Case Studies (Final Report)

Science.gov (United States)

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 physi...

The physiological challenges of the 1952 Copenhagen poliomyelitis epidemic and a renaissance in clinical respiratory physiology

Science.gov (United States)

West, John B.

2005-01-01

The 1952 Copenhagen poliomyelitis epidemic provided extraordinary challenges in applied physiology. Over 300 patients developed respiratory paralysis within a few weeks, and the ventilator facilities at the infectious disease hospital were completely overwhelmed. The heroic solution was to call upon 200 medical students to provide round-the-clock manual ventilation using a rubber bag attached to a tracheostomy tube. Some patients were ventilated in this way for several weeks. A second challenge was to understand the gas exchange and acid-base status of these patients. At the onset of the epidemic, the only measurement routinely available in the hospital was the carbon dioxide concentration in the blood, and the high values were initially misinterpreted as a mysterious “alkalosis.” However, pH measurements were quickly instituted, the PCO2 was shown to be high, and modern clinical respiratory acid-base physiology was born. Taking a broader view, the problems highlighted by the epidemic underscored the gap between recent advances made by physiologists and their application to the clinical environment. However, the 1950s ushered in a renaissance in clinical respiratory physiology. In 1950 the coverage of respiratory physiology in textbooks was often woefully inadequate, but the decade saw major advances in topics such as mechanics and gas exchange. An important development was the translation of the new knowledge from departments of physiology to the clinical setting. In many respects, this period was therefore the beginning of modern clinical respiratory physiology. PMID:16020437

Physiologic AV valvular insufficiency in cine MR imaging

Energy Technology Data Exchange (ETDEWEB)

Jang, Yoon Hyung; Kang, Eun Joo; Baik, Seung Kug; Ahn, Woo Hyun; Choi, Han Yong; Kim, Bong Gi [Wallace Memorial Baptist Hospital, Pusan (Korea, Republic of)

1994-05-15

To give a help in the interpretation of cardiac cine-MR examination, the extent, shape, and timing of appearance of signal void regions near atrioventricular(A-V) valve prospectively evaluate in the healthy population. Using an axial gradient-echo technique with small flip angle, repetition time(TR) of 36 msec and echo time(TE) of 22 msec, 20 volunteers without known valvular abnormalities undertook cardiac cine-MR imaging including atrioventricular valve areas. Transient signal void was observed within the near the tricuspid(13/20 = 65%) and mitral valves(9/20 = 45%), respectively, which is so called {sup p}hysioloic atrioventricular valvular insufficiency{sup .} Eight subjects revealed the signal void areas near both tricuspid and mitral valves but, 5 subjects did not show any evidence of physiologic insufficiency. This physiologic condition does not extend more than 1 cm proximal to A-V valve plane and is generally observed only during early systole. Its morphology is semilunar or triangular configuration with the base to the valve plane in most cases of normal tricuspid insufficiency and small globular appearance in most cases of normal mitral insufficiency. Awareness of normal signal void areas near the A-V valve and their characteristics is critical in the interpretation of cardiac cine MR examinations and maybe helpful in the study of the normal cardiac physiology.

Physiologic AV valvular insufficiency in cine MR imaging

International Nuclear Information System (INIS)

Jang, Yoon Hyung; Kang, Eun Joo; Baik, Seung Kug; Ahn, Woo Hyun; Choi, Han Yong; Kim, Bong Gi

1994-01-01

To give a help in the interpretation of cardiac cine-MR examination, the extent, shape, and timing of appearance of signal void regions near atrioventricular(A-V) valve prospectively evaluate in the healthy population. Using an axial gradient-echo technique with small flip angle, repetition time(TR) of 36 msec and echo time(TE) of 22 msec, 20 volunteers without known valvular abnormalities undertook cardiac cine-MR imaging including atrioventricular valve areas. Transient signal void was observed within the near the tricuspid(13/20 = 65%) and mitral valves(9/20 = 45%), respectively, which is so called p hysioloic atrioventricular valvular insufficiency . Eight subjects revealed the signal void areas near both tricuspid and mitral valves but, 5 subjects did not show any evidence of physiologic insufficiency. This physiologic condition does not extend more than 1 cm proximal to A-V valve plane and is generally observed only during early systole. Its morphology is semilunar or triangular configuration with the base to the valve plane in most cases of normal tricuspid insufficiency and small globular appearance in most cases of normal mitral insufficiency. Awareness of normal signal void areas near the A-V valve and their characteristics is critical in the interpretation of cardiac cine MR examinations and maybe helpful in the study of the normal cardiac physiology

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

Directory of Open Access Journals (Sweden)

Xia Zhao

2015-01-01

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

A physiologically based pharmacokinetic model of vitamin D

Science.gov (United States)

Despite the plethora of studies discussing the benefits of vitamin D on physiological functioning, few mathematical models of vitamin D predict the response of the body on low-concentration supplementation of vitamin D under sunlight-restricted conditions. This study developed a ...

Mathematical modeling and validation in physiology applications to the cardiovascular and respiratory systems

CERN Document Server

Bachar, Mostafa; Kappel, Franz

2013-01-01

This volume synthesizes theoretical and practical aspects of both the mathematical and life science viewpoints needed for modeling of the cardiovascular-respiratory system specifically and physiological systems generally.  Theoretical points include model design, model complexity and validation in the light of available data, as well as control theory approaches to feedback delay and Kalman filter applications to parameter identification. State of the art approaches using parameter sensitivity are discussed for enhancing model identifiability through joint analysis of model structure and data. Practical examples illustrate model development at various levels of complexity based on given physiological information. The sensitivity-based approaches for examining model identifiability are illustrated by means of specific modeling  examples. The themes presented address the current problem of patient-specific model adaptation in the clinical setting, where data is typically limited.

Abstracts of the 9. Brazilian Congress of Biophysics, 2. Brazilian Congress of Pharmacology and Experimental Therapeutics and 19. Brazilian Congress of Physiology

International Nuclear Information System (INIS)

1984-01-01

Abstracts about biophysics, pharmacology, experimental therapeutics and physiology are presented. The use of radioisotopes in radioassays involve topics like biophysics and renal physiology; central nervous system; endocrinology; animal and comparative physiology; general physiology, digestion and nutrition; general pharmacology. (M.A.C.) [pt

Toxico-kinetic, chemical and radiological toxicity of uranium on zebra fish (Danio rerio); Toxicocinetique, toxicite chimique et radiologique de l'uranium chez le poisson zebre (Danio rerio)

Energy Technology Data Exchange (ETDEWEB)

Barillet, S

2007-06-15

This thesis explores the toxico-kinetic and toxicological aspects of uranium in fish. Uranium, appears to be highly bio accumulated and bio concentrated in fish. It spreads all through the whole organism. Nevertheless, its distribution is heterogeneous (gills and liver being the main sites of accumulation).From a toxicological point of view, we notice perturbations of the antioxidant system (inhibitions of hepatic Sod, Cat and G Px activities; depletion of total GSH) and of the cholinergic system (inhibition/over-activation of brain AChE). Genotoxic effects also appear in red blood cells, hepatocytes and gonad cells. The kinetics of these biochemical perturbations depend on the radiological activity of uranium, responses appearing earlier with increasing delivered activity. Histological effects (differing in types depending on delivered radiological activity) are also observed (in gills and muscles). (author)

Comprehensive profiling of mercapturic acid metabolites from dietary acrylamide as short-term exposure biomarkers for evaluation of toxicokinetics in rats and daily internal exposure in humans using isotope dilution ultra-high performance liquid chromatography tandem mass spectrometry

Energy Technology Data Exchange (ETDEWEB)

Zhang, Yu [Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, Zhejiang (China); Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang R & D Center for Food Technology and Equipment, Fuli Institute of Food Science, Zhejiang University, Hangzhou 310058, Zhejiang (China); Wang, Qiao; Cheng, Jun [Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, Zhejiang (China); Zhang, Jingshun; Xu, Jiaojiao [Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, Zhejiang (China); Ren, Yiping, E-mail: renyiping@263.net [Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, Zhejiang (China)

2015-09-24

Mercapturic acid metabolites from dietary acrylamide are important short-term exposure biomarkers for evaluating the in vivo toxicity of acrylamide. Most of studies have focused on the measurement of two metabolites, N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA) and N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA). Thus, the comprehensive profile of acrylamide urinary metabolites cannot be fully understood. We developed an isotope dilution ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for the simultaneous determination of all four mercapturic acid adducts of acrylamide and its primary metabolite glycidamide under the electroscopy ionization negative (ESI-) mode in the present study. The limit of detection (LOD) and limit of quantification (LOQ) of the analytes ranged 0.1–0.3 ng/mL and 0.4–1.0 ng/mL, respectively. The recovery rates with low, intermediate and high spiking levels were calculated as 95.5%–105.4%, 98.2%–114.0% and 92.2%–108.9%, respectively. Acceptable within-laboratory reproducibility (RSD < 7.0%) substantially supported the use of current method for robust analysis. Rapid pretreatment procedures and short run time (8 min per sample) ensured good efficiency of metabolism profiling, indicating a wide application for investigating short-term internal exposure of dietary acrylamide. Our proposed UHPLC-MS/MS method was successfully applied to the toxicokinetic study of acrylamide in rats. Meanwhile, results of human urine analysis indicated that the levels of N-acetyl-S-(2-carbamoylethyl)-L-cysteine-sulfoxide (AAMA-sul), which did not appear in the mercapturic acid metabolites in rodents, were more than the sum of GAMA and N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-L-cysteine (iso-GAMA). Thus, AAMA-sul may alternatively become a specific biomarker for investigating the acrylamide exposure in humans. Current proposed method provides a substantial methodology support for comprehensive

Comprehensive profiling of mercapturic acid metabolites from dietary acrylamide as short-term exposure biomarkers for evaluation of toxicokinetics in rats and daily internal exposure in humans using isotope dilution ultra-high performance liquid chromatography tandem mass spectrometry

International Nuclear Information System (INIS)

Zhang, Yu; Wang, Qiao; Cheng, Jun; Zhang, Jingshun; Xu, Jiaojiao; Ren, Yiping

2015-01-01

Mercapturic acid metabolites from dietary acrylamide are important short-term exposure biomarkers for evaluating the in vivo toxicity of acrylamide. Most of studies have focused on the measurement of two metabolites, N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA) and N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA). Thus, the comprehensive profile of acrylamide urinary metabolites cannot be fully understood. We developed an isotope dilution ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for the simultaneous determination of all four mercapturic acid adducts of acrylamide and its primary metabolite glycidamide under the electroscopy ionization negative (ESI-) mode in the present study. The limit of detection (LOD) and limit of quantification (LOQ) of the analytes ranged 0.1–0.3 ng/mL and 0.4–1.0 ng/mL, respectively. The recovery rates with low, intermediate and high spiking levels were calculated as 95.5%–105.4%, 98.2%–114.0% and 92.2%–108.9%, respectively. Acceptable within-laboratory reproducibility (RSD < 7.0%) substantially supported the use of current method for robust analysis. Rapid pretreatment procedures and short run time (8 min per sample) ensured good efficiency of metabolism profiling, indicating a wide application for investigating short-term internal exposure of dietary acrylamide. Our proposed UHPLC-MS/MS method was successfully applied to the toxicokinetic study of acrylamide in rats. Meanwhile, results of human urine analysis indicated that the levels of N-acetyl-S-(2-carbamoylethyl)-L-cysteine-sulfoxide (AAMA-sul), which did not appear in the mercapturic acid metabolites in rodents, were more than the sum of GAMA and N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-L-cysteine (iso-GAMA). Thus, AAMA-sul may alternatively become a specific biomarker for investigating the acrylamide exposure in humans. Current proposed method provides a substantial methodology support for comprehensive

Effects of uranium on the metabolism of zebrafish, Danio rerio

International Nuclear Information System (INIS)

Augustine, Starrlight; Gagnaire, Béatrice; Adam-Guillermin, Christelle; Kooijman, Sebastiaan A.L.M.

2012-01-01

The increasing demand for nuclear energy results in heightened levels of uranium (U) in aquatic systems which present a potential health hazard to resident organisms. The aim of this study was to mechanistically assess how chronic exposure to environmentally relevant concentrations of U perturbs the complex interplay between feeding, growth, maintenance, maturation and reproduction throughout the life-cycle of an individual. To this end we analysed literature-based and original zebrafish toxicity data within a same mass and energy balancing conceptual framework. U was found to increase somatic maintenance leading to inhibition of spawning as well as increase hazard rate and costs for growth during the early life stages. The fish's initial conditions and elimination through reproduction greatly affected toxico-kinetics and effects. We demonstrate that growth and reproduction should be measured on specific individuals since mean values were hardly interpretable. The mean food level differed between experiments, conditions and individuals. This last ‘detail’ contributed substantially to the observed variability by its combined effect on metabolism, toxic effects and toxico-kinetics. The significance of this work is that we address exactly how these issues are related and derive conclusions which are independent of experimental protocol and coherent with a very large body of literature on zebrafish eco-physiology.

Effects of uranium on the metabolism of zebrafish, Danio rerio

Energy Technology Data Exchange (ETDEWEB)

Augustine, Starrlight, E-mail: starr-light.augustine@irsn.fr [Laboratory of Radionuclide Ecotoxicology, PRP-ENV/SERIS/LECO, Institute of Radioprotection and Nuclear Safety (IRSN), Caradache, Building 186, BP3, 13115 St-Paul-lez-Durance Cedex (France); Gagnaire, Beatrice, E-mail: beatrice.gagnaire@irsn.fr [Laboratory of Radionuclide Ecotoxicology, PRP-ENV/SERIS/LECO, Institute of Radioprotection and Nuclear Safety (IRSN), Caradache, Building 186, BP3, 13115 St-Paul-lez-Durance Cedex (France); Adam-Guillermin, Christelle, E-mail: christelle.adam-guillermin@irsn.fr [Laboratory of Radionuclide Ecotoxicology, PRP-ENV/SERIS/LECO, Institute of Radioprotection and Nuclear Safety (IRSN), Caradache, Building 186, BP3, 13115 St-Paul-lez-Durance Cedex (France); Kooijman, Sebastiaan A.L.M., E-mail: bas.kooijman@vu.nl [Department of Theoretical Biology, Vrije Universiteit, de Boelelaan 1087, 1081 HV Amsterdam (Netherlands)

2012-08-15

The increasing demand for nuclear energy results in heightened levels of uranium (U) in aquatic systems which present a potential health hazard to resident organisms. The aim of this study was to mechanistically assess how chronic exposure to environmentally relevant concentrations of U perturbs the complex interplay between feeding, growth, maintenance, maturation and reproduction throughout the life-cycle of an individual. To this end we analysed literature-based and original zebrafish toxicity data within a same mass and energy balancing conceptual framework. U was found to increase somatic maintenance leading to inhibition of spawning as well as increase hazard rate and costs for growth during the early life stages. The fish's initial conditions and elimination through reproduction greatly affected toxico-kinetics and effects. We demonstrate that growth and reproduction should be measured on specific individuals since mean values were hardly interpretable. The mean food level differed between experiments, conditions and individuals. This last 'detail' contributed substantially to the observed variability by its combined effect on metabolism, toxic effects and toxico-kinetics. The significance of this work is that we address exactly how these issues are related and derive conclusions which are independent of experimental protocol and coherent with a very large body of literature on zebrafish eco-physiology.

Auditory analysis for speech recognition based on physiological models

Science.gov (United States)

Jeon, Woojay; Juang, Biing-Hwang

2004-05-01

To address the limitations of traditional cepstrum or LPC based front-end processing methods for automatic speech recognition, more elaborate methods based on physiological models of the human auditory system may be used to achieve more robust speech recognition in adverse environments. For this purpose, a modified version of a model of the primary auditory cortex featuring a three dimensional mapping of auditory spectra [Wang and Shamma, IEEE Trans. Speech Audio Process. 3, 382-395 (1995)] is adopted and investigated for its use as an improved front-end processing method. The study is conducted in two ways: first, by relating the model's redundant representation to traditional spectral representations and showing that the former not only encompasses information provided by the latter, but also reveals more relevant information that makes it superior in describing the identifying features of speech signals; and second, by observing the statistical features of the representation for various classes of sound to show how different identifying features manifest themselves as specific patterns on the cortical map, thereby becoming a place-coded data set on which detection theory could be applied to simulate auditory perception and cognition.

Estimation of physiological parameters using knowledge-based factor analysis of dynamic nuclear medicine image sequences

International Nuclear Information System (INIS)

Yap, J.T.; Chen, C.T.; Cooper, M.

1995-01-01

The authors have previously developed a knowledge-based method of factor analysis to analyze dynamic nuclear medicine image sequences. In this paper, the authors analyze dynamic PET cerebral glucose metabolism and neuroreceptor binding studies. These methods have shown the ability to reduce the dimensionality of the data, enhance the image quality of the sequence, and generate meaningful functional images and their corresponding physiological time functions. The new information produced by the factor analysis has now been used to improve the estimation of various physiological parameters. A principal component analysis (PCA) is first performed to identify statistically significant temporal variations and remove the uncorrelated variations (noise) due to Poisson counting statistics. The statistically significant principal components are then used to reconstruct a noise-reduced image sequence as well as provide an initial solution for the factor analysis. Prior knowledge such as the compartmental models or the requirement of positivity and simple structure can be used to constrain the analysis. These constraints are used to rotate the factors to the most physically and physiologically realistic solution. The final result is a small number of time functions (factors) representing the underlying physiological processes and their associated weighting images representing the spatial localization of these functions. Estimation of physiological parameters can then be performed using the noise-reduced image sequence generated from the statistically significant PCs and/or the final factor images and time functions. These results are compared to the parameter estimation using standard methods and the original raw image sequences. Graphical analysis was performed at the pixel level to generate comparable parametric images of the slope and intercept (influx constant and distribution volume)

Video-based lectures: An emerging paradigm for teaching human anatomy and physiology to student nurses

OpenAIRE

Rabab El-Sayed Hassan El-Sayed; Samar El-Hoseiny Abd El-Raouf El-Sayed

2013-01-01

Video-based teaching material is a rich and powerful medium being used in computer assisted learning. This paper aimed to assess the learning outcomes and student nurses’ acceptance and satisfaction with the video-based lectures versus the traditional method of teaching human anatomy and physiology courses. Data were collected from 27 students in a Bachelor of Nursing program and experimental control was achieved using an alternating-treatments design. Overall, students experienced 10 lecture...

A general model for membrane-based separation processes

DEFF Research Database (Denmark)

Soni, Vipasha; Abildskov, Jens; Jonsson, Gunnar Eigil

2009-01-01

behaviour will play an important role. In this paper, modelling of membrane-based processes for separation of gas and liquid mixtures are considered. Two general models, one for membrane-based liquid separation processes (with phase change) and another for membrane-based gas separation are presented....... The separation processes covered are: membrane-based gas separation processes, pervaporation and various types of membrane distillation processes. The specific model for each type of membrane-based process is generated from the two general models by applying the specific system descriptions and the corresponding...

Physiologically Based Pharmacokinetic Modeling of Therapeutic Proteins.

Science.gov (United States)

Wong, Harvey; Chow, Timothy W

2017-09-01

Biologics or therapeutic proteins are becoming increasingly important as treatments for disease. The most common class of biologics are monoclonal antibodies (mAbs). Recently, there has been an increase in the use of physiologically based pharmacokinetic (PBPK) modeling in the pharmaceutical industry in drug development. We review PBPK models for therapeutic proteins with an emphasis on mAbs. Due to their size and similarity to endogenous antibodies, there are distinct differences between PBPK models for small molecules and mAbs. The high-level organization of a typical mAb PBPK model consists of a whole-body PBPK model with organ compartments interconnected by both blood and lymph flows. The whole-body PBPK model is coupled with tissue-level submodels used to describe key mechanisms governing mAb disposition including tissue efflux via the lymphatic system, elimination by catabolism, protection from catabolism binding to the neonatal Fc (FcRn) receptor, and nonlinear binding to specific pharmacological targets of interest. The use of PBPK modeling in the development of therapeutic proteins is still in its infancy. Further application of PBPK modeling for therapeutic proteins will help to define its developing role in drug discovery and development. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

The emergence of Applied Physiology within the discipline of Physiology.

Science.gov (United States)

Tipton, Charles M

2016-08-01

Despite the availability and utilization of the physiology textbooks authored by Albrecht von Haller during the 18th century that heralded the modern age of physiology, not all physicians or physiologists were satisfied with its presentation, contents, or application to medicine. Initial reasons were fundamental disagreements between the "mechanists," represented by Boerhaave, Robinson, and von Haller, and the "vitalists," represented by the faculty and graduates of the Montpellier School of Medicine in France, notably, Bordeu and Barthez. Subsequently, objections originated from Europe, United Kingdom, and the United States in publications that focused not only on the teaching of physiology to medical and secondary students, but on the specific applications of the content of physiology to medicine, health, hygiene, pathology, and chronic diseases. At the turn of the 20th century, texts began to appear with applied physiology in their titles and in 1926, physician Samson Wright published a textbook entitled Applied Physiology that was intended for both medical students and the medical profession. Eleven years later, physicians Best and Taylor published The Physiological Basis of Medical Practice: A University of Toronto Texbook in Applied Physiology Although both sets of authors defined the connection between applied physiology and physiology, they failed to define the areas of physiology that were included within applied physiology. This was accomplished by the American Physiological Society (APS) Publications Committee in 1948 with the publication of the Journal of Appplied Physiology, that stated the word "applied" would broadly denote human physiology whereas the terms stress and environment would broadly include work, exercise, plus industrial, climatic and social factors. NIH established a study section (SS) devoted to applied physiology in 1964 which remained active until 2001 when it became amalgamated into other SSs. Before the end of the 20th century when

Role of environmental stress in the physiological response to chemical toxicants

International Nuclear Information System (INIS)

Gordon, C.J.

2003-01-01

Environmental physiology is the study of the physiological mechanisms that allow animals to cope with and adapt to changes in temperature, humidity, atmospheric pressure, and other natural factors of their physical environment. Nearly all toxicological and pharmacological studies are performed in resting (i.e., non exercising) experimental animals acclimatized to standard environmental conditions that are usually considered ideal to the animal's physiological well-being. These ideal test conditions are clearly not representative of the fluctuations in the natural environment encountered by humans and other animals on a day-to-day basis. It behooves the toxicologist, especially those interested in extrapolating experimental data from laboratory animals to humans, to consider how variations in the natural environment will alter physiological responses to toxicants. Temperature and exercise are the two most well-studied parameters in the fields of environmental physiology and toxicology. In general, high temperatures exacerbate the toxic effects of many environmental toxicants. Moreover, exercising subjects are generally more vulnerable to airborne toxic agents. The prospect of global warming also warrants a better assessment of how higher environmental temperatures may impact on the response of humans and other species to toxic chemicals. Hence, this paper and accompanying papers from the proceedings of a symposium focus on the salient aspects of the interaction between environmental stress and physiological response to toxic agents with particular emphasis on temperature and exercise

DNA hydrogel-based supercapacitors operating in physiological fluids

Science.gov (United States)

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

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

Directory of Open Access Journals (Sweden)

Dusica eMaysinger

2015-12-01

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

Physiological Studies of Arctic Carnivores.

Science.gov (United States)

1982-12-01

All transmitters were maintained in a cold sterilant ( benzalkonium chloride ) until implanted in a bear. Radio-transmitters for monitoring temperature...body was unknown, particularly during the winter when bears are in dens and there is a generalized reduction in metabolism and other physiological... reduction in core body temperature from summer to winter closely agrees with those reported earlier for bears maintained in captivity under simulated

[Project HRANAFINA--Croatian anatomical and physiological terminology].

Science.gov (United States)

Vodanović, Marin

2012-01-01

HRANAFINA--Croatian Anatomical and Physiological Terminology is a project of the University of Zagreb School of Dental Medicine funded by the Croatian Science Foundation. It is performed in cooperation with other Croatian universities with medical schools. This project has a two-pronged aim: firstly, building of Croatian anatomical and physiological terminology and secondly, Croatian anatomical and physiological terminology usage popularization between health professionals, medical students, scientists and translators. Internationally recognized experts from Croatian universities with medical faculties and linguistics experts are involved in the project. All project activities are coordinated in agreement with the National Coordinator for Development of Croatian Professional Terminology. The project enhances Croatian professional terminology and Croatian language in general, increases competitiveness of Croatian scientists on international level and facilitates the involvement of Croatian scientists, health care providers and medical students in European projects.

Understanding the physiology of postharvest needle abscission in balsam fir

Directory of Open Access Journals (Sweden)

Mason Thane Macdonald

2015-11-01

Full Text Available Balsam fir (Abies balsamea trees are commonly used as a specialty horticultural species for Christmas trees and associated greenery in eastern Canada and United States. Postharvest needle abscission has always been a problem, but is becoming an even bigger challenge in recent years presumably due to increased autumn temperatures and earlier harvesting practices. An increased understanding of postharvest abscission physiology in balsam fir may benefit the Christmas tree industry while simultaneously advancing our knowledge in senescence and abscission of conifers in general. Our paper describes the dynamics of needle abscission in balsam fir while identifying key factors that modify abscission patterns. Concepts such as genotypic abscission resistance, nutrition, environmental factors, and postharvest changes in water conductance and hormone evolution are discussed as they relate to our understanding of the balsam fir abscission physiology. Our paper ultimately proposes a pathway for needle abscission via ethylene and also suggests other potential alternative pathways based on our current understanding.

A Community-based Stress Management Program: Using Wearable Devices to Assess Whole Body Physiological Responses in Non-laboratory Settings.

Science.gov (United States)

Carter, Robert; Carter, Kirtigandha Salwe; Holliday, John; Holliday, Alice; Harrison, Carlton Keith

2018-01-22

A pragmatic breath-based intervention to benefit human performance and stress management is timely and valuable to individuals seeking holistic approaches for emotional regulation and optimizing compensatory reserve mechanisms. This protocol is designed to not only teach mind-body awareness but also to provide feedback utilizing physiological data and survey results. The primary findings of this study showed that heart coherence and alpha variables were significantly correlated after four weeks of the breath-based meditation stress protocol. Meditation and rhythmic breathing produced significant increases in alpha brain activity. These brain physiological responses conformed to the Pleth Variability Index (PVI) changes, suggesting the ability of the human body to enter into a meditative state and effectively manage stress. When assessed after four weeks of daily practicing the techniques employed in the stress management protocol, based on the Five Facet Mindfulness Questionnaire, subjects improved in applying mindfulness skills. The overall mindfulness score, Pleth variability index (PVI), and perfusion index (PI) increased after the 4-week intervention period. Results from electroencephalography (brain waves) were consistent with a meditative state during the post-study follow-up session. This provides evidence that wearable devices are feasible for data collection during a breath-based stress management intervention. This protocol can be easily and efficiently implemented into any study design in which physiological data are desired in a non-laboratory-based setting.

Toxicokinetics of ibogaine and noribogaine in a patient with prolonged multiple cardiac arrhythmias after ingestion of internet purchased ibogaine.

Science.gov (United States)

Henstra, Marieke; Wong, Liza; Chahbouni, Abdel; Swart, Noortje; Allaart, Cor; Sombogaard, Ferdi

2017-07-01

Ibogaine is an agent that has been evaluated as an unapproved anti-addictive agent for the management of drug dependence. Sudden cardiac death has been described to occur secondary to its use. We describe the clinical effects and toxicokinetics of ibogaine and noribogaine in a single patient. For this purpose, we developed a LC-MS/MS-method to measure ibogaine and noribogaine plasma-concentrations. We used two compartments with first order absorption. The maximum concentration of ibogaine was 1.45 mg/L. Our patient developed markedly prolonged QTc interval of 647ms maximum, several multiple cardiac arrhythmias (i.e., atrial tachycardia and ventricular tachycardia and Torsades des Pointes). QTc-prolongation remained present until 12 days after ingestion, several days after ibogaine plasma-levels were low, implicating clinically relevant noribogaine concentrations long after ibogaine had been cleared from the plasma. The ratio k 12 /k 21 for noribogaine was 21.5 and 4.28 for ibogaine, implicating a lower distribution of noribogaine from the peripheral compartment into the central compartment compared to ibogaine. We demonstrated a linear relationship between the concentration of the metabolite and long duration of action, rather than with parent ibogaine. Therefore, after (prolonged) ibogaine ingestion, clinicians should beware of long-term effects due to its metabolite.

A General Simulator for Acid-Base Titrations

Science.gov (United States)

de Levie, Robert

1999-07-01

General formal expressions are provided to facilitate the automatic computer calculation of acid-base titration curves of arbitrary mixtures of acids, bases, and salts, without and with activity corrections based on the Davies equation. Explicit relations are also given for the buffer strength of mixtures of acids, bases, and salts.

Impact of a plant-based diet on behavioural and physiological traits in sea bass (Dicentrarchus labrax)

OpenAIRE

Benhaim, David; Begout, Marie-laure; Pean, Samuel; Manca, Michael; Prunet, Patrick; Chatain, Beatrice

2013-01-01

Replacing aquaculture feeds based on fisheries-derived resources with plant-based diets could be a relevant strategy to improve the sustainability of aquaculture. Recent studies on sea bass have shown that the total and early replacement of marine products by plant products would have a moderate effect on fish growth and body lipid content. Whether a plant-based diet impacts behavioural and physiological traits possibly linked to fish welfare, is not known, however. Here, we studied the effec...

Toxicokinetics of the ciguatoxin P-CTX-1 in rats after intraperitoneal or oral administration.

Science.gov (United States)

Bottein, Marie-Yasmine Dechraoui; Wang, Zhihong; Ramsdell, John S

2011-06-18

Ciguatoxins are voltage-gated selective algal toxins responsible for ciguatera fish poisoning. In this study we evaluate the toxicokinetics of one of the most common ciguatoxins found in the Pacific, the P-CTX-1, in rat after an oral or intraperitoneal (ip) dose of 0.26 μg/kg body weight. We report levels of ciguatoxin activity assessed over time in blood, urine and feces, and at 4 days in liver, muscle and brain, using the functional in vitro N2A cytotoxicity assay. Following exposure, the ciguatoxin activity exhibited a rapid systemic absorption that was followed by a bi-exponential decline, and data best fit a two-compartment model analysis. Maximum blood concentrations were reached at 1.97 and 0.43 h after the oral and ip dose, respectively. Ciguatoxin elimination from blood was slow with terminal half lives (t(½)β) estimated at 82 h for oral and 112 h for ip dosing. Ciguatoxin activity remained in liver, muscle and brain 96 h after ip and oral administration. While smaller amounts appeared in the urine, the main excretion route was feces, with peak rates reaching > 10 pg P-CTX-1 equivalents/h in both routes of administration. Assay guided fractionation showed the presence in the feces and liver of peaks of activity corresponding to the P-CTX-1 and to other less polar metabolites. In conclusion, biologically active ciguatoxins are detectable in blood, liver, muscle and brain, and continued to be excreted in urine and feces 4 days following exposure. Blood, as well as urine and feces may be useful matrices for low-invasive testing methods for ciguatera clinical cases. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

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

Science.gov (United States)

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

Toxico-kinetic, chemical and radiological toxicity of uranium on zebra fish (Danio rerio); Toxicocinetique, toxicite chimique et radiologique de l'uranium chez le poisson zebre (Danio rerio)

Energy Technology Data Exchange (ETDEWEB)

Barillet, S

2007-06-15

This thesis explores the toxico-kinetic and toxicological aspects of uranium in fish. Uranium, appears to be highly bio accumulated and bio concentrated in fish. It spreads all through the whole organism. Nevertheless, its distribution is heterogeneous (gills and liver being the main sites of accumulation).From a toxicological point of view, we notice perturbations of the antioxidant system (inhibitions of hepatic Sod, Cat and G Px activities; depletion of total GSH) and of the cholinergic system (inhibition/over-activation of brain AChE). Genotoxic effects also appear in red blood cells, hepatocytes and gonad cells. The kinetics of these biochemical perturbations depend on the radiological activity of uranium, responses appearing earlier with increasing delivered activity. Histological effects (differing in types depending on delivered radiological activity) are also observed (in gills and muscles). (author)

Methods and systems for the processing of physiological signals

International Nuclear Information System (INIS)

Cosnac, B. de; Gariod, R.; Max, J.; Monge, V.

1975-01-01

This note is a general survey of the processing of physiological signals. After an introduction about electrodes and their limitations, the physiological nature of the main signals are shortly recalled. Different methods (signal averaging, spectral analysis, shape morphological analysis) are described as applications to the fields of magnetocardiography, electro-encephalography, cardiography, electronystagmography. As for processing means (single portable instruments and programmable), they are described through the example of application to rheography and to the Plurimat'S general system. As a conclusion the methods of signal processing are dominated by the morphological analysis of curves and by the necessity of a more important introduction of the statistical classification. As for the instruments, microprocessors will appear but specific operators linked to computer will certainly grow [fr

Toxicokinetic and toxicodynamic analyses of Androctonus australis hector venom in rats: Optimization of antivenom therapy

International Nuclear Information System (INIS)

Hammoudi-Triki, D.; Lefort, J.; Rougeot, C.; Robbe-Vincent, A.; Bon, C.; Laraba-Djebari, F.; Choumet, V.

2007-01-01

This paper reports the simultaneous determination of toxicokinetic and toxicodynamic properties of Androctonus australis hector venom, in the absence and presence of antivenom (F(ab') 2 and Fab), in envenomed rats. After subcutaneous injection of the venom, toxins showed a complete absorption phase from the site of injection associated with a distribution into a large extravascular compartment. The injection of Fab and F(ab') 2 induced the neutralization of venom antigens in the blood compartment, as well as the redistribution of venom components from the extravascular compartment to the blood compartment. Interestingly, F(ab') 2 and Fab showed distinct efficiencies depending on their route of injection. F(ab') 2 induced a faster venom neutralization and redistribution than Fab when injected intravenously. Fab was more effective than F(ab') 2 by the intramuscular route. The hemodynamic effects of Aah venom were further investigated. Changes in mean arterial pressure and heart rate were observed in parallel with an upper airway obstruction. Fab was more effective than F(ab') 2 for preventing early symptoms of envenomation, whatever their route of administration. Intraperitoneal injection of F(ab') 2 and Fab was similar for the prevention of the delayed symptoms, even after a late administration. Fab was more effective than F(ab') 2 in the inhibition of airway resistance, independent of the route and time of administration. These results show that the treatment for scorpion stings might be improved by the intravascular injection of a mixture of Fab and F(ab') 2 . If antivenom cannot be administered intravenously, Fab might be an alternative as they are more effective than F(ab') 2 when injected intramuscularly

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

NARCIS (Netherlands)

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

2006-01-01

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

Physiological responses at short distances from a parametric speaker

Directory of Open Access Journals (Sweden)

Lee Soomin

2012-06-01

Full Text Available Abstract In recent years, parametric speakers have been used in various circumstances. In our previous studies, we verified that the physiological burden of the sound of parametric speaker set at 2.6 m from the subjects was lower than that of the general speaker. However, nothing has yet been demonstrated about the effects of the sound of a parametric speaker at the shorter distance between parametric speakers the human body. Therefore, we studied this effect on physiological functions and task performance. Nine male subjects participated in this study. They completed three consecutive sessions: a 20-minute quiet period as a baseline, a 30-minute mental task period with general speakers or parametric speakers, and a 20-minute recovery period. We measured electrocardiogram (ECG photoplethysmogram (PTG, electroencephalogram (EEG, systolic and diastolic blood pressure. Four experiments, one with a speaker condition (general speaker and parametric speaker, the other with a distance condition (0.3 m and 1.0 m, were conducted respectively at the same time of day on separate days. To examine the effects of the speaker and distance, three-way repeated measures ANOVA (speaker factor x distance factor x time factor were conducted. In conclusion, we found that the physiological responses were not significantly different between the speaker condition and the distance condition. Meanwhile, it was shown that the physiological burdens increased with progress in time independently of speaker condition and distance condition. In summary, the effects of the parametric speaker at the 2.6 m distance were not obtained at the distance of 1 m or less.

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

Science.gov (United States)

Longmuir, Kenneth J

2014-03-01

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

Toxicokinetics of tetrabromoethylcyclohexane (TBECH) in juvenile brown trout (Salmo trutta) and effects on plasma sex hormones

International Nuclear Information System (INIS)

Gemmill, Bonnie; Pleskach, Kerri; Peters, Lisa; Palace, Vince; Wautier, Kerry; Park, Brad; Darling, Colin; Rosenberg, Bruno; McCrindle, Robert; Tomy, Gregg T.

2011-01-01

Technical 1,2-dibromo-4-(1,2 dibromoethyl)cyclohexane or tetrabromoethylcyclohexane (TBECH) used primarily as an additive flame retardant in polystyrene foams, contains two diastereoisomers, α- and β- present in equimolar amounts. At temperatures in excess of 125 o C, isomerization to two other isoforms, δ- and γ- is possible. The recent detection of TBECH in the environment and studies suggesting that isomers are androgenic prompted us to examine the toxicokinetics and biochemical effects of one of the isomers, β-, in a controlled laboratory environment. Juvenile brown trout (Salmo trutta) were exposed to three different amounts of the β-isomer (low, medium and high) via the food followed by a period in which they were exposed to unfortified food. A fourth group of fish was exposed to unfortified food for the duration of the experiment. On days 0, 7, 14, 21, 35, 49, 56, 63, 77, 91, 105, and 133, eight fish from each treatment group were euthanized and liver, plasma, lower jaw (i.e., thyroid tissue) and gonad were collected and the remaining tissue ('whole-fish') was retained. β-Isomer content was measured in whole-fish and in liver while estradiol (E2), 11-ketotestosterone (11-KT) and testosterone (T) were measured in plasma. Based on liver and gonad somatic indices, no apparent effects on liver or gonad development in fish from any of the treatment groups were observed. The bioaccumulation of β-isomer was similar in fish from all treatment groups with steady-state occurring before the end of the uptake phase. Depuration of the β-isomer from fish obeyed first order kinetics and there were no statistically significant differences in the depuration half life (t 1/2 ) among the treatment groups: 22.5 ± 10.4 (low), 13.5 ± 5.9 (med) and 13.8 ± 2.2 (high) days. Steady-state biomagnification factors were much smaller than 1 for fish in all treatment groups. Debrominated metabolites were not detected in composite liver or whole-fish extracts and there was no

Toxicokinetics of tetrabromoethylcyclohexane (TBECH) in juvenile brown trout (Salmo trutta) and effects on plasma sex hormones

Energy Technology Data Exchange (ETDEWEB)

Gemmill, Bonnie [Fisheries and Oceans Canada, Arctic Aquatic Research Division, Winnipeg, Manitoba R3T 2N6 (Canada); Department of Environment and Geography, University of Manitoba, Winnipeg, Manitoba R3T 2N2 (Canada); Pleskach, Kerri [Fisheries and Oceans Canada, Arctic Aquatic Research Division, Winnipeg, Manitoba R3T 2N6 (Canada); Peters, Lisa [Fisheries and Oceans Canada, Arctic Aquatic Research Division, Winnipeg, Manitoba R3T 2N6 (Canada); Department of Environment and Geography, University of Manitoba, Winnipeg, Manitoba R3T 2N2 (Canada); Palace, Vince [Department of Environment and Geography, University of Manitoba, Winnipeg, Manitoba R3T 2N2 (Canada); Fisheries and Oceans Canada, Environmental Science Division, Winnipeg, Manitoba R3T 2N6 (Canada); Wautier, Kerry; Park, Brad [Fisheries and Oceans Canada, Environmental Science Division, Winnipeg, Manitoba R3T 2N6 (Canada); Darling, Colin; Rosenberg, Bruno [Fisheries and Oceans Canada, Arctic Aquatic Research Division, Winnipeg, Manitoba R3T 2N6 (Canada); McCrindle, Robert [Wellington Laboratories Incorporated, Research Division, Guelph, ON N1G 3M5 (Canada); Tomy, Gregg T., E-mail: gregg.tomy@dfo-mpo.gc.ca [Fisheries and Oceans Canada, Arctic Aquatic Research Division, Winnipeg, Manitoba R3T 2N6 (Canada); Department of Environment and Geography, University of Manitoba, Winnipeg, Manitoba R3T 2N2 (Canada)

2011-01-25

Technical 1,2-dibromo-4-(1,2 dibromoethyl)cyclohexane or tetrabromoethylcyclohexane (TBECH) used primarily as an additive flame retardant in polystyrene foams, contains two diastereoisomers, {alpha}- and {beta}- present in equimolar amounts. At temperatures in excess of 125 {sup o}C, isomerization to two other isoforms, {delta}- and {gamma}- is possible. The recent detection of TBECH in the environment and studies suggesting that isomers are androgenic prompted us to examine the toxicokinetics and biochemical effects of one of the isomers, {beta}-, in a controlled laboratory environment. Juvenile brown trout (Salmo trutta) were exposed to three different amounts of the {beta}-isomer (low, medium and high) via the food followed by a period in which they were exposed to unfortified food. A fourth group of fish was exposed to unfortified food for the duration of the experiment. On days 0, 7, 14, 21, 35, 49, 56, 63, 77, 91, 105, and 133, eight fish from each treatment group were euthanized and liver, plasma, lower jaw (i.e., thyroid tissue) and gonad were collected and the remaining tissue ('whole-fish') was retained. {beta}-Isomer content was measured in whole-fish and in liver while estradiol (E2), 11-ketotestosterone (11-KT) and testosterone (T) were measured in plasma. Based on liver and gonad somatic indices, no apparent effects on liver or gonad development in fish from any of the treatment groups were observed. The bioaccumulation of {beta}-isomer was similar in fish from all treatment groups with steady-state occurring before the end of the uptake phase. Depuration of the {beta}-isomer from fish obeyed first order kinetics and there were no statistically significant differences in the depuration half life (t{sub 1/2}) among the treatment groups: 22.5 {+-} 10.4 (low), 13.5 {+-} 5.9 (med) and 13.8 {+-} 2.2 (high) days. Steady-state biomagnification factors were much smaller than 1 for fish in all treatment groups. Debrominated metabolites were not

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

International Nuclear Information System (INIS)

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

2007-01-01

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

Nitric oxide: a physiologic messenger.

Science.gov (United States)

Lowenstein, C J; Dinerman, J L; Snyder, S H

1994-02-01

To review the physiologic role of nitric oxide, an unusual messenger molecule that mediates blood vessel relaxation, neurotransmission, and pathogen suppression. A MEDLINE search of articles published from 1987 to 1993 that addressed nitric oxide and the enzyme that synthesizes it, nitric oxide synthase. Animal and human studies were selected from 3044 articles to analyze the clinical importance of nitric oxide. Descriptions of the structure and function of nitric oxide synthase were selected to show how nitric oxide acts as a biological messenger molecule. Biochemical and physiologic studies were analyzed if the same results were found by three or more independent observers. Two major classes of nitric oxide synthase enzymes produce nitric oxide. The constitutive isoforms found in endothelial cells and neurons release small amounts of nitric oxide for brief periods to signal adjacent cells, whereas the inducible isoform found in macrophages releases large amounts of nitric oxide continuously to eliminate bacteria and parasites. By diffusing into adjacent cells and binding to enzymes that contain iron, nitric oxide plays many important physiologic roles. It regulates blood pressure, transmits signals between neurons, and suppresses pathogens. Excess amounts, however, can damage host cells, causing neurotoxicity during strokes and causing the hypotension associated with sepsis. Nitric oxide is a simple molecule with many physiologic roles in the cardiovascular, neurologic, and immune systems. Although the general principles of nitric oxide synthesis are known, further research is necessary to determine what role it plays in causing disease.

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

NARCIS (Netherlands)

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

2015-01-01

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

Physiologically-based pharmacokinetic model of vaginally administered dapivirine ring and film formulations.

Science.gov (United States)

Kay, Katherine; Shah, Dhaval K; Rohan, Lisa; Bies, Robert

2018-05-01

A physiologically-based pharmacokinetic (PBPK) model of the vaginal space was developed with the aim of predicting concentrations in the vaginal and cervical space. These predictions can be used to optimize the probability of success of vaginally administered dapivirine (DPV) for HIV prevention. We focus on vaginal delivery using either a ring or film. A PBPK model describing the physiological structure of the vaginal tissue and fluid was defined mathematically and implemented in MATLAB. Literature reviews provided estimates for relevant physiological and physiochemical parameters. Drug concentration-time profiles were simulated in luminal fluids, vaginal tissue and plasma after administration of ring or film. Patient data were extracted from published clinical trials and used to test model predictions. The DPV ring simulations tested the two dosing regimens and predicted PK profiles and area under the curve of luminal fluids (29 079 and 33 067 mg h l -1 in groups A and B, respectively) and plasma (0.177 and 0.211 mg h l -1 ) closely matched those reported (within one standard deviation). While the DPV film study reported drug concentration at only one time point per patient, our simulated profiles pass through reported concentration range. HIV is a major public health issue and vaginal microbicides have the potential to provide a crucial, female-controlled option for protection. The PBPK model successfully simulated realistic representations of drug PK. It provides a reliable, inexpensive and accessible platform where potential effectiveness of new compounds and the robustness of treatment modalities for pre-exposure prophylaxis can be evaluated. © 2018 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

[History of physiology physiologists Evgeniy Borisovich Babski (1902-1973)].

Science.gov (United States)

Reutov, V P

2012-01-01

The paper analyzes works of eminent physiologists of the twentieth century the Academician of Ukraine SSR, professor Eugene Borisovich Babskii. During 50 years of research in Moscow and Kiev E.B. Babskii published more than 400 works. His main research devoted to investigation of the motility of the digestive tract, general physiology of the nervous system, chemical factors of excitation, mechanisms of muscle contraction, medical electronics and cybernetics and history of human and animal physiology. However, the most significant contribution of Babskii E.B. is his analysis of circulation physiology--the investigation of miocard energy, the physiological effects of electrical stimulation of the heart in the experiment, neural regulation, the ionic mechanisms of automaticity of the heart and myocardial metabolism in different phases of the cardiac cycle. Babskii E.B. and his colleagues firstly created the original method of study of cardiac activity--dinamocardiografy. Academician Babskii E.B. is considered the progenitor of heart electrical stimulation method of Russian Physiology and Medicine. These and many other ideas of Babskii E.B. has been further developed by his students, colleagues and followers.

Generic Physiological Features as Predictors of Player Experience

DEFF Research Database (Denmark)

Martínez, Héctor Pérez; Garbarino, Maurizio; Yannakakis, Georgios N.

2011-01-01

This paper examines the generality of features extracted from heart rate (HR) and skin conductance (SC) signals as predictors of self-reported player affect expressed as pairwise preferences. Artificial neural networks are trained to accurately map physiological features to expressed affect in two...

Evaluation of three physiologically based pharmacokinetic (PBPK) modeling tools for emergency risk assessment after acute dichloromethane exposure

NARCIS (Netherlands)

Boerleider, R. Z.; Olie, J. D N; van Eijkeren, J. C H; Bos, P. M J; Hof, B. G H; de Vries, I.; Bessems, J. G M; Meulenbelt, J.; Hunault, C. C.

2015-01-01

Introduction: Physiologically based pharmacokinetic (PBPK) models may be useful in emergency risk assessment, after acute exposure to chemicals, such as dichloromethane (DCM). We evaluated the applicability of three PBPK models for human risk assessment following a single exposure to DCM: one model

From inverse problems in mathematical physiology to quantitative differential diagnoses.

Directory of Open Access Journals (Sweden)

Sven Zenker

2007-11-01

Full Text Available The improved capacity to acquire quantitative data in a clinical setting has generally failed to improve outcomes in acutely ill patients, suggesting a need for advances in computer-supported data interpretation and decision making. In particular, the application of mathematical models of experimentally elucidated physiological mechanisms could augment the interpretation of quantitative, patient-specific information and help to better target therapy. Yet, such models are typically complex and nonlinear, a reality that often precludes the identification of unique parameters and states of the model that best represent available data. Hypothesizing that this non-uniqueness can convey useful information, we implemented a simplified simulation of a common differential diagnostic process (hypotension in an acute care setting, using a combination of a mathematical model of the cardiovascular system, a stochastic measurement model, and Bayesian inference techniques to quantify parameter and state uncertainty. The output of this procedure is a probability density function on the space of model parameters and initial conditions for a particular patient, based on prior population information together with patient-specific clinical observations. We show that multimodal posterior probability density functions arise naturally, even when unimodal and uninformative priors are used. The peaks of these densities correspond to clinically relevant differential diagnoses and can, in the simplified simulation setting, be constrained to a single diagnosis by assimilating additional observations from dynamical interventions (e.g., fluid challenge. We conclude that the ill-posedness of the inverse problem in quantitative physiology is not merely a technical obstacle, but rather reflects clinical reality and, when addressed adequately in the solution process, provides a novel link between mathematically described physiological knowledge and the clinical concept of

From Inverse Problems in Mathematical Physiology to Quantitative Differential Diagnoses

Science.gov (United States)

Zenker, Sven; Rubin, Jonathan; Clermont, Gilles

2007-01-01

The improved capacity to acquire quantitative data in a clinical setting has generally failed to improve outcomes in acutely ill patients, suggesting a need for advances in computer-supported data interpretation and decision making. In particular, the application of mathematical models of experimentally elucidated physiological mechanisms could augment the interpretation of quantitative, patient-specific information and help to better target therapy. Yet, such models are typically complex and nonlinear, a reality that often precludes the identification of unique parameters and states of the model that best represent available data. Hypothesizing that this non-uniqueness can convey useful information, we implemented a simplified simulation of a common differential diagnostic process (hypotension in an acute care setting), using a combination of a mathematical model of the cardiovascular system, a stochastic measurement model, and Bayesian inference techniques to quantify parameter and state uncertainty. The output of this procedure is a probability density function on the space of model parameters and initial conditions for a particular patient, based on prior population information together with patient-specific clinical observations. We show that multimodal posterior probability density functions arise naturally, even when unimodal and uninformative priors are used. The peaks of these densities correspond to clinically relevant differential diagnoses and can, in the simplified simulation setting, be constrained to a single diagnosis by assimilating additional observations from dynamical interventions (e.g., fluid challenge). We conclude that the ill-posedness of the inverse problem in quantitative physiology is not merely a technical obstacle, but rather reflects clinical reality and, when addressed adequately in the solution process, provides a novel link between mathematically described physiological knowledge and the clinical concept of differential diagnoses

Physiology for engineers applying engineering methods to physiological systems

CERN Document Server

Chappell, Michael

2016-01-01

This book provides an introduction to qualitative and quantitative aspects of human physiology. It looks at biological and physiological processes and phenomena, including a selection of mathematical models, showing how physiological problems can be mathematically formulated and studied. It also illustrates how a wide range of engineering and physics topics, including electronics, fluid dynamics, solid mechanics and control theory can be used to describe and understand physiological processes and systems. Throughout the text there are introductions to measuring and quantifying physiological processes using both signal and imaging technologies. Physiology for Engineers describes the basic structure and models of cellular systems, the structure and function of the cardiovascular system, the electrical and mechanical activity of the heart and provides an overview of the structure and function of the respiratory and nervous systems. It also includes an introduction to the basic concepts and applications of reacti...

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

NARCIS (Netherlands)

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

2016-01-01

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

Translational physiology: from molecules to public health.

Science.gov (United States)

Seals, Douglas R

2013-07-15

The term 'translational research' was coined 20 years ago and has become a guiding influence in biomedical research. It refers to a process by which the findings of basic research are extended to the clinical research setting (bench to bedside) and then to clinical practice and eventually health policy (bedside to community). It is a dynamic, multidisciplinary research approach. The concept of translational physiology applies the translational research model to the physiological sciences. It differs from the traditional areas of integrative and clinical physiology by its broad investigative scope of basic research to community health. Translational physiology offers exciting opportunities, but presently is under-developed and -utilized. A key challenge will be to expand physiological research by extending investigations to communities of patients and healthy (or at risk) individuals. This will allow bidirectional physiological investigation throughout the translational continuum: basic research observations can be studied up to the population level, and mechanisms can be assessed by 'reverse translation' in clinical research settings and preclinical models based on initial observations made in populations. Examples of translational physiology questions, experimental approaches, roadblocks and strategies for promotion are discussed. Translational physiology provides a novel framework for physiology programs and an investigational platform for physiologists to study function from molecular events to public health. It holds promise for enhancing the completeness and societal impact of our work, while further solidifying the critical role of physiology in the biomedical research enterprise.

Nonlinear dynamics, fractals, cardiac physiology and sudden death

Science.gov (United States)

Goldberger, Ary L.

1987-01-01

The authors propose a diametrically opposite viewpoint to the generally accepted tendency of equating healthy function with order and disease with chaos. With regard to the question of sudden cardiac death and chaos, it is suggested that certain features of dynamical chaos related to fractal structure and fractal dynamics may be important organizing principles in normal physiology and that certain pathologies, including ventricular fibrillation, represent a class of 'pathological periodicities'. Some laboratory work bearing on the relation of nonlinear analysis to physiological and pathophysiological data is briefly reviewed, with tentative theories and models described in reference to the mechanism of ventricular fibrillation.

Misophonia: physiological investigations and case descriptions

Directory of Open Access Journals (Sweden)

Miren eEdelstein

2013-06-01

Full Text Available Misophonia is a relatively unexplored chronic condition in which a person experiences autonomic arousal (analogous to an involuntary fight-or-flight response to certain innocuous or repetitive sounds such as chewing, pen clicking and lip smacking. Misophonics report anxiety, panic and rage when exposed to trigger sounds, compromising their ability to complete everyday tasks and engage in healthy and normal social interactions. Across two experiments, we measured behavioral and physiological characteristics of the condition. Interviews (Experiment 1 with misophonics showed that the most problematic sounds are generally related to other people's behavior (pen clicking, chewing sounds. Misophonics are however not bothered when they produce these trigger sounds themselves, and some report mimicry as a coping strategy. Next, (Experiment 2 we tested the hypothesis that misophonics’ subjective experiences evoke an anomalous physiological response to certain auditory stimuli. Misophonic individuals showed heightened ratings and skin conductance responses to auditory, but not visual stimuli, relative to a group of typically developed controls, supporting this general viewpoint and indicating that misophonia is a disorder that produces distinct autonomic effects not seen in typically developed individuals.

Regulating plant physiology with organic electronics.

Science.gov (United States)

Poxson, David J; Karady, Michal; Gabrielsson, Roger; Alkattan, Aziz Y; Gustavsson, Anna; Doyle, Siamsa M; Robert, Stéphanie; Ljung, Karin; Grebe, Markus; Simon, Daniel T; Berggren, Magnus

2017-05-02

The organic electronic ion pump (OEIP) provides flow-free and accurate delivery of small signaling compounds at high spatiotemporal resolution. To date, the application of OEIPs has been limited to delivery of nonaromatic molecules to mammalian systems, particularly for neuroscience applications. However, many long-standing questions in plant biology remain unanswered due to a lack of technology that precisely delivers plant hormones, based on cyclic alkanes or aromatic structures, to regulate plant physiology. Here, we report the employment of OEIPs for the delivery of the plant hormone auxin to induce differential concentration gradients and modulate plant physiology. We fabricated OEIP devices based on a synthesized dendritic polyelectrolyte that enables electrophoretic transport of aromatic substances. Delivery of auxin to transgenic Arabidopsis thaliana seedlings in vivo was monitored in real time via dynamic fluorescent auxin-response reporters and induced physiological responses in roots. Our results provide a starting point for technologies enabling direct, rapid, and dynamic electronic interaction with the biochemical regulation systems of plants.

Common “transmission block” in understanding cardiovascular physiology

Directory of Open Access Journals (Sweden)

Hwee-Ming Cheng

2017-01-01

Full Text Available We obtained responses from 69 medical and 65 pharmacy students who had cardiovascular (CVS physiology taught in the previous academic year. A real-time response exercise using an online game-based learning platform (Kahoot! (https://getkahoot.com/ was conducted during a lecture class using true/false questions that cover certain core aspects of CVS physiology. Comments will be made on some of the common, incomplete understanding of CVS conceptual mechanisms. Some follow-up thoughts on our role as physiology educators in fine-tuning our teaching as we encounter persistent mistakes among our students' learning physiology.

Physiology of woody plants

CERN Document Server

Hazewinkel, Michiel; Pallardy, Stephen G

1996-01-01

This completely revised classic volume is an up-to-date synthesis of the intensive research devoted to woody plants. Intended primarily as a text for students and a reference for researchers, this interdisciplinary book should be useful to a broad range of scientists from agroforesters, agronomists, and arborists to plant pathologists, ecophysiologists, and soil scientists. Anyone interested in plant physiology will find this text invaluable. Key Features * Includes supplementary chapter summaries and lists of general references * Provides a solid foundation of reference information * Thoroughly updated classic text/reference.

Cardiovascular anatomy and physiology of the fetus, neonate, infant, child, and adolescent.

Science.gov (United States)

Alyn, I B; Baker, L K

1992-04-01

Practicing cardiovascular nurses are aware that significant differences exist in the cardiac anatomy and physiology of children and adults. Generally, the younger the child the greater these differences are. The cellular anatomy and physiology are markedly different in the fetus, neonate, and infant. As development progresses, cardiac function begins to more closely approximate that of an adult. This article describes the anatomical and physiologic development of the fetus, neonate, infant, child, and adolescent. The developmental differences in preload, afterload, contractility, and heart rate are summarized.

Modelling survival

DEFF Research Database (Denmark)

Ashauer, Roman; Albert, Carlo; Augustine, Starrlight

2016-01-01

The General Unified Threshold model for Survival (GUTS) integrates previously published toxicokinetic-toxicodynamic models and estimates survival with explicitly defined assumptions. Importantly, GUTS accounts for time-variable exposure to the stressor. We performed three studies to test...

Rice Physiology

Science.gov (United States)

P.A. Counce; Davidi R. Gealy; Shi-Jean Susana Sung

2002-01-01

Physiology occurs tn physical space through chemical reactions constrained by anatomy and morphology, yet guided by genetics. Physiology has been called the logic of life. Genes encode structural and fimcdonal proteins. These proteins are subsequently processed to produce enzymes that direct and govern the biomechanical processes involved in the physiology of the...

Love-hate for man-machine metaphors in Soviet physiology: from Pavlov to "physiological cybernetics".

Science.gov (United States)

Gerovitch, Slava

2002-06-01

This article reinterprets the debate between orthodox followers of the Pavlovian reflex theory and Soviet "cybernetic physiologists" in the 1950s and 60s as a clash of opposing man-machine metaphors. While both sides accused each other of "mechanistic," reductionist methodology, they did not see anything "mechanistic" about their own central metaphors: the telephone switchboard metaphor for nervous activity (the Pavlovians), and the analogies between the human brain and a computer (the cyberneticians). I argue that the scientific utility of machine analogies was closely intertwined with their philosophical and political meanings and that new interpretations of these metaphors emerged as a result of political conflicts and a realignment of forces within the scientific community and in society at large. I suggest that the constant travel of man-machine analogies, back and forth between physiology and technology has blurred the traditional categories of the "mechanistic" and the "organic" in Soviet neurophysiology, as perhaps in the history of physiology in general.

Black hole based tests of general relativity

International Nuclear Information System (INIS)

Yagi, Kent; Stein, Leo C

2016-01-01

General relativity has passed all solar system experiments and neutron star based tests, such as binary pulsar observations, with flying colors. A more exotic arena for testing general relativity is in systems that contain one or more black holes. Black holes are the most compact objects in the Universe, providing probes of the strongest-possible gravitational fields. We are motivated to study strong-field gravity since many theories give large deviations from general relativity only at large field strengths, while recovering the weak-field behavior. In this article, we review how one can probe general relativity and various alternative theories of gravity by using electromagnetic waves from a black hole with an accretion disk, and gravitational waves from black hole binaries. We first review model-independent ways of testing gravity with electromagnetic/gravitational waves from a black hole system. We then focus on selected examples of theories that extend general relativity in rather simple ways. Some important characteristics of general relativity include (but are not limited to) (i) only tensor gravitational degrees of freedom, (ii) the graviton is massless, (iii) no quadratic or higher curvatures in the action, and (iv) the theory is four-dimensional. Altering a characteristic leads to a different extension of general relativity: (i) scalar–tensor theories, (ii) massive gravity theories, (iii) quadratic gravity, and (iv) theories with large extra dimensions. Within each theory, we describe black hole solutions, their properties, and current and projected constraints on each theory using black hole based tests of gravity. We close this review by listing some of the open problems in model-independent tests and within each specific theory. (paper)

Performance Evaluation of Glottal Inverse Filtering Algorithms Using a Physiologically Based Articulatory Speech Synthesizer

Science.gov (United States)

2017-01-05

vol. 74, pp. 279–295, 1999. [11] M. Fröhlich, D. Michaelis, and H. W. Strube, “SIM— simultaneous inverse filtering and matching of a glottal flow...1 Performance Evaluation of Glottal Inverse Filtering Algorithms Using a Physiologically Based Articulatory Speech Synthesizer Yu-Ren Chien, Daryush...D. Mehta, Member, IEEE, Jón Guðnason, Matías Zañartu, Member, IEEE, and Thomas F. Quatieri, Fellow, IEEE Abstract—Glottal inverse filtering aims to

Physiological parameters

International Nuclear Information System (INIS)

Natera, E.S.

1998-01-01

The physiological characteristics of man depend on the intake, metabolism and excretion of stable elements from food, water, and air. The physiological behavior of natural radionuclides and radionuclides from nuclear weapons testing and from the utilization of nuclear energy is believed to follow the pattern of stable elements. Hence information on the normal physiological processes occurring in the human body plays an important role in the assessment of the radiation dose received by man. Two important physiological parameters needed for internal dose determination are the pulmonary function and the water balance. In the Coordinated Research Programme on the characterization of Asian population, five participants submitted data on these physiological characteristics - China, India, Japan, Philippines and Viet Nam. During the CRP, data on other pertinent characteristics such as physical and dietary were simultaneously being collected. Hence, the information on the physiological characteristics alone, coming from the five participants were not complete and are probably not sufficient to establish standard values for the Reference Asian Man. Nonetheless, the data collected is a valuable contribution to this research programme

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-08-01

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

Why fish oil fails: a comprehensive 21st century lipids-based physiologic analysis.

Science.gov (United States)

Peskin, B S

2014-01-01

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

Generalized SMO algorithm for SVM-based multitask learning.

Science.gov (United States)

Cai, Feng; Cherkassky, Vladimir

2012-06-01

Exploiting additional information to improve traditional inductive learning is an active research area in machine learning. In many supervised-learning applications, training data can be naturally separated into several groups, and incorporating this group information into learning may improve generalization. Recently, Vapnik proposed a general approach to formalizing such problems, known as "learning with structured data" and its support vector machine (SVM) based optimization formulation called SVM+. Liang and Cherkassky showed the connection between SVM+ and multitask learning (MTL) approaches in machine learning, and proposed an SVM-based formulation for MTL called SVM+MTL for classification. Training the SVM+MTL classifier requires the solution of a large quadratic programming optimization problem which scales as O(n(3)) with sample size n. So there is a need to develop computationally efficient algorithms for implementing SVM+MTL. This brief generalizes Platt's sequential minimal optimization (SMO) algorithm to the SVM+MTL setting. Empirical results show that, for typical SVM+MTL problems, the proposed generalized SMO achieves over 100 times speed-up, in comparison with general-purpose optimization routines.

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

NARCIS (Netherlands)

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

2002-01-01

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

A temperature-dependent physiologically based model for the invasive apple snail Pomacea canaliculata

Science.gov (United States)

Gilioli, Gianni; Pasquali, Sara; Martín, Pablo R.; Carlsson, Nils; Mariani, Luigi

2017-11-01

In order to set priorities in management of costly and ecosystem-damaging species, policymakers and managers need accurate predictions not only about where a specific invader may establish but also about its potential abundance at different geographical scales. This is because density or biomass per unit area of an invasive species is a key predictor of the magnitude of environmental and economic impact in the invaded habitat. Here, we present a physiologically based demographic model describing and explaining the population dynamics of a widespread freshwater invader, the golden apple snail Pomacea canaliculata, which is causing severe environmental and economic impacts in invaded wetlands and rice fields in Southeastern Asia and has also been introduced to North America and Europe . The model is based on bio-demographic functions for mortality, development and fecundity rates that are driven by water temperature for the aquatic stages (juveniles and adults) and by air temperature for the aerial egg masses. Our model has been validated against data on the current distribution in South America and Japan, and produced consistent and realistic patterns of reproduction, growth, maturation and mortality under different scenarios in accordance to what is known from real P. canaliculata populations in different regions and climates. The model further shows that P. canaliculata will use two different reproductive strategies (semelparity and iteroparity) within the potential area of establishment, a plasticity that may explain the high invasiveness of this species across a wide range of habitats with different climates. Our results also suggest that densities, and thus the magnitude of environmental and agricultural damage, will be largely different in locations with distinct climatic regimes within the potential area of establishment. We suggest that physiologically based demographic modelling of invasive species will become a valuable tool for invasive species managers.

Subject-independent emotion recognition based on physiological signals: a three-stage decision method.

Science.gov (United States)

Chen, Jing; Hu, Bin; Wang, Yue; Moore, Philip; Dai, Yongqiang; Feng, Lei; Ding, Zhijie

2017-12-20

Collaboration between humans and computers has become pervasive and ubiquitous, however current computer systems are limited in that they fail to address the emotional component. An accurate understanding of human emotions is necessary for these computers to trigger proper feedback. Among multiple emotional channels, physiological signals are synchronous with emotional responses; therefore, analyzing physiological changes is a recognized way to estimate human emotions. In this paper, a three-stage decision method is proposed to recognize four emotions based on physiological signals in the multi-subject context. Emotion detection is achieved by using a stage-divided strategy in which each stage deals with a fine-grained goal. The decision method consists of three stages. During the training process, the initial stage transforms mixed training subjects to separate groups, thus eliminating the effect of individual differences. The second stage categorizes four emotions into two emotion pools in order to reduce recognition complexity. The third stage trains a classifier based on emotions in each emotion pool. During the testing process, a test case or test trial will be initially classified to a group followed by classification into an emotion pool in the second stage. An emotion will be assigned to the test trial in the final stage. In this paper we consider two different ways of allocating four emotions into two emotion pools. A comparative analysis is also carried out between the proposal and other methods. An average recognition accuracy of 77.57% was achieved on the recognition of four emotions with the best accuracy of 86.67% to recognize the positive and excited emotion. Using differing ways of allocating four emotions into two emotion pools, we found there is a difference in the effectiveness of a classifier on learning each emotion. When compared to other methods, the proposed method demonstrates a significant improvement in recognizing four emotions in the

Database of Physiological Parameters for Early Life Rats and Mice

Data.gov (United States)

U.S. Environmental Protection Agency — The Database of Physiological Parameters for Early Life Rats and Mice provides information based on scientific literature about physiological parameters. Modelers...

Physiologically Based Pharmacokinetic Model for Terbinafine in Rats and Humans

Science.gov (United States)

Hosseini-Yeganeh, Mahboubeh; McLachlan, Andrew J.

2002-01-01

The aim of this study was to develop a physiologically based pharmacokinetic (PB-PK) model capable of describing and predicting terbinafine concentrations in plasma and tissues in rats and humans. A PB-PK model consisting of 12 tissue and 2 blood compartments was developed using concentration-time data for tissues from rats (n = 33) after intravenous bolus administration of terbinafine (6 mg/kg of body weight). It was assumed that all tissues except skin and testis tissues were well-stirred compartments with perfusion rate limitations. The uptake of terbinafine into skin and testis tissues was described by a PB-PK model which incorporates a membrane permeability rate limitation. The concentration-time data for terbinafine in human plasma and tissues were predicted by use of a scaled-up PB-PK model, which took oral absorption into consideration. The predictions obtained from the global PB-PK model for the concentration-time profile of terbinafine in human plasma and tissues were in close agreement with the observed concentration data for rats. The scaled-up PB-PK model provided an excellent prediction of published terbinafine concentration-time data obtained after the administration of single and multiple oral doses in humans. The estimated volume of distribution at steady state (Vss) obtained from the PB-PK model agreed with the reported value of 11 liters/kg. The apparent volume of distribution of terbinafine in skin and adipose tissues accounted for 41 and 52%, respectively, of the Vss for humans, indicating that uptake into and redistribution from these tissues dominate the pharmacokinetic profile of terbinafine. The PB-PK model developed in this study was capable of accurately predicting the plasma and tissue terbinafine concentrations in both rats and humans and provides insight into the physiological factors that determine terbinafine disposition. PMID:12069977

Anatomy and Physiology. Health Occupations Education. Teacher's Guide.

Science.gov (United States)

East Texas State Univ., Commerce. Occupational Curriculum Lab.

Nine units on anatomy and physiology are presented in this teacher's guide. The units are the following: organization and general plan of the body; skeletal and muscular systems; digestive system; circulatory system; respiratory system; nervous system and special senses; urinary system; reproductive system; and endocrine glands. Each instructional…

General Stress Responses in the Honey Bee

Directory of Open Access Journals (Sweden)

Naïla Even

2012-12-01

Full Text Available The biological concept of stress originated in mammals, where a “General Adaptation Syndrome” describes a set of common integrated physiological responses to diverse noxious agents. Physiological mechanisms of stress in mammals have been extensively investigated through diverse behavioral and physiological studies. One of the main elements of the stress response pathway is the endocrine hypothalamo-pituitary-adrenal (HPA axis, which underlies the “fight-or-flight” response via a hormonal cascade of catecholamines and corticoid hormones. Physiological responses to stress have been studied more recently in insects: they involve biogenic amines (octopamine, dopamine, neuropeptides (allatostatin, corazonin and metabolic hormones (adipokinetic hormone, diuretic hormone. Here, we review elements of the physiological stress response that are or may be specific to honey bees, given the economical and ecological impact of this species. This review proposes a hypothetical integrated honey bee stress pathway somewhat analogous to the mammalian HPA, involving the brain and, particularly, the neurohemal organ corpora cardiaca and peripheral targets, including energy storage organs (fat body and crop. We discuss how this system can organize rapid coordinated changes in metabolic activity and arousal, in response to adverse environmental stimuli. We highlight physiological elements of the general stress responses that are specific to honey bees, and the areas in which we lack information to stimulate more research into how this fascinating and vital insect responds to stress.

Extrapolation of systemic bioavailability assessing skin absorption and epidermal and hepatic metabolism of aromatic amine hair dyes in vitro

Energy Technology Data Exchange (ETDEWEB)

Manwaring, John, E-mail: manwaring.jd@pg.com [Procter & Gamble Inc., Mason Business Center, Mason, OH 45040 (United States); Rothe, Helga [Procter & Gamble Service GmbH, Sulzbacher Str. 40, 65823 Schwalbach am Taunus (Germany); Obringer, Cindy; Foltz, David J.; Baker, Timothy R.; Troutman, John A. [Procter & Gamble Inc., Mason Business Center, Mason, OH 45040 (United States); Hewitt, Nicola J. [SWS, Erzhausen (Germany); Goebel, Carsten [Procter & Gamble Service GmbH, Sulzbacher Str. 40, 65823 Schwalbach am Taunus (Germany)

2015-09-01

Approaches to assess the role of absorption, metabolism and excretion of cosmetic ingredients that are based on the integration of different in vitro data are important for their safety assessment, specifically as it offers an opportunity to refine that safety assessment. In order to estimate systemic exposure (AUC) to aromatic amine hair dyes following typical product application conditions, skin penetration and epidermal and systemic metabolic conversion of the parent compound was assessed in human skin explants and human keratinocyte (HaCaT) and hepatocyte cultures. To estimate the amount of the aromatic amine that can reach the general circulation unchanged after passage through the skin the following toxicokinetically relevant parameters were applied: a) Michaelis–Menten kinetics to quantify the epidermal metabolism; b) the estimated keratinocyte cell abundance in the viable epidermis; c) the skin penetration rate; d) the calculated Mean Residence Time in the viable epidermis; e) the viable epidermis thickness and f) the skin permeability coefficient. In a next step, in vitro hepatocyte K{sub m} and V{sub max} values and whole liver mass and cell abundance were used to calculate the scaled intrinsic clearance, which was combined with liver blood flow and fraction of compound unbound in the blood to give hepatic clearance. The systemic exposure in the general circulation (AUC) was extrapolated using internal dose and hepatic clearance, and C{sub max} was extrapolated (conservative overestimation) using internal dose and volume of distribution, indicating that appropriate toxicokinetic information can be generated based solely on in vitro data. For the hair dye, p-phenylenediamine, these data were found to be in the same order of magnitude as those published for human volunteers. - Highlights: • An entirely in silico/in vitro approach to predict in vivo exposure to dermally applied hair dyes • Skin penetration and epidermal conversion assessed in human

Extrapolation of systemic bioavailability assessing skin absorption and epidermal and hepatic metabolism of aromatic amine hair dyes in vitro

International Nuclear Information System (INIS)

Manwaring, John; Rothe, Helga; Obringer, Cindy; Foltz, David J.; Baker, Timothy R.; Troutman, John A.; Hewitt, Nicola J.; Goebel, Carsten

2015-01-01

Approaches to assess the role of absorption, metabolism and excretion of cosmetic ingredients that are based on the integration of different in vitro data are important for their safety assessment, specifically as it offers an opportunity to refine that safety assessment. In order to estimate systemic exposure (AUC) to aromatic amine hair dyes following typical product application conditions, skin penetration and epidermal and systemic metabolic conversion of the parent compound was assessed in human skin explants and human keratinocyte (HaCaT) and hepatocyte cultures. To estimate the amount of the aromatic amine that can reach the general circulation unchanged after passage through the skin the following toxicokinetically relevant parameters were applied: a) Michaelis–Menten kinetics to quantify the epidermal metabolism; b) the estimated keratinocyte cell abundance in the viable epidermis; c) the skin penetration rate; d) the calculated Mean Residence Time in the viable epidermis; e) the viable epidermis thickness and f) the skin permeability coefficient. In a next step, in vitro hepatocyte K m and V max values and whole liver mass and cell abundance were used to calculate the scaled intrinsic clearance, which was combined with liver blood flow and fraction of compound unbound in the blood to give hepatic clearance. The systemic exposure in the general circulation (AUC) was extrapolated using internal dose and hepatic clearance, and C max was extrapolated (conservative overestimation) using internal dose and volume of distribution, indicating that appropriate toxicokinetic information can be generated based solely on in vitro data. For the hair dye, p-phenylenediamine, these data were found to be in the same order of magnitude as those published for human volunteers. - Highlights: • An entirely in silico/in vitro approach to predict in vivo exposure to dermally applied hair dyes • Skin penetration and epidermal conversion assessed in human skin explants and

Understanding the Psycho-Physiological Implications of Interaction With a Virtual Reality-Based System in Adolescents With Autism: A Feasibility Study.

Science.gov (United States)

Kuriakose, Selvia; Lahiri, Uttama

2015-07-01

Individuals with Autism are characterized by deficits in socialization and communication. In recent years several assistive technologies, e.g., Virtual Reality (VR), have been investigated to address the socialization deficits in these individuals. Presently available VR-based systems address various aspects of social communication in an isolated manner and without monitoring one's affective state such as, anxiety. However, in conventional observation-based therapy, a therapist adjusts the intervention paradigm by monitoring one's anxiety level. But, often these individuals have an inherent inability to explicitly express their anxiety thereby inducing limitations on conventional techniques. Physiological signals being continuously available and not directly impacted by these communication difficulties can be alternatively used as markers of one's anxiety level. In our research we aim at designing a Virtual-reality bAsed Social-communication Task (VAST) system that can address the various aspects of social communication, e.g., social context, subtle social cues, emotional expression, etc., in a cumulative and structured way. In addition, we augment this with a capability to use one's physiological signals as markers of one's anxiety level. In our preliminary feasibility study we investigate the potential of VAST to cause variations in one's performance and anxiety level that can be mapped from one's physiological indices.

Physiologically Based Pharmacokinetic Modeling in Lead Optimization. 1. Evaluation and Adaptation of GastroPlus To Predict Bioavailability of Medchem Series.

Science.gov (United States)

Daga, Pankaj R; Bolger, Michael B; Haworth, Ian S; Clark, Robert D; Martin, Eric J

2018-03-05

When medicinal chemists need to improve bioavailability (%F) within a chemical series during lead optimization, they synthesize new series members with systematically modified properties mainly by following experience and general rules of thumb. More quantitative models that predict %F of proposed compounds from chemical structure alone have proven elusive. Global empirical %F quantitative structure-property (QSPR) models perform poorly, and projects have too little data to train local %F QSPR models. Mechanistic oral absorption and physiologically based pharmacokinetic (PBPK) models simulate the dissolution, absorption, systemic distribution, and clearance of a drug in preclinical species and humans. Attempts to build global PBPK models based purely on calculated inputs have not achieved the optimization. In this work, local GastroPlus PBPK models are instead customized for individual medchem series. The key innovation was building a local QSPR for a numerically fitted effective intrinsic clearance (CL loc ). All inputs are subsequently computed from structure alone, so the models can be applied in advance of synthesis. Training CL loc on the first 15-18 rat %F measurements gave adequate predictions, with clear improvements up to about 30 measurements, and incremental improvements beyond that.

Evaluation of eco-physiological indicators in Northeast Asia dryland regions based on MODIS products and ecological models

Science.gov (United States)

Kang, W.

2017-12-01

Ecosystem carbon-energy-water circles have significant effect on function and structure and vice verse. Based on these circles mechanism, some eco-physiological indicators, like Transpiration (T), gross primary productivity (GPP), light use efficiency (LUE) and water use efficiency (WUE), are commonly applied to assess terrestrial ecosystem function and structure dynamics. The ecosystem weakened function and simple structure in Northeast dryland regions resulted from land degradation or desertification, which could be demonstrated by above-mentioned indicators. In this study, based on MODIS atmosphere (MYD07, MYD04, MYD06 data) and land products (MYD13A2 NDVI, MYD11A1 LST, MYD15A2 LAI and land cover data), we first retrieved transpiration and LUE via Penman-Monteith Model and modified Vegetation Photosynthesis Model (VPM), respectively; and then evaluated dynamics of these eco-physiological indicators (Tair, VPD, T, LUE, GPP and WUE) and some hotspots were found for next land degradation assessment. The results showed: (1) LUE and WUE are lower in barren or sparsely vegetated area and grasslands than in forest and croplands. (2) Whereas, all indicators presented higher variability in grassland area, particularly in east Mongolia. (3) GPP and transpiration have larger variability than other indicators due to fraction of absorbed Photosynthetically active radiation (FPAR). These eco-physiological indicators are expected to continue to change under future climate change and to help to assess land degradation from ecosystem energy-water-carbon perspectives.

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

Science.gov (United States)

Miao, Changyun; Shi, Boya; Li, Hongqiang

2008-12-01

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

Toxicology elements

International Nuclear Information System (INIS)

Viala, A.

1998-01-01

This work studies the different aspects of the modern toxicology: toxico-kinetic, biological, medico legal, food, professional, pharmaceuticals, environmental, social and regulatory. It is divided in three parts that consider the principle problems of general toxicology and analytical toxicology. (N.C.)

Maternal Confidence for Physiologic Childbirth: A Concept Analysis.

Science.gov (United States)

Neerland, Carrie E

2018-06-06

Confidence is a term often used in research literature and consumer media in relation to birth, but maternal confidence has not been clearly defined, especially as it relates to physiologic labor and birth. The aim of this concept analysis was to define maternal confidence in the context of physiologic labor and childbirth. Rodgers' evolutionary method was used to identify attributes, antecedents, and consequences of maternal confidence for physiologic birth. Databases searched included Ovid MEDLINE, CINAHL, PsycINFO, and Sociological Abstracts from the years 1995 to 2015. A total of 505 articles were retrieved, using the search terms pregnancy, obstetric care, prenatal care, and self-efficacy and the keyword confidence. Articles were identified for in-depth review and inclusion based on whether the term confidence was used or assessed in relationship to labor and/or birth. In addition, a hand search of the reference lists of the selected articles was performed. Twenty-four articles were reviewed in this concept analysis. We define maternal confidence for physiologic birth as a woman's belief that physiologic birth can be achieved, based on her view of birth as a normal process and her belief in her body's innate ability to birth, which is supported by social support, knowledge, and information founded on a trusted relationship with a maternity care provider in an environment where the woman feels safe. This concept analysis advances the concept of maternal confidence for physiologic birth and provides new insight into how women's confidence for physiologic birth might be enhanced during the prenatal period. Further investigation of confidence for physiologic birth across different cultures is needed to identify cultural differences in constructions of the concept. © 2018 by the American College of Nurse-Midwives.

Conceptual design of wearpack with physiology detector feature based on wearable instrumentation

Science.gov (United States)

Sukirman, Melani; Laksono, Pringgo Widyo; Priadythama, Ilham; Susmartini, Susy; Suhardi, Bambang

2017-11-01

Every company in Indonesia is responsible for their worker health and safety condition as mentioned in UU No I year 1970. In manufacturing industries, there are many manual tasks dealing with high work load and risk, so that they require excellent concentration and physical condition. There is no ideal way to guarantee worker safety without a real time physiological monitoring. This paper reports our ongoing study in conceptual design development of worker's clothing which is equipped with a wearable instrumentation system. The system is designed to detect and measure body temperature and pulse in real time. Some electrical components such as, LCD (liquid crystal display), LEDs (light emitting diode), batteries, and physiological sensors were assembled. All components are controlled by a wearable on board controller. LEDs is used as alert which can indicate abnormal physical conditions. The LCD was added to provide more detail information. TMP 36 and XD-58C were selected as the physiological sensors. Finally, an Arduino Lilypad was chosen for the controller. This instrumentation system was verified by accurately detected and inform physiological condition of 3 subjects. Further we are going to attach the system to a worker's clothing which was specifically designed to simplify and comfortable usage.

Detection of generalized synchronization using echo state networks

Science.gov (United States)

Ibáñez-Soria, D.; Garcia-Ojalvo, J.; Soria-Frisch, A.; Ruffini, G.

2018-03-01

Generalized synchronization between coupled dynamical systems is a phenomenon of relevance in applications that range from secure communications to physiological modelling. Here, we test the capabilities of reservoir computing and, in particular, echo state networks for the detection of generalized synchronization. A nonlinear dynamical system consisting of two coupled Rössler chaotic attractors is used to generate temporal series consisting of time-locked generalized synchronized sequences interleaved with unsynchronized ones. Correctly tuned, echo state networks are able to efficiently discriminate between unsynchronized and synchronized sequences even in the presence of relatively high levels of noise. Compared to other state-of-the-art techniques of synchronization detection, the online capabilities of the proposed Echo State Network based methodology make it a promising choice for real-time applications aiming to monitor dynamical synchronization changes in continuous signals.

The Physiology of Fear and Sound

DEFF Research Database (Denmark)

Garner, Tom Alexander; Grimshaw, Mark

2013-01-01

and systematically altering the game environment in response. This article presents empirical data the analysis of which advocates electrodermal activity and electromyography as suitable physiological measures to work effectively within a computer video game-based biometric feedback loop, within which sound......The potential value of a looping biometric feedback system as a key component of adaptive computer video games is significant. Psychophysiological measures are essential to the development of an automated emotion recognition program, capable of interpreting physiological data into models of affect...

Development of a Physiologically-Based Pharmacokinetic Model of Trichloroethylene and Its Metabolities for Use in Risk Assessment

Science.gov (United States)

2004-09-01

Stenner , R.D., Merdink, J.L., Fisher, J.W., and Bull, R., Physiologically-based pharmacokinetic model for trichloroethylene considering enterohepatic...B6C3F1 mice. Toxicol. Appl. Pharmacol., 123, 1- 8, 1993. 21. Templin, M.V., Stevens, D.K., Stenner , R.D., Bonate, P.L., Tuman, D., and Bull, R.J

Behavioral and Physiological Responses to Nicotine Patch Administration Among Nonsmokers Based on Acute and Chronic Secondhand Tobacco Smoke Exposure.

Science.gov (United States)

Okoli, Chizimuzo; Kodet, Jonathan; Robertson, Heather

2016-01-01

Despite the large amount that is known about the physical health effects of secondhand tobacco smoke (SHS) exposure, little is known about the behavioral health effects. Nicotine, the principle psychoactive substance in SHS, elicits subjective mood and physiological responses in nonsmokers. However, no studies have examined the subjective mood or physiological responses to nicotine in nonsmokers while accounting for prior chronic or acute SHS exposure. A 7-mg nicotine patch was administered to 17 adult nonsmokers for 2 hr. Main outcome measures obtained at ½ hr, 1 hr, and 2 hr were subjective behavioral drug effects (based on eleven 10-cm Visual Analog Scales [VASs]) and the physiological measures of heart rate, blood pressure, and serum nicotine levels. Analysis of outcome data was based on participants' chronic (using hair nicotine) or acute (using saliva cotinine) SHS exposure. Greater chronic SHS exposure was negatively associated with pleasurable responses to nicotine administration ("drug feels good" score at 2-hr time point, Spearman's ρ = -.65, p < .004), whereas greater acute SHS exposure was associated with positive responses ("like feeling of drug" score at 2-hr time point, Spearman's ρ = .63, p < .01). There were no associations between chronic or acute exposure and physiological changes in response to nicotine administration. The findings of this study may be useful in providing preliminary empirical data for future explorations of the mechanism whereby SHS exposure can influence behavioral outcomes in nonsmokers. Such studies can inform future interventions to reduce the physical and behavioral health risks associated with SHS exposure. © The Author(s) 2015.

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

Science.gov (United States)

Hadi, Ria Fitriyani; Subali, Bambang

2017-08-01

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

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

Directory of Open Access Journals (Sweden)

Raj K. Singh Badhan

2014-03-01

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

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

Directory of Open Access Journals (Sweden)

B. S. Peskin

2014-01-01

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

Green perspectives for public health: a narrative review on the physiological effects of experiencing outdoor nature.

Science.gov (United States)

Haluza, Daniela; Schönbauer, Regina; Cervinka, Renate

2014-05-19

Natural environments offer a high potential for human well-being, restoration and stress recovery in terms of allostatic load. A growing body of literature is investigating psychological and physiological health benefits of contact with Nature. So far, a synthesis of physiological health outcomes of direct outdoor nature experiences and its potential for improving Public Health is missing. We were interested in summarizing the outcomes of studies that investigated physiological outcomes of experiencing Nature measuring at least one physiological parameter during the last two decades. Studies on effects of indoor or simulated Nature exposure via videos or photos, animal contact, and wood as building material were excluded from further analysis. As an online literature research delivered heterogeneous data inappropriate for quantitative synthesis approaches, we descriptively summarized and narratively synthesized studies. The procedure started with 1,187 titles. Research articles in English language published in international peer-reviewed journals that investigated the effects of natural outdoor environments on humans by were included. We identified 17 relevant articles reporting on effects of Nature by measuring 20 different physiological parameters. We assigned these parameters to one of the four body systems brain activity, cardiovascular system, endocrine system, and immune function. These studies reported mainly direct and positive effects, however, our analyses revealed heterogeneous outcomes regarding significance of results. Most of the studies were conducted in Japan, based on quite small samples, predominantly with male students as participants in a cross-sectional design. In general, our narrative review provided an ambiguous illustration of the effects outdoor nature exerted on physiological parameters. However, the majority of studies reported significant positive effects. A harmonizing effect of Nature, especially on physiological stress reactions, was

Green Perspectives for Public Health: A Narrative Review on the Physiological Effects of Experiencing Outdoor Nature

Directory of Open Access Journals (Sweden)

Daniela Haluza

2014-05-01

Full Text Available Natural environments offer a high potential for human well-being, restoration and stress recovery in terms of allostatic load. A growing body of literature is investigating psychological and physiological health benefits of contact with Nature. So far, a synthesis of physiological health outcomes of direct outdoor nature experiences and its potential for improving Public Health is missing. We were interested in summarizing the outcomes of studies that investigated physiological outcomes of experiencing Nature measuring at least one physiological parameter during the last two decades. Studies on effects of indoor or simulated Nature exposure via videos or photos, animal contact, and wood as building material were excluded from further analysis. As an online literature research delivered heterogeneous data inappropriate for quantitative synthesis approaches, we descriptively summarized and narratively synthesized studies. The procedure started with 1,187 titles. Research articles in English language published in international peer-reviewed journals that investigated the effects of natural outdoor environments on humans by were included. We identified 17 relevant articles reporting on effects of Nature by measuring 20 different physiological parameters. We assigned these parameters to one of the four body systems brain activity, cardiovascular system, endocrine system, and immune function. These studies reported mainly direct and positive effects, however, our analyses revealed heterogeneous outcomes regarding significance of results. Most of the studies were conducted in Japan, based on quite small samples, predominantly with male students as participants in a cross-sectional design. In general, our narrative review provided an ambiguous illustration of the effects outdoor nature exerted on physiological parameters. However, the majority of studies reported significant positive effects. A harmonizing effect of Nature, especially on physiological

Accuracy and Efficiency of Recording Pediatric Early Warning Scores Using an Electronic Physiological Surveillance System Compared With Traditional Paper-Based Documentation.

Science.gov (United States)

Sefton, Gerri; Lane, Steven; Killen, Roger; Black, Stuart; Lyon, Max; Ampah, Pearl; Sproule, Cathryn; Loren-Gosling, Dominic; Richards, Caitlin; Spinty, Jean; Holloway, Colette; Davies, Coral; Wilson, April; Chean, Chung Shen; Carter, Bernie; Carrol, E D

2017-05-01

Pediatric Early Warning Scores are advocated to assist health professionals to identify early signs of serious illness or deterioration in hospitalized children. Scores are derived from the weighting applied to recorded vital signs and clinical observations reflecting deviation from a predetermined "norm." Higher aggregate scores trigger an escalation in care aimed at preventing critical deterioration. Process errors made while recording these data, including plotting or calculation errors, have the potential to impede the reliability of the score. To test this hypothesis, we conducted a controlled study of documentation using five clinical vignettes. We measured the accuracy of vital sign recording, score calculation, and time taken to complete documentation using a handheld electronic physiological surveillance system, VitalPAC Pediatric, compared with traditional paper-based charts. We explored the user acceptability of both methods using a Web-based survey. Twenty-three staff participated in the controlled study. The electronic physiological surveillance system improved the accuracy of vital sign recording, 98.5% versus 85.6%, P < .02, Pediatric Early Warning Score calculation, 94.6% versus 55.7%, P < .02, and saved time, 68 versus 98 seconds, compared with paper-based documentation, P < .002. Twenty-nine staff completed the Web-based survey. They perceived that the electronic physiological surveillance system offered safety benefits by reducing human error while providing instant visibility of recorded data to the entire clinical team.

An Internet of Things based physiological signal monitoring and receiving system for virtual enhanced health care network.

Science.gov (United States)

Rajan, J Pandia; Rajan, S Edward

2018-01-01

Wireless physiological signal monitoring system designing with secured data communication in the health care system is an important and dynamic process. We propose a signal monitoring system using NI myRIO connected with the wireless body sensor network through multi-channel signal acquisition method. Based on the server side validation of the signal, the data connected to the local server is updated in the cloud. The Internet of Things (IoT) architecture is used to get the mobility and fast access of patient data to healthcare service providers. This research work proposes a novel architecture for wireless physiological signal monitoring system using ubiquitous healthcare services by virtual Internet of Things. We showed an improvement in method of access and real time dynamic monitoring of physiological signal of this remote monitoring system using virtual Internet of thing approach. This remote monitoring and access system is evaluated in conventional value. This proposed system is envisioned to modern smart health care system by high utility and user friendly in clinical applications. We claim that the proposed scheme significantly improves the accuracy of the remote monitoring system compared to the other wireless communication methods in clinical system.

The importance of inclusion of kinetic information in the extrapolation of high-to-low concentrations for human limit setting.

NARCIS (Netherlands)

Geraets, Liesbeth; Zeilmaker, Marco J; Bos, Peter M J

2018-01-01

Human health risk assessment of inhalation exposures generally includes a high-to-low concentration extrapolation. Although this is a common step in human risk assessment, it introduces various uncertainties. One of these uncertainties is related to the toxicokinetics. Many kinetic processes such as

The influence of microplastics and halogenated contaminants in feed on toxicokinetics and gene expression in European seabass (Dicentrarchus labrax).

Science.gov (United States)

Granby, Kit; Rainieri, Sandra; Rasmussen, Rie Romme; Kotterman, Michiel J J; Sloth, Jens Jørgen; Cederberg, Tommy Licht; Barranco, Alex; Marques, António; Larsen, Bodil Katrine

2018-07-01

When microplastics pollute fish habitats, it may be ingested by fish, thereby contaminating fish with sorbed contaminants. The present study investigates how combinations of halogenated contaminants and microplastics associated with feed are able to alter toxicokinetics in European seabass and affect the fish. Microplastic particles (2%) were added to the feed either with sorbed contaminants or as a mixture of clean microplastics and chemical contaminants, and compared to feed containing contaminants without microplastics. For the contaminated microplastic diet, the accumulation of polychlorinated biphenyls (PCBs) and brominated flame retardants (BFRs) in fish was significantly higher, increasing up to 40 days of accumulation and then reversing to values comparable to the other diets at the end of accumulation. The significant gene expression results of liver (cyp1a, il1β, gstα) after 40 days of exposure indicate that microplastics might indeed exacerbate the toxic effects (liver metabolism, immune system, oxidative stress) of some chemical contaminants sorbed to microplastics. Seabass quickly metabolised BDE99 to BDE47 by debromination, probably mediated by deiodinase enzymes, and unlike other contaminants, this metabolism was unaffected by the presence of microplastics. For the other PCBs and BFRs, the elimination coefficients were significantly lower in fish fed the diet with contaminants sorbed to microplastic compared to the other diets. The results indicate that microplastics affects liver detoxification and lipid distribution, both of which affect the concentration of contaminants. Copyright © 2018 Elsevier Inc. All rights reserved.

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

NARCIS (Netherlands)

Zeilmaker MJ; van Eijkeren JCH; LBO

1998-01-01

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

Tissue physiology and the response to heat

DEFF Research Database (Denmark)

Horsman, Michael Robert

2006-01-01

physiological effects should occur in normal tissues, such combination therapies must be carefully applied. Heating tumours to higher temperatures typically causes a transient increase in perfusion during heating, followed by vascular collapse which if sufficient will increase tumour necrosis. The speed...... and degree of vascular collapse is dependent on heating time, temperature and tumour model used. Such vascular collapse generally occurs at temperatures that cause a substantial blood flow increase in certain normal tissues, thus preferential anti-tumour effects can be achieved. The tumour vascular supply...... can also be exploited to improve the response to heat. Decreasing blood flow, using transient physiological modifiers or longer acting vascular disrupting agents prior to the initiation of heating, can both increase the accumulation of physical heat in the tumour, as well as increase heat sensitivity...

Occupational physiology

CERN Document Server

Toomingas, Allan; Tornqvist, Ewa Wigaeus

2011-01-01

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

Update on a Pharmacokinetic-Centric Alternative Tier II Program for MMT—Part II: Physiologically Based Pharmacokinetic Modeling and Manganese Risk Assessment

Directory of Open Access Journals (Sweden)

Michael D. Taylor

2012-01-01

Full Text Available Recently, a variety of physiologically based pharmacokinetic (PBPK models have been developed for the essential element manganese. This paper reviews the development of PBPK models (e.g., adult, pregnant, lactating, and neonatal rats, nonhuman primates, and adult, pregnant, lactating, and neonatal humans and relevant risk assessment applications. Each PBPK model incorporates critical features including dose-dependent saturable tissue capacities and asymmetrical diffusional flux of manganese into brain and other tissues. Varied influx and efflux diffusion rate and binding constants for different brain regions account for the differential increases in regional brain manganese concentrations observed experimentally. We also present novel PBPK simulations to predict manganese tissue concentrations in fetal, neonatal, pregnant, or aged individuals, as well as individuals with liver disease or chronic manganese inhalation. The results of these simulations could help guide risk assessors in the application of uncertainty factors as they establish exposure guidelines for the general public or workers.

Physiology education in North American dental schools: the basic science survey series.

Science.gov (United States)

Gautam, Medha; Shaw, David H; Pate, Ted D; Lambert, H Wayne

2014-06-01

As part of the Basic Science Survey Series for Dentistry, members of the American Dental Education Association (ADEA) Physiology, Pharmacology, and Therapeutics Section surveyed directors of physiology courses in North American dental schools. The survey was designed to assess, among other things, faculty affiliation and experience of course directors, teaching methods, general course content and emphasis, extent of interdisciplinary (shared) instruction, and impact of recent curricular changes. Responses were received from forty-four of sixty-seven (65.7 percent) U.S. and Canadian dental schools. The findings suggest the following: substantial variation exists in instructional hours, faculty affiliation, class size, and interdisciplinary nature of physiology courses; physiology course content emphasis is similar between schools; student contact hours in physiology, which have remained relatively stable in the past fifteen years, are starting to be reduced; recent curricular changes have often been directed towards enhancing the integrative and clinically relevant aspects of physiology instruction; and a trend toward innovative content delivery, such as use of computer-assisted instruction, is evident. Data from this study may be useful to physiology course directors, curriculum committees, and other dental educators with an interest in integrative and interprofessional education.

Success stories and emerging themes in conservation physiology.

Science.gov (United States)

Madliger, Christine L; Cooke, Steven J; Crespi, Erica J; Funk, Jennifer L; Hultine, Kevin R; Hunt, Kathleen E; Rohr, Jason R; Sinclair, Brent J; Suski, Cory D; Willis, Craig K R; Love, Oliver P

2016-01-01

The potential benefits of physiology for conservation are well established and include greater specificity of management techniques, determination of cause-effect relationships, increased sensitivity of health and disturbance monitoring and greater capacity for predicting future change. While descriptions of the specific avenues in which conservation and physiology can be integrated are readily available and important to the continuing expansion of the discipline of 'conservation physiology', to date there has been no assessment of how the field has specifically contributed to conservation success. However, the goal of conservation physiology is to foster conservation solutions and it is therefore important to assess whether physiological approaches contribute to downstream conservation outcomes and management decisions. Here, we present eight areas of conservation concern, ranging from chemical contamination to invasive species to ecotourism, where physiological approaches have led to beneficial changes in human behaviour, management or policy. We also discuss the shared characteristics of these successes, identifying emerging themes in the discipline. Specifically, we conclude that conservation physiology: (i) goes beyond documenting change to provide solutions; (ii) offers a diversity of physiological metrics beyond glucocorticoids (stress hormones); (iii) includes approaches that are transferable among species, locations and times; (iv) simultaneously allows for human use and benefits to wildlife; and (v) is characterized by successes that can be difficult to find in the primary literature. Overall, we submit that the field of conservation physiology has a strong foundation of achievements characterized by a diversity of conservation issues, taxa, physiological traits, ecosystem types and spatial scales. We hope that these concrete successes will encourage the continued evolution and use of physiological tools within conservation-based research and management

Dinosaur energetics: setting the bounds on feasible physiologies and ecologies.

Science.gov (United States)

Clarke, Andrew

2013-09-01

The metabolic status of dinosaurs has long been debated but remains unresolved as no consistent picture has emerged from a range of anatomical and isotopic evidence. Quantitative analysis of dinosaur energetics, based on general principles applicable to all vertebrates, shows that many features of dinosaur lifestyle are compatible with a physiology similar to that of extant lizards, scaled up to dinosaur body masses and temperatures. The analysis suggests that sufficient metabolic scope would have been available to support observed dinosaur growth rates and allow considerable locomotor activity, perhaps even migration. Since at least one dinosaur lineage evolved true endothermy, this study emphasizes there was no single dinosaur physiology. Many small theropods were insulated with feathers and appear to have been partial or full endotherms. Uninsulated small taxa, and all juveniles, presumably would have been ectothermic, with consequent diurnal and seasonal variations in body temperature. In larger taxa, inertial homeothermy would have resulted in warm and stable body temperatures but with a basal metabolism significantly below that of extant mammals or birds of the same size. It would appear that dinosaurs exhibited a range of metabolic levels to match the broad spectrum of ecological niches they occupied.

Physical Activity, Aging, and Physiological Function.

Science.gov (United States)

Harridge, Stephen D R; Lazarus, Norman R

2017-03-01

Human evolution suggests that the default position for health is to be physically active. Inactivity, by contrast, has serious negative effects on health across the lifespan. Therefore, only in physically active people can the inherent aging process proceed unaffected by disuse complications. In such individuals, although the relationship between age and physiological function remains complex, function is generally superior with health, well being, and the aging process optimized. ©2017 Int. Union Physiol. Sci./Am. Physiol. Soc.

Habitat and sex differences in physiological condition of breeding Southwestern Willow Flycatchers (Empidonax traillii extimus)

Science.gov (United States)

Owen, J.C.; Sogge, M.K.; Kern, M.D.

2005-01-01

The Southwestern Willow Flycatcher (Empidonax traillii extimus; here- after “flycatcher”) is a federally listed endangered species that breeds in densely vegetated riparian habitats dominated by native and exotic plants, including introduced monotypic saltcedar (Tamarix ramosissima). Some workers have theorized that saltcedar is unsuitable habitat for the flycatcher, primarily because it generally supports a smaller and less diverse invertebrate community (the flycatcher's food base) than native habitats (e.g. Salix spp.). However, differences in insect communities between native and saltcedar habitats are not proof that saltcedar habitats are inferior. The only way to evaluate whether the habitats differ in dietary or energetic quality is to document actual food limitation or its manifestations. Measurements of an individual's body condition and metabolic state can serve as indicators of environmental stressors, such as food limitation and environmental extremes. We captured 130 flycatchers breeding in native and saltcedar habitats in Arizona and New Mexico and measured 12 variables of physiological condition. These variables included body mass, fat level, body condition index, hematocrit, plasma triglycerides, plasma free fatty acids and glycerol, plasma glucose and beta-hydroxybutyrate, plasma uric acid, total leukocyte count, and heterophil-to-lymphocyte ratio. We found substantial sex-based differences in the condition of male and female flycatchers. Ten of the 12 measures of physiological condition differed significantly between the sexes. In all cases where male and female condition differed (except mass), the differences suggest that males were in poorer condition than females. We found few habitat-based differences in flycatcher condition. Only 3 of the 12 physiological condition indices differed significantly between habitats. Our data show that, at least in some parts of the flycatcher's range, there is no evidence that flycatchers breeding in

Investigating the state of physiologically based kinetic modelling practices and challenges associated with gaining regulatory acceptance of model applications

Science.gov (United States)

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...

General programmed system for physiological signal processing

Energy Technology Data Exchange (ETDEWEB)

Tournier, E; Monge, J; Magnet, C; Sonrel, C

1975-01-01

Improvements made to the general programmed signal acquisition and processing system, Plurimat S, are described, the aim being to obtain a less specialized system adapted to the biological and medical field. In this modified system the acquisition will be simplified. The standard processings offered will be integrated to a real advanced language which will enable the user to create his own processings, the loss of speed being compensated by a greater flexibility and universality. The observation screen will be large and the quality of the recording very good so that a large signal fraction may be displayed. The data will be easily indexed and filed for subsequent display and processing. This system will be used for two kinds of task: it can either be specialized, as an integral part of measurement and diagnostic preparation equipment used routinely in clinical work (e.g. vectocardiographic examination), or its versatility can be used for studies of limited duration to gain information in a given field or to study new diagnosis or treatment methods.

Physiological response of the nematode Caenorhabditis elegans exposed to binary mixture of uranium and cadmium

Energy Technology Data Exchange (ETDEWEB)

Margerit, A.; Gilbin, R. [French Institute for Radiological Protection and Nuclear Safety - IRSN (France); Gomez, E. [Universite Montpellier 1 (France)

2014-07-01

Both uranium (U) and cadmium (Cd) are natural ubiquitous substances whose occurrence may be magnified in the vicinity of some Nuclear Fuel Cycle Facility (NFCF) (e.g. uranium mining area) or intensive farming areas. Natural U is a mainly chemo-toxic radioelement, with a slight radio-toxic activity, while Cd is a fully chemo-toxic trace metal. Due to their possible co-occurrence, the study of their combined effects on ecosystems may be of interest in a risk assessment perspective. MixTox tool is a simple descriptive model commonly used to study the effects of chemical mixtures. It relies on dose response, concentration addition and response addition concepts to describe combined toxicant effects and identify possible Synergistic/Antagonistic - Constant/Dose-level/Dose ratio dependent - interactions. In the present study, toxicity of binary mixture of U and Cd was assessed on physiological parameters, maximal length and brood size, in the soil nematode Caenorhabditis elegans. A 49 condition fractional factorial design was used with U and Cd concentrations ranging from 0.95 to 1.3 mM and 0.006 to 0.04 mM, respectively. Dose response curves obtained for U and Cd on maximal length and brood size were consistent with published data. Using MixTox tool, the best description of these endpoints was met with the response addition concept and the dose-ratio dependent interaction model. A significant antagonism was identified when Cd toxicity is preponderant in the mixture and was confirmed with experimental observations. On the other hand, no significant interaction could be identified when U toxicity was preponderant in the mixture. Interaction between the two chemicals may occur during the exposure, the toxicokinetics and/or during the toxico-dynamic phases. Based on the results of this study, a probable hypothesis would be that U, whose toxicity is in the mM range, reduces bioaccumulation of Cd, whose toxicity is in the range of 10 μM. A bioaccumulation assay of U and Cd

What Makes the Learning of Physiology in a PBL Medical Curriculum Challenging? Student Perceptions

Science.gov (United States)

Tufts, Mark A.; Higgins-Opitz, Susan B.

2009-01-01

Physiology is an integral component of any medical curriculum. Traditionally, the learning of physiology has relied heavily on systems-based didactic lectures. In 2001, the Nelson R. Mandela School of Medicine (NRMSM; Durban, South Africa) embarked on a problem-based curriculum in which the learning of physiology was integrated with relevant…

The physiology analysis system: an integrated approach for warehousing, management and analysis of time-series physiology data.

Science.gov (United States)

McKenna, Thomas M; Bawa, Gagandeep; Kumar, Kamal; Reifman, Jaques

2007-04-01

The physiology analysis system (PAS) was developed as a resource to support the efficient warehousing, management, and analysis of physiology data, particularly, continuous time-series data that may be extensive, of variable quality, and distributed across many files. The PAS incorporates time-series data collected by many types of data-acquisition devices, and it is designed to free users from data management burdens. This Web-based system allows both discrete (attribute) and time-series (ordered) data to be manipulated, visualized, and analyzed via a client's Web browser. All processes occur on a server, so that the client does not have to download data or any application programs, and the PAS is independent of the client's computer operating system. The PAS contains a library of functions, written in different computer languages that the client can add to and use to perform specific data operations. Functions from the library are sequentially inserted into a function chain-based logical structure to construct sophisticated data operators from simple function building blocks, affording ad hoc query and analysis of time-series data. These features support advanced mining of physiology data.

New concepts in white adipose tissue physiology

International Nuclear Information System (INIS)

Proença, A.R.G.; Sertié, R.A.L.; Oliveira, A.C.; Campaãa, A.B.; Caminhotto, R.O.; Chimin, P.; Lima, F.B.

2014-01-01

Numerous studies address the physiology of adipose tissue (AT). The interest surrounding the physiology of AT is primarily the result of the epidemic outburst of obesity in various contemporary societies. Briefly, the two primary metabolic activities of white AT include lipogenesis and lipolysis. Throughout the last two decades, a new model of AT physiology has emerged. Although AT was considered to be primarily an abundant energy source, it is currently considered to be a prolific producer of biologically active substances, and, consequently, is now recognized as an endocrine organ. In addition to leptin, other biologically active substances secreted by AT, generally classified as cytokines, include adiponectin, interleukin-6, tumor necrosis factor-alpha, resistin, vaspin, visfatin, and many others now collectively referred to as adipokines. The secretion of such biologically active substances by AT indicates its importance as a metabolic regulator. Cell turnover of AT has also recently been investigated in terms of its biological role in adipogenesis. Consequently, the objective of this review is to provide a comprehensive critical review of the current literature concerning the metabolic (lipolysis, lipogenesis) and endocrine actions of AT

New concepts in white adipose tissue physiology

Energy Technology Data Exchange (ETDEWEB)

Proença, A.R.G. [Universidade Estadual de Campinas, Laboratório de Biotecnologia, Faculdade de Ciências Aplicadas, Limeira, SP, Brasil, Laboratório de Biotecnologia, Faculdade de Ciências Aplicadas, Universidade Estadual de Campinas, Limeira, SP (Brazil); Sertié, R.A.L. [Universidade de São Paulo, Instituto de Ciências Biomédicas, Departamento de Fisiologia e Biofísica, São Paulo, SP, Brasil, Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP (Brazil); Oliveira, A.C. [Universidade Estadual do Ceará, Instituto Superior de Ciências Biomédicas, Fortaleza, CE, Brasil, Instituto Superior de Ciências Biomédicas, Universidade Estadual do Ceará, Fortaleza, CE (Brazil); Campaãa, A.B.; Caminhotto, R.O.; Chimin, P.; Lima, F.B. [Universidade de São Paulo, Instituto de Ciências Biomédicas, Departamento de Fisiologia e Biofísica, São Paulo, SP, Brasil, Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP (Brazil)

2014-03-03

Numerous studies address the physiology of adipose tissue (AT). The interest surrounding the physiology of AT is primarily the result of the epidemic outburst of obesity in various contemporary societies. Briefly, the two primary metabolic activities of white AT include lipogenesis and lipolysis. Throughout the last two decades, a new model of AT physiology has emerged. Although AT was considered to be primarily an abundant energy source, it is currently considered to be a prolific producer of biologically active substances, and, consequently, is now recognized as an endocrine organ. In addition to leptin, other biologically active substances secreted by AT, generally classified as cytokines, include adiponectin, interleukin-6, tumor necrosis factor-alpha, resistin, vaspin, visfatin, and many others now collectively referred to as adipokines. The secretion of such biologically active substances by AT indicates its importance as a metabolic regulator. Cell turnover of AT has also recently been investigated in terms of its biological role in adipogenesis. Consequently, the objective of this review is to provide a comprehensive critical review of the current literature concerning the metabolic (lipolysis, lipogenesis) and endocrine actions of AT.

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

Science.gov (United States)

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

2015-01-01

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

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

Science.gov (United States)

Aarif, Ovais; Aggarwal, Anjali

2016-03-01

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

Success stories and emerging themes in conservation physiology

Science.gov (United States)

Madliger, Christine L.; Cooke, Steven J.; Crespi, Erica J.; Funk, Jennifer L.; Hultine, Kevin R.; Hunt, Kathleen E.; Rohr, Jason R.; Sinclair, Brent J.; Suski, Cory D.; Willis, Craig K. R.; Love, Oliver P.

2016-01-01

The potential benefits of physiology for conservation are well established and include greater specificity of management techniques, determination of cause–effect relationships, increased sensitivity of health and disturbance monitoring and greater capacity for predicting future change. While descriptions of the specific avenues in which conservation and physiology can be integrated are readily available and important to the continuing expansion of the discipline of ‘conservation physiology’, to date there has been no assessment of how the field has specifically contributed to conservation success. However, the goal of conservation physiology is to foster conservation solutions and it is therefore important to assess whether physiological approaches contribute to downstream conservation outcomes and management decisions. Here, we present eight areas of conservation concern, ranging from chemical contamination to invasive species to ecotourism, where physiological approaches have led to beneficial changes in human behaviour, management or policy. We also discuss the shared characteristics of these successes, identifying emerging themes in the discipline. Specifically, we conclude that conservation physiology: (i) goes beyond documenting change to provide solutions; (ii) offers a diversity of physiological metrics beyond glucocorticoids (stress hormones); (iii) includes approaches that are transferable among species, locations and times; (iv) simultaneously allows for human use and benefits to wildlife; and (v) is characterized by successes that can be difficult to find in the primary literature. Overall, we submit that the field of conservation physiology has a strong foundation of achievements characterized by a diversity of conservation issues, taxa, physiological traits, ecosystem types and spatial scales. We hope that these concrete successes will encourage the continued evolution and use of physiological tools within conservation-based research and

General Base-General Acid Catalysis in Human Histone Deacetylase 8.

Science.gov (United States)

Gantt, Sister M Lucy; Decroos, Christophe; Lee, Matthew S; Gullett, Laura E; Bowman, Christine M; Christianson, David W; Fierke, Carol A

2016-02-09

Histone deacetylases (HDACs) regulate cellular processes such as differentiation and apoptosis and are targeted by anticancer therapeutics in development and in the clinic. HDAC8 is a metal-dependent class I HDAC and is proposed to use a general acid-base catalytic pair in the mechanism of amide bond hydrolysis. Here, we report site-directed mutagenesis and enzymological measurements to elucidate the catalytic mechanism of HDAC8. Specifically, we focus on the catalytic function of Y306 and the histidine-aspartate dyads H142-D176 and H143-D183. Additionally, we report X-ray crystal structures of four representative HDAC8 mutants: D176N, D176N/Y306F, D176A/Y306F, and H142A/Y306F. These structures provide a useful framework for understanding enzymological measurements. The pH dependence of kcat/KM for wild-type Co(II)-HDAC8 is bell-shaped with two pKa values of 7.4 and 10.0. The upper pKa reflects the ionization of the metal-bound water molecule and shifts to 9.1 in Zn(II)-HDAC8. The H142A mutant has activity 230-fold lower than that of wild-type HDAC8, but the pKa1 value is not altered. Y306F HDAC8 is 150-fold less active than the wild-type enzyme; crystal structures show that Y306 hydrogen bonds with the zinc-bound substrate carbonyl, poised for transition state stabilization. The H143A and H142A/H143A mutants exhibit activity that is >80000-fold lower than that of wild-type HDAC8; the buried D176N and D176A mutants have significant catalytic effects, with more subtle effects caused by D183N and D183A. These enzymological and structural studies strongly suggest that H143 functions as a single general base-general acid catalyst, while H142 remains positively charged and serves as an electrostatic catalyst for transition state stabilization.

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

Directory of Open Access Journals (Sweden)

Yu-Wei Chiou

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

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

Science.gov (United States)

Chiou, Yu-Wei; Lin, Hsiu-Kuan; Tang, Ming-Jer; Lin, Hsi-Hui; Yeh, Ming-Long

2013-01-01

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

Cell physiology based pharmacodynamic modeling of antimicrobial drug combinations

OpenAIRE

Hethey, Christoph Philipp

2017-01-01

Mathematical models of bacterial growth have been successfully applied to study the relationship between antibiotic drug exposure and the antibacterial effect. Since these models typically lack a representation of cellular processes and cell physiology, the mechanistic integration of drug action is not possible on the cellular level. The cellular mechanisms of drug action, however, are particularly relevant for the prediction, analysis and understanding of interactions between antibiotics. In...

Effect of a care plan based on Roy adaptation model biological dimension on stroke patients' physiologic adaptation level.

Science.gov (United States)

Alimohammadi, Nasrollah; Maleki, Bibi; Shahriari, Mohsen; Chitsaz, Ahmad

2015-01-01

Stroke is a stressful event with several functional, physical, psychological, social, and economic problems that affect individuals' different living balances. With coping strategies, patients try to control these problems and return to their natural life. The aim of this study is to investigate the effect of a care plan based on Roy adaptation model biological dimension on stroke patients' physiologic adaptation level. This study is a clinical trial in which 50 patients, affected by brain stroke and being admitted in the neurology ward of Kashani and Alzahra hospitals, were randomly assigned to control and study groups in Isfahan in 2013. Roy adaptation model care plan was administered in biological dimension in the form of four sessions and phone call follow-ups for 1 month. The forms related to Roy adaptation model were completed before and after intervention in the two groups. Chi-square test and t-test were used to analyze the data through SPSS 18. There was a significant difference in mean score of adaptation in physiological dimension in the study group after intervention (P adaptation in the patients affected by brain stroke in the study and control groups showed a significant increase in physiological dimension in the study group by 47.30 after intervention (P adaptation model biological dimension care plan can result in an increase in adaptation in patients with stroke in physiological dimension. Nurses can use this model for increasing patients' adaptation.

[Construction of a physiological aging scale for healthy people based on a modified Delphi method].

Science.gov (United States)

Long, Yao; Zhou, Xuan; Deng, Pengfei; Liao, Xiong; Wu, Lei; Zhou, Jianming; Huang, Helang

2016-04-01

To build a physiological aging scale for healthy people.
 We collected age-related physiologic items through literature screening and expert interview. Two rounds of Delphi were implemented. The importance, feasibility and the degree of authority for the physiological index system were graded. Using analytic hierarchy process, we determined the weight of dimensions and items.
 Using Delphy mothod, 17 physiological and other professional experts offered the results as follow: coefficient of expert authorities Cr was 0.86±0.03, coordination coefficients for the first and second round were 0.264(χ2=229.691, Paging scale for healthy people included 3 dimensions, namely physical form, feeling movement and functional status. Each dimension had 8 items. The weight coefficients for the 3 dimensions were 0.54, 0.16, and 0.30, respectively. The Cronbach's α coefficient of the scale was 0.893, the reliability was 0.796, and the variance of the common factor was 58.17%.
 The improved Delphi method or physiological aging scale is satisfied, which can provide reference for the evaluation of aging.

A day of immersive physiology experiments increases knowledge and excitement towards physiology and scientific careers in Native American students.

Science.gov (United States)

Becker, Bryan K; Schiller, Alicia M; Zucker, Irving H; Eager, Eric A; Bronner, Liliana P; Godfrey, Maurice

2017-03-01

Underserved minority groups are disproportionately absent from the pursuit of careers in science, technology, engineering, and mathematics (STEM) fields. One such underserved population, Native Americans, are particularly underrepresented in STEM fields. Although recent advocacy and outreach designed toward increasing minority involvement in health care-related occupations have been mostly successful, little is known about the efficacy of outreach programs in increasing minority enthusiasm toward careers in traditional scientific professions. Furthermore, very little is known about outreach among Native American schools toward increasing involvement in STEM. We collaborated with tribal middle and high schools in South Dakota and Nebraska through a National Institutes of Health Science Education Partnership Award to hold a day-long physiology, activity-based event to increase both understanding of physiology and enthusiasm to scientific careers. We recruited volunteer biomedical scientists and trainees from the University of Nebraska Medical Center, Nebraska Wesleyan University, and University of South Dakota. To evaluate the effectiveness of the day of activities, 224 of the ~275-300 participating students completed both a pre- and postevent evaluation assessment. We observed increases in both students self-perceived knowledge of physiology and enthusiasm toward scientific career opportunities after the day of outreach activities. We conclude that activity-based learning opportunities in underserved populations are effective in increasing both knowledge of science and interest in scientific careers. Copyright © 2017 the American Physiological Society.

The employment of Support Vector Machine to classify high and low performance archers based on bio-physiological variables

Science.gov (United States)

Taha, Zahari; Muazu Musa, Rabiu; Majeed, Anwar P. P. Abdul; Razali Abdullah, Mohamad; Amirul Abdullah, Muhammad; Hasnun Arif Hassan, Mohd; Khalil, Zubair

2018-04-01

The present study employs a machine learning algorithm namely support vector machine (SVM) to classify high and low potential archers from a collection of bio-physiological variables trained on different SVMs. 50 youth archers with the average age and standard deviation of (17.0 ±.056) gathered from various archery programmes completed a one end shooting score test. The bio-physiological variables namely resting heart rate, resting respiratory rate, resting diastolic blood pressure, resting systolic blood pressure, as well as calories intake, were measured prior to their shooting tests. k-means cluster analysis was applied to cluster the archers based on their scores on variables assessed. SVM models i.e. linear, quadratic and cubic kernel functions, were trained on the aforementioned variables. The k-means clustered the archers into high (HPA) and low potential archers (LPA), respectively. It was demonstrated that the linear SVM exhibited good accuracy with a classification accuracy of 94% in comparison the other tested models. The findings of this investigation can be valuable to coaches and sports managers to recognise high potential athletes from the selected bio-physiological variables examined.

Comparison of physiological and acid-base balance response during uphill, level and downhill running performed at constant velocity.

Science.gov (United States)

Maciejczyk, Marcin; Więcek, M; Szymura, J; Szyguła, Z

2013-09-01

The purpose of this study was to compare the physiological and the acid-base balance response to running at various slope angles. Ten healthy men 22.3 ± 1.56 years old participated in the study. The study consisted of completing the graded test until exhaustion and three 45-minute runs. For the first 30 minutes, runs were performed with an intensity of approximately 50% VO2max, while in the final 15 minutes the slope angle of treadmill was adjusted (0°; +4.5°; -4.5°), and a fixed velocity of running was maintained. During concentric exercise, a significant increase in the levels of physiological indicators was reported; during eccentric exercise, a significant decrease in the level of the analyzed indicators was observed. Level running did not cause significant changes in the indicators of acid-base balance. The indicators of acid-base balance changed significantly in the case of concentric muscle work (in comparison to level running) and after the eccentric work, significant and beneficial changes were observed in most of the biochemical indicators. The downhill run can be used for a partial regeneration of the body during exercise, because during this kind of effort an improvement of running economy was observed, and this type of effort did not impair the acid-base balance of body.

Advances in heuristically based generalized perturbation theory

International Nuclear Information System (INIS)

Gandini, A.

1994-01-01

A distinctive feature of heuristically based generalized perturbation theory methodology consists in the systematic use of importance conservation concepts. As well known, this use leads to fundamental reciprocity relationship. Instead, the alternative variational and differential one approaches make a consistent use of the properties and adjoint functions. The equivalence between the importance and the adjoint functions have been demonstrated in important cases. There are some instances, however, in which the commonly known operator governing the adjoint function are not adequate. In this paper ways proposed to generalize this rules, as adopted with the heuristic generalized perturbation theory methodology, are illustrated. When applied to the neutron/nuclide field characterizing the core evolution in a power reactor system, in which also an intensive control variable (ρ) is defined, these rules leas to an orthogonality relationship connected to this same control variable. A set of ρ-mode eigenfunctions may be correspondingly defined and an extended concept of reactivity (generalizing that commonly associated with the multiplication factor) proposed as more directly indicative of the controllability of a critical reactor system. (author). 25 refs

Physiology of bile secretion.

Science.gov (United States)

Esteller, Alejandro

2008-10-07

The formation of bile depends on the structural and functional integrity of the bile-secretory apparatus and its impairment, in different situations, results in the syndrome of cholestasis. The structural bases that permit bile secretion as well as various aspects related with its composition and flow rate in physiological conditions will first be reviewed. Canalicular bile is produced by polarized hepatocytes that hold transporters in their basolateral (sinusoidal) and apical (canalicular) plasma membrane. This review summarizes recent data on the molecular determinants of this primary bile formation. The major function of the biliary tree is modification of canalicular bile by secretory and reabsorptive processes in bile-duct epithelial cells (cholangiocytes) as bile passes through bile ducts. The mechanisms of fluid and solute transport in cholangiocytes will also be discussed. In contrast to hepatocytes where secretion is constant and poorly controlled, cholangiocyte secretion is regulated by hormones and nerves. A short section dedicated to these regulatory mechanisms of bile secretion has been included. The aim of this revision was to set the bases for other reviews in this series that will be devoted to specific issues related with biliary physiology and pathology.

Elderly fall risk prediction based on a physiological profile approach using artificial neural networks.

Science.gov (United States)

Razmara, Jafar; Zaboli, Mohammad Hassan; Hassankhani, Hadi

2016-11-01

Falls play a critical role in older people's life as it is an important source of morbidity and mortality in elders. In this article, elders fall risk is predicted based on a physiological profile approach using a multilayer neural network with back-propagation learning algorithm. The personal physiological profile of 200 elders was collected through a questionnaire and used as the experimental data for learning and testing the neural network. The profile contains a series of simple factors putting elders at risk for falls such as vision abilities, muscle forces, and some other daily activities and grouped into two sets: psychological factors and public factors. The experimental data were investigated to select factors with high impact using principal component analysis. The experimental results show an accuracy of ≈90 percent and ≈87.5 percent for fall prediction among the psychological and public factors, respectively. Furthermore, combining these two datasets yield an accuracy of ≈91 percent that is better than the accuracy of single datasets. The proposed method suggests a set of valid and reliable measurements that can be employed in a range of health care systems and physical therapy to distinguish people who are at risk for falls.

Electronic Textbook in Human Physiology.

Science.gov (United States)

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…

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

Science.gov (United States)

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

2012-01-01

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

Using a Molecular-Genetic Approach to Investigate Bacterial Physiology in a Continuous, Research-Based, Semester-Long Laboratory for Undergraduates

Directory of Open Access Journals (Sweden)

Jeremiah Foster Ault

2011-09-01

Full Text Available Designing investigative laboratory exercises that encourage critical thinking, problem solving, and independent thought for upper-division biology courses is a difficult but worthwhile task. In an effort to do so, we developed a semester-long, continuous, research-based investigative laboratory that integrates numerous genetic and molecular biology methods into the investigation of a bacterial physiological process. In this lab, students use random Tn5 transposon mutagenesis to create prodigiosin pigment mutants in the bacterium, Serratia marcescens. This is followed by phenotypic characterization, cloning, and sequencing the Tn insertion site to identify genes involved in pigment biosynthesis. During this lab, students gain ample experience performing basic lab techniques while learning about — and applying — methods for elucidating gene function. The approach to the laboratory and the outcomes are intimately integrated into the teaching of many fundamental physiological processes underlying prodigiosin production in bacteria. The result is a cohesive course that integrates the theory and application of molecular genetic techniques with the study of bacterial physiology. Assessments of student learning objectives demonstrated that students greatly improved their understanding of both physiological processes and the genetic techniques used to investigate them. In addition, students felt that this semester-long exercise provided the necessary laboratory experience they needed and desired in preparation for careers in molecular biology, microbiology, and biochemistry.

Toxicokinetics and biotransformation of 3-(4-methylbenzylidene)camphor in rats after oral administration

International Nuclear Information System (INIS)

Voelkel, Wolfgang; Colnot, Thomas; Schauer, Ute M.D.; Broschard, Thomas H.; Dekant, Wolfgang

2006-01-01

3-(4-Methylbenzylidene)camphor (4-MBC) is an UV-filter frequently used in sunscreens and cosmetics. Equivocal findings in some screening tests for hormonal activity initiated a discussion on a possible weak estrogenicity of 4-MBC. In this study, the toxicokinetics and biotransformation of 4-MBC were characterized in rats after oral administration. Male and female Sprague-Dawley rats (n = 3 per group) were administered single oral doses of 25 or 250 mg/kg bw of 4-MBC in corn oil. Metabolites formed were characterized and the kinetics of elimination for 4-MBC and its metabolites from blood and with urine were determined. Metabolites of 4-MBC were characterized by 1 H NMR and LC-MS/MS as 3-(4-carboxybenzylidene)camphor and as four isomers of 3-(4-carboxybenzylidene)hydroxycamphor containing the hydroxyl group located in the camphor ring system with 3-(4-carboxybenzylidene)-6-hydroxycamphor as the major metabolite. After oral administration of 4-MBC, only very low concentrations of 4-MBC were present in blood and the peak concentrations of 3-(4-carboxybenzylidene)camphor were approximately 500-fold above those of 4-MBC; blood concentrations of 3-(4-carboxybenzylidene)-6-hydroxycamphor were below the limit of detection. Blood concentration of 4-MBC and 3-(4-carboxybenzylidene)camphor peaked within 10 h after 4-MBC administration and then decreased with half-lives of approximately 15 h. No major differences in peak blood levels between male and female rats were seen. In urine, one isomer of 3-(4-carboxybenzylidene)hydroxycamphor was the predominant metabolite [3-(4-carboxybenzylidene)-6-hydroxycamphor], the other isomers and 3-(4-carboxybenzylidene)camphor were only minor metabolites excreted with urine. However, urinary excretion of 4-MBC-metabolites represents only a minor pathway of elimination for 4-MBC, since most of the applied dose was recovered in feces as 3-(4-carboxybenzylidene)camphor and, to a smaller extent, as 3-(4-carboxybenzylidene)-6-hydroxycamphor

Use of the physiologically-based extraction test to assess the oral bioaccessibility of metals in vegetable plants grown in contaminated soil

Energy Technology Data Exchange (ETDEWEB)

Intawongse, Marisa [Biomolecular and Biomedical Research Centre, School of Applied Sciences, University of Northumbria at Newcastle, Ellison Building, Newcastle upon Tyne NE1 8ST (United Kingdom); Dean, John R. [Biomolecular and Biomedical Research Centre, School of Applied Sciences, University of Northumbria at Newcastle, Ellison Building, Newcastle upon Tyne NE1 8ST (United Kingdom)], E-mail: john.dean@unn.ac.uk

2008-03-15

The oral bioaccessibility of metals in vegetable plants grown on contaminated soil was assessed. This was done using the physiologically-based extraction test (PBET) to simulate the human digestion of plant material. A range of vegetable plants, i.e. carrot, lettuce, radish and spinach, were grown on metal contaminated soil. After reaching maturity the plants were harvested and analysed for their total metal content (i.e. Cr, Cd, Cu, Fe, Mn, Mo, Ni, Pb and Zn) by inductively coupled plasma-mass spectrometry (ICP-MS). The plant samples were then subsequently extracted using an in vitro gastrointestinal approach or PBET to assess the likelihood of oral bioaccessibility if the material was consumed by humans. - Evaluation of a physiologically-based extraction test to assess the risk to humans of consuming contaminated vegetables.

Use of the physiologically-based extraction test to assess the oral bioaccessibility of metals in vegetable plants grown in contaminated soil

International Nuclear Information System (INIS)

Intawongse, Marisa; Dean, John R.

2008-01-01

The oral bioaccessibility of metals in vegetable plants grown on contaminated soil was assessed. This was done using the physiologically-based extraction test (PBET) to simulate the human digestion of plant material. A range of vegetable plants, i.e. carrot, lettuce, radish and spinach, were grown on metal contaminated soil. After reaching maturity the plants were harvested and analysed for their total metal content (i.e. Cr, Cd, Cu, Fe, Mn, Mo, Ni, Pb and Zn) by inductively coupled plasma-mass spectrometry (ICP-MS). The plant samples were then subsequently extracted using an in vitro gastrointestinal approach or PBET to assess the likelihood of oral bioaccessibility if the material was consumed by humans. - Evaluation of a physiologically-based extraction test to assess the risk to humans of consuming contaminated vegetables

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

Science.gov (United States)

Kesner, Michael H.; Linzey, Alicia V.

2005-01-01

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

Active Learning Improves Student Performance in a Respiratory Physiology Lab

Science.gov (United States)

Wolf, Alex M.; Liachovitzky, Carlos; Abdullahi, Abass S.

2015-01-01

This study assessed the effectiveness of the introduction of active learning exercises into the anatomy and physiology curriculum in a community college setting. Specifically, the incorporation of a spirometry-based respiratory physiology lab resulted in improved student performance in two concepts (respiratory volumes and the hallmarks of…

The coherence of life: A new physiology challenging (neo)Darwinism

International Nuclear Information System (INIS)

Jaeken, Laurent

2009-01-01

Schroedinger argued that coherent behaviour is one of the most remarkable properties of life. Despite this, it is one of the most neglected properties, studied only by a few groups of rather independent scientists in the domains of physiology but also of fundamental physics. In contrast, classical cell physiology, built on membrane theory, does not take coherent behaviour into account. Recently several independent approaches to the problem of coherence have been unified yielding a new paradigm for cell physiology, which can be derived from a non-linear Schroedinger equation. The new paradigm replaces outdated membrane theory. Similarly (neo)Darwinism is not firmly grounded on fundamental physics. However, during the eighties (neo)Darwinism was taken up in a broader theory of evolution, based on the non-linear equations of fundamental physics. It is argued here that life's coherent behaviour and the new physiology built on these coherent properties is directly compatible with the modern view on evolution, since both are based on the same principles of non-linearity.

USE OF SENSITIVITY ANALYSIS ON A PHYSIOLOGICALLY-BASED PHARMACOKINETIC (PBPK) MODEL FOR CHLOROFORM IN RATS TO DETERMINE AGE-RELATED TOXICITY

Science.gov (United States)

USE OF SENSITIVITY ANALYSIS ON A PHYSIOLOGICALLY BASED PHARMACOKINETIC (PBPK) MODEL FOR CHLOROFORM IN RATS TO DETERMINE AGE-RELATED TOXICITY.CR Eklund, MV Evans, and JE Simmons. US EPA, ORD, NHEERL, ETD,PKB, Research Triangle Park, NC. Chloroform (CHCl3) is a disinfec...

Physiology of Sedentary Behavior and Its Relationship to Health Outcomes

Science.gov (United States)

Thyfault, John P; Du, Mengmeng; Kraus, William E; Levine, James A; Booth, Frank W

2014-01-01

Purpose This paper reports on the findings and recommendations of the “Physiology of Sedentary Behavior and its Relationship to Health Outcomes” group, a part of a larger workshop entitled Sedentary Behavior: Identifying Research Priorities sponsored by the National Heart, and Lung and Blood Institute and the National Institute on Aging, which aimed to establish sedentary behavior research priorities. Methods The discussion within our workshop lead to the formation of critical physiological research objectives related to sedentary behaviors, that if appropriately researched would greatly impact our overall understanding of human health and longevity. Results and Conclusions Primary questions are related to physiological “health outcomes” including the influence of physical activity vs. sedentary behavior on function of a number of critical physiological systems (aerobic capacity, skeletal muscle metabolism and function, telomeres/genetic stability, and cognitive function). The group also derived important recommendations related to the “central and peripheral mechanisms” that govern sedentary behavior and how energy balance has a role in mediating these processes. General recommendations for future sedentary physiology research efforts include that studies of sedentary behavior, including that of sitting time only, should focus on the physiological impact of a “lack of human movement” in contradistinction to the effects of physical movement and that new models or strategies for studying sedentary behavior induced adaptations and links to disease development are needed to elucidate underlying mechanism(s). PMID:25222820

A New Model of Master of Philosophy in Physiological Sciences.

Science.gov (United States)

Ahmad, H R; Arain, F M; Khan, N A

2016-01-01

The objectives of Master of Philosophy (MPhil) in Physiological Sciences are: 1) to describe the new ways in which anatomy, biochemistry and physiology on one hand, and microbiology, pathology and pharmacology on other hand meet their functional requirements through multidisciplinary integrated concepts; 2) to elucidate relationships between cell biology, molecular biology and molecular genetics by connecting dots of how cell functions are driven by molecules and being controlled by genes. This forms the basis of cell, molecular and genetics [CMG] module upon which 7 multidisciplinary modules of Physiological Sciences follow; 3) these 24 credit hours provide the physiological basis for PhD studies as well as faculty development to enhance learning abilities of medical student; 4) the modules constitute Cardio- Respiratory Physiological Sciences, GI and Renal Physiological Sciences, Neurosciences, Endo-Reproductive Physiological Sciences.; 5) it has integrated microbiology, pathology and pharmacology in a unique way through CMG of microbes leading to associated pathology and mechanisms of prescribed drugs; 6) it has additional synopsis and thesis friendly course work leading to comprehensive examinations; 7) the year two deals with research work of 6 credit hours leading to defense of thesis; 8) The MPhil in Physiological Sciences is fundamentally different from what is being offered elsewhere. It prepares and offers a good spring board to dovetail PhD studies as well as faculty and institutional development. This is the first study that deals with innovative programmes in research, learning and education in the field of physiological sciences. This broad-based MPhil would make its recipients competent, critical, confident and productive learner. This is a completely unique design of a curriculum that has no comparable examples elsewhere. Our mission is to educate graduate students in the field of Physiological Sciences such that they have a complete grasp over the

Physiological scoring: an aid to emergency medical services transport decisions?

Science.gov (United States)

Challen, Kirsty; Walter, Darren

2010-01-01

Attendance at UK emergency departments is rising steadily despite the proliferation of alternative unscheduled care providers. Evidence is mixed on the willingness of emergency medical services (EMS) providers to decline to transport patients and the safety of incorporating such an option into EMS provision. Physiologically based Early Warning Scores are in use in many hospitals and emergency departments, but not yet have been proven to be of benefit in the prehospital arena. The use of a physiological-social scoring system could safely identify patients calling EMS who might be diverted from the emergency department to an alternative, unscheduled, care provider. This was a retrospective, cohort study of patients with a presenting complaint of "shortness of breath" or "difficulty breathing" transported to the emergency department by EMS. Retrospective calculation of a physiological social score (PMEWS) based on first recorded data from EMS records was performed. Outcome measures of hospital admission and need for physiologically stabilizing treatment in the emergency department also were performed. A total of 215 records were analyzed. One hundred thirty-nine (65%) patients were admitted from the emergency department or received physiologically stabilizing treatment in the emergency department. Area Under the Receiver Operating Characteristic Curve (AUROC) for hospital admission was 0.697 and for admission or physiologically stabilizing treatment was 0.710. No patient scoringemergency department to alternative, unscheduled, care providers.

Real-Time Physiological and Psycho-Physiological Status Monitoring (Suivi en Temps reel de l’Etat Physiologique et Psycho-Physiologique)

Science.gov (United States)

2010-07-01

Physiol, 98:591-597. [35] Maggiorini, M., Melot, C., Pierre, S., Pfeiffer, F., Greve, I., Sartori, C., Lepori, M., Hauser , M., Scherrer, U. and Naeije, R...A PHYSIOLOGICAL MONITORING SYSTEM (DESCRIPTION OF THE WORK IN THE CZECH REPUBLIC) Pavel Smrcka, Karel Hana, Jan Kaspar , Radek Fiala Clever...variability analysis in general medicine. Indian Pacing Electrophysiol. Journal, 2003; 3(1):34. [6] Hana, K., Fiala, R., Kaspar , J., Smrcka, P. and Brada

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

Science.gov (United States)

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. Copyright © 2011 Wiley Periodicals, Inc.

Impact of human emotions on physiological characteristics

Science.gov (United States)

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.

['Anatomia actuosa et apta'. The mechanist 'proto'-physiology of B.S. Albinus].

Science.gov (United States)

van der Korst, J K

1993-01-01

Already during his tenure as professor of anatomy and surgery (1721-1746) and before he became a professor of physiology and medicine at the University of Leiden, Bernard Siegfried Albinus held private lecture courses on physiology. In these lectures he pleaded for a separation of physiology from theoretical medicine, which was still its customary place in the medical curriculum of the first half of the eighteenth century. According to Albinus, physiology was a science in its own right and should be solely based on the careful observation of forms and structures of the human body. From the 'fabrica', the function ('aptitudo') could be derived by careful reasoning. As shown by a set of lecture notes, which recently came to light, Albinus adhered, initially, to a strictly mechanistic explanatory model, which was almost completely based on the physiological concepts of Herman Boerhaave. However, in contrast to the latter, he even rejected the involvement of chemical processes in digestion. Although his lectures were highly acclaimed as demonstrations of minute anatomy, Albinus met with little or no direct response in regard to his concept of physiology.

Anemia of chronic kidney disease: novel physiological approaches to therapy based on simulation of hypoxic response

Directory of Open Access Journals (Sweden)

K. A. Aitbaev

2017-01-01

Full Text Available Anemia is a modifiable risk factor for the progression of chronic kidney disease (CKD and is characterized by a  decrease in the hemoglobin level, the hematocrit, and the number of circulating red blood cells. In the pre-erythropoietin era blood transfusion was a  common practice for the adequate correction of anemia in patients with CKD. However, a  recombinant human erythropoietin, that was developed and implemented into a clinical practice three decades ago, made a revolution in the renal anemia treatment. Today the management of anemia is based on the use of exogenous erythropoiesis-stimulating agents, such as erythropoietin and its analogues, as well as an oral or parenteral administration of iron. Nevertheless, despite of the high efficacy in the majority of patients this approach has a  negative side. The hemoglobin excursions, increased risk of cardiovascular complications, as well as the development of iron deficiency and chronic inflammation become additional factors in the pathogenesis of anemia associated with the renal failure. In this regard, the development of effective and safe methods of anemia management in CKD is of immediate interest. New medications based mainly on physiological approach are developed. A pharmacological activation of hypoxia-inducible factor (HIF response is one of them. HIF is the main hormonal regulator of erythropoiesis that stimulates the production of endogenous erythropoietin. It is known that in patients with renal failure, the activation of this factor in response to hypoxia is compromised, resulting in a lack of erythropoietin production. This review covers the new mechanistic views on the hypoxic regulation of erythropoiesis and the production of erythropoietin by the kidneys, and presents the newly discovered interactions between the synthesis of erythropoietin, iron metabolism, and the chronic inflammation. Besides that, ongoing clinical trials of pharmacological HIF activators, such as

Physiological monitoring of team and task stressors

Science.gov (United States)

Orasanu, Judith; Tada, Yuri; Kraft, Norbert; Fischer, Ute

2005-05-01

Sending astronauts into space, especially on long-durations missions (e.g. three-year missions to Mars), entails enormous risk. Threats include both physical dangers of radiation, bone loss and other consequences of weightlessness, and also those arising from interpersonal problems associated with extended life in a high-risk isolated and confined environment. Before undertaking long-duration missions, NASA seeks to develop technologies to monitor indicators of potentially debilitating stress at both the individual and team level so that countermeasures can be introduced to prevent further deterioration. Doing so requires a better understanding of indicators of team health and performance. To that end, a study of team problem solving in a simulation environment was undertaken to explore effects of team and task stress. Groups of four males (25-45 yrs) engaged in six dynamic computer-based Antarctic search and rescue missions over four days. Both task and team stressors were manipulated. Physiological responses (ECG, respiration rate and amplitude, SCL, EMG, and PPG); communication (voice and email); individual personality and subjective team dynamics responses were collected and related to task performance. Initial analyses found that physiological measures can be used to identify transient stress, predict performance, and reflect subjective workload. Muscle tension and respiration were the most robust predictors. Not only the level of arousal but its variability during engagement in the task is important to consider. In general, less variability was found to be associated with higher levels of performance. Individuals scoring high on specific personality characteristics responded differently to task stress.

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

Science.gov (United States)

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. ©2016 Int. Union Physiol. Sci./Am. Physiol. Soc.

Pulpal status of human primary teeth with physiological root resorption.

Science.gov (United States)

Monteiro, Joana; Day, Peter; Duggal, Monty; Morgan, Claire; Rodd, Helen

2009-01-01

The overall aim of this study was to determine whether any changes occur in the pulpal structure of human primary teeth in association with physiological root resorption. The experimental material comprised 64 sound primary molars, obtained from children requiring routine dental extractions under general anaesthesia. Pulp sections were processed for indirect immunofluorescence using combinations of: (i) protein gene product 9.5 (a general neuronal marker); (ii) leucocyte common antigen CD45 (a general immune cell marker); and (iii) Ulex europaeus I lectin (a marker of vascular endothelium). Image analysis was then used to determine the percentage area of staining for each label within both the pulp horn and mid-coronal region. Following measurement of the greatest degree of root resorption in each sample, teeth were subdivided into three groups: those with physiological resorption involving less than one-third, one-third to two-thirds, and more than two-thirds of their root length. Wide variation was evident between different tooth samples with some resorbed teeth showing marked changes in pulpal histology. Decreased innervation density, increased immune cell accumulation, and increased vascularity were evident in some teeth with advanced root resorption. Analysis of pooled data, however, did not reveal any significant differences in mean percentage area of staining for any of these variables according to the three root resorption subgroups (P > 0.05, analysis of variance on transformed data). This investigation has revealed some changes in pulpal status of human primary teeth with physiological root resorption. These were not, however, as profound as one may have anticipated. It is therefore speculated that teeth could retain the potential for sensation, healing, and repair until advanced stages of root resorption.

Why did Kant reject physiological explanations in his anthropology?

Science.gov (United States)

Sturm, Thomas

2008-12-01

One of Kant's central tenets concerning the human sciences is the claim that one need not, and should not, use a physiological vocabulary if one studies human cognitions, feelings, desires, and actions from the point of view of his 'pragmatic' anthropology. The claim is well known, but the arguments Kant advances for it have not been closely discussed. I argue against misguided interpretations of the claim, and I present his actual reasons in favor of it. Contemporary critics of a 'physiological anthropology' reject physiological explanations of mental states as more or less epistemologically dubious. Kant does not favor such ignorance claims--and this is for the good, since none of these claims was sufficiently justified at that time. Instead, he develops an original irrelevance thesis concerning the empirical knowledge of the physiological basis of the mind. His arguments for this claim derive from his original and, up to now, little understood criticism of a certain conception of pragmatic history, related to his anthropological insights concerning our ability to create new rules of action, the social dynamics of human action, and the relative inconstancy of human nature. The irrelevance thesis also changes his views of the goal and methodology of anthropology. Kant thereby argues for a distinctive approach in quest for a general 'science of man'.

Microbial physiology-based model of ethanol metabolism in subsurface sediments

Science.gov (United States)

Jin, Qusheng; Roden, Eric E.

2011-07-01

A biogeochemical reaction model was developed based on microbial physiology to simulate ethanol metabolism and its influence on the chemistry of anoxic subsurface environments. The model accounts for potential microbial metabolisms that degrade ethanol, including those that oxidize ethanol directly or syntrophically by reducing different electron acceptors. Out of the potential metabolisms, those that are active in the environment can be inferred by fitting the model to experimental observations. This approach was applied to a batch sediment slurry experiment that examined ethanol metabolism in uranium-contaminated aquifer sediments from Area 2 at the U.S. Department of Energy Field Research Center in Oak Ridge, TN. According to the simulation results, complete ethanol oxidation by denitrification, incomplete ethanol oxidation by ferric iron reduction, ethanol fermentation to acetate and H 2, hydrogenotrophic sulfate reduction, and acetoclastic methanogenesis: all contributed significantly to the degradation of ethanol in the aquifer sediments. The assemblage of the active metabolisms provides a frame work to explore how ethanol amendment impacts the chemistry of the environment, including the occurrence and levels of uranium. The results can also be applied to explore how diverse microbial metabolisms impact the progress and efficacy of bioremediation strategies.

Prediction of interindividual variation in drug plasma levels in vivo from individual enzyme kinetic data and physiologically based pharmacokinetic modeling

NARCIS (Netherlands)

Bogaards, J.J.P.; Hissink, E.M.; Briggs, M.; Weaver, R.; Jochemsen, R.; Jackson, P.; Bertrand, M.; Bladeren, P. van

2000-01-01

A strategy is presented to predict interindividual variation in drug plasma levels in vivo by the use of physiologically based pharmacokinetic modeling and human in vitro metabolic parameters, obtained through the combined use of microsomes containing single cytochrome P450 enzymes and a human liver

What about getting physiological information into dynamic gamma camera studies

International Nuclear Information System (INIS)

Kiuru, A.; Nickles, R. J.; Holden, J. E.; Polcyn, R. E.

1976-01-01

A general technique has been developed for the multiplexing of time dependent analog signals into the individual frames of a gamma camera dynamic function study. A pulse train, frequency-modulated by the physiological signal, is capacitively coupled to the preamplifier servicing anyone of the outer phototubes of the camera head. These negative tail pulses imitate photoevents occuring at a point outside of the camera field of view, chosen to occupy a data cell in an unused corner of the computer-stored square image. By defining a region of interest around this cell, the resulting time-activity curve displays the physiological variable in temporal synchrony with the radiotracer distribution. (author)

Does improved decision-making ability reduce the physiological demands of game-based activities in field sport athletes?

Science.gov (United States)

Gabbett, Tim J; Carius, Josh; Mulvey, Mike

2008-11-01

This study investigated the effects of video-based perceptual training on pattern recognition and pattern prediction ability in elite field sport athletes and determined whether enhanced perceptual skills influenced the physiological demands of game-based activities. Sixteen elite women soccer players (mean +/- SD age, 18.3 +/- 2.8 years) were allocated to either a video-based perceptual training group (N = 8) or a control group (N = 8). The video-based perceptual training group watched video footage of international women's soccer matches. Twelve training sessions, each 15 minutes in duration, were conducted during a 4-week period. Players performed assessments of speed (5-, 10-, and 20-m sprint), repeated-sprint ability (6 x 20-m sprints, with active recovery on a 15-second cycle), estimated maximal aerobic power (V O2 max, multistage fitness test), and a game-specific video-based perceptual test of pattern recognition and pattern prediction before and after the 4 weeks of video-based perceptual training. The on-field assessments included time-motion analysis completed on all players during a standardized 45-minute small-sided training game, and assessments of passing, shooting, and dribbling decision-making ability. No significant changes were detected in speed, repeated-sprint ability, or estimated V O2 max during the training period. However, video-based perceptual training improved decision accuracy and reduced the number of recall errors, indicating improved game awareness and decision-making ability. Importantly, the improvements in pattern recognition and prediction ability transferred to on-field improvements in passing, shooting, and dribbling decision-making skills. No differences were detected between groups for the time spent standing, walking, jogging, striding, and sprinting during the small-sided training game. These findings demonstrate that video-based perceptual training can be used effectively to enhance the decision-making ability of field

Neuroticism and extraversion in relation to physiological stress reactivity during adolescence

NARCIS (Netherlands)

Evans, Brittany E.; Stam, Jacqueline; Huizink, Anja C.; Willemen, Agnes M.; Westenberg, P. Michiel; Branje, Susan; Meeus, W.H.J.; Koot, Hans M.; van Lier, Pol A. C.

2016-01-01

The current study examined mean level and change in extraversion and neuroticism across adolescence in relation to physiological stress reactivity to social evaluation. Adolescents (n=327) from the Dutch general population reported on personality measures at five annual assessments. At age 17 years,

A General Attribute and Rule Based Role-Based Access Control Model

Institute of Scientific and Technical Information of China (English)

无

2007-01-01

Growing numbers of users and many access control policies which involve many different resource attributes in service-oriented environments bring various problems in protecting resource. This paper analyzes the relationships of resource attributes to user attributes in all policies, and propose a general attribute and rule based role-based access control(GAR-RBAC) model to meet the security needs. The model can dynamically assign users to roles via rules to meet the need of growing numbers of users. These rules use different attribute expression and permission as a part of authorization constraints, and are defined by analyzing relations of resource attributes to user attributes in many access policies that are defined by the enterprise. The model is a general access control model, and can support many access control policies, and also can be used to wider application for service. The paper also describes how to use the GAR-RBAC model in Web service environments.

Coupled in silico platform: Computational fluid dynamics (CFD) and physiologically-based pharmacokinetic (PBPK) modelling.

Science.gov (United States)

Vulović, Aleksandra; Šušteršič, Tijana; Cvijić, Sandra; Ibrić, Svetlana; Filipović, Nenad

2018-02-15

One of the critical components of the respiratory drug delivery is the manner in which the inhaled aerosol is deposited in respiratory tract compartments. Depending on formulation properties, device characteristics and breathing pattern, only a certain fraction of the dose will reach the target site in the lungs, while the rest of the drug will deposit in the inhalation device or in the mouth-throat region. The aim of this study was to link the Computational fluid dynamics (CFD) with physiologically-based pharmacokinetic (PBPK) modelling in order to predict aerolisolization of different dry powder formulations, and estimate concomitant in vivo deposition and absorption of amiloride hydrochloride. Drug physicochemical properties were experimentally determined and used as inputs for the CFD simulations of particle flow in the generated 3D geometric model of Aerolizer® dry powder inhaler (DPI). CFD simulations were used to simulate air flow through Aerolizer® inhaler and Discrete Phase Method (DPM) was used to simulate aerosol particles deposition within the fluid domain. The simulated values for the percent emitted dose were comparable to the values obtained using Andersen cascade impactor (ACI). However, CFD predictions indicated that aerosolized DPI have smaller particle size and narrower size distribution than assumed based on ACI measurements. Comparison with the literature in vivo data revealed that the constructed drug-specific PBPK model was able to capture amiloride absorption pattern following oral and inhalation administration. The PBPK simulation results, based on the CFD generated particle distribution data as input, illustrated the influence of formulation properties on the expected drug plasma concentration profiles. The model also predicted the influence of potential changes in physiological parameters on the extent of inhaled amiloride absorption. Overall, this study demonstrated the potential of the combined CFD-PBPK approach to model inhaled drug

An alternate metabolic hypothesis for a binary mixture of trichloroethylene and carbon tetrachloride: application of physiologically based pharmacokinetic (PBPK) modeling in rats.

Science.gov (United States)

Carbon tetrachloride (CC4) and trichloroethylene (TCE) are hepatotoxic volatile organic compounds (VOCs) and environmental contaminants. Previous physiologically based pharmacokinetic (PBPK) models describe the kinetics ofindividual chemical disposition and metabolic clearance fo...

Personalized physiological medicine.

Science.gov (United States)

Ince, Can

2017-12-28

This paper introduces the concept of personalized physiological medicine that is specifically directed at the needs of the critically ill patient. This differs from the conventional view of personalized medicine, characterized by biomarkers and gene profiling, instead focusing on time-variant changes in the pathophysiology and regulation of various organ systems and their cellular and subcellular constituents. I propose that personalized physiological medicine is composed of four pillars relevant to the critically ill patient. Pillar 1 is defined by the frailty and fitness of the patient and their physiological reserve to cope with the stress of critical illness and therapy. Pillar 2 involves monitoring of the key physiological variables of the different organ systems and their response to disease and therapy. Pillar 3 concerns the evaluation of the success of resuscitation by assessment of the hemodynamic coherence between the systemic and microcirculation and parenchyma of the organ systems. Finally, pillar 4 is defined by the integration of the physiological and clinical data into a time-learning adaptive model of the patient to provide feedback about the function of organ systems and to guide and assess the response to disease and therapy. I discuss each pillar and describe the challenges to research and development that will allow the realization of personalized physiological medicine to be practiced at the bedside for critically ill patients.

Plant Physiology in Greenhouses

NARCIS (Netherlands)

Heuvelink, E.; Kierkels, T.

2015-01-01

Since 2004 Ep Heuvelink and Tijs Kierkels have been writing a continuing series of plant physiology articles for the Dutch horticultural journal Onder Glas and the international edition In Greenhouses. The book Plant Physiology in Greenhouses consists of 50 of their plant physiology articles. The

Renal response to acute acid loading--an organ physiological approach

DEFF Research Database (Denmark)

Osther, P J; Engel, K; Kildeberg, P

2004-01-01

, as the extracellular acid-base status would be expected to be the key physiological trigger for renal NAE. The object of this study was to investigate the renal response to acute non-carbonic acid loading using a quantitative organ physiological approach. MATERIAL AND METHODS: Five-h NH4Cl loading studies were...

Application of Physiologically Based Absorption Modeling to Characterize the Pharmacokinetic Profiles of Oral Extended Release Methylphenidate Products in Adults.

Directory of Open Access Journals (Sweden)

Xiaoxia Yang

Full Text Available A previously presented physiologically-based pharmacokinetic model for immediate release (IR methylphenidate (MPH was extended to characterize the pharmacokinetic behaviors of oral extended release (ER MPH formulations in adults for the first time. Information on the anatomy and physiology of the gastrointestinal (GI tract, together with the biopharmaceutical properties of MPH, was integrated into the original model, with model parameters representing hepatic metabolism and intestinal non-specific loss recalibrated against in vitro and in vivo kinetic data sets with IR MPH. A Weibull function was implemented to describe the dissolution of different ER formulations. A variety of mathematical functions can be utilized to account for the engineered release/dissolution technologies to achieve better model performance. The physiological absorption model tracked well the plasma concentration profiles in adults receiving a multilayer-release MPH formulation or Metadate CD, while some degree of discrepancy was observed between predicted and observed plasma concentration profiles for Ritalin LA and Medikinet Retard. A local sensitivity analysis demonstrated that model parameters associated with the GI tract significantly influenced model predicted plasma MPH concentrations, albeit to varying degrees, suggesting the importance of better understanding the GI tract physiology, along with the intestinal non-specific loss of MPH. The model provides a quantitative tool to predict the biphasic plasma time course data for ER MPH, helping elucidate factors responsible for the diverse plasma MPH concentration profiles following oral dosing of different ER formulations.

Physiology Of Prolonged Bed Rest

Science.gov (United States)

Greenleaf, John E.

1991-01-01

Report describes physiological effects of prolonged bed rest. Rest for periods of 24 hours or longer deconditions body to some extent; healing proceeds simultaneously with deconditioning. Report provides details on shifts in fluid electrolytes and loss of lean body mass, which comprises everything in body besides fat - that is, water, muscle, and bone. Based on published research.

The 2015 Nobel Prize in Physiology or Medicine: A Soil Bacterium ...

Indian Academy of Sciences (India)

Home; Journals; Resonance – Journal of Science Education; Volume 21; Issue 4. The 2015 Nobel Prize in Physiology or Medicine: A Soil Bacterium and a Chinese Herb Steal the Show. Pundi N Rangarajan. General Article Volume 21 Issue 4 April 2016 pp 315-326 ...

Taxonomy, physiology and growth of Lactococcus lactis: a review

Directory of Open Access Journals (Sweden)

Dubravka Samaržija

2001-01-01

Full Text Available Lactococcus lactis species is one of the most important groups of lactic acid bacteria that are used in the dairy industry. The major functions of this species in dairy fermentation are the production of lactic acid from lactose, hydrolysis of casein and citric acid fermentation. Thus their metabolic end products and enzymes directly or indirectly have significant influence in determining the texture and flavour of the final products. In recent years, genetics and physiological properties of lactococci have considerable changed. Therefore, both for basic research and for application purposes in this paper the general view of the new taxonomic classification of Lactococcus lactis, the role of their plasmids and the physiology and nutritional requirements during growth are discussed.

Analysis of artifact and infrequent physiological uptake in 18F-FDG PET/CT

International Nuclear Information System (INIS)

Li Tianran; Zhao Chunlei; Qian Gennian; Chen Ziqian; Wang Kaitang; You Xueyu; Zheng Chunyu

2006-01-01

Objective: To explore the artifact and infrequent physiological uptake in PET/CT with its imaging and formation features. Methods: The data of PET/CT imaging were retrospectively analyzed and classified based on their cause. Besides, the infrequent physiological uptakes were also analyzed. Results: Artifacts could be classified into natural and technological causes. In natural causes, respiratory movement and high-density matters artifacts were frequently found, whereas in technological cause, the truncation, radioactive leakage and pollution commonly appeared. Infrequent physiological uptakes included uterine endometrium, breast and fat uptakes. Conclusions: The imaging features of artifact in PET can be divided into 'hot' or 'cold' area while infrequent physiological uptakes mainly are 'hot' area. Among the cause of artifact formation, CT-based attenuation corrected physical factor is the commonest. The infrequent physiological uptake somewhat relates to technological error. (authors)

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

Science.gov (United States)

Tresguerres, Martin; Hamilton, Trevor J

2017-06-15

Experimental exposure to ocean and freshwater acidification affects the behaviour of multiple aquatic organisms in laboratory tests. One proposed cause involves an imbalance in plasma chloride and bicarbonate ion concentrations as a result of acid-base regulation, causing the reversal of ionic fluxes through GABA A receptors, which leads to altered neuronal function. This model is exclusively based on differential effects of the GABA A receptor antagonist gabazine on control animals and those exposed to elevated CO 2 However, direct measurements of actual chloride and bicarbonate concentrations in neurons and their extracellular fluids and of GABA A receptor properties in aquatic organisms are largely lacking. Similarly, very little is known about potential compensatory mechanisms, and about alternative mechanisms that might lead to ocean acidification-induced behavioural changes. This article reviews the current knowledge on acid-base physiology, neurobiology, pharmacology and behaviour in relation to marine CO 2 -induced acidification, and identifies important topics for future research that will help us to understand the potential effects of predicted levels of aquatic acidification on organisms. © 2017. Published by The Company of Biologists Ltd.

Mechanistic Physiologically Based Pharmacokinetic (PBPK) Model of the Heart Accounting for Inter-Individual Variability: Development and Performance Verification.

Science.gov (United States)

Tylutki, Zofia; Mendyk, Aleksander; Polak, Sebastian

2018-04-01

Modern model-based approaches to cardiac safety and efficacy assessment require accurate drug concentration-effect relationship establishment. Thus, knowledge of the active concentration of drugs in heart tissue is desirable along with inter-subject variability influence estimation. To that end, we developed a mechanistic physiologically based pharmacokinetic model of the heart. The models were described with literature-derived parameters and written in R, v.3.4.0. Five parameters were estimated. The model was fitted to amitriptyline and nortriptyline concentrations after an intravenous infusion of amitriptyline. The cardiac model consisted of 5 compartments representing the pericardial fluid, heart extracellular water, and epicardial intracellular, midmyocardial intracellular, and endocardial intracellular fluids. Drug cardiac metabolism, passive diffusion, active efflux, and uptake were included in the model as mechanisms involved in the drug disposition within the heart. The model accounted for inter-individual variability. The estimates of optimized parameters were within physiological ranges. The model performance was verified by simulating 5 clinical studies of amitriptyline intravenous infusion, and the simulated pharmacokinetic profiles agreed with clinical data. The results support the model feasibility. The proposed structure can be tested with the goal of improving the patient-specific model-based cardiac safety assessment and offers a framework for predicting cardiac concentrations of various xenobiotics. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Complexity analysis based on generalized deviation for financial markets

Science.gov (United States)

Li, Chao; Shang, Pengjian

2018-03-01

In this paper, a new modified method is proposed as a measure to investigate the correlation between past price and future volatility for financial time series, known as the complexity analysis based on generalized deviation. In comparison with the former retarded volatility model, the new approach is both simple and computationally efficient. The method based on the generalized deviation function presents us an exhaustive way showing the quantization of the financial market rules. Robustness of this method is verified by numerical experiments with both artificial and financial time series. Results show that the generalized deviation complexity analysis method not only identifies the volatility of financial time series, but provides a comprehensive way distinguishing the different characteristics between stock indices and individual stocks. Exponential functions can be used to successfully fit the volatility curves and quantify the changes of complexity for stock market data. Then we study the influence for negative domain of deviation coefficient and differences during the volatile periods and calm periods. after the data analysis of the experimental model, we found that the generalized deviation model has definite advantages in exploring the relationship between the historical returns and future volatility.

Physiological Assessment of Water Stress in Potato Using Spectral Information.

Science.gov (United States)

Romero, Angela P; Alarcón, Andrés; Valbuena, Raúl I; Galeano, Carlos H

2017-01-01

Water stress in potato ( Solanum tuberosum L.) causes considerable losses in yield, and therefore, potato is often considered to be a drought sensitive crop. Identification of water deficit tolerant potato genotypes is an adaptation strategy to mitigate the climatic changes that are occurring in the Cundiboyacense region in Colombia. Previous studies have evaluated potato plants under water stress conditions using physiological analyses. However, these methodologies require considerable amounts of time and plant material to perform these measurements. This study evaluated and compared the physiological and spectral traits between two genotypes, Diacol Capiro and Perla Negra under two drought levels (10 and 15 days without irrigation from flowering). Reflectance information was used to calculate indexes which were associated with the physiological behavior in plants. The results showed that spectral information was correlated (ρ < 0.0001) with physiological variables such as foliar area (FA), total water content (H 2 Ot), relative growth rate of potato tubers (RGTtub), leaf area ratio (LAR), and foliar area index (AFI). In general, there was a higher concentration of chlorophyll under drought treatments. In addition, Perla Negra under water deficit treatments did not show significant differences in its physiological variables. Therefore, it could be considered a drought tolerant genotype because its physiological performance was not affected under water stress conditions. However, yield was affected in both genotypes after being subject to 15 days of drought. The results suggested that reflectance indexes are a useful and affordable approach for potato phenotyping to select parent and segregant populations in breeding programs.

Application of Physiologically-Based Pharmacokinetic Modeling for the Prediction of Tofacitinib Exposure in Japanese.

Science.gov (United States)

Suzuki, Misaki; Tse, Susanna; Hirai, Midori; Kurebayashi, Yoichi

2017-05-09

Tofacitinib (3-[(3R,4R)-4-methyl-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidin-1-yl]-3 -oxopropanenitrile) is an oral Janus kinase inhibitor that is approved in countries including Japan and the United States for the treatment of rheumatoid arthritis, and is being developed across the globe for the treatment of inflammatory diseases. In the present study, a physiologically-based pharmacokinetic model was applied to compare the pharmacokinetics of tofacitinib in Japanese and Caucasians to assess the potential impact of ethnicity on the dosing regimen in the two populations. Simulated plasma concentration profiles and pharmacokinetic parameters, i.e. maximum concentration and area under plasma concentration-time curve, in Japanese and Caucasian populations after single or multiple doses of 1 to 30 mg tofacitinib were in agreement with clinically observed data. The similarity in simulated exposure between Japanese and Caucasian populations supports the currently approved dosing regimen in Japan and the United States, where there is no recommendation for dose adjustment according to race. Simulated results for single (1 to 100 mg) or multiple doses (5 mg twice daily) of tofacitinib in extensive and poor metabolizers of CYP2C19, an enzyme which has been shown to contribute in part to tofacitinib elimination and is known to exhibit higher frequency in Japanese compared to Caucasians, were also in support of no recommendation for dose adjustment in CYP2C19 poor metabolizers. This study demonstrated a successful application of physiologically-based pharmacokinetic modeling in evaluating ethnic sensitivity in pharmacokinetics at early stages of development, presenting its potential value as an efficient and scientific method for optimal dose setting in the Japanese population.

Metabolism and physiologically based pharmacokinetic modeling of flumioxazin in pregnant animals

Energy Technology Data Exchange (ETDEWEB)

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

2014-06-15

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

Metabolism and physiologically based pharmacokinetic modeling of flumioxazin in pregnant animals

International Nuclear Information System (INIS)

Takaku, Tomoyuki; Nagahori, Hirohisa; Sogame, Yoshihisa

2014-01-01

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- 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 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 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

Conceptual analysis of Physiology of vision in Ayurveda

Directory of Open Access Journals (Sweden)

Praveen Balakrishnan

2014-01-01

Full Text Available The process by which the world outside is seen is termed as visual process or physiology of vision. There are three phases in this visual process: phase of refraction of light, phase of conversion of light energy into electrical impulse and finally peripheral and central neurophysiology. With the advent of modern instruments step by step biochemical changes occurring at each level of the visual process has been deciphered. Many investigations have emerged to track these changes and helping to diagnose the exact nature of the disease. Ayurveda has described this physiology of vision based on the functions of vata and pitta. Philosophical textbook of ayurveda, Tarka Sangraha, gives certain basics facts of visual process. This article discusses the second and third phase of visual process. Step by step analysis of the visual process through the spectacles of ayurveda amalgamated with the basics of philosophy from Tarka Sangraha has been analyzed critically to generate a concrete idea regarding the physiology and hence thereby interpret the pathology on the grounds of ayurveda based on the investigative reports.

DigitalHuman (DH): An Integrative Mathematical Model ofHuman Physiology

Science.gov (United States)

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

Invasive physiological indices to determine the functional significance of coronary stenosis

Directory of Open Access Journals (Sweden)

Firas R. AL-Obaidi

2018-03-01

Full Text Available Physiological measurements are now commonly used to assess coronary lesions in the cardiac catheterisation laboratory, and this practice is evidence-based and supported by clinical guidelines. Fractional flow reserve is currently the gold standard method to determine whether coronary lesions are functionally significant, and is used to guide revascularization. There are however several other physiological measurements that have been proposed as alternatives to the fractional flow reserve. This review aims to comprehensively discuss physiological indices that can be used in the cardiac catheterisation laboratory to determine the functional significance of coronary lesions. We will focus on their advantages and disadvantages, and the current evidence supporting their use. Keywords: Coronary physiology, Fractional flow reserve, Resting physiological indices, Coronary flow reserve

The coherence of life: A new physiology challenging (neo)Darwinism

Energy Technology Data Exchange (ETDEWEB)

Jaeken, Laurent [Laboratory of Biochemistry, Department of Industrial Sciences and Technology, Karel de Grote-Hogeschool University College, Salesianenlaan 30, B-2660 Hoboken (Belgium)], E-mail: laurent.jaeken@Kdg.be

2009-10-15

Schroedinger argued that coherent behaviour is one of the most remarkable properties of life. Despite this, it is one of the most neglected properties, studied only by a few groups of rather independent scientists in the domains of physiology but also of fundamental physics. In contrast, classical cell physiology, built on membrane theory, does not take coherent behaviour into account. Recently several independent approaches to the problem of coherence have been unified yielding a new paradigm for cell physiology, which can be derived from a non-linear Schroedinger equation. The new paradigm replaces outdated membrane theory. Similarly (neo)Darwinism is not firmly grounded on fundamental physics. However, during the eighties (neo)Darwinism was taken up in a broader theory of evolution, based on the non-linear equations of fundamental physics. It is argued here that life's coherent behaviour and the new physiology built on these coherent properties is directly compatible with the modern view on evolution, since both are based on the same principles of non-linearity.

PBTK modeling demonstrates contribution of dermal and inhalation exposure components to end-exhaled breath concentrations of naphthalene.

Science.gov (United States)

Kim, David; Andersen, Melvin E; Chao, Yi-Chun E; Egeghy, Peter P; Rappaport, Stephen M; Nylander-French, Leena A

2007-06-01

Dermal and inhalation exposure to jet propulsion fuel 8 (JP-8) have been measured in a few occupational exposure studies. However, a quantitative understanding of the relationship between external exposures and end-exhaled air concentrations has not been described for occupational and environmental exposure scenarios. Our goal was to construct a physiologically based toxicokinetic (PBTK) model that quantitatively describes the relative contribution of dermal and inhalation exposures to the end-exhaled air concentrations of naphthalene among U.S. Air Force personnel. The PBTK model comprised five compartments representing the stratum corneum, viable epidermis, blood, fat, and other tissues. The parameters were optimized using exclusively human exposure and biological monitoring data. The optimized values of parameters for naphthalene were a) permeability coefficient for the stratum corneum 6.8 x 10(-5) cm/hr, b) permeability coefficient for the viable epidermis 3.0 x 10(-3) cm/hr, c) fat:blood partition coefficient 25.6, and d) other tissue:blood partition coefficient 5.2. The skin permeability coefficient was comparable to the values estimated from in vitro studies. Based on simulations of workers' exposures to JP-8 during aircraft fuel-cell maintenance operations, the median relative contribution of dermal exposure to the end-exhaled breath concentration of naphthalene was 4% (10th percentile 1% and 90th percentile 11%). PBTK modeling allowed contributions of the end-exhaled air concentration of naphthalene to be partitioned between dermal and inhalation routes of exposure. Further study of inter- and intraindividual variations in exposure assessment is required to better characterize the toxicokinetic behavior of JP-8 components after occupational and/or environmental exposures.

Nigerian Journal of Physiological Sciences

African Journals Online (AJOL)

Nigerian Journal of Physiological Sciences (Niger. J. Physiol. Sci.) is a biannual publication of the Physiological Society of Nigeria. It covers diverse areas of research in physiological sciences, publishing reviews in current research areas and original laboratory and clinical research in physiological sciences. Other websites ...

Physiological and biochemical aspects of the effect of ionizing radiations on the lung parenchyma

International Nuclear Information System (INIS)

Pasquier, Christian.

1975-03-01

Concerning the biochemical reactions of the lung parenchyma to irradiation the following points have been developed. Role of biochemically active substances (histamine, serotonin, kinins, catecholamines, prostaglandins) in the early reaction of the lung to irradiation, their common feature being their vascular impact point. Lung irradiation and lipids (fatty acids and lipid metabolism in general); irradiation, by raising the proportion of unsaturated at the expense of saturated fatty acids, may give rise to serious physiological respiratory disorders. Lung irradiation and blood fluidity (fibrinolytic activity, heparin, platelet factors). Pulmonary interstitium and irradiation (of the three interstitium components collagen plays a preferential part). Irradiation and immunological lung reaction (reasons behind the immunological theory, immunological assistance, immunological mechanism of pulmonary reactions towards pollutants). Enzymatic lung radiolesion indicators. Three kinds of physiological changes have been considered. Vascular physiology disturbances caused by the initial biochemical reactions; anomalies of physiological or functional trials, images of the lesion formed; disorders of the cell physiology of carcinogenesis [fr

Chewing Over Physiology Integration

Science.gov (United States)

Abdulkader, Fernando; Azevedo-Martins, Anna Karenina; de Arcisio Miranda, Manoel; Brunaldi, Kellen

2005-01-01

An important challenge for both students and teachers of physiology is to integrate the differentareas in which physiological knowledge is didactically divided. In developing countries, such an issue is even more demanding, because budget restrictions often affect the physiology program with laboratory classes being the first on the list when it…

Implementing evidence-based medicine in general practice: a focus group based study

Directory of Open Access Journals (Sweden)

Aertgeerts Bert

2005-09-01

Full Text Available Abstract Background Over the past years concerns are rising about the use of Evidence-Based Medicine (EBM in health care. The calls for an increase in the practice of EBM, seem to be obstructed by many barriers preventing the implementation of evidence-based thinking and acting in general practice. This study aims to explore the barriers of Flemish GPs (General Practitioners to the implementation of EBM in routine clinical work and to identify possible strategies for integrating EBM in daily work. Methods We used a qualitative research strategy to gather and analyse data. We organised focus groups between September 2002 and April 2003. The focus group data were analysed using a combined strategy of 'between-case' analysis and 'grounded theory approach'. Thirty-one general practitioners participated in four focus groups. Purposeful sampling was used to recruit participants. Results A basic classification model documents the influencing factors and actors on a micro-, meso- as well as macro-level. Patients, colleagues, competences, logistics and time were identified on the micro-level (the GPs' individual practice, commercial and consumer organisations on the meso-level (institutions, organisations and health care policy, media and specific characteristics of evidence on the macro-level (policy level and international scientific community. Existing barriers and possible strategies to overcome these barriers were described. Conclusion In order to implement EBM in routine general practice, an integrated approach on different levels needs to be developed.

THE ANXIETY SPECTRUM AND THE REFLEX PHYSIOLOGY OF DEFENSE: FROM CIRCUMSCRIBED FEAR TO BROAD DISTRESS

Science.gov (United States)

McTeague, Lisa M.; Lang, Peter J.

2013-01-01

Guided by the diagnostic nosology, anxiety patients are expected to show defensive hyperarousal during affective challenge, irrespective of the principal phenotype. In the current study, patients representing the whole spectrum of anxiety disorders (i.e., specific phobia, social phobia, panic disorder with or without agoraphobia, obsessive-compulsive disorder, generalized anxiety disorder (GAD), posttraumatic stress disorder(PTSD)), and healthy community control participants, completed an imagery-based fear elicitation paradigm paralleling conventional intervention techniques. Participants imagined threatening and neutral narratives as physiological responses were recorded. Clear evidence emerged for exaggerated reactivity to clinically relevant imagery—most pronounced in startle reflex responding. However, defensive propensity varied across principal anxiety disorders. Disorders characterized by focal fear and impairment (e.g., specific phobia) showed robust fear potentiation. Conversely, for disorders of long-enduring, pervasive apprehension and avoidance with broad anxiety and depression comorbidity (e.g., PTSD secondary to cumulative trauma, GAD), startle responses were paradoxically diminished to all aversive contents. Patients whose expressed symptom profiles were intermediate between focal fearfulness and broad anxious-misery in both severity and chronicity exhibited a still heightened but more generalized physiological propensity to respond defensively. Importantly, this defensive physiological gradient—the inverse of self-reported distress—was evident not only between but also within disorders. These results highlight that fear circuitry could be dysregulated in chronic, pervasive anxiety, and preliminary functional neuroimaging findings suggest that deficient amygdala recruitment could underlie attenuated reflex responding. In summary, adaptive defensive engagement during imagery may be compromised by long-term dysphoria and stress—a phenomenon

Satellite-detected fluorescence reveals global physiology of ocean phytoplankton

Directory of Open Access Journals (Sweden)

M. J. Behrenfeld

2009-05-01

Full Text Available Phytoplankton photosynthesis links global ocean biology and climate-driven fluctuations in the physical environment. These interactions are largely expressed through changes in phytoplankton physiology, but physiological status has proven extremely challenging to characterize globally. Phytoplankton fluorescence does provide a rich source of physiological information long exploited in laboratory and field studies, and is now observed from space. Here we evaluate the physiological underpinnings of global variations in satellite-based phytoplankton chlorophyll fluorescence. The three dominant factors influencing fluorescence distributions are chlorophyll concentration, pigment packaging effects on light absorption, and light-dependent energy-quenching processes. After accounting for these three factors, resultant global distributions of quenching-corrected fluorescence quantum yields reveal a striking consistency with anticipated patterns of iron availability. High fluorescence quantum yields are typically found in low iron waters, while low quantum yields dominate regions where other environmental factors are most limiting to phytoplankton growth. Specific properties of photosynthetic membranes are discussed that provide a mechanistic view linking iron stress to satellite-detected fluorescence. Our results present satellite-based fluorescence as a valuable tool for evaluating nutrient stress predictions in ocean ecosystem models and give the first synoptic observational evidence that iron plays an important role in seasonal phytoplankton dynamics of the Indian Ocean. Satellite fluorescence may also provide a path for monitoring climate-phytoplankton physiology interactions and improving descriptions of phytoplankton light use efficiencies in ocean productivity models.

The Scientific Development of the Physiology of Plants in the American Tropics

Directory of Open Access Journals (Sweden)

Marco V. Gutiérrez

2002-06-01

Full Text Available This paper is a research and journalistic work that summarizes and synthesizes the scientific development of the physiology of plants in the American tropics, also known as the Neotropics. It contains the contributions of numerous biologists interested in the physiology of tropical plants. The fabulous structural and functional diversity of tropical forests is still the major driver of research in this field. Classical physiological work involving tropical plants, such as the discovery of C4 photosynthesis in sugarcane, is invoked to exemplify the historical and current importance of physiological research in the tropics, and its applications in agriculture, forestry and conservation. An historical background describing the early and more recent development of a tradition on the physiological study of tropical plants is followed by a summary of the research conducted on the physiology of tropical crops. Common areas of interest and influence between the fields of crop physiology and plant ecophysiology are identified and exemplified with problems on the environmental physiology of crops like coffee and cassava. The physiology of tropical forest plants is discussed in terms of its contributions to general plant physiological knowledge in areas such as photosynthetic metabolism and plant water relations. Despite the impressive technical advances achieved during the past decade, the importance of continuous development of appropriate instrumentation to study and measure the physiology of plants in situ is stressed. Although the basic metabolic processes that underlie the mechanisms of plant responses to the environment are probably highly conserved and qualitatively similar among tropical and temperate plants, it is also apparent that tropical plants exhibit metabolic peculiarities. These include aspects of photosynthetic metabolism, phloem transport physiology, sensitivity to low temperatures, reproduction, responses to climatic seasonality, and a

Detection of generalized synchronization using echo state networks

OpenAIRE

Ibáñez-Soria, D.; García Ojalvo, Jordi; Soria Frisch, Aureli; Ruffini, G.

2018-01-01

Generalized synchronization between coupled dynamical systems is a phenomenon of relevance in applications that range from secure communications to physiological modelling. Here, we test the capabilities of reservoir computing and, in particular, echo state networks for the detection of generalized synchronization. A nonlinear dynamical system consisting of two coupled Rössler chaotic attractors is used to generate temporal series consisting of time-locked generalized synchronized sequences i...

Predicting dermal penetration for ToxCast chemicals using in silico estimates for diffusion in combination with physiologically based pharmacokinetic (PBPK) modeling.

Science.gov (United States)

Predicting dermal penetration for ToxCast chemicals using in silico estimates for diffusion in combination with physiologically based pharmacokinetic (PBPK) modeling.Evans, M.V., Sawyer, M.E., Isaacs, K.K, and Wambaugh, J.With the development of efficient high-throughput (HT) in ...

Integration of Life-Stage Physiologically Based Pharmacokinetic Models with Adverse Outcome Pathways and Environmental Exposure Models to Screen for Environmental Hazards

Science.gov (United States)

A Life-stage Physiologically-Based Pharmacokinetic (PBPK) model was developed to include descriptions of several life-stage events such as pregnancy, fetal development, the neonate and child growth. The overall modeling strategy was used for in vitro to in vivo (IVIVE) extrapolat...

Generalized Empirical Likelihood-Based Focused Information Criterion and Model Averaging

Directory of Open Access Journals (Sweden)

Naoya Sueishi

2013-07-01

Full Text Available This paper develops model selection and averaging methods for moment restriction models. We first propose a focused information criterion based on the generalized empirical likelihood estimator. We address the issue of selecting an optimal model, rather than a correct model, for estimating a specific parameter of interest. Then, this study investigates a generalized empirical likelihood-based model averaging estimator that minimizes the asymptotic mean squared error. A simulation study suggests that our averaging estimator can be a useful alternative to existing post-selection estimators.

Computer-based, Jeopardy™-like game in general chemistry for engineering majors

Science.gov (United States)

Ling, S. S.; Saffre, F.; Kadadha, M.; Gater, D. L.; Isakovic, A. F.

2013-03-01

We report on the design of Jeopardy™-like computer game for enhancement of learning of general chemistry for engineering majors. While we examine several parameters of student achievement and attitude, our primary concern is addressing the motivation of students, which tends to be low in a traditionally run chemistry lectures. The effect of the game-playing is tested by comparing paper-based game quiz, which constitutes a control group, and computer-based game quiz, constituting a treatment group. Computer-based game quizzes are Java™-based applications that students run once a week in the second part of the last lecture of the week. Overall effectiveness of the semester-long program is measured through pretest-postest conceptual testing of general chemistry. The objective of this research is to determine to what extent this ``gamification'' of the course delivery and course evaluation processes may be beneficial to the undergraduates' learning of science in general, and chemistry in particular. We present data addressing gender-specific difference in performance, as well as background (pre-college) level of general science and chemistry preparation. We outline the plan how to extend such approach to general physics courses and to modern science driven electives, and we offer live, in-lectures examples of our computer gaming experience. We acknowledge support from Khalifa University, Abu Dhabi

Allocation base of general production costs as optimization of prime costs

Directory of Open Access Journals (Sweden)

Levytska I.O.

2017-03-01

Full Text Available Qualified management aimed at optimizing financial results is the key factor in today's society. Effective management decisions depend on the necessary information about the costs of production process in all its aspects – their structure, types, accounting policies of reflecting costs. General production costs, the so-called indirect costs that are not directly related to the production process, but provide its functioning in terms of supporting structural divisions and create the necessary conditions of production, play a significant role in calculating prime costs of goods (works, services. However, the accurate estimate of prime costs of goods (works, services should be determined with the value of indirect costs (in other words, general production costs, and properly determined with the base of their allocation. The choice of allocation base of general production costs is the significant moment, depending on the nature of business, which must guarantee fair distribution regarding to the largest share of direct expenses in the total structure of production costs. The study finds the essence of general production costs based on the analysis of key definitions of leading Ukrainian economists. The optimal allocation approach of general production costs is to calculate these costs as direct production costs within each subsidiary division (department separately without selecting a base as the main one to the their total amount.

A conceptual framework for the emerging discipline of conservation physiology

Science.gov (United States)

Coristine, Laura E.; Robillard, Cassandra M.; Kerr, Jeremy T.; O'Connor, Constance M.; Lapointe, Dominique; Cooke, Steven J.

2014-01-01

Current rates of biodiversity decline are unprecedented and largely attributed to anthropogenic influences. Given the scope and magnitude of conservation issues, policy and management interventions must maximize efficiency and efficacy. The relatively new field of conservation physiology reveals the physiological mechanisms associated with population declines, animal–environment relationships and population or species tolerance thresholds, particularly where these relate to anthropogenic factors that necessitate conservation action. We propose a framework that demonstrates an integrative approach between physiology, conservation and policy, where each can inform the design, conduct and implementation of the other. Each junction of the conservation physiology process has the capacity to foster dialogue that contributes to effective implementation, monitoring, assessment and evaluation. This approach enables effective evaluation and implementation of evidence-based conservation policy and management decisions through a process of ongoing refinement, but may require that scientists (from the disciplines of both physiology and conservation) and policy-makers bridge interdisciplinary knowledge gaps. Here, we outline a conceptual framework that can guide and lead developments in conservation physiology, as well as promote innovative research that fosters conservation-motivated policy. PMID:27293654

A PHYSIOLOGICALLY BASED COMPUTATIONAL MODEL OF THE BPG AXIS IN FATHEAD MINNOWS: PREDICTING EFFECTS OF ENDOCRINE DISRUPTING CHEMICAL EXPOSURE ON REPRODUCTIVE ENDPOINTS

Science.gov (United States)

This presentation describes development and application of a physiologically-based computational model that simulates the brain-pituitary-gonadal (BPG) axis and other endpoints important in reproduction such as concentrations of sex steroid hormones, 17-estradiol, testosterone, a...

Application of Physiologically Based Pharmacokinetic Models in Chemical Risk Assessment

Directory of Open Access Journals (Sweden)

Moiz Mumtaz

2012-01-01

Full Text Available 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.

Biological properties of extracellular vesicles and their physiological functions

Directory of Open Access Journals (Sweden)

María Yáñez-Mó

2015-05-01

Full Text Available In the past decade, extracellular vesicles (EVs have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system.

Biological properties of extracellular vesicles and their physiological functions

Science.gov (United States)

Yáñez-Mó, María; Siljander, Pia R.-M.; Andreu, Zoraida; Zavec, Apolonija Bedina; Borràs, Francesc E.; Buzas, Edit I.; Buzas, Krisztina; Casal, Enriqueta; Cappello, Francesco; Carvalho, Joana; Colás, Eva; Silva, Anabela Cordeiro-da; Fais, Stefano; Falcon-Perez, Juan M.; Ghobrial, Irene M.; Giebel, Bernd; Gimona, Mario; Graner, Michael; Gursel, Ihsan; Gursel, Mayda; Heegaard, Niels H. H.; Hendrix, An; Kierulf, Peter; Kokubun, Katsutoshi; Kosanovic, Maja; Kralj-Iglic, Veronika; Krämer-Albers, Eva-Maria; Laitinen, Saara; Lässer, Cecilia; Lener, Thomas; Ligeti, Erzsébet; Linē, Aija; Lipps, Georg; Llorente, Alicia; Lötvall, Jan; Manček-Keber, Mateja; Marcilla, Antonio; Mittelbrunn, Maria; Nazarenko, Irina; Hoen, Esther N.M. Nolte-‘t; Nyman, Tuula A.; O'Driscoll, Lorraine; Olivan, Mireia; Oliveira, Carla; Pállinger, Éva; del Portillo, Hernando A.; Reventós, Jaume; Rigau, Marina; Rohde, Eva; Sammar, Marei; Sánchez-Madrid, Francisco; Santarém, N.; Schallmoser, Katharina; Ostenfeld, Marie Stampe; Stoorvogel, Willem; Stukelj, Roman; Van der Grein, Susanne G.; Vasconcelos, M. Helena; Wauben, Marca H. M.; De Wever, Olivier

2015-01-01

In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system. PMID:25979354

General practice-based clinical trials in Germany - a problem analysis

Directory of Open Access Journals (Sweden)

Hummers-Pradier Eva

2012-11-01

Full Text Available Abstract Background In Germany, clinical trials and comparative effectiveness studies in primary care are still very rare, while their usefulness has been recognised in many other countries. A network of researchers from German academic general practice has explored the reasons for this discrepancy. Methods Based on a comprehensive literature review and expert group discussions, problem analyses as well as structural and procedural prerequisites for a better implementation of clinical trials in German primary care are presented. Results In Germany, basic biomedical science and technology is more reputed than clinical or health services research. Clinical trials are funded by industry or a single national programme, which is highly competitive, specialist-dominated, exclusive of pilot studies, and usually favours innovation rather than comparative effectiveness studies. Academic general practice is still not fully implemented, and existing departments are small. Most general practitioners (GPs work in a market-based, competitive setting of small private practices, with a high case load. They have no protected time or funding for research, and mostly no research training or experience. Good Clinical Practice (GCP training is compulsory for participation in clinical trials. The group defined three work packages to be addressed regarding clinical trials in German general practice: (1 problem analysis, and definition of (2 structural prerequisites and (3 procedural prerequisites. Structural prerequisites comprise specific support facilities for general practice-based research networks that could provide practices with a point of contact. Procedural prerequisites consist, for example, of a summary of specific relevant key measures, for example on a web platform. The platform should contain standard operating procedures (SOPs, templates, checklists and other supporting materials for researchers. Conclusion All in all, our problem analyses revealed that

Supervised machine learning algorithms to diagnose stress for vehicle drivers based on physiological sensor signals.

Science.gov (United States)

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

2015-01-01

Machine learning algorithms play an important role in computer science research. Recent advancement in sensor data collection in clinical sciences lead to a complex, heterogeneous data processing, and analysis for patient diagnosis and prognosis. Diagnosis and treatment of patients based on manual analysis of these sensor data are difficult and time consuming. Therefore, development of Knowledge-based systems to support clinicians in decision-making is important. However, it is necessary to perform experimental work to compare performances of different machine learning methods to help to select appropriate method for a specific characteristic of data sets. This paper compares classification performance of three popular machine learning methods i.e., case-based reasoning, neutral networks and support vector machine to diagnose stress of vehicle drivers using finger temperature and heart rate variability. The experimental results show that case-based reasoning outperforms other two methods in terms of classification accuracy. Case-based reasoning has achieved 80% and 86% accuracy to classify stress using finger temperature and heart rate variability. On contrary, both neural network and support vector machine have achieved less than 80% accuracy by using both physiological signals.

From Physiology to Prevention: Further remarks on a physiological imperative

Directory of Open Access Journals (Sweden)

B Jouanjean

2012-05-01

Full Text Available Physiology, is the fundamental and functional expression of life. It is the study of all the representative functions of Man in all his capacities, and in particular, his capacity to work. It is very possible to establish a link between a physiological and physiopathological state, the capacity of work and the economy, which can be understood as the articulation between the physiological capacities of Man and the production of work. If these functions are innately acquired by Man they are likewise maintained by regulatory functions throughout life. The stability of these regulatory mechanisms represent the state of good health. The management of this state, constitutes Primary Prevention where both chronic and acute physiopathology defines an alteration in these regulatory mechanisms. We deduce from this reasoning that a tripartite management adapted to the physiological situation is viable and that by choosing parameters specific to individual and collective behavior, it is possible to inject, and combine, at each level and to each demand in order to budget a healthcare system in a more balanced and equitable way. 

Proposed Guideline Revisions for Dental Sedation and General Anesthesia: Why Target the Safest Level of Sedation?

Science.gov (United States)

Dionne, Raymond A

2016-09-01

Recently proposed revisions to the American Dental Association's Guidelines for the Use of Sedation and General Anesthesia by Dentists, aimed at improving safety in dental offices, differentiate between levels of sedation based on drug-induced changes in physiologic and behavioral states. However, the author of this op-ed is concerned the proposed revisions may have far-reaching and unintended consequences.

Imaging-Based Screen Identifies Laminin 411 as a Physiologically Relevant Niche Factor with Importance for i-Hep Applications

Directory of Open Access Journals (Sweden)

John Ong

2018-03-01

Full Text Available Summary: Use of hepatocytes derived from induced pluripotent stem cells (i-Heps is limited by their functional differences in comparison with primary cells. Extracellular niche factors likely play a critical role in bridging this gap. Using image-based characterization (high content analysis; HCA of freshly isolated hepatocytes from 17 human donors, we devised and validated an algorithm (Hepatocyte Likeness Index; HLI for comparing the hepatic properties of cells against a physiological gold standard. The HLI was then applied in a targeted screen of extracellular niche factors to identify substrates driving i-Heps closer to the standard. Laminin 411, the top hit, was validated in two additional induced pluripotent stem cell (iPSC lines, primary tissue, and an in vitro model of α1-antitrypsin deficiency. Cumulatively, these data provide a reference method to control and screen for i-Hep differentiation, identify Laminin 411 as a key niche protein, and underscore the importance of combining substrates, soluble factors, and HCA when developing iPSC applications. : Rashid and colleagues demonstrate the utility of a high-throughput imaging platform for identification of physiologically relevant extracellular niche factors to advance i-Heps closer to their primary tissue counterparts. The extracellular matrix (ECM protein screen identified Laminin 411 as an important niche factor facilitating i-Hep-based disease modeling in vitro. Keywords: iPS hepatocytes, extracellular niche, image-based screening, disease modeling, laminin

Preemptive analgesia I: physiological pathways and pharmacological modalities.

LENUS (Irish Health Repository)

Kelly, D J

2012-02-03

PURPOSE: This two-part review summarizes the current knowledge of physiological mechanisms, pharmacological modalities and controversial issues surrounding preemptive analgesia. SOURCE: Articles from 1966 to present were obtained from the MEDLINE databases. Search terms included: analgesia, preemptive; neurotransmitters; pain, postoperative; hyperalgesia; sensitization, central nervous system; pathways, nociception; anesthetic techniques; analgesics, agents. Principal findings: The physiological basis of preemptive analgesia is complex and involves modification of the pain pathways. The pharmacological modalities available may modify the physiological responses at various levels. Effective preemptive analgesic techniques require multi-modal interception of nociceptive input, increasing threshold for nociception, and blocking or decreasing nociceptor receptor activation. Although the literature is controversial regarding the effectiveness of preemptive analgesia, some general recommendations can be helpful in guiding clinical care. Regional anesthesia induced prior to surgical trauma and continued well into the postoperative period is effective in attenuating peripheral and central sensitization. Pharmacologic agents such as NSAIDs (non-steroidal anti-inflammatory drugs) opioids, and NMDA (N-methyl-D-aspartate) - and alpha-2-receptor antagonists, especially when used in combination, act synergistically to decrease postoperative pain. CONCLUSION: The variable patient characteristics and timing of preemptive analgesia in relation to surgical noxious input requires individualization of the technique(s) chosen. Multi-modal analgesic techniques appear most effective.

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

Directory of Open Access Journals (Sweden)

Feras Khalil

2011-01-01

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

Acute ischaemic stroke prediction from physiological time series patterns

Directory of Open Access Journals (Sweden)

Qing Zhang,

2013-05-01

Full Text Available BackgroundStroke is one of the major diseases with human mortality. Recent clinical research has indicated that early changes in common physiological variables represent a potential therapeutic target, thus the manipulation of these variables may eventually yield an effective way to optimise stroke recovery.AimsWe examined correlations between physiological parameters of patients during the first 48 hours after a stroke, and their stroke outcomes after 3 months. We wanted to discover physiological determinants that could be used to improve health outcomes by supporting the medical decisions that need to be made early on a patient’s stroke experience.Method We applied regression-based machine learning techniques to build a prediction algorithm that can forecast 3-month outcomes from initial physiological time series data during the first 48 hours after stroke. In our method, not only did we use statistical characteristics as traditional prediction features, but also we adopted trend patterns of time series data as new key features.ResultsWe tested our prediction method on a real physiological data set of stroke patients. The experiment results revealed an average high precision rate: 90%. We also tested prediction methods only considering statistical characteristics of physiological data, and concluded an average precision rate: 71%.ConclusionWe demonstrated that using trend pattern features in prediction methods improved the accuracy of stroke outcome prediction. Therefore, trend patterns of physiological time series data have an important role in the early treatment of patients with acute ischaemic stroke.

Physiologic quality of sweet maize seeds according to thickness and width

Directory of Open Access Journals (Sweden)

Claudemir Zucareli

2014-03-01

Full Text Available Sweet maize seeds present lower physiologic quality, when compared to regular maize seeds, due to the influence of several features, such as the seed size and shape. Thus, this study aimed at evaluating the seed physiologic quality of two sweet maize cultivars (BR-401 and BR-402, separately classified according to thickness, by using slotted screen sieves (8/64" x 3/4, 9/64" x 3/4, 10/64" x 3/4, 11/64" x 3/4, 12/64" x 3/4 and 13/64" x 3/4, and width, with round screen sieves (17/64", 18/64", 19/64", 20/64", 21/64" and 22/64". For each cultivar, sorted lots were compared with the unrated batch, following a completely randomized design, in a 2x7 factorial scheme, with four replications. The biometric parameters evaluated were sieve retention, 100 seeds weight and water content. The physiologic quality was determined according to the first counting, germination, cold test, accelerated aging, electric conductivity and seedling emergence in the field. The classification with sieves improved the physiologic quality of sweet maize seeds. Seeds with intermediate thickness, for both cultivars, generally presented greater vigor. Concerning width, larger seeds, for the BR-401 cultivar, and intermediate seeds, for the BR-402 cultivar, showed better physiologic quality.

Uncertainty Analysis of Few Group Cross Sections Based on Generalized Perturbation Theory

International Nuclear Information System (INIS)

Han, Tae Young; Lee, Hyun Chul; Noh, Jae Man

2014-01-01

In this paper, the methodology of the sensitivity and uncertainty analysis code based on GPT was described and the preliminary verification calculations on the PMR200 pin cell problem were carried out. As a result, they are in a good agreement when compared with the results by TSUNAMI. From this study, it is expected that MUSAD code based on GPT can produce the uncertainty of the homogenized few group microscopic cross sections for a core simulator. For sensitivity and uncertainty analyses for general core responses, a two-step method is available and it utilizes the generalized perturbation theory (GPT) for homogenized few group cross sections in the first step and stochastic sampling method for general core responses in the second step. The uncertainty analysis procedure based on GPT in the first step needs the generalized adjoint solution from a cell or lattice code. For this, the generalized adjoint solver has been integrated into DeCART in our previous work. In this paper, MUSAD (Modues of Uncertainty and Sensitivity Analysis for DeCART) code based on the classical perturbation theory was expanded to the function of the sensitivity and uncertainty analysis for few group cross sections based on GPT. First, the uncertainty analysis method based on GPT was described and, in the next section, the preliminary results of the verification calculation on a VHTR pin cell problem were compared with the results by TSUNAMI of SCALE 6.1

Meta-analysis of digital game and study characteristics eliciting physiological stress responses

NARCIS (Netherlands)

van der Vijgh, Benny; Beun, Robbert Jan; van Rood, Maarten; Werkhoven, Peter

2015-01-01

Digital games have been used as stressors in a range of disciplines for decades. Nonetheless, the underlying characteristics of these stressors and the study in which the stressor was applied are generally not recognized for their moderating effect on the measured physiological stress responses. We

General-base catalysed hydrolysis and nucleophilic substitution of activated amides in aqueous solutions

NARCIS (Netherlands)

Buurma, NJ; Blandamer, MJ; Engberts, JBFN; Buurma, Niklaas J.

The reactivity of 1-benzoyl-3-phenyl-1,2,4-triazole (1a) was studied in the presence of a range of weak bases in aqueous solution. A change in mechanism is observed from general-base catalysed hydrolysis to nucleophilic substitution and general-base catalysed nucleophilic substitution. A slight

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

Science.gov (United States)

Chen, Chih-Chen

2016-04-01

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

An Age-Dependent Physiologically-Based Pharmacokinetic/Pharmacodynamic Model for the Organophosphorus Insecticide Chlorpyrifos in the Preweanling Rat

Energy Technology Data Exchange (ETDEWEB)

Timchalk, Chuck; Kousba, Ahmed A.; Poet, Torka S.

2007-08-01

Juvenile rats are more susceptible than adults to the acute toxicity of organophosphorus insecticides like chlorpyrifos (CPF). Age- and dose-dependent differences in metabolism may be responsible. Of importance is CYP450 activation and detoxification of CPF to chlorpyrifos-oxon (CPF-oxon) and trichloropyridinol (TCP), as well as B-esterase (cholinesterase; ChE) and A-esterase (PON-1) detoxification of CPF-oxon to TCP. In the current study, a modified physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model incorporating age-dependent changes in CYP450, PON-1, and tissue ChE levels for rats was developed. In this model, age was used as a dependent function to estimate body weight which was then used to allometrically scale both metabolism and tissue ChE levels. Model simulations suggest that preweanling rats are particularly sensitive to CPF toxicity, with levels of CPF-oxon in blood and brain disproportionately increasing, relative to the response in adult rats. This age-dependent non-linear increase in CPF-oxon concentration may potentially result from the depletion of non-target B-esterases, and a lower PON-1 metabolic capacity in younger animals. These results indicate that the PBPK/PD model behaves consistently with the general understanding of CPF toxicity, pharmacokinetics and tissue ChE inhibition in neonatal and adult rats. Hence, this model represents an important starting point for developing a computational model to assess the neurotoxic potential of environmentally relevant organophosphate exposures in infants and children.

Evolutionary plant physiology: Charles Darwin's forgotten synthesis

Science.gov (United States)

Kutschera, Ulrich; Niklas, Karl J.

2009-11-01

Charles Darwin dedicated more than 20 years of his life to a variety of investigations on higher plants (angiosperms). It has been implicitly assumed that these studies in the fields of descriptive botany and experimental plant physiology were carried out to corroborate his principle of descent with modification. However, Darwin’s son Francis, who was a professional plant biologist, pointed out that the interests of his father were both of a physiological and an evolutionary nature. In this article, we describe Darwin’s work on the physiology of higher plants from a modern perspective, with reference to the following topics: circumnutations, tropisms and the endogenous oscillator model; the evolutionary patterns of auxin action; the root-brain hypothesis; phloem structure and photosynthesis research; endosymbioses and growth-promoting bacteria; photomorphogenesis and phenotypic plasticity; basal metabolic rate, the Pfeffer-Kleiber relationship and metabolic optimality theory with respect to adaptive evolution; and developmental constraints versus functional equivalence in relationship to directional natural selection. Based on a review of these various fields of inquiry, we deduce the existence of a Darwinian (evolutionary) approach to plant physiology and define this emerging scientific discipline as the experimental study and theoretical analysis of the functions of green, sessile organisms from a phylogenetic perspective.

Evolutionary plant physiology: Charles Darwin's forgotten synthesis.

Science.gov (United States)

Kutschera, Ulrich; Niklas, Karl J

2009-11-01

Charles Darwin dedicated more than 20 years of his life to a variety of investigations on higher plants (angiosperms). It has been implicitly assumed that these studies in the fields of descriptive botany and experimental plant physiology were carried out to corroborate his principle of descent with modification. However, Darwin's son Francis, who was a professional plant biologist, pointed out that the interests of his father were both of a physiological and an evolutionary nature. In this article, we describe Darwin's work on the physiology of higher plants from a modern perspective, with reference to the following topics: circumnutations, tropisms and the endogenous oscillator model; the evolutionary patterns of auxin action; the root-brain hypothesis; phloem structure and photosynthesis research; endosymbioses and growth-promoting bacteria; photomorphogenesis and phenotypic plasticity; basal metabolic rate, the Pfeffer-Kleiber relationship and metabolic optimality theory with respect to adaptive evolution; and developmental constraints versus functional equivalence in relationship to directional natural selection. Based on a review of these various fields of inquiry, we deduce the existence of a Darwinian (evolutionary) approach to plant physiology and define this emerging scientific discipline as the experimental study and theoretical analysis of the functions of green, sessile organisms from a phylogenetic perspective.

Physiological and psychological effects of walking in stay-in forest therapy.

Science.gov (United States)

Park, Bum-Jin; Tsunetsugu, Yuko; Morikawa, Takeshi; Kagawa, Takahide; Lee, Juyoung; Ikei, Harumi; Song, Chorong; Miyazaki, Yoshifumi

2014-01-01

To provide scientific evidence of the physiological and psychological effects of forest and urban environments on 47 young male adults undergoing stay-in forest therapy. Field experiments were conducted at four sites in Japan. At each site, 12 subjects participated in the experiment. The experiments were conducted in forest and urban environments, and the subjects' physiological and psychological responses to these environments were compared. On the first day, six subjects were sent to a forest area, and the other six were sent to an urban area as controls. The groups were switched the next day. Heart rate variability and heart rate were measured to assess physiological responses. The semantic differential method for assessing emotions, the reports of "refreshed" feeling, and the Profile of Mood States (POMS) were used to assess psychological responses. The physiological and psychological responses of each subject were recorded during and after walking, and the differences in indices were compared between the two environments. The forest environment was associated with a higher parasympathetic nervous activity, a lower sympathetic nervous activity, and a lower heart rate than the urban environment. The subjective evaluation scores were generally in accordance with the physiological reactions and were significantly higher in the forest environment than in the urban environment. POMS measurements showed that the forest environment was psychologically relaxing and enhanced psychological vigor. This study provided clear scientific evidence of the physiological effects of forest therapy. The results will contribute to the development of forest therapy research and support the inclusion of forest therapy in preventive medicine.

Mathematical physiology

CERN Document Server

Sneyd, James

2009-01-01

There has been a long history of interaction between mathematics and physiology. This book looks in detail at a wide selection of mathematical models in physiology, showing how physiological problems can be formulated and studied mathematically, and how such models give rise to interesting and challenging mathematical questions. With its coverage of many recent models it gives an overview of the field, while many older models are also discussed, to put the modern work in context. In this second edition the coverage of basic principles has been expanded to include such topics as stochastic differential equations, Markov models and Gibbs free energy, and the selection of models has also been expanded to include some of the basic models of fluid transport, respiration/perfusion, blood diseases, molecular motors, smooth muscle, neuroendrocine cells, the baroreceptor loop, turboglomerular oscillations, blood clotting and the retina. Owing to this extensive coverage, the second edition is published in two volumes. ...

Vegetation physiology controls continental water cycle responses to climate change

Science.gov (United States)

Lemordant, L. A.; Swann, A. L. S.; Cook, B.; Scheff, J.; Gentine, P.

2017-12-01

Abstract per se:Predicting how climate change will affect the hydrologic cycle is of utmost importance for ecological systems and for human life and activities. A typical perspective is that global warming will cause an intensification of the mean state, the so-called "dry gets drier, wet gets wetter" paradigm. While this result is robust over the oceans, recent works suggest it may be less appropriate for terrestrial regions. Using Earth System Models (ESMs) with decoupled surface (vegetation physiology, PHYS) and atmospheric (radiative, ATMO) CO2 responses, we show that the CO2 physiological response dominates the change in the continental hydrologic cycle compared to radiative and precipitation changes due to increased atmospheric CO2, counter to previous assumptions. Using multiple linear regression analysis, we estimate the individual contribution of each of the three main drivers, precipitation, radiation and physiological CO2 forcing (see attached figure). Our analysis reveals that physiological effects dominate changes for 3 key indicators of dryness and/or vegetation stress (namely LAI, P-ET and EF) over the largest fraction of the globe, except for soil moisture which exhibits a more complex response. This highlights the key role of vegetation in controlling future terrestrial hydrologic response.Legend of the Figure attached:Decomposition along the three main drivers of LAI (a), P-ET (b), EF (c) in the control run. Green quantifies the effect of the vegetation physiology based on the run PHYS; red and blue quantify the contribution of, respectively, net radiation and precipitation, based on multiple linear regression in ATMO. Pie charts show for each variable the fraction (labelled in %) of land under the main influence (more than 50% of the changes is attributed to this driver) of one the three main drivers (green for grid points dominated by vegetation physiology, red for grid points dominated by net radiation, and blue for grid points dominated by the

Developing a Physiologically-Based Pharmacokinetic Model Knowledgebase in Support of Provisional Model Construction

Science.gov (United States)

Grulke, Christopher M.; Chang, Daniel T.; Brooks, Raina D.; Leonard, Jeremy A.; Phillips, Martin B.; Hypes, Ethan D.; Fair, Matthew J.; Tornero-Velez, Rogelio; Johnson, Jeffre; Dary, Curtis C.; Tan, Yu-Mei

2016-01-01

Developing physiologically-based pharmacokinetic (PBPK) models for chemicals can be resource-intensive, as neither chemical-specific parameters nor in vivo pharmacokinetic data are easily available for model construction. Previously developed, well-parameterized, and thoroughly-vetted models can be a great resource for the construction of models pertaining to new chemicals. A PBPK knowledgebase was compiled and developed from existing PBPK-related articles and used to develop new models. From 2,039 PBPK-related articles published between 1977 and 2013, 307 unique chemicals were identified for use as the basis of our knowledgebase. Keywords related to species, gender, developmental stages, and organs were analyzed from the articles within the PBPK knowledgebase. A correlation matrix of the 307 chemicals in the PBPK knowledgebase was calculated based on pharmacokinetic-relevant molecular descriptors. Chemicals in the PBPK knowledgebase were ranked based on their correlation toward ethylbenzene and gefitinib. Next, multiple chemicals were selected to represent exact matches, close analogues, or non-analogues of the target case study chemicals. Parameters, equations, or experimental data relevant to existing models for these chemicals and their analogues were used to construct new models, and model predictions were compared to observed values. This compiled knowledgebase provides a chemical structure-based approach for identifying PBPK models relevant to other chemical entities. Using suitable correlation metrics, we demonstrated that models of chemical analogues in the PBPK knowledgebase can guide the construction of PBPK models for other chemicals. PMID:26871706

Physiological Actions of Fibroblast Growth Factor-23

Directory of Open Access Journals (Sweden)

Reinhold G. Erben

2018-05-01

Full Text Available Fibroblast growth factor-23 (FGF23 is a bone-derived hormone suppressing phosphate reabsorption and vitamin D hormone synthesis in the kidney. At physiological concentrations of the hormone, the endocrine actions of FGF23 in the kidney are αKlotho-dependent, because high-affinity binding of FGF23 to FGF receptors requires the presence of the co-receptor αKlotho on target cells. It is well established that excessive concentrations of intact FGF23 in the blood lead to phosphate wasting in patients with normal kidney function. Based on the importance of diseases associated with gain of FGF23 function such as phosphate-wasting diseases and chronic kidney disease, a large body of literature has focused on the pathophysiological consequences of FGF23 excess. Less emphasis has been put on the role of FGF23 in normal physiology. Nevertheless, during recent years, lessons we have learned from loss-of-function models have shown that besides the paramount physiological roles of FGF23 in the control of 1α-hydroxylase expression and of apical membrane expression of sodium-phosphate co-transporters in proximal renal tubules, FGF23 also is an important stimulator of calcium and sodium reabsorption in distal renal tubules. In addition, there is an emerging role of FGF23 as an auto-/paracrine regulator of alkaline phosphatase expression and mineralization in bone. In contrast to the renal actions of FGF23, the FGF23-mediated suppression of alkaline phosphatase in bone is αKlotho-independent. Moreover, FGF23 may be a physiological suppressor of differentiation of hematopoietic stem cells into the erythroid lineage in the bone microenvironment. At present, there is little evidence for a physiological role of FGF23 in organs other than kidney and bone. The purpose of this mini-review is to highlight the current knowledge about the complex physiological functions of FGF23.

Problem-Based Learning in a General Psychology Course.

Science.gov (United States)

Willis, Sandra A.

2002-01-01

Describes the adoption of problem-based learning (PBL) techniques in a general psychology course. States that the instructor used a combination of techniques, including think-pair-share, lecture/discussion, and PBL. Notes means and standard deviations for graded components of PBL format versus lecture/discussion format. (Contains 18 references.)…

Physiologically based pharmacokinetic modeling of dibromoacetic acid in F344 rats

International Nuclear Information System (INIS)

Matthews, Jessica L.; Schultz, Irvin R.; Easterling, Michael R.; Melnick, Ronald L.

2010-01-01

A novel physiologically based pharmacokinetic (PBPK) model structure, which includes submodels for the common metabolites (glyoxylate (GXA) and oxalate (OXA)) that may be involved in the toxicity or carcinogenicity of dibromoacetic acid (DBA), has been developed. Particular attention is paid to the representation of hepatic metabolism, which is the primary elimination mechanism. DBA-induced suicide inhibition is modeled by irreversible covalent binding of the intermediate metabolite α-halocarboxymethylglutathione (αH1) to the glutathione-S-transferase zeta (GSTzeta) enzyme. We also present data illustrating the presence of a secondary non-GSTzeta metabolic pathway for DBA, but not dichloroacetic acid (DCA), that produces GXA. The model is calibrated with plasma and urine concentration data from DBA exposures in female F344 rats through intravenous (IV), oral gavage, and drinking water routes. Sensitivity analysis is performed to confirm identifiability of estimated parameters. Finally, model validation is performed with data sets not used during calibration. Given the structural similarity of dihaloacetates (DHAs), we hypothesize that the PBPK model presented here has the capacity to describe the kinetics of any member or mixture of members of this class in any species with the alteration of chemical-and species-specific parameters.

Integration of Genome Scale Metabolic Networks and Gene Regulation of Metabolic Enzymes With Physiologically Based Pharmacokinetics.

Science.gov (United States)

Maldonado, Elaina M; Leoncikas, Vytautas; Fisher, Ciarán P; Moore, J Bernadette; Plant, Nick J; Kierzek, Andrzej M

2017-11-01

The scope of physiologically based pharmacokinetic (PBPK) modeling can be expanded by assimilation of the mechanistic models of intracellular processes from systems biology field. The genome scale metabolic networks (GSMNs) represent a whole set of metabolic enzymes expressed in human tissues. Dynamic models of the gene regulation of key drug metabolism enzymes are available. Here, we introduce GSMNs and review ongoing work on integration of PBPK, GSMNs, and metabolic gene regulation. We demonstrate example models. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

From Claude Bernard to the Batcave and Beyond: Using Batman as a Hook for Physiology Education

Science.gov (United States)

Zehr, E. Paul

2011-01-01

Communicating physiology to the general public and popularizing science can be tremendously rewarding activities. Providing relevant and compelling points of linkage, however, between the scientific experiences and the interests of the general public can be challenging. One avenue for popularizing science is to link scientific concepts to images,…

Physiological and molecular characterization of cowpea [Vigna ...

African Journals Online (AJOL)

Diaga Diouf

Cowpea, Vigna unguiculata (L.) Walp. presents phenotypical variabilities and in order to study the genetic diversity of cultivated Senegalese varieties, two experimental approaches were used. First, a physiological characterization based on nitrogen fixation was used to assess cowpea breeding lines. Inoculation with two ...

A human life-stage physiologically based pharmacokinetic and pharmacodynamic model for chlorpyrifos: development and validation.

Science.gov (United States)

Smith, Jordan Ned; Hinderliter, Paul M; Timchalk, Charles; Bartels, Michael J; Poet, Torka S

2014-08-01

Sensitivity to some 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 predict disposition of chlorpyrifos 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, previously measured age-dependent metabolism of chlorpyrifos and chlorpyrifos-oxon were integrated into age-related descriptions of human anatomy and physiology. The life-stage PBPK/PD model was calibrated and tested against controlled adult human exposure studies. Simulations suggest age-dependent pharmacokinetics and response may exist. At oral doses ⩾0.6mg/kg of chlorpyrifos (100- to 1000-fold higher than environmental exposure levels), 6months 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 doses. At lower doses more relevant to environmental exposures, simulations predict 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 chlorpyrifos disposition and biological response over various postnatal life stages. Copyright © 2013 Elsevier Inc. All rights reserved.

Physiomodel - an integrative physiology in Modelica.

Science.gov (United States)

Matejak, Marek; Kofranek, Jiri

2015-08-01

Physiomodel (http://www.physiomodel.org) is our reimplementation and extension of an integrative physiological model called HumMod 1.6 (http://www.hummod.org) using our Physiolibrary (http://www.physiolibrary.org). The computer language Modelica is well-suited to exactly formalize integrative physiology. Modelica is an equation-based, and object-oriented language for hybrid ordinary differential equations (http:// www.modelica.org). Almost every physiological term can be defined as a class in this language and can be instantiated as many times as it occurs in the body. Each class has a graphical icon for use in diagrams. These diagrams are self-describing; the Modelica code generated from them is the full representation of the underlying mathematical model. Special Modelica constructs of physical connectors from Physiolibrary allow us to create diagrams that are analogies of electrical circuits with Kirchhoff's laws. As electric currents and electric potentials are connected in electrical domain, so are molar flows and concentrations in the chemical domain; volumetric flows and pressures in the hydraulic domain; flows of heat energy and temperatures in the thermal domain; and changes and amounts of members in the population domain.

First trimester fetal physiologic midgut herniation: Transvaginal sonographic findings

International Nuclear Information System (INIS)

Kwon, Tae Hee; Park, Yong Hyun

1999-01-01

To evaluate the sonographic features and appearance time of the physiologic midgut herniation early in pregnancy. Sonograms of 87 features ranging from 7 to 13 weeks were obtained over a 2-month period. The presence or absence, the size and echogenecity of the physiologic midgut herniation were evaluate on each examination. Disappearance of the midgut herniation was confirmed on follow-up sonogram at 13-20 weeks, 3-12 weeks after the first sonogram. The results were analyzed in terms of appearance or disappearance time of midgut herniation. In all cases of physiologic midgut herination, an echogenic mass measuring 0.4-0.7 cm wa demonstrated within the base of the umbilical cord at its insertion into the fetal abdomen. This herniation was detected in 3/6 cases (50%) at 8 weeks, in 15/16 cases (94%) at 9 weeks, in 22/24 cases (92%) at 10 weeks and in 12/27 cases (44%) at 11 weeks gestation. None of the features studied at 7 weeks and 12 weeks had a midgut herniation. Sonographic findings of a 0.4-0.7 cm sized echogenic mass within the base of the umbilical cord which appears from 8 weeks to 12 weeks pregnancy represent physiologic midgut herniation in early pregnancy and should not be confused with pathologic ventral wall defected such as omphalocele or gastroschisis.

First trimester fetal physiologic midgut herniation: Transvaginal sonographic findings

Energy Technology Data Exchange (ETDEWEB)

Kwon, Tae Hee; Park, Yong Hyun [CHA General Hospital. Pochon College of Medicine, Seoul (Korea, Republic of)

1999-06-15

To evaluate the sonographic features and appearance time of the physiologic midgut herniation early in pregnancy. Sonograms of 87 features ranging from 7 to 13 weeks were obtained over a 2-month period. The presence or absence, the size and echogenecity of the physiologic midgut herniation were evaluate on each examination. Disappearance of the midgut herniation was confirmed on follow-up sonogram at 13-20 weeks, 3-12 weeks after the first sonogram. The results were analyzed in terms of appearance or disappearance time of midgut herniation. In all cases of physiologic midgut herination, an echogenic mass measuring 0.4-0.7 cm wa demonstrated within the base of the umbilical cord at its insertion into the fetal abdomen. This herniation was detected in 3/6 cases (50%) at 8 weeks, in 15/16 cases (94%) at 9 weeks, in 22/24 cases (92%) at 10 weeks and in 12/27 cases (44%) at 11 weeks gestation. None of the features studied at 7 weeks and 12 weeks had a midgut herniation. Sonographic findings of a 0.4-0.7 cm sized echogenic mass within the base of the umbilical cord which appears from 8 weeks to 12 weeks pregnancy represent physiologic midgut herniation in early pregnancy and should not be confused with pathologic ventral wall defected such as omphalocele or gastroschisis.

Ibrutinib Dosing Strategies Based on Interaction Potential of CYP3A4 Perpetrators Using Physiologically Based Pharmacokinetic Modeling.

Science.gov (United States)

de Zwart, L; Snoeys, J; De Jong, J; Sukbuntherng, J; Mannaert, E; Monshouwer, M

2016-11-01

Based on ibrutinib pharmacokinetics and potential sensitivity towards CYP3A4-mediated drug-drug interactions (DDIs), a physiologically based pharmacokinetic approach was developed to mechanistically describe DDI with various CYP3A4 perpetrators in healthy men under fasting conditions. These models were verified using clinical data for ketoconazole (strong CYP3A4 inhibitor) and used to prospectively predict and confirm the inducing effect of rifampin (strong CYP3A4 inducer); DDIs with mild (fluvoxamine, azithromycin) and moderate inhibitors (diltiazem, voriconazole, clarithromycin, itraconazole, erythromycin), and moderate (efavirenz) and strong CYP3A4 inducers (carbamazepine), were also predicted. Ketoconazole increased ibrutinib area under the curve (AUC) by 24-fold, while rifampin decreased ibrutinib AUC by 10-fold; coadministration of ibrutinib with strong inhibitors or inducers should be avoided. The ibrutinib dose should be reduced to 140 mg (quarter of maximal prescribed dose) when coadministered with moderate CYP3A4 inhibitors so that exposures remain within observed ranges at therapeutic doses. Thus, dose recommendations for CYP3A4 perpetrator use during ibrutinib treatment were developed and approved for labeling. © 2016 American Society for Clinical Pharmacology and Therapeutics.

Generalized double-humped logistic map-based medical image encryption

Directory of Open Access Journals (Sweden)

Samar M. Ismail

2018-03-01

Full Text Available This paper presents the design of the generalized Double Humped (DH logistic map, used for pseudo-random number key generation (PRNG. The generalized parameter added to the map provides more control on the map chaotic range. A new special map with a zooming effect of the bifurcation diagram is obtained by manipulating the generalization parameter value. The dynamic behavior of the generalized map is analyzed, including the study of the fixed points and stability ranges, Lyapunov exponent, and the complete bifurcation diagram. The option of designing any specific map is made possible through changing the general parameter increasing the randomness and controllability of the map. An image encryption algorithm is introduced based on pseudo-random sequence generation using the proposed generalized DH map offering secure communication transfer of medical MRI and X-ray images. Security analyses are carried out to consolidate system efficiency including: key sensitivity and key-space analyses, histogram analysis, correlation coefficients, MAE, NPCR and UACI calculations. System robustness against noise attacks has been proved along with the NIST test ensuring the system efficiency. A comparison between the proposed system with respect to previous works is presented.

Acquisition of gamma camera and physiological data by computer

International Nuclear Information System (INIS)

Hack, S.N.; Chang, M.; Line, B.R.; Cooper, J.A.; Robeson, G.H.

1986-01-01

We have designed, implemented, and tested a new Research Data Acquisition System (RDAS) that permits a general purpose digital computer to acquire signals from both gamma camera sources and physiological signal sources concurrently. This system overcomes the limited multi-source, high speed data acquisition capabilities found in most clinically oriented nuclear medicine computers. The RDAS can simultaneously input signals from up to four gamma camera sources with a throughput of 200 kHz per source and from up to eight physiological signal sources with an aggregate throughput of 50 kHz. Rigorous testing has found the RDAS to exhibit acceptable linearity and timing characteristics. In addition, flood images obtained by this system were compared with flood images acquired by a commercial nuclear medicine computer system. National Electrical Manufacturers Association performance standards of the flood images were found to be comparable

Recognition of emotions using multimodal physiological signals and an ensemble deep learning model.

Science.gov (United States)

Yin, Zhong; Zhao, Mengyuan; Wang, Yongxiong; Yang, Jingdong; Zhang, Jianhua

2017-03-01

Using deep-learning methodologies to analyze multimodal physiological signals becomes increasingly attractive for recognizing human emotions. However, the conventional deep emotion classifiers may suffer from the drawback of the lack of the expertise for determining model structure and the oversimplification of combining multimodal feature abstractions. In this study, a multiple-fusion-layer based ensemble classifier of stacked autoencoder (MESAE) is proposed for recognizing emotions, in which the deep structure is identified based on a physiological-data-driven approach. Each SAE consists of three hidden layers to filter the unwanted noise in the physiological features and derives the stable feature representations. An additional deep model is used to achieve the SAE ensembles. The physiological features are split into several subsets according to different feature extraction approaches with each subset separately encoded by a SAE. The derived SAE abstractions are combined according to the physiological modality to create six sets of encodings, which are then fed to a three-layer, adjacent-graph-based network for feature fusion. The fused features are used to recognize binary arousal or valence states. DEAP multimodal database was employed to validate the performance of the MESAE. By comparing with the best existing emotion classifier, the mean of classification rate and F-score improves by 5.26%. The superiority of the MESAE against the state-of-the-art shallow and deep emotion classifiers has been demonstrated under different sizes of the available physiological instances. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Toxicokinetics and toxicological effects of single oral dose of fumonisin B1 containing Fusarium verticillioides culture material in weaned piglets.

Science.gov (United States)

Dilkin, P; Direito, G; Simas, M M S; Mallmann, C A; Corrêa, B

2010-05-14

Toxicokinetics and the toxicological effects of culture material containing fumonisin B(1) (FB(1)) were studied in male weaned piglets by clinical, pathological, biochemical and sphingolipid analyses. The animals received a single oral dose of 5 mg FB(1)/kg of body weight, obtained from Fusarium verticillioides culture material. FB(1) was detected by HPLC in plasma collected at 1-h intervals up to 6h and at 12-h intervals up to 96 h. FB(1) eliminated in feces and urine was quantified over a 96-h period and in liver samples collected 96 h post-intoxication. Blood samples were obtained at the beginning and end of the experiment to determine serum enzyme activity, total bilirubin, cholesterol, sphinganine (Sa), sphingosine (So) and the Sa/So ratio. FB(1) was detected in plasma between 30 min and 36 h after administration. The highest concentration of FB(1) was observed after 2 h, with a mean concentration of 282 microg/ml. Only 0.93% of the total FB(1) was detected in urine between 75 min and 41 h after administration, the highest mean concentration (561 microg/ml) was observed during the interval after 8 at 24 h. Approximately 76.5% of FB(1) was detected in feces eliminated between 8 and 84 h after administration, with the highest levels observed between 8 and 24 h. Considering the biochemical parameters, a significant increase only occurred in cholesterol, alkaline phosphatase and aspartate aminotransferase activities. In plasma and urine, the highest Sa and Sa/So ratios were obtained at 12 and 48 h, respectively. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Simultaneous determination of lercanidipine, benazepril and benazeprilat in plasma by LC-MS/MS and its application to a toxicokinetics study.

Science.gov (United States)

Chen, Keguang; Zhang, Jing; Liu, Sha; Zhang, Dujuan; Teng, Yanni; Wei, Chunmin; Wang, Benjie; Liu, Xiaoyan; Yuan, Guiyan; Zhang, Rui; Zhao, Wenjing; Guo, Ruichen

2012-06-15

We aim to develop a rapid, simple, sensitive and specific LC-MS/MS method for the simultaneous quantification of lercanidipine, benazepril and benazeprilat in plasma. It is performed on the Agilent 6410 LC-MS/MS under the multiple-reaction monitoring (MRM) mode with electrospray ionization. Gliclazide was used as the internal standard (IS). Analytes and IS were extracted from plasma by solid-phase extraction. The reconstituted samples were chromatographed on a Diamond C₁₈(150 mm × 4.6 mm, 5 μm) column. The mobile phase was composed of 0.1% acetic acid-acetonitrile (50:50, v/v), with gradient flow rates: 0.6 mL/min (0-4.55 min); 4.55-4.65 min, 1 mL/min; 1 mL/min (4.65-9.5 min); 9.5-9.6 min, 0.6 mL/min; 0.6 mL/min (9.6-10 min). Method validation demonstrated that the method was of satisfactory specificity, sensitivity, precision and accuracy in linear ranges of 1-2000 ng/mL for lercanidipine, 1-2000 ng/mL for benazepril and 1-1600 ng/mL for benazeprilat, respectively. The precision (RSD%) was better than 15, and the lower limit of quantitation was identifiable and reproducible at 1 ng/mL for the three analytes. The plasma samples were stable after being stored for more than 60 days and after two freeze-thaw cycles (-20 to -25 °C). It is demonstrated that this method was successfully applied to samples from a toxicokinetics study of a compound of lercanidipine and benazepril in beagle dogs. Copyright © 2012 Elsevier B.V. All rights reserved.

Seasonal variations in the physiological stress response to discrete bouts of aerial exposure in the little skate, Leucoraja erinacea.

Science.gov (United States)