WorldWideScience

Sample records for human exposure pathways

  1. Sampling strategy for estimating human exposure pathways to consumer chemicals

    NARCIS (Netherlands)

    Papadopoulou, Eleni; Padilla-Sanchez, Juan A.; Collins, Chris D.; Cousins, Ian T.; Covaci, Adrian; de Wit, Cynthia A.; Leonards, Pim E.G.; Voorspoels, Stefan; Thomsen, Cathrine; Harrad, Stuart; Haug, Line S.

    2016-01-01

    Human exposure to consumer chemicals has become a worldwide concern. In this work, a comprehensive sampling strategy is presented, to our knowledge being the first to study all relevant exposure pathways in a single cohort using multiple methods for assessment of exposure from each exposure pathway.

  2. Sampling strategy for estimating human exposure pathways to consumer chemicals

    Directory of Open Access Journals (Sweden)

    Eleni Papadopoulou

    2016-03-01

    Full Text Available Human exposure to consumer chemicals has become a worldwide concern. In this work, a comprehensive sampling strategy is presented, to our knowledge being the first to study all relevant exposure pathways in a single cohort using multiple methods for assessment of exposure from each exposure pathway. The selected groups of chemicals to be studied are consumer chemicals whose production and use are currently in a state of transition and are; per- and polyfluorinated alkyl substances (PFASs, traditional and “emerging” brominated flame retardants (BFRs and EBFRs, organophosphate esters (OPEs and phthalate esters (PEs. Information about human exposure to these contaminants is needed due to existing data gaps on human exposure intakes from multiple exposure pathways and relationships between internal and external exposure. Indoor environment, food and biological samples were collected from 61 participants and their households in the Oslo area (Norway on two consecutive days, during winter 2013-14. Air, dust, hand wipes, and duplicate diet (food and drink samples were collected as indicators of external exposure, and blood, urine, blood spots, hair, nails and saliva as indicators of internal exposure. A food diary, food frequency questionnaire (FFQ and indoor environment questionnaire were also implemented. Approximately 2000 samples were collected in total and participant views on their experiences of this campaign were collected via questionnaire. While 91% of our participants were positive about future participation in a similar project, some tasks were viewed as problematic. Completing the food diary and collection of duplicate food/drink portions were the tasks most frequent reported as “hard”/”very hard”. Nevertheless, a strong positive correlation between the reported total mass of food/drinks in the food record and the total weight of the food/drinks in the collection bottles was observed, being an indication of accurate performance

  3. Soil is an important pathway of human lead exposure.

    OpenAIRE

    Mielke, H W; Reagan, P L

    1998-01-01

    This review shows the equal or greater importance of leaded gasoline-contaminated dust compared to lead-based paint to the child lead problem, and that soil lead, resulting from leaded gasoline and pulverized lead-based paint, is at least or more important than lead-based paint (intact and not pulverized) as a pathway of human lead exposure. Because lead-based paint is a high-dose source, the biologically relevant dosage is similar to lead in soil. Both lead-based paint and soil lead are asso...

  4. The evaluation of stack metal emissions from hazardous waste incinerators: assessing human exposure through noninhalation pathways.

    OpenAIRE

    Sedman, R M; Polisini, J M; Esparza, J R

    1994-01-01

    Potential public health effects associated with exposure to metal emissions from hazardous waste incinerators through noninhalation pathways were evaluated. Instead of relying on modeling the movement of toxicants through various environmental media, an approach based on estimating changes from baseline levels of exposure was employed. Changes in soil and water As, Cd, Hg, Pb, Cr, and Be concentrations that result from incinerator emissions were first determined. Estimates of changes in human...

  5. Multi-pathway human exposure assessment of phthalate esters and DINCH.

    Science.gov (United States)

    Giovanoulis, Georgios; Bui, Thuy; Xu, Fuchao; Papadopoulou, Eleni; Padilla-Sanchez, Juan A; Covaci, Adrian; Haug, Line S; Cousins, Anna Palm; Magnér, Jörgen; Cousins, Ian T; de Wit, Cynthia A

    2018-03-01

    Phthalate esters are substances mainly used as plasticizers in various applications. Some have been restricted and phased out due to their adverse health effects and ubiquitous presence, leading to the introduction of alternative plasticizers, such as DINCH. Using a comprehensive dataset from a Norwegian study population, human exposure to DMP, DEP, DnBP, DiBP, BBzP, DEHP, DINP, DIDP, DPHP and DINCH was assessed by measuring their presence in external exposure media, allowing an estimation of the total intake, as well as the relative importance of different uptake pathways. Intake via different uptake routes, in particular inhalation, dermal absorption, and oral uptake was estimated and total intake based on all uptake pathways was compared to the calculated intake from biomonitoring data. Hand wipe results were used to determine dermal uptake and compared to other exposure sources such as air, dust and personal care products. Results showed that the calculated total intakes were similar, but slightly higher than those based on biomonitoring methods by 1.1 to 3 times (median), indicating a good understanding of important uptake pathways. The relative importance of different uptake pathways was comparable to other studies, where inhalation was important for lower molecular weight phthalates, and negligible for the higher molecular weight phthalates and DINCH. Dietary intake was the predominant exposure route for all analyzed substances. Dermal uptake based on hand wipes was much lower (median up to 2000 times) than the total dermal uptake via air, dust and personal care products. Still, dermal uptake is not a well-studied exposure pathway and several research gaps (e.g. absorption fractions) remain. Based on calculated intakes, the exposure for the Norwegian participants to the phthalates and DINCH was lower than health based limit values. Nevertheless, exposure to alternative plasticizers, such as DPHP and DINCH, is expected to increase in the future and continuous

  6. Comparison of human exposure pathways in an urban brownfield: reduced risk from paving roads.

    Science.gov (United States)

    James, Kyle; Farrell, Richard E; Siciliano, Steven D

    2012-10-01

    Risk assessments often do not quantify the risk associated with soil inhalation. This pathway generally makes a negligible contribution to the cumulative risk, because soil ingestion is typically the dominant exposure pathway. Conditions in northern or rural centers in Canada characterized by large areas of exposed soil, including unpaved roads, favor the resuspension of soil particles, making soil inhalation a relevant risk pathway. The authors determined and compared human exposure to metals and polycyclic aromatic hydrocarbons (PAHs) from soil ingestion and inhalation and analyzed the carcinogenic and noncarcinogenic risks before and after roads were paved in a northern community. To determine the inhalation exposure, three size fractions of airborne particulate matter were collected (total suspended particulates [TSP], particulate matter with an aerodynamic diameter less than 10 µm [PM10], and particulate matter with an aerodynamic diameter less than 2.5 µm [PM2.5]) before and after roads were paved. Road paving reduced the concentration of many airborne contaminants by 25 to 75%, thus reducing risk. For example, before paving, the carcinogenic risk associated with inhalation of Cr was 3.4 excess cancers per 100,000 people exposed, whereas after paving, this risk was reduced to 1.6 in 100,000. Paving roads reduced the concentrations of total suspended particulates (TSP; p roads is an effective method of reducing risk from the inhalation of soil particles. Copyright © 2012 SETAC.

  7. Cell cycle pathway dysregulation in human keratinocytes during chronic exposure to low arsenite.

    Science.gov (United States)

    Al-Eryani, Laila; Waigel, Sabine; Jala, Venkatakrishna; Jenkins, Samantha F; States, J Christopher

    2017-09-15

    Arsenic is naturally prevalent in the earth's crust and widely distributed in air and water. Chronic low arsenic exposure is associated with several cancers in vivo, including skin cancer, and with transformation in vitro of cell lines including immortalized human keratinocytes (HaCaT). Arsenic also is associated with cell cycle dysregulation at different exposure levels in multiple cell lines. In this work, we analyzed gene expression in HaCaT cells to gain an understanding of gene expression changes contributing to transformation at an early time point. HaCaT cells were exposed to 0 or 100nM NaAsO 2 for 7weeks. Total RNA was purified and analyzed by microarray hybridization. Differential expression with fold change≥|1.5| and p-value≤0.05 was determined using Partek Genomic Suite™ and pathway and network analyses using MetaCore™ software (FDR≤0.05). Cell cycle analysis was performed using flow cytometry. 644 mRNAs were differentially expressed. Cell cycle/cell cycle regulation pathways predominated in the list of dysregulated pathways. Genes involved in replication origin licensing were enriched in the network. Cell cycle assay analysis showed an increase in G2/M compartment in arsenite-exposed cells. Arsenite exposure induced differential gene expression indicating dysregulation of cell cycle control, which was confirmed by cell cycle analysis. The results suggest that cell cycle dysregulation is an early event in transformation manifested in cells unable to transit G2/M efficiently. Further study at later time points will reveal additional changes in gene expression related to transformation processes. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. [Indoor dust as a pathway of human exposure to polybrominated diphenyl ethers (PBDEs)].

    Science.gov (United States)

    Góralczyk, Katarzyna; Struciński, Paweł; Hernik, Agnieszka; Czaja, Katarzyna; Korcz, Wojciech; Minorczyk, Maria; Ludwicki, Jan K

    2012-01-01

    The brominated diphenyl ethers (PBDEs) belong to a class of synthetic, additive brominated flame retardants (BFRs). PBDEs are used to reduce the flammability of commercial and household products such as textiles, various plastic polymers, furnishing foam, and electronic equipment. People spend a large percentage of their life-time indoors at home, in offices and cars, etc, providing many opportunities for lengthy exposure to PBDEs from residential settings and commercial products in an indoor environment. In recent time, the foodstuffs, mainly food of animal origin, have been indicated as the main pathway of human exposure to PBDEs. However, many studies have shown that the indoor environment, mainly indoor dust, can be also a significant source of exposure to PBDEs, especially for younger children (toddlers) because of their behavioral patterns, eg. putting fingers, toys, and other items in their mouth. Numerous studies show that the median intakes of PBDEs via dust for adult range from 1.41 to 277 ng x day(-1) is lower than that via food which range from 135 to 333 ng x day-', while the median intake of these compounds via indoor dust for children range from 101 to 404 ng x day(-1) is much higher than via food: 77-190 ng x day(-1). The congener pattern observed in the indoor dust is different to that found in food. The indoor dust is dominated by the congener BDE-209 vs. food where the most dominated congeners are BDE-47 and BDE-99. Human exposure to PBDEs and other brominated flame retardants (BFRs) is widely widespread throughout the world and it depends on a country range of usage, production and legislation concerning these chemicals as well as a citizen's behavior. Generally, human exposure has been found higher in North America than in Europe and Asia. Within European countries the significant highest concentrations in dust have been found in the United Kingdom. It should be noted that many uncertainty factors such as personal habits, dietary preferences

  9. Exposure of Human Lung Cells to Tobacco Smoke Condensate Inhibits the Nucleotide Excision Repair Pathway.

    Directory of Open Access Journals (Sweden)

    Nathaniel Holcomb

    Full Text Available Exposure to tobacco smoke is the number one risk factor for lung cancer. Although the DNA damaging properties of tobacco smoke have been well documented, relatively few studies have examined its effect on DNA repair pathways. This is especially true for the nucleotide excision repair (NER pathway which recognizes and removes many structurally diverse DNA lesions, including those introduced by chemical carcinogens present in tobacco smoke. The aim of the present study was to investigate the effect of tobacco smoke on NER in human lung cells. We studied the effect of cigarette smoke condensate (CSC, a surrogate for tobacco smoke, on the NER pathway in two different human lung cell lines; IMR-90 lung fibroblasts and BEAS-2B bronchial epithelial cells. To measure NER, we employed a slot-blot assay to quantify the introduction and removal of UV light-induced 6-4 photoproducts and cyclobutane pyrimidine dimers. We find a dose-dependent inhibition of 6-4 photoproduct repair in both cell lines treated with CSC. Additionally, the impact of CSC on the abundance of various NER proteins and their respective RNAs was investigated. The abundance of XPC protein, which is required for functional NER, is significantly reduced by treatment with CSC while the abundance of XPA protein, also required for NER, is unaffected. Both XPC and XPA RNA levels are modestly reduced by CSC treatment. Finally, treatment of cells with MG-132 abrogates the reduction in the abundance of XPC protein produced by treatment with CSC, suggesting that CSC enhances proteasome-dependent turnover of the protein that is mediated by ubiquitination. Together, these findings indicate that tobacco smoke can inhibit the same DNA repair pathway that is also essential for the removal of some of the carcinogenic DNA damage introduced by smoke itself, increasing the DNA damage burden of cells exposed to tobacco smoke.

  10. ARSENIC: A Review on Exposure Pathways, Accumulation, Mobility and Transmission into the Human Food Chain.

    Science.gov (United States)

    Arslan, Beste; Djamgoz, Mustafa B A; Akün, Ertan

    This review deals with exposure pathways of arsenic (As), as well as its transfer and uptake processes from its source to the human body. It is proven fact that uptake of inorganic As for a long period can lead to chronic As poisoning and a variety of adverse health effects such as skin, lung and bladder cancer, in addition to cardiovascular diseases, diabetes and gastrointestinal symptoms. As exposure occurs primarily from consumption of potable water containing high amounts of inorganic As and also from consumption of crops cultivated in As contaminated agricultural fields-either naturally or anthropogenically through contaminated air or pesticides-or irrigated with As containing water. In this review, light is shed on the transfer mechanism of As through the food chain and the parameters that enhance mobility of As in the environment. Amounts of As accumulation in plants and the transfer mechanisms are also quite different. These differences in As accumulation, such as in leaves, stems, fruits and roots, are discussed in detail. Moreover, presence of As in some vegetables consumed is given by investigating recent research articles that deal with As concentrations, especially in edible parts. Some comparative data are also presented, concerning the level of concentration of As in rice during washing, cooking and processing stages.

  11. Uncertainty versus variability in Monte Carlo simulations of human exposure through food pathways

    International Nuclear Information System (INIS)

    McKone, T.E.

    1994-01-01

    An important issue in both the risk characterization and subsequent risk management of contaminated soil is how precisely we can characterize the distribution among individuals of potential doses associated with chemical contaminants in soil and whether this level of precision favors the use of population distributions of exposure over the use of single scenario representations. For lipophilic contaminants, such as dioxins, furans, polychlorinated biphenyls, pesticides, and for metals such as lead and mercury, exposures through food have been demonstrated to be dominant contributors to total dose within non-occupationally exposed populations. However, overall uncertainties in estimating potential doses through food chains are much larger than uncertainties associated with other exposure pathways. A general model is described here for estimating the ratio of potential dose to contaminant concentration in soil for homegrown foods contaminated by lipophilic, nonionic organic chemicals. This model includes parameters describing homegrown food consumption rates, exposure duration, biotransfer factors, and partition factors. For the parameters needed in this model, the mean and variance are often the only moments of the parameter distribution available. Parameters are divided into three categories, uncertain parameters, variable parameters, and mixed uncertain/variable parameters. Using soils contaminated by hexachlorbenzene (HCB) and benzo(a)pyrene (BaP) as cases studies, a stepwise Monte Carlo analysis is used to develop a histogram that apportions variance in the outcome (ratio of potential dose by food pathways to soil concentration) to variance in each of the three input categories. The results represent potential doses in households consuming homegrown foods

  12. Human exposure to per- and polyfluoroalkyl substances (PFASs) via house dust in Korea: Implication to exposure pathway.

    Science.gov (United States)

    Tian, Zhexi; Kim, Seung-Kyu; Shoeib, Mahiba; Oh, Jeong-Eun; Park, Jong-Eun

    2016-05-15

    A wide range of per- and polyfluoroalkyl substances (PFASs), including fluorotelomer alcohols (FTOHs), perfluorooctane sulfonamidoethanols (FOSEs), perfluoroalkyl carboxylic acids (PFCAs), and perfluoroalkane sulfonic acids (PFSAs), were measured in fifteen house dust and two nonresidential indoor dust of Korea. Total concentrations of PFASs in house dust ranged from 29.9 to 97.6 ng g(-1), with a dominance of perfluorooctane sulfonic acid (PFOS), followed by 8:2 FTOH, N-Ethyl perfluorooctane sulfonamidoethanol (EtFOSE), perfluoroctanoic acid (PFOA). In a typical exposure scenario, the estimated daily intakes (EDIs) of total PFASs via house dust ingestion were 2.83 ng d(-1) for toddlers and 1.13 ng d(-1) for adults, which were within the range of the mean EDIs reported from several countries. For PFOA and PFOS exposure via house dust ingestion, indirect exposure (via precursors) was a minor contributor, accounting for 5% and 12%, respectively. An aggregated exposure (hereafter, overall-EDIs) of PFOA and PFOS occurring via all pathways, estimated using data compiled from the literature, were 53.6 and 14.8 ng d(-1) for toddlers, and 20.5 and 40.6 ng d(-1) for adults, respectively, in a typical scenario. These overall-EDIs corresponded to 82% (PFOA) and 92% (PFOS) of a pharmacokinetic model-based EDIs estimated from adults' serum data. Direct dietary exposure was a major contributor (>89% of overall-EDI) to PFOS in both toddlers and adults, and PFOA in toddlers. As for PFOA exposure of adults, however direct exposure via tap water drinking (37%) and indirect exposure via inhalation (22%) were as important as direct dietary exposure (41%). House dust-ingested exposure (direct+indirect) was responsible for 5% (PFOS in toddlers) and house-dust ingestion was a minor contributor in this study, but should not be ignored for toddlers' PFOS exposure due to its significance in the worst-case scenario. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Long-term human exposure to lead from different media and intake pathways.

    Science.gov (United States)

    Pizzol, Massimo; Thomsen, Marianne; Andersen, Mikael Skou

    2010-10-15

    Lead (Pb) is well known as an environmental pollutant: it can accumulate in various media, so actual lead exposure reflects both historical and present contaminations. Two main challenges then emerge: obtaining updated information to gain an overall picture of the sources of exposure, and predicting the resulting internal body exposure levels and effects that occur under long-term exposure conditions. In this paper, a modeling approach is used to meet these challenges with reference to Danish exposure conditions. Levels of lead content in various media have been coupled with data for lead intake and absorption in the human body, for both children and adults. An age-dependent biokinetic model allows then for determination of the blood lead levels resulting from chronic exposure. The study shows that the actual intake of lead is up to 27% of the Provisional Tolerable Daily Intake (PTDI) for children and around 8% for adults. It is confirmed that the critical route of exposure is via ingestion, accounting for 99% of total lead intake, while inhalation contributes only to 1% of total lead intake. The resulting lead levels in the blood after 2 years of exposure to actual contamination conditions have been estimated as up to 2.2μg/dl in children and almost 1μg/dl in adults. Impacts from lead can occur even at such levels. The role of historical and present sources to lead in the environment is discussed, and, for specific child and adult exposure scenarios, external-internal concentration relationships for the direct linkage between lead in environmental media and resulting concentrations of lead in blood are then presented. Copyright © 2010 Elsevier B.V. All rights reserved.

  14. Exposures from aquatic pathways

    International Nuclear Information System (INIS)

    Berkovski, V.; Voitsekhovitch, O.; Nasvit, O.; Zhelezniak, M.; Sansone, U.

    1996-01-01

    Methods for estimation aquatic pathways contribution to the total population exposure are discussed. Aquatic pathways are the major factor for radionuclides spreading from the Chernobyl Exclusion zone. An annual outflow of 90 Sr and 137 Cs comprised 10-20 TBq and 2-4 TBq respectively and the population exposed by this effluence constitutes almost 30 million people. The dynamic of doses from 90 Sr and ' C s, which Dnieper water have to delivered, is calculated. The special software has been developed to simulate the process of dose formation in the of diverse Dnieper regions. Regional peculiarities of municipal tap, fishing and irrigation are considered. Seventy-year prediction of dose structure and function of dose forming is performed. The exposure is estimated for 12 regions of the Dnieper basin and the Crimea. The maximal individual annual committed effective doses due to the use of water by ordinary members of the population in Kiev region from 90 Sr and 137 Cs in 1986 are 1.7*10 -5 Sv and 2.7*10 -5 Sv respectively. A commercial fisherman on Kiev reservoir in 1986 received 4.7*10 -4 Sv and 5*10 -3 Sv from 90 Sr and 137 Cs, respectively. The contributions to the collective cumulative (over 70 years) committed effective dose (CCCED 70 ) of irrigation, municipal tap water and fish consumption for members of the population respectively are 18%, 43%, 39% in Kiev region, 8%, 25%, 67% in Poltava region, and 50%, 50%, 0% (consumption of Dnieper fish is absent) in the Crimea. The predicted contribution of the Strontium-90 to CCCED 70 resulting from the use of water is 80%. The CCCED 70 to the population of the Dnieper regions (32.5 million people) is 3000 person-Sv due to the use the Dnieper water

  15. Exposure scenarios of the German Federal Soil Protection and Contamination Ordinance - impact pathway from soil to humans

    International Nuclear Information System (INIS)

    Konietzka, R.

    2005-01-01

    The soil uptake values used for calculating soil values have not undergone strict scientific validation by extensive testing. As far as possible be they can and should be based on empirical data. In many cases it is inevitable to resort to conventions, but these should be made plausible through empirical studies. Land use scenarios relevant to the calculation of test values for direct uptake from soil to humans are playgrounds, residential areas, park and leisure facilities and industrial and commercial properties. The relevant exposure pathways are assumed to differ between scenarios depending on certain characteristics of the potentially exposed population groups. In most cases the pathways oral, inhalational (inhalation of contaminated dusts) and dermal uptake from the soil are considered

  16. MERS-CoV at the Animal-Human interface: inputs on exposure pathways from an Expert-Opinion elicitation

    Directory of Open Access Journals (Sweden)

    Anna Funk

    2016-10-01

    Full Text Available Nearly four years after the first report of the emergence of Middle-East respiratory syndrome Coronavirus (MERS-CoV and nearly 1800 human cases later, the ecology of MERS-CoV, its epidemiology, and risk factors of MERS-CoV transmission between camels are poorly understood. Knowledge about the pathways and mechanisms of transmission from animals to humans is limited; as of yet, transmission risks have not been quantified. Moreover the divergent sanitary situations and exposures to animals among populations in the Arabian Peninsula, where human primary cases appear to dominate, vs. other regions in the Middle East and Africa, with no reported human clinical cases and where the virus has been detected only in dromedaries, represents huge scientific and health challenges. Here, we have used expert opinion elicitation in order to obtain ideas on relative importance of MERS-CoV risk factors and estimates of transmission risks from various types of contact between humans and dromedaries. Fourteen (14 experts with diverse and extensive experience in MERS-CoV relevant fields were enrolled and completed an online questionnaire that examined pathways based on several scenarios e.g. camels-camels, camels-human, bats/other species to camels/humans and the role of diverse biological substances (milk, urine etc. and potential fomites.Experts believed that dromedary camels play the largest role in MERS-CoV infection of other dromedaries; however, they also indicated a significant influence of the season (i.e. calving or weaning periods on transmission risk. All experts thought that MERS-CoV infected dromedaries and asymptomatic humans play the most important role in infection of humans, with bats and other species presenting a possible, but yet undefined, risk. Direct and indirect contact of humans with dromedary camels were identified as the most risky types of contact, when compared to consumption of various camel products, with estimated 'most

  17. Long-term human exposure to lead from different media and intake pathways

    DEFF Research Database (Denmark)

    Pizzol, Massimo; Thomsen, Marianne; Andersen, Mikael Skou

    2010-01-01

    , and predicting the resulting internal body exposure levels and effects that occur under long-term exposure conditions. In this paper, a modeling approach is used to meet these challenges with reference to Danish exposure conditions. Levels of lead content in various media have been coupled with data for lead......Lead (Pb) is well known as an environmental pollutant: it can accumulate in various media, so actual lead exposure reflects both historical and present contaminations. Two main challenges then emerge: obtaining updated information to gain an overall picture of the sources of exposure......–internalconcentration relationships for the direct linkage between lead in environmental media and resultingconcentrations of lead in blood are then presented....

  18. Adaptive pathways of zoonotic influenza viruses: from exposure to establishment in humans.

    Science.gov (United States)

    Reperant, Leslie A; Kuiken, Thijs; Osterhaus, Albert D M E

    2012-06-22

    Human influenza viruses have their ultimate origin in avian reservoirs and may adapt, either directly or after passage through another mammalian species, to circulate independently in the human population. Three sets of barriers must be crossed by a zoonotic influenza virus before it can become a human virus: animal-to-human transmission barriers; virus-cell interaction barriers; and human-to-human transmission barriers. Adaptive changes allowing zoonotic influenza viruses to cross these barriers have been studied extensively, generating key knowledge for improved pandemic preparedness. Most of these adaptive changes link acquired genetic alterations of the virus to specific adaptation mechanisms that can be screened for, both genetically and phenotypically, as part of zoonotic influenza virus surveillance programs. Human-to-human transmission barriers are only sporadically crossed by zoonotic influenza viruses, eventually triggering a worldwide influenza outbreak or pandemic. This is the most devastating consequence of influenza virus cross-species transmission. Progress has been made in identifying some of the determinants of influenza virus transmissibility. However, interdisciplinary research is needed to further characterize these ultimate barriers to the development of influenza pandemics, at both the level of the individual host and that of the population. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Highly pathogenic avian influenza (H5N1: pathways of exposure at the animal-human interface, a systematic review.

    Directory of Open Access Journals (Sweden)

    Maria D Van Kerkhove

    Full Text Available BACKGROUND: The threat posed by highly pathogenic avian influenza A H5N1 viruses to humans remains significant, given the continued occurrence of sporadic human cases (499 human cases in 15 countries with a high case fatality rate (approximately 60%, the endemicity in poultry populations in several countries, and the potential for reassortment with the newly emerging 2009 H1N1 pandemic strain. Therefore, we review risk factors for H5N1 infection in humans. METHODS AND FINDINGS: Several epidemiologic studies have evaluated the risk factors associated with increased risk of H5N1 infection among humans who were exposed to H5N1 viruses. Our review shows that most H5N1 cases are attributed to exposure to sick poultry. Most cases are sporadic, while occasional limited human-to-human transmission occurs. The most commonly identified factors associated with H5N1 virus infection included exposure through contact with infected blood or bodily fluids of infected poultry via food preparation practices; touching and caring for infected poultry; [corrected] exposure to H5N1 via swimming or bathing in potentially virus laden ponds; and exposure to H5N1 at live bird markets. CONCLUSIONS: Research has demonstrated that despite frequent and widespread contact with poultry, transmission of the H5N1 virus from poultry to humans is rare. Available research has identified several risk factors that may be associated with infection including close direct contact with poultry and transmission via the environment. However, several important data gaps remain that limit our understanding of the epidemiology of H5N1 in humans. Although infection in humans with H5N1 remains rare, human cases continue to be reported and H5N1 is now considered endemic among poultry in parts of Asia and in Egypt, providing opportunities for additional human infections and for the acquisition of virus mutations that may lead to more efficient spread among humans and other mammalian species

  20. The application of equilibrium models to incidence situations using the example of the exposure pathway human milk

    International Nuclear Information System (INIS)

    Steiner, Martin; Karcher, Klaus; Nosske, Dietmar

    2012-01-01

    The radiation exposure after a short-term release of radioactive substances is often calculated assuming equilibrium conditions. An example is that of the German Incident Calculation Bases for nuclear power plants with pressurized water reactors. Here, the contamination of human milk is calculated using transfer factors. Applying this equilibrium model to incident situations raises the question whether baby's radiation exposure is adequately assessed. This contribution shows that compliance with the relevant dose limits of paragraph 49 of the German Radiation Protection Ordinance is ensured for design basis accidents on the assumption that the hypothetical breastfeeding period starts at the beginning of the activity release. Comparative analyses were performed against the biokinetic models applied by ICRP for radiation protection purposes, taking the reference nuclides 137 Cs, 90 Sr, 131 I, 241 Am and long-lived plutonium isotopes as examples. (orig.)

  1. The application of equilibrium models to incidence situations using the example of the exposure pathway human milk

    Energy Technology Data Exchange (ETDEWEB)

    Steiner, Martin; Karcher, Klaus; Nosske, Dietmar [Bundesamt fuer Strahlenschutz, Oberschleissheim (Germany)

    2012-06-15

    The radiation exposure after a short-term release of radioactive substances is often calculated assuming equilibrium conditions. An example is that of the German Incident Calculation Bases for nuclear power plants with pressurized water reactors. Here, the contamination of human milk is calculated using transfer factors. Applying this equilibrium model to incident situations raises the question whether baby's radiation exposure is adequately assessed. This contribution shows that compliance with the relevant dose limits of paragraph 49 of the German Radiation Protection Ordinance is ensured for design basis accidents on the assumption that the hypothetical breastfeeding period starts at the beginning of the activity release. Comparative analyses were performed against the biokinetic models applied by ICRP for radiation protection purposes, taking the reference nuclides {sup 137}Cs, {sup 90}Sr, {sup 131}I, {sup 241}Am and long-lived plutonium isotopes as examples. (orig.)

  2. Merging Models and Biomonitoring Data to Characterize Sources andPathways of Human Exposure to Organophosphorous Pesticides in the SalinasValley of California

    Energy Technology Data Exchange (ETDEWEB)

    McKone, Thomas E.; Castorina, Rosemary; Kuwabara, Yu; Harnly,Martha E.; Eskenazi, Brenda; Bradman, Asa

    2006-06-01

    By drawing on human biomonitoring data and limited environmental samples together with outputs from the CalTOX multimedia, multipathway source-to-dose model, we characterize cumulative intake of organophosphorous (OP) pesticides in an agricultural region of California. We assemble regional OP pesticide use, environmental sampling, and biological tissue monitoring data for a large and geographically dispersed population cohort of 592 pregnant Latina women in California (the CHAMACOS cohort). We then use CalTOX with regional pesticide usage data to estimate the magnitude and uncertainty of exposure and intake from local sources. We combine model estimates of intake from local sources with food intake based on national residue data to estimate for the CHAMACOS cohort cumulative median OP intake, which corresponds to expected levels of urinary dialkylphosphate (DAP) metabolite excretion for this cohort. From these results we develop premises about relative contributions from different sources and pathways of exposure. We evaluate these premises by comparing the magnitude and variation of DAPs in the CHAMACOS cohort with the whole U.S. population using data from the National Health and Nutrition Evaluation Survey (NHANES). This comparison supports the premise that in both populations diet is the common and dominant exposure pathway. Both the model results and biomarker comparison supports the observation that the CHAMACOS population has a statistically significant higher intake of OP pesticides that appears as an almost constant additional dose among all participants. We attribute the magnitude and small variance of this intake to non-dietary exposure in residences from local sources.

  3. Human Exposure and Health

    Science.gov (United States)

    The ROE is divided into 5 themes: Air, Water, Land, Human Exposure and Health and Ecological Condition. From these themes, the report indicators address fundamental questions that the ROE attempts to answer. For human health there are 3 questions.

  4. Assessment of human exposures

    Energy Technology Data Exchange (ETDEWEB)

    Lebret, E [RIVM-National Inst. of Public Health and Environmental Protection (Netherlands)

    1996-12-31

    This article describes some of the features of the assessment of human exposure to environmental pollutants in epidemiological studies. Since exposure assessment in air pollution epidemiology studies typically involve professionals from various backgrounds, interpretation of a concepts like `exposure` may vary. A brief descriptions is therefore given by way of introduction

  5. Assessment of human exposures

    Energy Technology Data Exchange (ETDEWEB)

    Lebret, E. [RIVM-National Inst. of Public Health and Environmental Protection (Netherlands)

    1995-12-31

    This article describes some of the features of the assessment of human exposure to environmental pollutants in epidemiological studies. Since exposure assessment in air pollution epidemiology studies typically involve professionals from various backgrounds, interpretation of a concepts like `exposure` may vary. A brief descriptions is therefore given by way of introduction

  6. Pathways of human exposure to cobalt in Katanga, a mining area of the D.R. Congo.

    Science.gov (United States)

    Cheyns, Karlien; Banza Lubaba Nkulu, Célestin; Ngombe, Léon Kabamba; Asosa, Jimmy Ngoy; Haufroid, Vincent; De Putter, Thierry; Nawrot, Tim; Kimpanga, Célestin Muleka; Numbi, Oscar Luboya; Ilunga, Benjamin Kabyla; Nemery, Benoit; Smolders, Erik

    2014-08-15

    Human exposure biomonitoring in the African Copperbelt (Katanga, southern D.R. Congo) revealed elevated cobalt (Co) exposure in the general population. This study was designed to identify the Co exposure routes for the non-occupationally exposed population in that area. The concentration of Co was measured in environmental and urine samples collected in urban and rural communities close to metal mining and/or refining plants, villages near a lake receiving effluents from metal refining plants, and control rural areas without industrial pollution. Drinking water, uncooked food items (maize flour, washed vegetables, fish and meat), indoor and outdoor dust samples were collected at each location. A food questionnaire was used to estimate dietary Co intake for adults and children. Geometric mean urine-Co (U-Co) concentrations were 4.5-fold (adults) and 6.6-fold (children) higher in the polluted than in the control area, with U-Co values being intermediate in the lakeside area. Average Co concentrations in environmental samples differed 6-40-fold between these areas. U-Co was positively correlated with most environmental Co concentrations, the highest correlations being found with Co in drinking water, vegetables and fruit. Estimated average total Co intake for adults was 63 (±42) μg/day in the control area, 94 (±55) μg/day in the lakeside villages and 570 (±100) μg Co/day in the polluted areas. U-Co was significantly related to modelled Co intake (R(2)=0.48, adults and R(2)=0.47, children; log-log relationship). Consumption of legumes, i.e. sweet potato leaves (polluted) and cereals+fish (lakeside) was the largest contributor to Co intake in adults, whereas dust ingestion appeared to contribute substantially in children in the polluted area. In conclusion, dietary Co is the main source of Co exposure in the polluted area and Co is efficiently transferred from soil and water in the human food chain. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. An assessment of sources and pathways of human exposure to polybrominated diphenyl ethers in the United States.

    Science.gov (United States)

    Johnson-Restrepo, Boris; Kannan, Kurunthachalam

    2009-07-01

    Polybrominated diphenyl ethers (PBDEs) are ubiquitous in the indoor environment, owing to their use in consumer products ranging from electronics to mattresses, furniture, and carpets. People are exposed to PBDEs through inhalation of indoor air and ingestion, and dermal absorption of dust particles present in the air. In this study, concentrations of PBDEs were determined in indoor air and house dust collected from homes in Albany, New York, USA. Based on the measured concentrations of PBDEs in indoor air and dust, we estimated daily exposure dose (DED) of PBDEs. In addition, we used previously published PBDE concentrations reported for breast milk from Massachusetts, USA [Johnson-Restrepo, B., Addink, R., Wong, C., Arcaro, K., Kannan, K., 2007. Polybrominated diphenyl ethers and organochlorine pesticides in human breast milk from Massachusetts. USA. J. Environ. Monitor. 9, 1205-1212] and foodstuffs collected from Texas and Florida, USA [Schecter, A., Päpke, O., Harris, T.R., Tung, K.C., Musumba, A., Olson, J., Birnbaum, L., 2006. Polybrominated diphenyl ether (PBDE) levels in an expanded market basket survey of U.S. food and estimated PBDE dietary intake by age and sex. Environ. Health Perspect. 114, 1515-1520, Johnson-Restrepo, B., Kannan, K., Addink, R., Adams, D.H., 2005b. Polybrominated diphenyl ethers and polychlorinated biphenyls in a marine foodweb of coastal Florida. Environ. Sci. Technol. 39, 8243-8250], in an estimation of dietary exposure to PBDEs. The exposure assessment was performed for five age groups: infants (accounting for, on average, 56-77% of the total PBDE intake.

  8. A case study to illustrate the utility of the Aggregate Exposure Pathway and Adverse Outcome Pathway frameworks for integrating human health and ecological data into cumulative risk assessment

    Science.gov (United States)

    Cumulative risk assessment (CRA) methods, which evaluate the risk of multiple adverse outcomes (AOs) from multiple chemicals, promote the use of a conceptual site model (CSM) to integrate risk from relevant stressors. The Adverse Outcome Pathway (AOP) framework can inform these r...

  9. Interactions between polymorphisms in the aryl hydrocarbon receptor signalling pathway and exposure to persistent organochlorine pollutants affect human semen quality

    DEFF Research Database (Denmark)

    Brokken, L J S; Lundberg, P J; Spanò, M

    2014-01-01

    Persistent organic pollutants (POPs) may affect male reproductive function. Many dioxin-like POPs exert their effects by activation of the aryl hydrocarbon receptor (AHR) signalling pathway. We analysed whether gene-environment interactions between polymorphisms in AHR (R554K) and AHR repressor (...

  10. Freshwater exposure pathways in the Nordic countries

    International Nuclear Information System (INIS)

    Tveten, U.

    1984-06-01

    The report relates to a subproject under a Nordic project called ''Large reactor accidents - consequences and mitigating actions''. The report summarizes information available, primarily in the Nordic countries, on freshwater exposure pathways. Experimental and theoretical data concerning the deposition and run-off of the nuclides *sp90*Sr and*Sp137*Cs is presented. Internal exposure via drinking water and freshwater fish is dealt with, as well as external exposure due to swimming, boating, contact with fishing utensils and use of beach areas. In addition is exposure via irrigated agricultural products considered. (RF)

  11. Human exposure to aluminium.

    Science.gov (United States)

    Exley, Christopher

    2013-10-01

    Human activities have circumvented the efficient geochemical cycling of aluminium within the lithosphere and therewith opened a door, which was previously only ajar, onto the biotic cycle to instigate and promote the accumulation of aluminium in biota and especially humans. Neither these relatively recent activities nor the entry of aluminium into the living cycle are showing any signs of abating and it is thus now imperative that we understand as fully as possible how humans are exposed to aluminium and the future consequences of a burgeoning exposure and body burden. The aluminium age is upon us and there is now an urgent need to understand how to live safely and effectively with aluminium.

  12. Human exposure to nickel

    Energy Technology Data Exchange (ETDEWEB)

    Grandjean, P

    1984-01-01

    In order of abundance in the earth's crust, nickel ranks as the 24th element and has been detected in different media in all parts of the biosphere. Thus, humans are constantly exposed to this ubiquitous element, though in variable amounts. Occupational exposures may lead to the retention of 100 micrograms of nickel per day. Environmental nickel levels depend particularly on natural sources, pollution from nickel-manufacturing industries and airborne particles from combustion of fossil fuels. Absorption from atmospheric nickel pollution is of minor concern. Vegetables usually contain more nickel than do other food items. Certain products, such as baking powder and cocoa powder, have been found to contain excessive amounts of nickel, perhaps related to nickel leaching during the manufacturing process. Soft drinking-water and acid beverages may dissolve nickel from pipes and containers. Scattered studies indicate a highly variable dietary intake of nickel, but most averages are about 200-300 micrograms/day. In addition, skin contact to a multitude of metal objects may be of significance to the large number of individuals suffering from contact dermatitis and nickel allergy. Finally, nickel alloys are often used in nails and prostheses for orthopaedic surgery, and various sources may contaminate intravenous fluids. Thus, human nickel exposure originates from a variety of sources and is highly variable. Occupational nickel exposure is of major significance, and leaching of nickel may add to dietary intakes and to cutaneous exposures. 79 references.

  13. Long-term exposure to abnormal glucose levels alters drug metabolism pathways and insulin sensitivity in primary human hepatocytes

    Science.gov (United States)

    Davidson, Matthew D.; Ballinger, Kimberly R.; Khetani, Salman R.

    2016-06-01

    Hyperglycemia in type 2 diabetes mellitus has been linked to non-alcoholic fatty liver disease, which can progress to inflammation, fibrosis/cirrhosis, and hepatocellular carcinoma. Understanding how chronic hyperglycemia affects primary human hepatocytes (PHHs) can facilitate the development of therapeutics for these diseases. Conversely, elucidating the effects of hypoglycemia on PHHs may provide insights into how the liver adapts to fasting, adverse diabetes drug reactions, and cancer. In contrast to declining PHH monocultures, micropatterned co-cultures (MPCCs) of PHHs and 3T3-J2 murine embryonic fibroblasts maintain insulin-sensitive glucose metabolism for several weeks. Here, we exposed MPCCs to hypo-, normo- and hyperglycemic culture media for ~3 weeks. While albumin and urea secretion were not affected by glucose level, hypoglycemic MPCCs upregulated CYP3A4 enzyme activity as compared to other glycemic states. In contrast, hyperglycemic MPCCs displayed significant hepatic lipid accumulation in the presence of insulin, while also showing decreased sensitivity to insulin-mediated inhibition of glucose output relative to a normoglycemic control. In conclusion, we show for the first time that PHHs exposed to hypo- and hyperglycemia can remain highly functional, but display increased CYP3A4 activity and selective insulin resistance, respectively. In the future, MPCCs under glycemic states can aid in novel drug discovery and mechanistic investigations.

  14. Evaluation of skin and ingestion exposure pathways

    International Nuclear Information System (INIS)

    Aaberg, Rosanne; Logsdon, Joe E.

    1989-06-01

    After a nuclear accident when there has been a release of radionuclides into the atmosphere with consequential deposition on the ground, decisions are necessary on whether protective action guides should be implemented. In order to do this, several pathways for radiation exposure must be evaluated to determine the projected dose to individuals. The objective of this study, conducted by Pacific Northwest Laboratories for the U.S. Environmental Protection Agency, is to provide background information on exposure pathways for use in the development of Protective Action Guides. The relative importance of three exposure pathways that are usually considered to be unimportant compared to other pathways expected to control relocation decisions following a nuclear power plant accident is evaluated. The three pathways are the skin dose from contact with radionuclides transferred from the ground, the skin dose from radionuclides on the ground surface, and ingestion of radionuclides transferred directly to the mouth from the hands or other contaminated surfaces. Ingestion of contaminated food is not included in this evaluation, except for situations where the food is contaminated as a result of actions by the person who consumes the food (e.g., transfer of contamination from hands to food). Estimates of skin and ingestion doses are based on a source term with a radionuclide mix predicted for an SST2-type nuclear accident in an area where the first year reference whole-body dose equivalent from whole body external exposure to gamma radiation plus the committed effective dose equivalent from inhalation of resuspended radionuclides is 1 rem. Appendixes have been included to allow the reader to examine dose factor calculations, source-term data, and quantification of contact and ingestion parameters in more detail

  15. Evaluation of skin and ingestion exposure pathways

    Energy Technology Data Exchange (ETDEWEB)

    Aaberg, Rosanne [Pacific Northwest Laboratory, Richland, WA (United States); Logsdon, Joe E [United States Environmental Protection Agency, Office of Radiation Programs, Washington, DC (United States)

    1989-06-01

    After a nuclear accident when there has been a release of radionuclides into the atmosphere with consequential deposition on the ground, decisions are necessary on whether protective action guides should be implemented. In order to do this, several pathways for radiation exposure must be evaluated to determine the projected dose to individuals. The objective of this study, conducted by Pacific Northwest Laboratories for the U.S. Environmental Protection Agency, is to provide background information on exposure pathways for use in the development of Protective Action Guides. The relative importance of three exposure pathways that are usually considered to be unimportant compared to other pathways expected to control relocation decisions following a nuclear power plant accident is evaluated. The three pathways are the skin dose from contact with radionuclides transferred from the ground, the skin dose from radionuclides on the ground surface, and ingestion of radionuclides transferred directly to the mouth from the hands or other contaminated surfaces. Ingestion of contaminated food is not included in this evaluation, except for situations where the food is contaminated as a result of actions by the person who consumes the food (e.g., transfer of contamination from hands to food). Estimates of skin and ingestion doses are based on a source term with a radionuclide mix predicted for an SST2-type nuclear accident in an area where the first year reference whole-body dose equivalent from whole body external exposure to gamma radiation plus the committed effective dose equivalent from inhalation of resuspended radionuclides is 1 rem. Appendixes have been included to allow the reader to examine dose factor calculations, source-term data, and quantification of contact and ingestion parameters in more detail.

  16. Transcriptional Modulation of the ERK1/2 MAPK and NF-kB pathways in Human Urothelial cells after trivalent arsenical exposure: Implications for urinary bladder cancer

    Science.gov (United States)

    Chronic exposure to drinking water contaminated with inorganic arsenic (iAs) is associated with an increased risk ofurinary bladder (DB) cancers in humans. Rodent models administered particular arsenicals have indicated urothelial necrosis followed by regenerative proliferation i...

  17. Activation of stress-related signalling pathway in human cells upon SiO2 nanoparticles exposure as an early indicator of cytotoxicity

    LENUS (Irish Health Repository)

    Mohamed, Bashir M

    2011-07-29

    Abstract Background Nanomaterials such as SiO2 nanoparticles (SiO2NP) are finding increasing applications in the biomedical and biotechnological fields such as disease diagnostics, imaging, drug delivery, food, cosmetics and biosensors development. Thus, a mechanistic and systematic evaluation of the potential biological and toxic effects of SiO2NP becomes crucial in order to assess their complete safe applicability limits. Results In this study, human monocytic leukemia cell line THP-1 and human alveolar epithelial cell line A549 were exposed to a range of amorphous SiO2NP of various sizes and concentrations (0.01, 0.1 and 0.5 mg\\/ml). Key biological indicators of cellular functions including cell population density, cellular morphology, membrane permeability, lysosomal mass\\/pH and activation of transcription factor-2 (ATF-2) were evaluated utilizing quantitative high content screening (HCS) approach and biochemical techniques. Despite the use of extremely high nanoparticle concentrations, our findings showed a low degree of cytotoxicity within the panel of SiO2NP investigated. However, at these concentrations, we observed the onset of stress-related cellular response induced by SiO2NP. Interestingly, cells exposed to alumina-coated SiO2NP showed low level, and in some cases complete absence, of stress response and this was consistent up to the highest dose of 0.5 mg\\/ml. Conclusions The present study demonstrates and highlights the importance of subtle biological changes downstream of primary membrane and endocytosis-associated phenomena resulting from high dose SiO2NP exposure. Increased activation of transcription factors, such as ATF-2, was quantitatively assessed as a function of i) human cell line specific stress-response, ii) SiO2NP size and iii) concentration. Despite the low level of cytotoxicity detected for the amorphous SiO2NP investigated, these findings prompt an in-depth focus for future SiO2NP-cell\\/tissue investigations based on the combined

  18. Activation of stress-related signalling pathway in human cells upon SiO2 nanoparticles exposure as an early indicator of cytotoxicity

    Directory of Open Access Journals (Sweden)

    Mohamed Bashir

    2011-07-01

    Full Text Available Abstract Background Nanomaterials such as SiO2 nanoparticles (SiO2NP are finding increasing applications in the biomedical and biotechnological fields such as disease diagnostics, imaging, drug delivery, food, cosmetics and biosensors development. Thus, a mechanistic and systematic evaluation of the potential biological and toxic effects of SiO2NP becomes crucial in order to assess their complete safe applicability limits. Results In this study, human monocytic leukemia cell line THP-1 and human alveolar epithelial cell line A549 were exposed to a range of amorphous SiO2NP of various sizes and concentrations (0.01, 0.1 and 0.5 mg/ml. Key biological indicators of cellular functions including cell population density, cellular morphology, membrane permeability, lysosomal mass/pH and activation of transcription factor-2 (ATF-2 were evaluated utilizing quantitative high content screening (HCS approach and biochemical techniques. Despite the use of extremely high nanoparticle concentrations, our findings showed a low degree of cytotoxicity within the panel of SiO2NP investigated. However, at these concentrations, we observed the onset of stress-related cellular response induced by SiO2NP. Interestingly, cells exposed to alumina-coated SiO2NP showed low level, and in some cases complete absence, of stress response and this was consistent up to the highest dose of 0.5 mg/ml. Conclusions The present study demonstrates and highlights the importance of subtle biological changes downstream of primary membrane and endocytosis-associated phenomena resulting from high dose SiO2NP exposure. Increased activation of transcription factors, such as ATF-2, was quantitatively assessed as a function of i human cell line specific stress-response, ii SiO2NP size and iii concentration. Despite the low level of cytotoxicity detected for the amorphous SiO2NP investigated, these findings prompt an in-depth focus for future SiO2NP-cell/tissue investigations based on the

  19. 40 CFR 194.52 - Consideration of exposure pathways.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Consideration of exposure pathways... Individual and Ground-Water Protection Requirements § 194.52 Consideration of exposure pathways. In compliance assessments that analyze compliance with § 191.15 of this chapter, all potential exposure pathways...

  20. An investigation of the ingestion exposure pathways in Hong Kong

    International Nuclear Information System (INIS)

    Yeung, Mankit Ray; Lui, Wai Sing

    1995-01-01

    An investigation of the food supply and the dietetic pattern of Hong Kong was conducted and some of the important factors affecting the ingestion exposure pathways following a severe nuclear accident were examined. It was found that the nuclide concentrations in the vegetables are very sensitive to time and substantial saving in effective dose resulted from ingesting contaminated vegetables can be achieved by appropriate imposition of restriction on the consumption of local produce. The consumption of locally grown vegetables in large quantity and the proximity of the Hong Kong vegetable farms to the Guangdong Nuclear Power Station suggests that the vegetable-human pathway is important and warrants special attention

  1. Pentose pathway in human liver

    International Nuclear Information System (INIS)

    Magnusson, I.; Chandramouli, V.; Schumann, W.C.; Kumaran, K.; Wahren, J.; Landau, B.R.

    1988-01-01

    [1- 14 C]Ribose and [1- 14 C]glucose were given to normal subjects along with glucose loads (1 g per kg of body weight) after administration of diflunisal and acetaminophen, drugs that are excreted in urine as glucuronides. Distributions of 14 C were determined in the carbons of the excreted glucoronides and in the glucose from blood samples drawn from hepatic veins before and after glucagon administration. Eighty percent or more of the 14 C from [1- 14 C]ribose incorporated into the glucuronic acid moiety of the glucuronides was in carbons 1 and 3, with less than 8% in carbon 2. In glucuronic acid from glucuronide excreted when [2- 14 C]glucose was given, 3.5-8.1% of the 14 C was in carbon 1, 2.5-4.3% in carbon 3, and more than 70% in carbon 2. These distributions are in accord with the glucuronides sampling the glucose unit of the glucose 6-phosphate pool that is a component of the pentose pathway and is intermediate in glycogen formation. It is concluded that the glucuronic acid conjugates of the drugs can serve as a noninvasive means of sampling hepatic glucose 6-phosphate. In human liver, as in animal liver, the classical pentose pathway functions, not the L-type pathway, and only a small percentage of the glucose is metabolized via the pathway

  2. SVOC exposure indoors: fresh look at dermal pathways.

    Science.gov (United States)

    Weschler, C J; Nazaroff, W W

    2012-10-01

    This paper critically examines indoor exposure to semivolatile organic compounds (SVOCs) via dermal pathways. First, it demonstrates that--in central tendency--an SVOC's abundance on indoor surfaces and in handwipes can be predicted reasonably well from gas-phase concentrations, assuming that thermodynamic equilibrium prevails. Then, equations are developed, based upon idealized mass-transport considerations, to estimate transdermal penetration of an SVOC either from its concentration in skin-surface lipids or its concentration in air. Kinetic constraints limit air-to-skin transport in the case of SVOCs that strongly sorb to skin-surface lipids. Air-to-skin transdermal uptake is estimated to be comparable to or larger than inhalation intake for many SVOCs of current or potential interest indoors, including butylated hydroxytoluene, chlordane, chlorpyrifos, diethyl phthalate, Galaxolide, geranyl acetone, nicotine (in free-base form), PCB28, PCB52, Phantolide, Texanol and Tonalide. Although air-to-skin transdermal uptake is anticipated to be slow for bisphenol A, we find that transdermal permeation may nevertheless be substantial following its transfer to skin via contact with contaminated surfaces. The paper concludes with explorations of the influence of particles and dust on dermal exposure, the role of clothing and bedding as transport vectors, and the potential significance of hair follicles as transport shunts through the epidermis. Human exposure to indoor pollutants can occur through dietary and nondietary ingestion, inhalation, and dermal absorption. Many factors influence the relative importance of these pathways, including physical and chemical properties of the pollutants. This paper argues that exposure to indoor semivolatile organic compounds (SVOCs) through the dermal pathway has often been underestimated. Transdermal permeation of SVOCs can be substantially greater than is commonly assumed. Transport of SVOCs from the air to and through the skin is

  3. Modeled exposure assessment via inhalation and dermal pathways to airborne semivolatile organic compounds (SVOCs) in residences.

    Science.gov (United States)

    Shi, Shanshan; Zhao, Bin

    2014-05-20

    Exposure to airborne semivolatile organic compounds (SVOCs) in indoor and outdoor environments of humans may lead to adverse health risks. Thus, we established a model to evaluate exposure to airborne SVOCs. In this model, SVOCs phase-specific concentrations were estimated by a kinetic partition model accounting for particle dynamics. The exposure pathways to airborne SVOCs included inhalation exposure to gas- and particle-phases, dermal exposure by direct gas-to-skin pathway and dermal exposure by direct particle deposition. Exposures of defined "reference people" to two typical classifications of SVOCs, one generated from both indoor and outdoor sources, represented by polycyclic aromatic hydrocarbons (PAHs), and the other generated mainly from only indoor sources, represented by di 2-ethylhexyl phthalate (DEHP), were analyzed as an example application of the model. For PAHs with higher volatility, inhalation exposure to gas-phase, ranging from 6.03 to 16.4 ng/kg/d, accounted for the most of the exposure to the airborne phases. For PAHs with lower volatility, inhalation exposure to particle-phase, ranging from 1.48 to 1.53 ng/kg/d, was the most important exposure pathway. As for DEHP, dermal exposure via direct gas-to-skin pathway was 460 ng/kg/d, which was the most striking exposure pathway when the barrier effect of clothing was neglected.

  4. Human dose pathways of radionuclides in forests

    International Nuclear Information System (INIS)

    Rantavaara, A.

    2009-01-01

    Forest soil, understorey vegetation and trees are all sources of radionuclides and human radiation doses after contaminating atmospheric deposition. People are exposed to radiation externally from sources outside the body and internally via ingestion and inhalation of radionuclides. Understorey vegetation contributes to ingestion doses through berries, herbs, wild honey, mushrooms and game meat; also trees provide feed to terrestrial birds and big game. During stay in forests people are subject to external radiation from forest floor and overstorey, and they may inhale airborne radioactive aerosol or gaseous radionuclides in ground level air. In the early phase of contamination also resuspended radionuclides may add to the internal dose of people via inhalation. People in Nordic countries are most exposed to radiation via ingestion of radionuclides in wild foods. The distribution of radionuclides in forests is changed by environmental processes, and thereby also the significance of various dose pathways to humans will change with time. External exposure is received in living environment from contaminated stemwood used as building timber and for manufacturing of furniture and other wood products. The aim of this paper is to outline the significance of various human dose pathways of radionuclides in forests considering the public and workers in forestry and production of bioenergy. Examples on effective doses are given based on two historical events, atmospheric nuclear weapon tests (mostly in 1950's and in 1960's) and the Chernobyl nuclear power plant accident in 1986. (au)

  5. Breastfeeding as an Exposure Pathway for Perfluorinated Alkylates

    DEFF Research Database (Denmark)

    Mogensen, Ulla B; Grandjean, Philippe; Nielsen, Flemming

    2015-01-01

    Perfluorinated alkylate substances (PFASs) are widely used and have resulted in human exposures worldwide. PFASs occur in breast milk, and the duration of breastfeeding is associated with serum-PFAS concentrations in children. To determine the time-dependent impact of this exposure pathway, we...... examined the serum concentrations of five major PFASs in a Faroese birth cohort at birth, and at ages 11, 18, and 60 months. Information about the children's breastfeeding history was obtained from the mothers. The trajectory of serum-PFAS concentrations during months with and without breastfeeding...... was examined by linear mixed models that accounted for the correlations of the PFAS measurements for each child. The models were adjusted for confounders such as body size. The duration of exclusive breastfeeding was associated with increases of most PFAS concentrations by up to 30% per month, with lower...

  6. Contribution of the Exposure Pathways After a Severe Accident

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Joeun; Hwang, Wontae; Han, Moonhee [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Jae, Moosung [Hanyang University, Seoul (Korea, Republic of)

    2016-10-15

    A radiological dose assessment calculates the amount of radiation energy absorbed by a potentially exposed individual as a result of a specific exposure. Public can be exposure from several exposure pathways. External doses occur when the body is exposed to radioactive material outside the body. When making the emergency preparedness for severe accident from NPPs, therefore, we need to have comprehension about those exposure pathways. Thus, in this study, an evaluation of external and internal dose from radioactive materials during severe accident was performed to find out exposure pathway from which the dose has the highest value for several radionuclides. The basic study to make out the relation between exposure pathways and dose from them was performed. In the emergency phase, the most affecting nuclide type on public was noble gas, especially {sup 133}Xe, and the dominant exposure pathway was could shine. Also, in the long term-phase, the most affecting nuclide type on public was fission product, especially {sup 90}Sr, and the dominant exposure pathway was water ingestion. The information of the dose composition from exposure pathway obtained in this study might be basic data for making emergency preparedness plan for severe accident. In the future, assessment of the source term is expected to enhance the reliability of dose assessment during severe accident.

  7. Genome Wide Evaluation of Normal Human Tissue in Response to Controlled, In vivo Low-Dose Low LET Ionizing Radiation Exposure: Pathways and Mechanisms Final Report, September 2013

    Energy Technology Data Exchange (ETDEWEB)

    Rocke, David M. [University of California Davis

    2013-09-09

    During course of this project, we have worked in several areas relevant to low-dose ionizing radiation. Using gene expression to measure biological response, we have examined the response of human skin exposed in-vivo to radation, human skin exposed ex-vivo to radiation, and a human-skin model exposed to radiation. We have learned a great deal about the biological response of human skin to low-dose ionizing radiation.

  8. EPA EcoBox Tools by Exposure Pathways - Exposure Pathways In ERA

    Science.gov (United States)

    Eco-Box is a toolbox for exposure assessors. Its purpose is to provide a compendium of exposure assessment and risk characterization tools that will present comprehensive step-by-step guidance and links to relevant exposure assessment data bases

  9. A Case Study Application of the Aggregate Exposure Pathway (AEP) and Adverse Outcome Pathway (AOP) Frameworks to Facilitate the Integration of Human Health and Ecological End Points for Cumulative Risk Assessment (CRA)

    Science.gov (United States)

    Cumulative risk assessment (CRA) methods promote the use of a conceptual site model (CSM) to apportion exposures and integrate risk from multiple stressors. While CSMs may encompass multiple species, evaluating end points across taxa can be challenging due to data availability an...

  10. The modelling of external exposure and inhalation pathways in COSYMA

    International Nuclear Information System (INIS)

    Brown, J.; Simmonds, JR.; Ehrhardt, J.; Hasemann, I.

    1991-01-01

    Following an accidental release of radionuclides to atmosphere the major direct exposure pathways of concern are: external irradiation from material in the cloud; internal exposure following inhalation of material in the cloud; external irradiation from material deposited on the ground; and external irradiation due to contamination of skin and clothes. In addition material resuspended from the ground can be inhaled and lead to internal exposure. In this paper the way that these exposure pathways are modelled in COSYMA is described. At present in COSYMA external exposure from deposited material is modelled using a dataset of doses per unit deposit of various radionuclides. This dataset, is based on activity deposited on undisturbed soil. The basic data are for doses outdoors and shielding factors are used to estimate doses for people indoors. Various groups of people spending different amounts of time indoors and out can be considered and shielding factors appropriate to three building types can be adopted. A more complex model has also been developed to predict radiation exposure following deposition to different surfaces in the environment. This model called EXPURT is briefly described in this paper. Using EXPURT, doses as a function of time after a single deposit have been calculated for people living in three types of area. These results are described in the paper and compared with those that are currently used in COSYMA. The paper will also discuss what future work is required in this area and the adequacy of existing models

  11. Connectome imaging for mapping human brain pathways.

    Science.gov (United States)

    Shi, Y; Toga, A W

    2017-09-01

    With the fast advance of connectome imaging techniques, we have the opportunity of mapping the human brain pathways in vivo at unprecedented resolution. In this article we review the current developments of diffusion magnetic resonance imaging (MRI) for the reconstruction of anatomical pathways in connectome studies. We first introduce the background of diffusion MRI with an emphasis on the technical advances and challenges in state-of-the-art multi-shell acquisition schemes used in the Human Connectome Project. Characterization of the microstructural environment in the human brain is discussed from the tensor model to the general fiber orientation distribution (FOD) models that can resolve crossing fibers in each voxel of the image. Using FOD-based tractography, we describe novel methods for fiber bundle reconstruction and graph-based connectivity analysis. Building upon these novel developments, there have already been successful applications of connectome imaging techniques in reconstructing challenging brain pathways. Examples including retinofugal and brainstem pathways will be reviewed. Finally, we discuss future directions in connectome imaging and its interaction with other aspects of brain imaging research.

  12. Pathways to Health Risk Exposure in Adult Film Performers

    OpenAIRE

    Grudzen, Corita R.; Ryan, Gery; Margold, William; Torres, Jacqueline; Gelberg, Lillian

    2008-01-01

    Despite being part of a large and legal industry in Los Angeles, little is known about adult film performers’ exposure to health risks and when and how these risks might occur. The objective was to identify exposure to physical, mental, and social health risks and the pathways to such risks among adult film performers and to determine how risks differ between different types of performers, such as men and women. Semi-structured in-depth interviews were conducted with 18 female and ten male pe...

  13. ATP-dependent human RISC assembly pathways.

    Science.gov (United States)

    Yoda, Mayuko; Kawamata, Tomoko; Paroo, Zain; Ye, Xuecheng; Iwasaki, Shintaro; Liu, Qinghua; Tomari, Yukihide

    2010-01-01

    The assembly of RNA-induced silencing complex (RISC) is a key process in small RNA-mediated gene silencing. In humans, small interfering RNAs (siRNAs) and microRNAs (miRNAs) are incorporated into RISCs containing the Argonaute (AGO) subfamily proteins Ago1-4. Previous studies have proposed that, unlike Drosophila melanogaster RISC assembly pathways, human RISC assembly is coupled with dicing and is independent of ATP. Here we show by careful reexamination that, in humans, RISC assembly and dicing are uncoupled, and ATP greatly facilitates RISC loading of small-RNA duplexes. Moreover, all four human AGO proteins show remarkably similar structural preferences for small-RNA duplexes: central mismatches promote RISC loading, and seed or 3'-mid (guide position 12-15) mismatches facilitate unwinding. All these features of human AGO proteins are highly reminiscent of fly Ago1 but not fly Ago2.

  14. A review of models for near-field exposure pathways of chemicals in consumer products

    DEFF Research Database (Denmark)

    Huang, Lei; Ernstoff, Alexi; Fantke, Peter

    2017-01-01

    able to quantify the multiple transfers of chemicals from products used near-field to humans. The present review therefore aims at an in-depth overview of modeling approaches for near-field chemical release and human exposure pathways associated with consumer products. It focuses on lower......-tier, mechanistic models suitable for life cycle assessments (LCA), chemical alternative assessment (CAA) and high-throughput screening risk assessment (HTS). Chemicals in a product enter the near-field via a defined “compartment of entry”, are transformed or transferred to adjacent compartments, and eventually end......Exposure to chemicals in consumer products has been gaining increasing attention, with multiple studies showing that near-field exposures from products is high compared to far-field exposures. Regarding the numerous chemical-product combinations, there is a need for an overarching review of models...

  15. A flexible matrix-based human exposure assessment framework suitable for LCA and CAA

    DEFF Research Database (Denmark)

    Jolliet, Olivier; Ernstoff, Alexi; Huang, Lei

    2016-01-01

    are not applicable to all types of near-field chemical releases from consumer products, e.g. direct dermal application. A consistent near-and far-field framework is needed for life cycle assessment (LCA) and chemical alternative assessment (CAA) to inform mitigation of human exposure to harmful chemicals. To close......Humans can be exposed to chemicals via near-field exposure pathways (e.g. through consumer product use) and far-field exposure pathways (e.g. through environmental emissions along product life cycles). Pathways are often complex where chemicals can transfer directly from products to humans during...... use or exchange between near-and far-field compartments until sub -fractions reach humans via inhalation, ingestion or dermal uptake. Currently, however, multimedia exposure models mainly focus on far-field exposure pathways. Metrics and modeling approaches used in far-field, emission-based models...

  16. Potassium recycling pathways in the human cochlea.

    Science.gov (United States)

    Weber, P C; Cunningham, C D; Schulte, B A

    2001-07-01

    Potential pathways for recycling potassium (K+) used in the maintenance of inner ear electrochemical gradients have been elucidated in animal models. However, little is known about K+ transport in the human cochlea. This study was designed to characterize putative K+ recycling pathways in the human ear and to determine whether observations from animal models can be extrapolated to humans. A prospective laboratory study using an immunohistochemical approach to analyze the distribution of key ion transport mediators in the human cochlea. Human temporal bones were fixed in situ within 1 to 6 hours of death and subsequently harvested at autopsy. Decalcification was accomplished with the aid of microwaving. Immunohistochemical staining was then performed to define the presence and cell type-specific distribution of Na,K-ATPase, sodium-potassium-chloride cotransporter (NKCC), and carbonic anhydrase (CA) in the inner ear. Staining patterns visualized in the human cochlea closely paralleled those seen in other species. Anti-Na,K-ATPase stained strongly the basolateral plasma membrane of strial marginal cells and nerve endings underlying hair cells. This antibody also localized Na,K-ATPase to type II, type IV, and type V fibrocytes in the spiral ligament and in limbal fibrocytes. NKCC was present in the basolateral membrane of strial marginal cells as well as in type II, type V, and limbal fibrocytes. Immunoreactive carbonic anhydrase was present in type I and type III fibrocytes and in epithelial cells lining Reissner's membrane and the spiral prominence. The distribution of several major ion transport proteins in the human cochlea is similar but not identical to that described in various rodent models. These results support the presence of a complex system for recycling and regulating K+ homeostasis in the human cochlea, similar to that described in other mammalian species.

  17. Understanding pathways of exposure using site-specific habits surveys, particularly new pathways and methodologies

    International Nuclear Information System (INIS)

    Grzechnik, M.; McTaggart, K.; Clyne, F.

    2006-01-01

    Full text of publication follows: UK policy on the control of radiation exposure via routine discharges from nuclear licensed sites has long been based on ICRP recommendations that embody the principles of justification of practices, optimisation of protection, and dose limitation. Radiological protection of the public is based on the concept of a critical group of individuals. This group is defined as those people who, as a result of the area they reside and their habits, receive the highest radiation dose due to the operations of a site. Therefore, if the dose to this critical group is acceptable in relation to relevant dose limits and constraints, then other members of the public will receive lower doses. Thus, the principle of critical groups provides overall protection for the public. Surveys to determine local habits involve an integrated methodology, whereby the potential radioactive exposure pathways from liquid and gaseous discharges and direct radiation from the site are investigated. Surveys to identify these habits must be undertaken rigorously for consistency, and have been known to reveal unexpected pathways of radiation exposure. Pathways typically include consumption of local foodstuffs and external exposure. Furthermore, a number of critical groups ma y be identified within a single survey area if the habits of one group do not adequately describe those of the other inhabitants of the area. Survey preparation involves the initial identification of high producers and consumers of local foods in a geographically defined area surrounding the nuclear facility. Pathways can be broken down into three general groups, which include exposure arising from; 1) Terrestrial (gaseous) discharges surveyed within 5 km of the site 2) Direct radiation surveyed within 1 km of the site 3) Aquatic (liquid) discharges surveyed within local areas affected by the discharges, including seas, rivers and sewage works. The survey fieldwork involves interviewing members of the

  18. Human exposure, health hazards, and environmental regulations

    International Nuclear Information System (INIS)

    Steinemann, Anne

    2004-01-01

    United States environmental regulations, intended to protect human health, generally fail to address major sources of pollutants that endanger human health. These sources are surprisingly close to us and within our control, such as consumer products and building materials that we use within our homes, workplaces, schools, and other indoor environments. Even though these indoor sources account for nearly 90% of our pollutant exposure, they are virtually unregulated by existing laws. Even pollutant levels found in typical homes, if found outdoors, would often violate federal environmental standards. This article examines the importance of human exposure as a way to understand and reduce effects of pollutants on human health. Results from exposure studies challenge traditional thinking about pollutant hazards, and reveal deficiencies in our patchwork of laws. And results from epidemiological studies, showing increases in exposure-related diseases, underscore the need for new protections. Because we cannot rely solely on regulations to protect us, and because health effects from exposures can develop insidiously, greater efforts are needed to reduce and prevent significant exposures before they occur. Recommendations include the development and use of safer alternatives to common products, public education on ways to reduce exposure, systematic monitoring of human exposure to pollutants, and a precautionary approach in decision-making

  19. Gene networks and toxicity pathways induced by acute cadmium exposure in adult largemouth bass (Micropterus salmoides).

    Science.gov (United States)

    Mehinto, Alvine C; Prucha, Melinda S; Colli-Dula, Reyna C; Kroll, Kevin J; Lavelle, Candice M; Barber, David S; Vulpe, Christopher D; Denslow, Nancy D

    2014-07-01

    Cadmium is a heavy metal that can accumulate to toxic levels in the environment leading to detrimental effects in animals and humans including kidney, liver and lung injuries. Using a transcriptomics approach, genes and cellular pathways affected by a low dose of cadmium were investigated. Adult largemouth bass were intraperitoneally injected with 20μg/kg of cadmium chloride (mean exposure level - 2.6μg of cadmium per fish) and microarray analyses were conducted in the liver and testis 48h after injection. Transcriptomic profiles identified in response to cadmium exposure were tissue-specific with the most differential expression changes found in the liver tissues, which also contained much higher levels of cadmium than the testis. Acute exposure to a low dose of cadmium induced oxidative stress response and oxidative damage pathways in the liver. The mRNA levels of antioxidants such as catalase increased and numerous transcripts related to DNA damage and DNA repair were significantly altered. Hepatic mRNA levels of metallothionein, a molecular marker of metal exposure, did not increase significantly after 48h exposure. Carbohydrate metabolic pathways were also disrupted with hepatic transcripts such as UDP-glucose, pyrophosphorylase 2, and sorbitol dehydrogenase highly induced. Both tissues exhibited a disruption of steroid signaling pathways. In the testis, estrogen receptor beta and transcripts linked to cholesterol metabolism were suppressed. On the contrary, genes involved in cholesterol metabolism were highly increased in the liver including genes encoding for the rate limiting steroidogenic acute regulatory protein and the catalytic enzyme 7-dehydrocholesterol reductase. Integration of the transcriptomic data using functional enrichment analyses revealed a number of enriched gene networks associated with previously reported adverse outcomes of cadmium exposure such as liver toxicity and impaired reproduction. Copyright © 2014 Elsevier B.V. All rights

  20. Exposure to UV radiation and human health

    Science.gov (United States)

    Kimlin, Michael G.

    2005-08-01

    This paper will overview the significant issues facing researchers in relating the impact of exposure to sunlight and human health. Exposure to solar ultraviolet radiation is the major causative factor in most sun-related skin and eye disorders, however, very little is known quantitatively about human UV exposures. Interestingly, human exposure to sunlight also has a nutritional impact, namely the development of pre-Vitamin D, which is an important nutrient in bone health. New research suggest that low vitamin D status may be a causative factor in the development of selective types of cancer and autoimminue diseases, as well as a contributing factor in bone health. The 'health duality' aspect of sunlight exposure is an interesting and controversial topic that is a research focus of Kimlin's research group.

  1. Pathway Interaction Network Analysis Identifies Dysregulated Pathways in Human Monocytes Infected by Listeria monocytogenes

    Directory of Open Access Journals (Sweden)

    Wufeng Fan

    2017-01-01

    Full Text Available In our study, we aimed to extract dysregulated pathways in human monocytes infected by Listeria monocytogenes (LM based on pathway interaction network (PIN which presented the functional dependency between pathways. After genes were aligned to the pathways, principal component analysis (PCA was used to calculate the pathway activity for each pathway, followed by detecting seed pathway. A PIN was constructed based on gene expression profile, protein-protein interactions (PPIs, and cellular pathways. Identifying dysregulated pathways from the PIN was performed relying on seed pathway and classification accuracy. To evaluate whether the PIN method was feasible or not, we compared the introduced method with standard network centrality measures. The pathway of RNA polymerase II pretranscription events was selected as the seed pathway. Taking this seed pathway as start, one pathway set (9 dysregulated pathways with AUC score of 1.00 was identified. Among the 5 hub pathways obtained using standard network centrality measures, 4 pathways were the common ones between the two methods. RNA polymerase II transcription and DNA replication owned a higher number of pathway genes and DEGs. These dysregulated pathways work together to influence the progression of LM infection, and they will be available as biomarkers to diagnose LM infection.

  2. Human exposure to dioxin from combustion sources

    International Nuclear Information System (INIS)

    Hattemer-Frey, H.A.; Travis, C.C.

    1988-01-01

    Because of their extreme toxicity, much concern and debate has arisen about the nature and extent of human exposure to dioxin. Since municipal solid waste (MSW) incinerators are known to emit polychorinated dibenzo-p-dioxins (PCDDs) and polycholorinated dibenzofurnas (PCDFs) many people who live near MSW incinerators fear that they will be exposed to high levels of dioxin and subsequently develop cancer. What is often overlooked in this debate, however, is the fact that the general population is continuously being exposed to trace amounts of dioxin as exemplified by the fact that virtually all human adipose tissue samples contain dioxin at levels of 3 parts per trillion (ppt) or greater. This paper provides a perspective on MSW incineration as a source of human exposure to dioxin by comparing this exposure source with exposure to background environmental contamination and evaluates some of the potential key sources of PCDD/PCDF input into the enviroment. 32 refs., 3 tabs

  3. Human dose pathways of radionuclides in forests; Forests ecosystems

    Energy Technology Data Exchange (ETDEWEB)

    Rantavaara, A. (Radiation and Nuclear Safety Authority, Research and Environmental Surveillance, Helsinki (Finland))

    2009-06-15

    Forest soil, understorey vegetation and trees are all sources of radionuclides and human radiation doses after contaminating atmospheric deposition. People are exposed to radiation externally from sources outside the body and internally via ingestion and inhalation of radionuclides. Understorey vegetation contributes to ingestion doses through berries, herbs, wild honey, mushrooms and game meat; also trees provide feed to terrestrial birds and big game. During stay in forests people are subject to external radiation from forest floor and overstorey, and they may inhale airborne radioactive aerosol or gaseous radionuclides in ground level air. In the early phase of contamination also resuspended radionuclides may add to the internal dose of people via inhalation. People in Nordic countries are most exposed to radiation via ingestion of radionuclides in wild foods. The distribution of radionuclides in forests is changed by environmental processes, and thereby also the significance of various dose pathways to humans will change with time. External exposure is received in living environment from contaminated stemwood used as building timber and for manufacturing of furniture and other wood products. The aim of this paper is to outline the significance of various human dose pathways of radionuclides in forests considering the public and workers in forestry and production of bioenergy. Examples on effective doses are given based on two historical events, atmospheric nuclear weapon tests (mostly in 1950's and in 1960's) and the Chernobyl nuclear power plant accident in 1986. (au)

  4. Protecting Critical Infrastructure by Identifying Pathways of Exposure to Risk

    Directory of Open Access Journals (Sweden)

    Philip O’Neill

    2013-08-01

    Full Text Available Increasingly, our critical infrastructure is managed and controlled by computers and the information networks that connect them. Cyber-terrorists and other malicious actors understand the economic and social impact that a successful attack on these systems could have. While it is imperative that we defend against such attacks, it is equally imperative that we realize how best to react to them. This article presents the strongest-path method of analyzing all potential pathways of exposure to risk – no matter how indirect or circuitous they may be – in a network model of infrastructure and operations. The method makes direct use of expert knowledge about entities and dependency relationships without the need for any simulation or any other models. By using path analysis in a directed graph model of critical infrastructure, planners can model and assess the effects of a potential attack and develop resilient responses.

  5. Exploring consumer exposure pathways and patterns of use for chemicals in the environment

    Directory of Open Access Journals (Sweden)

    Kathie L. Dionisio

    Full Text Available •To assign use-related information to chemicals to help prioritize which will be given more scrutiny relative to human exposure potential.•Categorical chemical use and functional information are presented through the Chemical/Product Categories Database (CPCat.•CPCat contains information on >43,000 unique chemicals mapped to ∼800 terms categorizing their usage or function.•The CPCat database is useful for modeling and prioritizing human chemical exposures.Humans are exposed to thousands of chemicals in the workplace, home, and via air, water, food, and soil. A major challenge in estimating chemical exposures is to understand which chemicals are present in these media and microenvironments. Here we describe the Chemical/Product Categories Database (CPCat, a new, publically available (http://actor.epa.gov/cpcat database of information on chemicals mapped to “use categories” describing the usage or function of the chemical. CPCat was created by combining multiple and diverse sources of data on consumer- and industrial-process based chemical uses from regulatory agencies, manufacturers, and retailers in various countries. The database uses a controlled vocabulary of 833 terms and a novel nomenclature to capture and streamline descriptors of chemical use for 43,596 chemicals from the various sources. Examples of potential applications of CPCat are provided, including identifying chemicals to which children may be exposed and to support prioritization of chemicals for toxicity screening. CPCat is expected to be a valuable resource for regulators, risk assessors, and exposure scientists to identify potential sources of human exposures and exposure pathways, particularly for use in high-throughput chemical exposure assessment. keywords: ACToR,Aggregated Computational Toxicology Resource,AICS,Australian Inventory of Chemical Substances,CAS RN,Chemical Abstracts Service Registry Number,CDR,Chemical Data Reporting Rule

  6. Perspectives for integrating human and environmental exposure assessments.

    Science.gov (United States)

    Ciffroy, P; Péry, A R R; Roth, N

    2016-10-15

    Integrated Risk Assessment (IRA) has been defined by the EU FP7 HEROIC Coordination action as "the mutual exploitation of Environmental Risk Assessment for Human Health Risk Assessment and vice versa in order to coherently and more efficiently characterize an overall risk to humans and the environment for better informing the risk analysis process" (Wilks et al., 2015). Since exposure assessment and hazard characterization are the pillars of risk assessment, integrating Environmental Exposure assessment (EEA) and Human Exposure assessment (HEA) is a major component of an IRA framework. EEA and HEA typically pursue different targets, protection goals and timeframe. However, human and wildlife species also share the same environment and they similarly inhale air and ingest water and food through often similar overlapping pathways of exposure. Fate models used in EEA and HEA to predict the chemicals distribution among physical and biological media are essentially based on common properties of chemicals, and internal concentration estimations are largely based on inter-species (i.e. biota-to-human) extrapolations. Also, both EEA and HEA are challenged by increasing scientific complexity and resources constraints. Altogether, these points create the need for a better exploitation of all currently existing data, experimental approaches and modeling tools and it is assumed that a more integrated approach of both EEA and HEA may be part of the solution. Based on the outcome of an Expert Workshop on Extrapolations in Integrated Exposure Assessment organized by the HEROIC project in January 2014, this paper identifies perspectives and recommendations to better harmonize and extrapolate exposure assessment data, models and methods between Human Health and Environmental Risk Assessments to support the further development and promotion of the concept of IRA. Ultimately, these recommendations may feed into guidance showing when and how to apply IRA in the regulatory decision

  7. Atmospheric Ionizing Radiation and Human Exposure

    Science.gov (United States)

    Wilson, John W.; Mertens, Christopher J.; Goldhagen, Paul; Friedberg, W.; DeAngelis, G.; Clem, J. M.; Copeland, K.; Bidasaria, H. B.

    2005-01-01

    Atmospheric ionizing radiation is of interest, apart from its main concern of aircraft exposures, because it is a principal source of human exposure to radiations with high linear energy transfer (LET). The ionizing radiations of the lower atmosphere near the Earth s surface tend to be dominated by the terrestrial radioisotopes. especially along the coastal plain and interior low lands, and have only minor contributions from neutrons (11 percent). The world average is substantially larger but the high altitude cities especially have substantial contributions from neutrons (25 to 45 percent). Understanding the world distribution of neutron exposures requires an improved understanding of the latitudinal, longitudinal, altitude and spectral distribution that depends on local terrain and time. These issues are being investigated in a combined experimental and theoretical program. This paper will give an overview of human exposures and describe the development of improved environmental models.

  8. Atmospheric Ionizing Radiation and Human Exposure

    Science.gov (United States)

    Wilson, J. W.; Goldhagen, P.; Friedberg, W.; DeAngelis, G.; Clem, J. M.; Copeland, K.; Bidasaria, H. B.

    2004-01-01

    Atmospheric ionizing radiation is of interest, apart from its main concern of aircraft exposures, because it is a principal source of human exposure to radiations with high linear energy transfer (LET). The ionizing radiations of the lower atmosphere near the Earth s surface tend to be dominated by the terrestrial radioisotopes especially along the coastal plain and interior low lands and have only minor contributions from neutrons (11 percent). The world average is substantially larger but the high altitude cities especially have substantial contributions from neutrons (25 to 45 percent). Understanding the world distribution of neutron exposures requires an improved understanding of the latitudinal, longitudinal, altitude and spectral distribution that depends on local terrain and time. These issues are being investigated in a combined experimental and theoretical program. This paper will give an overview of human exposures and describe the development of improved environmental models.

  9. Assessment of Human Exposure to ENMs.

    Science.gov (United States)

    Jiménez, Araceli Sánchez; van Tongeren, Martie

    2017-01-01

    Human exposure assessment of engineered nanomaterials (ENMs) is hampered, among other factors, by the difficulty to differentiate ENM from other nanomaterials (incidental to processes or naturally occurring) and the lack of a single metric that can be used for health risk assessment. It is important that the exposure assessment is carried out throughout the entire life-cycle as releases can occur at the different stages of the product life-cycle, from the synthesis, manufacture of the nano-enable product (occupational exposure) to the professional and consumer use of nano-enabled product (consumer exposure) and at the end of life.Occupational exposure surveys should follow a tiered approach, increasing in complexity in terms of instruments used and sampling strategy applied with higher tiers in order tailor the exposure assessment to the specific materials used and workplace exposure scenarios and to reduce uncertainty in assessment of exposure. Assessment of consumer exposure and of releases from end-of-life processes currently relies on release testing of nano-enabled products in laboratory settings.

  10. Human Exposure Assessment for Air Pollution.

    Science.gov (United States)

    Han, Bin; Hu, Li-Wen; Bai, Zhipeng

    2017-01-01

    Assessment of human exposure to air pollution is a fundamental part of the more general process of health risk assessment. The measurement methods for exposure assessment now include personal exposure monitoring, indoor-outdoor sampling, mobile monitoring, and exposure assessment modeling (such as proximity models, interpolation model, air dispersion models, and land-use regression (LUR) models). Among these methods, personal exposure measurement is considered to be the most accurate method of pollutant exposure assessment until now, since it can better quantify observed differences and better reflect exposure among smaller groups of people at ground level. And since the great differences of geographical environment, source distribution, pollution characteristics, economic conditions, and living habits, there is a wide range of differences between indoor, outdoor, and individual air pollution exposure in different regions of China. In general, the indoor particles in most Chinese families comprise infiltrated outdoor particles, particles generated indoors, and a few secondary organic aerosol particles, and in most cases, outdoor particle pollution concentrations are a major contributor to indoor concentrations in China. Furthermore, since the time, energy, and expense are limited, it is difficult to measure the concentration of pollutants for each individual. In recent years, obtaining the concentration of air pollutants by using a variety of exposure assessment models is becoming a main method which could solve the problem of the increasing number of individuals in epidemiology studies.

  11. Arsenic exposure induces the Warburg effect in cultured human cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Fei; Severson, Paul; Pacheco, Samantha; Futscher, Bernard W.; Klimecki, Walter T., E-mail: klimecki@pharmacy.arizona.edu

    2013-08-15

    Understanding how arsenic exacts its diverse, global disease burden is hampered by a limited understanding of the particular biological pathways that are disrupted by arsenic and underlie pathogenesis. A reductionist view would predict that a small number of basic pathways are generally perturbed by arsenic, and manifest as diverse diseases. Following an initial observation that arsenite-exposed cells in culture acidify their media more rapidly than control cells, the report here shows that low level exposure to arsenite (75 ppb) is sufficient to induce aerobic glycolysis (the Warburg effect) as a generalized phenomenon in cultured human primary cells and cell lines. Expanded studies in one such cell line, the non-malignant pulmonary epithelial line, BEAS-2B, established that the arsenite-induced Warburg effect was associated with increased accumulation of intracellular and extracellular lactate, an increased rate of extracellular acidification, and inhibition by the non-metabolized glucose analog, 2-deoxy-D-glucose. Associated with the induction of aerobic glycolysis was a pathway-wide induction of glycolysis gene expression, as well as protein accumulation of an established glycolysis master-regulator, hypoxia-inducible factor 1A. Arsenite-induced alteration of energy production in human cells represents the type of fundamental perturbation that could extend to many tissue targets and diseases. - Highlights: • Chronic arsenite exposure induces aerobic glycolysis, dubbed the “Warburg effect”. • Arsenite-induced Warburg effect is a general phenomenon in cultured human cells. • HIF-1A may mediate arsenite induced Warburg effect.

  12. Arsenic exposure induces the Warburg effect in cultured human cells

    International Nuclear Information System (INIS)

    Zhao, Fei; Severson, Paul; Pacheco, Samantha; Futscher, Bernard W.; Klimecki, Walter T.

    2013-01-01

    Understanding how arsenic exacts its diverse, global disease burden is hampered by a limited understanding of the particular biological pathways that are disrupted by arsenic and underlie pathogenesis. A reductionist view would predict that a small number of basic pathways are generally perturbed by arsenic, and manifest as diverse diseases. Following an initial observation that arsenite-exposed cells in culture acidify their media more rapidly than control cells, the report here shows that low level exposure to arsenite (75 ppb) is sufficient to induce aerobic glycolysis (the Warburg effect) as a generalized phenomenon in cultured human primary cells and cell lines. Expanded studies in one such cell line, the non-malignant pulmonary epithelial line, BEAS-2B, established that the arsenite-induced Warburg effect was associated with increased accumulation of intracellular and extracellular lactate, an increased rate of extracellular acidification, and inhibition by the non-metabolized glucose analog, 2-deoxy-D-glucose. Associated with the induction of aerobic glycolysis was a pathway-wide induction of glycolysis gene expression, as well as protein accumulation of an established glycolysis master-regulator, hypoxia-inducible factor 1A. Arsenite-induced alteration of energy production in human cells represents the type of fundamental perturbation that could extend to many tissue targets and diseases. - Highlights: • Chronic arsenite exposure induces aerobic glycolysis, dubbed the “Warburg effect”. • Arsenite-induced Warburg effect is a general phenomenon in cultured human cells. • HIF-1A may mediate arsenite induced Warburg effect

  13. Gene networks and toxicity pathways induced by acute cadmium exposure in adult largemouth bass (Micropterus salmoides)

    International Nuclear Information System (INIS)

    Mehinto, Alvine C.; Prucha, Melinda S.; Colli-Dula, Reyna C.; Kroll, Kevin J.; Lavelle, Candice M.; Barber, David S.; Vulpe, Christopher D.; Denslow, Nancy D.

    2014-01-01

    Highlights: • Low-level acute cadmium exposure elicited tissue-specific gene expression changes. • Molecular initiating events included oxidative stress and disruption of DNA repair. • Metallothionein, a marker of metal exposure, was not significantly affected. • We report effects of cadmium on cholesterol metabolism and steroid synthesis. • Diabetic complications and impaired reproduction are potential adverse outcomes. - Abstract: Cadmium is a heavy metal that can accumulate to toxic levels in the environment leading to detrimental effects in animals and humans including kidney, liver and lung injuries. Using a transcriptomics approach, genes and cellular pathways affected by a low dose of cadmium were investigated. Adult largemouth bass were intraperitoneally injected with 20 μg/kg of cadmium chloride (mean exposure level – 2.6 μg of cadmium per fish) and microarray analyses were conducted in the liver and testis 48 h after injection. Transcriptomic profiles identified in response to cadmium exposure were tissue-specific with the most differential expression changes found in the liver tissues, which also contained much higher levels of cadmium than the testis. Acute exposure to a low dose of cadmium induced oxidative stress response and oxidative damage pathways in the liver. The mRNA levels of antioxidants such as catalase increased and numerous transcripts related to DNA damage and DNA repair were significantly altered. Hepatic mRNA levels of metallothionein, a molecular marker of metal exposure, did not increase significantly after 48 h exposure. Carbohydrate metabolic pathways were also disrupted with hepatic transcripts such as UDP-glucose, pyrophosphorylase 2, and sorbitol dehydrogenase highly induced. Both tissues exhibited a disruption of steroid signaling pathways. In the testis, estrogen receptor beta and transcripts linked to cholesterol metabolism were suppressed. On the contrary, genes involved in cholesterol metabolism were highly

  14. Gene networks and toxicity pathways induced by acute cadmium exposure in adult largemouth bass (Micropterus salmoides)

    Energy Technology Data Exchange (ETDEWEB)

    Mehinto, Alvine C., E-mail: alvinam@sccwrp.org [Southern California Coastal Water Research Project, Costa Mesa, CA 92626 (United States); Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611 (United States); Prucha, Melinda S. [Department of Human Genetics, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322 (United States); Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611 (United States); Colli-Dula, Reyna C.; Kroll, Kevin J.; Lavelle, Candice M.; Barber, David S. [Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611 (United States); Vulpe, Christopher D. [Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720 (United States); Denslow, Nancy D. [Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611 (United States)

    2014-07-01

    Highlights: • Low-level acute cadmium exposure elicited tissue-specific gene expression changes. • Molecular initiating events included oxidative stress and disruption of DNA repair. • Metallothionein, a marker of metal exposure, was not significantly affected. • We report effects of cadmium on cholesterol metabolism and steroid synthesis. • Diabetic complications and impaired reproduction are potential adverse outcomes. - Abstract: Cadmium is a heavy metal that can accumulate to toxic levels in the environment leading to detrimental effects in animals and humans including kidney, liver and lung injuries. Using a transcriptomics approach, genes and cellular pathways affected by a low dose of cadmium were investigated. Adult largemouth bass were intraperitoneally injected with 20 μg/kg of cadmium chloride (mean exposure level – 2.6 μg of cadmium per fish) and microarray analyses were conducted in the liver and testis 48 h after injection. Transcriptomic profiles identified in response to cadmium exposure were tissue-specific with the most differential expression changes found in the liver tissues, which also contained much higher levels of cadmium than the testis. Acute exposure to a low dose of cadmium induced oxidative stress response and oxidative damage pathways in the liver. The mRNA levels of antioxidants such as catalase increased and numerous transcripts related to DNA damage and DNA repair were significantly altered. Hepatic mRNA levels of metallothionein, a molecular marker of metal exposure, did not increase significantly after 48 h exposure. Carbohydrate metabolic pathways were also disrupted with hepatic transcripts such as UDP-glucose, pyrophosphorylase 2, and sorbitol dehydrogenase highly induced. Both tissues exhibited a disruption of steroid signaling pathways. In the testis, estrogen receptor beta and transcripts linked to cholesterol metabolism were suppressed. On the contrary, genes involved in cholesterol metabolism were highly

  15. Exploring consumer exposure pathways and patterns of use for chemicals in the environment.

    Science.gov (United States)

    Dionisio, Kathie L; Frame, Alicia M; Goldsmith, Michael-Rock; Wambaugh, John F; Liddell, Alan; Cathey, Tommy; Smith, Doris; Vail, James; Ernstoff, Alexi S; Fantke, Peter; Jolliet, Olivier; Judson, Richard S

    2015-01-01

    Humans are exposed to thousands of chemicals in the workplace, home, and via air, water, food, and soil. A major challenge in estimating chemical exposures is to understand which chemicals are present in these media and microenvironments. Here we describe the Chemical/Product Categories Database (CPCat), a new, publically available (http://actor.epa.gov/cpcat) database of information on chemicals mapped to "use categories" describing the usage or function of the chemical. CPCat was created by combining multiple and diverse sources of data on consumer- and industrial-process based chemical uses from regulatory agencies, manufacturers, and retailers in various countries. The database uses a controlled vocabulary of 833 terms and a novel nomenclature to capture and streamline descriptors of chemical use for 43,596 chemicals from the various sources. Examples of potential applications of CPCat are provided, including identifying chemicals to which children may be exposed and to support prioritization of chemicals for toxicity screening. CPCat is expected to be a valuable resource for regulators, risk assessors, and exposure scientists to identify potential sources of human exposures and exposure pathways, particularly for use in high-throughput chemical exposure assessment.

  16. Variation in calculated human exposure. Comparison of calculations with seven European human exposure models

    NARCIS (Netherlands)

    Swartjes F; ECO

    2003-01-01

    Twenty scenarios, differing with respect to land use, soil type and contaminant, formed the basis for calculating human exposure from soil contaminants with the use of models contributed by seven European countries (one model per country). Here, the human exposures to children and children

  17. The Global Food System as a Transport Pathway for Hazardous Chemicals: The Missing Link between Emissions and Exposure

    OpenAIRE

    Ng, Carla A.; von Goetz, Natalie

    2016-01-01

    Background: Food is a major pathway for human exposure to hazardous chemicals. The modern food system is becoming increasingly complex and globalized, but models for food-borne exposure typically assume locally derived diets or use concentrations directly measured in foods without accounting for food origin. Such approaches may not reflect actual chemical intakes because concentrations depend on food origin, and representative analysis is seldom available. Processing, packaging, storage, and ...

  18. Harmonizing human exposure and toxicity characterization

    DEFF Research Database (Denmark)

    Fantke, Peter; Jolliet, O.; McKone, T.E.

    2017-01-01

    The UNEP-SETAC Life Cycle Initiative has launched a project to provide global guidance and build consensus on environmental life cycle impact assessment (LCIA) indicators. Human health effects from exposure to toxic chemicals was selected as impact category due to high relevance of human toxicity...... and harmonizing human toxicity characterization in LCIA. Building on initial work for the far-field and indoor air environments, and combining it with latest work on near-field consumer and occupational exposure assessment, dose-response and severity data, we aim at providing revised guidance on the development...... and use of impact factors for toxic chemicals. We propose to couple fate processes in consumer and occupational environments with existing environmental compartments and processes via a consistent and mass balance-based set of transfer fractions to quantify overall aggregated exposure to toxic substances...

  19. Human health effects of exposure to cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Hallenbeck, W.H.

    1986-01-01

    The health effects of human exposure to cadmium are discussed with emphases on intake, absorption, body burden, and excretion; osteomalacia in Japan; hypertension; and proteinuria, emphysema, osteomalacia, and cancer in workers. Elevated blood pressure has not been observed as a result of excessive exposures to cadmium in Japan or the workplace. Renal tubular dysfunction and consequent proteinuria is generally accepted as the main effect following long-term, low-level exposure to cadmium. Studies of workers show that proteinuria may develop after the first year of exposure or many years after the last exposure. Proteinuria and deterioration of renal function may continue even after cessation of exposure. The immediate health significance of low-level proteinuria is still under debate. However, there is evidence that long-term renal tubular dysfunction may lead to abnormalities of calcium metabolism and osteomalacia. The few autopsy and cross-sectional studies of workers do not permit conclusions to be drawn regarding the relationship between cadmium exposure and emphysema. Retrospective and historical-prospective studies are needed to settle this important question. No conclusive evidence has been published regarding cadmium-induced cancer in humans. However, there is sufficient evidence to regard cadmium as a suspect renal and prostate carcinogen. Because of equivocal results and the absence of dose-response relationships, the studies reviewed should be used with caution in making regulatory decisions and low-dose risk assessments. 62 references.

  20. Human health effects of exposure to cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Hallenbeck, W.H.

    1984-02-15

    The health effects of human exposure to cadmium are discussed with emphasis on intake, absorption, body burden, and excretion; osteomalacia in Japan; hypertension; and proteinuria, emphysema, osteomalacia, and cancer in workers. Elevated blood pressure has not been observed as a result of excessive exposures to cadmium in Japan or the workplace. Renal tubular dysfunction and consequent proteinuria is generally accepted as the main effect following long-term, low-level exposure to cadmium. Studies of workers show that proteinuria may develop after the first year of exposure or many years after the last exposure. Proteinuria and deterioration of renal function may continue even after cessation of exposure. The immediate health significance of low-level proteinuria is still under debate. However, there is evidence that long-term renal tubular dysfunction may lead to abnormalities of calcium metabolism and osteomalacia. The few autopsy and cross-sectional studies of workers do not permit conclusions to be drawn regarding the relationship between cadmium exposure and emphysema. Retrospective and historical-prospective studies are needed to settle this important question. No conclusive evidence has been published regarding cadmium-induced cancer in humans. However, there is sufficient evidence to regard cadmium as a suspect renal and prostate carcinogen. Because of equivocal results and the absence of dose-response relationships, the studies reviewed should be used with caution in making regulatory decisions and low-dose risk assessments.

  1. Completing the Link between Exposure Science and Toxicology for Improved Environmental Health Decision Making: The Aggregate Exposure Pathway Framework.

    Science.gov (United States)

    Teeguarden, Justin G; Tan, Yu-Mei; Edwards, Stephen W; Leonard, Jeremy A; Anderson, Kim A; Corley, Richard A; Kile, Molly L; Simonich, Staci M; Stone, David; Tanguay, Robert L; Waters, Katrina M; Harper, Stacey L; Williams, David E

    2016-05-03

    Driven by major scientific advances in analytical methods, biomonitoring, computation, and a newly articulated vision for a greater impact in public health, the field of exposure science is undergoing a rapid transition from a field of observation to a field of prediction. Deployment of an organizational and predictive framework for exposure science analogous to the "systems approaches" used in the biological sciences is a necessary step in this evolution. Here we propose the aggregate exposure pathway (AEP) concept as the natural and complementary companion in the exposure sciences to the adverse outcome pathway (AOP) concept in the toxicological sciences. Aggregate exposure pathways offer an intuitive framework to organize exposure data within individual units of prediction common to the field, setting the stage for exposure forecasting. Looking farther ahead, we envision direct linkages between aggregate exposure pathways and adverse outcome pathways, completing the source to outcome continuum for more meaningful integration of exposure assessment and hazard identification. Together, the two frameworks form and inform a decision-making framework with the flexibility for risk-based, hazard-based, or exposure-based decision making.

  2. A groundwater mass flux model for screening the groundwater-to-indoor-air exposure pathway

    Energy Technology Data Exchange (ETDEWEB)

    McHugh, T.; Blanc, P.C. de; Connor, J. [Groundwater Services Inc, Houston, TX (United States)

    2003-07-01

    The potential for human exposure via volatilisation of groundwater contaminants into indoor air has been a focus of increasing concern in recent years. At a small number of sites, elevated indoor vapour concentrations have been measured within buildings overlying shallow groundwater contaminated with chlorinated solvents, causing public concern over the potential for similar problems at other corrective action sites. In addition, use of the screening-levelmodel developed by Johnson and Ettinger (1991) for the groundwater-to-indoor-air exposure pathway has suggested that low microgram per litre (ug/L)-range concentrations of either chlorinated or non-chlorinated volatile organic compounds dissolved in groundwater could result in indoor vapour concentrations in excess of applicable risk-based exposure limits. As an alternative screening tool, this paper presents a groundwater mass flux model for evaluation of transport to indoor air. The mass flux model is intended to serve as a highly conservative screening tool that over-predicts groundwater-to-indoor-air mass flux, yet still provides sufficient sensitivity to identify sites for which the groundwater-to-indoor air exposure pathway is not a concern. (orig.)

  3. Human biological monitoring of occupational genotoxic exposures

    DEFF Research Database (Denmark)

    Knudsen, Lisbeth E.; Sorsa, M

    1993-01-01

    Human biological monitoring is a valuable tool for exposure assessment in groups of persons occupationally exposed to genotoxic agents. If the monitoring activity covers genetic material the term genetic monitoring is used. The methods used for genetic monitoring are either substance specific, e......) occupational exposure limit value of styrene in ambient air. The consideration of ethical issues in human genetic monitoring is an important but often overlooked aspect. This includes the scientific and preventional relevance of performing a test on individuals, pre- and post study information of donors...

  4. EPA EcoBox Tools by Exposure Pathways

    Science.gov (United States)

    Eco-Box is a toolbox for exposure assessors. Its purpose is to provide a compendium of exposure assessment and risk characterization tools that will present comprehensive step-by-step guidance and links to relevant exposure assessment data bases

  5. EPA EcoBox Tools by Exposure Pathways - Air

    Science.gov (United States)

    Eco-Box is a toolbox for exposure assessors. Its purpose is to provide a compendium of exposure assessment and risk characterization tools that will present comprehensive step-by-step guidance and links to relevant exposure assessment data bases

  6. EPA EcoBox Tools by Exposure Pathways - Soil

    Science.gov (United States)

    Eco-Box is a toolbox for exposure assessors. Its purpose is to provide a compendium of exposure assessment and risk characterization tools that will present comprehensive step-by-step guidance and links to relevant exposure assessment data bases

  7. Human exposure to low level ionising radiation

    International Nuclear Information System (INIS)

    Paix, David

    1988-01-01

    This paper describes the low-level radiation sources and their effects on human populations, from a global perspective. 'Low-level' means exposures in the range of the natural background to which everybody is exposed. The quoted values are whole-world averages, but individual variations are mentioned in a few cases. (author). 22 refs

  8. Human health and exposure to electromagnetic radiation

    International Nuclear Information System (INIS)

    Dennis, J.A.; Muirhead, C.R.; Ennis, J.R.

    1992-07-01

    This review consists of three main parts. In the first the general features of electromagnetic fields and their interactions with the human body are described. The second part deals with the epidemiological evidence for effects on general health and birth outcome. The third part describes the epidemiological evidence from occupational and residential studies of a possible association between electromagnetic field exposures and cancer. (author)

  9. Post exposure prophylaxis against human immunodeficiency virus ...

    African Journals Online (AJOL)

    Objective: To determine the level of awareness, knowledge and practice of human immunodeficiency virus post exposure prophylaxis (HIV PEP) among paediatricians in Nigeria. Methodology: The study was a cross sectional questionnairebased survey conducted among paediatrcians that attended the Paediatric ...

  10. A translatable predictor of human radiation exposure.

    Science.gov (United States)

    Lucas, Joseph; Dressman, Holly K; Suchindran, Sunil; Nakamura, Mai; Chao, Nelson J; Himburg, Heather; Minor, Kerry; Phillips, Gary; Ross, Joel; Abedi, Majid; Terbrueggen, Robert; Chute, John P

    2014-01-01

    Terrorism using radiological dirty bombs or improvised nuclear devices is recognized as a major threat to both public health and national security. In the event of a radiological or nuclear disaster, rapid and accurate biodosimetry of thousands of potentially affected individuals will be essential for effective medical management to occur. Currently, health care providers lack an accurate, high-throughput biodosimetric assay which is suitable for the triage of large numbers of radiation injury victims. Here, we describe the development of a biodosimetric assay based on the analysis of irradiated mice, ex vivo-irradiated human peripheral blood (PB) and humans treated with total body irradiation (TBI). Interestingly, a gene expression profile developed via analysis of murine PB radiation response alone was inaccurate in predicting human radiation injury. In contrast, generation of a gene expression profile which incorporated data from ex vivo irradiated human PB and human TBI patients yielded an 18-gene radiation classifier which was highly accurate at predicting human radiation status and discriminating medically relevant radiation dose levels in human samples. Although the patient population was relatively small, the accuracy of this classifier in discriminating radiation dose levels in human TBI patients was not substantially confounded by gender, diagnosis or prior exposure to chemotherapy. We have further incorporated genes from this human radiation signature into a rapid and high-throughput chemical ligation-dependent probe amplification assay (CLPA) which was able to discriminate radiation dose levels in a pilot study of ex vivo irradiated human blood and samples from human TBI patients. Our results illustrate the potential for translation of a human genetic signature for the diagnosis of human radiation exposure and suggest the basis for further testing of CLPA as a candidate biodosimetric assay.

  11. A translatable predictor of human radiation exposure.

    Directory of Open Access Journals (Sweden)

    Joseph Lucas

    Full Text Available Terrorism using radiological dirty bombs or improvised nuclear devices is recognized as a major threat to both public health and national security. In the event of a radiological or nuclear disaster, rapid and accurate biodosimetry of thousands of potentially affected individuals will be essential for effective medical management to occur. Currently, health care providers lack an accurate, high-throughput biodosimetric assay which is suitable for the triage of large numbers of radiation injury victims. Here, we describe the development of a biodosimetric assay based on the analysis of irradiated mice, ex vivo-irradiated human peripheral blood (PB and humans treated with total body irradiation (TBI. Interestingly, a gene expression profile developed via analysis of murine PB radiation response alone was inaccurate in predicting human radiation injury. In contrast, generation of a gene expression profile which incorporated data from ex vivo irradiated human PB and human TBI patients yielded an 18-gene radiation classifier which was highly accurate at predicting human radiation status and discriminating medically relevant radiation dose levels in human samples. Although the patient population was relatively small, the accuracy of this classifier in discriminating radiation dose levels in human TBI patients was not substantially confounded by gender, diagnosis or prior exposure to chemotherapy. We have further incorporated genes from this human radiation signature into a rapid and high-throughput chemical ligation-dependent probe amplification assay (CLPA which was able to discriminate radiation dose levels in a pilot study of ex vivo irradiated human blood and samples from human TBI patients. Our results illustrate the potential for translation of a human genetic signature for the diagnosis of human radiation exposure and suggest the basis for further testing of CLPA as a candidate biodosimetric assay.

  12. Projecting Drivers of Human Vulnerability under the Shared Socioeconomic Pathways.

    Science.gov (United States)

    Rohat, Guillaume

    2018-03-19

    The Shared Socioeconomic Pathways (SSPs) are the new set of alternative futures of societal development that inform global and regional climate change research. They have the potential to foster the integration of socioeconomic scenarios within assessments of future climate-related health impacts. To date, such assessments have primarily superimposed climate scenarios on current socioeconomic conditions only. Until now, the few assessments of future health risks that employed the SSPs have focused on future human exposure-i.e., mainly future population patterns-, neglecting future human vulnerability. This paper first explores the research gaps-mainly linked to the paucity of available projections-that explain such a lack of consideration of human vulnerability under the SSPs. It then highlights the need for projections of socioeconomic variables covering the wide range of determinants of human vulnerability, available at relevant spatial and temporal scales, and accounting for local specificities through sectoral and regional extended versions of the global SSPs. Finally, this paper presents two innovative methods of obtaining and computing such socioeconomic projections under the SSPs-namely the scenario matching approach and an approach based on experts' elicitation and correlation analyses-and applies them to the case of Europe. They offer a variety of possibilities for practical application, producing projections at sub-national level of various drivers of human vulnerability such as demographic and social characteristics, urbanization, state of the environment, infrastructure, health status, and living arrangements. Both the innovative approaches presented in this paper and existing methods-such as the spatial disaggregation of existing projections and the use of sectoral models-show great potential to enhance the availability of relevant projections of determinants of human vulnerability. Assessments of future climate-related health impacts should thus rely

  13. Gene expression profiling and pathway analysis of human bronchial epithelial cells exposed to airborne particulate matter collected from Saudi Arabia

    International Nuclear Information System (INIS)

    Sun, Hong; Shamy, Magdy; Kluz, Thomas; Muñoz, Alexandra B.; Zhong, Mianhua; Laulicht, Freda; Alghamdi, Mansour A.; Khoder, Mamdouh I.; Chen, Lung-Chi; Costa, Max

    2012-01-01

    Epidemiological studies have established a positive correlation between human mortality and increased concentration of airborne particulate matters (PM). However, the mechanisms underlying PM related human diseases, as well as the molecules and pathways mediating the cellular response to PM, are not fully understood. This study aims to investigate the global gene expression changes in human cells exposed to PM 10 and to identify genes and pathways that may contribute to PM related adverse health effects. Human bronchial epithelial cells were exposed to PM 10 collected from Saudi Arabia for 1 or 4 days, and whole transcript expression was profiled using the GeneChip human gene 1.0 ST array. A total of 140 and 230 genes were identified that significantly changed more than 1.5 fold after PM 10 exposure for 1 or 4 days, respectively. Ingenuity Pathway Analysis revealed that different exposure durations triggered distinct pathways. Genes involved in NRF2-mediated response to oxidative stress were up-regulated after 1 day exposure. In contrast, cells exposed for 4 days exhibited significant changes in genes related to cholesterol and lipid synthesis pathways. These observed changes in cellular oxidative stress and lipid synthesis might contribute to PM related respiratory and cardiovascular disease. -- Highlights: ► PM exposure modulated gene expression and associated pathways in BEAS-2B cells. ► One-day exposure to PM induced genes involved in responding to oxidative stress. ► 4-day exposure to PM changed genes associated to cholesterol and lipid synthesis.

  14. Human mutagens: evidence from paternal exposure

    International Nuclear Information System (INIS)

    Narod, S.A.; Douglas, G.R.; Nestmann, E.R.; Blakey, D.H.

    1988-01-01

    The importance of inherited mutations as a cause of human disease has been established clearly through examples of well-defined genetic anomalies, such as Down syndrome and retinoblastoma. Furthermore, it is suspected that environmental contaminants induce mutations resulting in increased risk for such defects in subsequent generations of persons exposed. The present lack of direct evidence for induced inherited genetic disorders in human beings hampers the development of risk estimation techniques for extrapolation from animal models. The most extensive prospective epidemiologic studies of inherited genetic effects have involved survivors of atomic bomb detonations and patients treated with cancer chemotherapy. In neither case has a significant elevation in inherited genetic effects or cancer been detected in the offspring of exposed individuals. Epidemiologic studies of subjects receiving chronic exposure may be confounded by the effect of maternal exposure during pregnancy. Consideration of only paternal exposure can minimize the confounding influence of teratogenicity, enhancing the resolving power of studies for inherited effects. Using this approach, retrospective (case-control) studies of childhood cancer patients have provided limited but suggestive evidence for inheritance of induced effects. Endpoints, such as congenital malformations and spontaneous abortion following paternal exposure, can also be considered as indicators of heritable mutagenic effects. For example, there is limited evidence suggesting that paternal exposure to anaesthetic gases may cause miscarriage and congenital abnormalities as a result of induced male germ cell mutations. 104 references

  15. ASSESSMENT OF HUMAN EXPOSURE TO TOLUENE DIISOCYANATE

    Directory of Open Access Journals (Sweden)

    OLIVIA ANCA RUSU

    2011-03-01

    Full Text Available Assessment of human exposure to toluene diisocyanate. Toluene diisocyanate (TDI, an aromatic compound, may be dangerous for human health. Diisocyanates have wide industrial use in the fabrication of flexible and rigid foams, fibers, elastomers, and coatings such as paints and varnishes. Isocyanates are known skin and respiratory sensitizers, and proper engineering controls should be in place to prevent exposure to isocyanate liquid and vapor; exposure to TDI vapors is well documented to increase asthma risk. The study focused on the exposure of workers and nearby populations to toluene diisocyanate in a Polyurethane Foam Factory located in Baia Mare, Romania. Workplace air measurements were performed in different departments of the plant, after sampling either in fixed points or as personal monitoring. Sampling in four different locations of Baia Mare town was carried out, - during and after the foaming process. TDI sampling was performed on silica cartridge followed by GC-MS analysis. TDI concentration at workplace was lower than 0,035 mg/m³, which represents the permissible exposure limit, while in the city the TDI concentration had shown values below 0,20 μg/m³. Health assessment of a group of 49 workers was based on questionnaire interview, determination of TDI antibodies and lung function tests. Data collected until this stage do not show any negative effects of TDI on the employees health. Since this plant had only recently begun operating, continuous workplace and ambient air TDI monitoring, along with workers health surveillance, is deemed necessary.

  16. Exposure to Hedione Increases Reciprocity in Humans

    Directory of Open Access Journals (Sweden)

    Sebastian Berger

    2017-05-01

    Full Text Available Cooperation among unrelated humans is frequently regarded as a defining feature in the evolutionary success of our species. Whereas, much research has addressed the strategic and cognitive mechanisms that underlie cooperation, investigations into chemosensory processes have received very limited research attention. To bridge that gap, we build on recent research that has identified the chemically synthesized odorant Hedione (HED as a ligand for the putative human pheromone receptor (VN1R1 expressed in the olfactory mucosa, and hypothesize that exposure to HED may increase reciprocity. Applying behavioral economics paradigms, the present research shows that exposure to the ligand causes differentiated behavioral effects in reciprocal punishments (Study 1 as well as rewards (Study 2, two types of behaviors that are frequently regarded as essential for the development and maintenance of cooperation.

  17. Exposure to Hedione Increases Reciprocity in Humans

    Science.gov (United States)

    Berger, Sebastian; Hatt, Hanns; Ockenfels, Axel

    2017-01-01

    Cooperation among unrelated humans is frequently regarded as a defining feature in the evolutionary success of our species. Whereas, much research has addressed the strategic and cognitive mechanisms that underlie cooperation, investigations into chemosensory processes have received very limited research attention. To bridge that gap, we build on recent research that has identified the chemically synthesized odorant Hedione (HED) as a ligand for the putative human pheromone receptor (VN1R1) expressed in the olfactory mucosa, and hypothesize that exposure to HED may increase reciprocity. Applying behavioral economics paradigms, the present research shows that exposure to the ligand causes differentiated behavioral effects in reciprocal punishments (Study 1) as well as rewards (Study 2), two types of behaviors that are frequently regarded as essential for the development and maintenance of cooperation. PMID:28512400

  18. Intestinal exposure to PCB 153 induces inflammation via the ATM/NEMO pathway.

    Science.gov (United States)

    Phillips, Matthew C; Dheer, Rishu; Santaolalla, Rebeca; Davies, Julie M; Burgueño, Juan; Lang, Jessica K; Toborek, Michal; Abreu, Maria T

    2018-01-15

    Polychlorinated biphenyls (PCBs) are persistent organic pollutants that adversely affect human health. PCBs bio-accumulate in organisms important for human consumption. PCBs accumulation in the body leads to activation of the transcription factor NF-κB, a major driver of inflammation. Despite dietary exposure being one of the main routes of exposure to PCBs, the gut has been widely ignored when studying the effects of PCBs. We investigated the effects of PCB 153 on the intestine and addressed whether PCB 153 affected intestinal permeability or inflammation and the mechanism by which this occurred. Mice were orally exposed to PCB 153 and gut permeability was assessed. Intestinal epithelial cells (IECs) were collected and evaluated for evidence of genotoxicity and inflammation. A human IEC line (SW480) was used to examine the direct effects of PCB 153 on epithelial function. NF-кB activation was measured using a reporter assay, DNA damage was assessed, and cytokine expression was ascertained with real-time PCR. Mice orally exposed to PCB 153 had an increase in intestinal permeability and inflammatory cytokine expression in their IECs; inhibition of NF-кB ameliorated both these effects. This inflammation was associated with genotoxic damage and NF-кB activation. Exposure of SW480 cells to PCB 153 led to similar effects as seen in vivo. We found that activation of the ATM/NEMO pathway by genotoxic stress was upstream of NF-kB activation. These results demonstrate that oral exposure to PCB 153 is genotoxic to IECs and induces downstream inflammation and barrier dysfunction in the intestinal epithelium. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. FOODCHAIN: a Monte Carlo model to estimate individual exposure to airborne pollutants via the foodchain pathway

    International Nuclear Information System (INIS)

    Dixon, E.; Holton, G.A.

    1984-01-01

    Ingestion of contaminated food due to the airborne release of radionuclides or chemical pollutants is a particularly difficult human exposure pathway to quantify. There are a number of important physical and biological processes such as atmospheric deposition and plant uptake to consider. These processes are approximate by techniques encoded in the computer program TEREX. Once estimates of pollutant concentrations are made, the problem can be reduced to computing exposure from ingestion of the food. Some assessments do not account for where the contaminated food is eaten, while others limit consumption to meat and vegetables produced within the affected area. While those approaches lead to an upper bound of exposure, a more realistic assumption is that if locally produced food is not sufficient to meet the dietary needs of the local populace, then uncontaminated food will be imported. This is the approach taken by the computer model FOODCHAIN. Exposures via ingestion of six basic types of food are modeled: beef, milk, grains, leafy vegetables, exposed produce (edible parts are exposed to atmospheric deposition), and protected produce (edible parts are protected from atmospheric deposition). Intake requirements for these six foods are based on a standard diet. Using TEREX-produced site-specific crop production values and food contamination values, FOODCHAIN randomly samples pollutant concentrations in each of the six foodstuffs in an inerative manner. Consumption of a particular food is weighted by a factor proportional to the total production of that food within the area studied. The exposures due to consumption of each of the six foodstuffs are summed to produce the total exposure for each randomly calculated diet

  20. Proteome Profiling Reveals Potential Toxicity and Detoxification Pathways Following Exposure of BEAS-2B Cells to Engineered Nanoparticle Titanium Dioxide

    Science.gov (United States)

    Identification of toxicity pathways linked to chemical -exposure is critical for a better understanding of biological effects of the exposure, toxic mechanisms, and for enhancement of the prediction of chemical toxicity and adverse health outcomes. To identify toxicity pathways a...

  1. Human germline hedgehog pathway mutations predispose to fatty liver.

    Science.gov (United States)

    Guillen-Sacoto, Maria J; Martinez, Ariel F; Abe, Yu; Kruszka, Paul; Weiss, Karin; Everson, Joshua L; Bataller, Ramon; Kleiner, David E; Ward, Jerrold M; Sulik, Kathleen K; Lipinski, Robert J; Solomon, Benjamin D; Muenke, Maximilian

    2017-10-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease. Activation of hedgehog (Hh) signaling has been implicated in the progression of NAFLD and proposed as a therapeutic target; however, the effects of Hh signaling inhibition have not been studied in humans with germline mutations that affect this pathway. Patients with holoprosencephaly (HPE), a disorder associated with germline mutations disrupting Sonic hedgehog (SHH) signaling, were clinically evaluated for NAFLD. A combined mouse model of Hh signaling attenuation (Gli2 heterozygous null: Gli2 +/- ) and diet-induced NAFLD was used to examine aspects of NAFLD and hepatic gene expression profiles, including molecular markers of hepatic fibrosis and inflammation. Patients with HPE had a higher prevalence of liver steatosis compared to the general population, independent of obesity. Exposure of Gli2 +/- mice to fatty liver-inducing diets resulted in increased liver steatosis compared to wild-type mice. Similar to humans, this effect was independent of obesity in the mutant mice and was associated with decreased expression of pro-fibrotic and pro-inflammatory genes, and increased expression of PPARγ, a potent anti-fibrogenic and anti-inflammatory regulator. Interestingly, tumor suppressors p53 and p16INK4 were found to be downregulated in the Gli2 +/- mice exposed to a high-fat diet. Our results indicate that germline mutations disrupting Hh signaling promotes liver steatosis, independent of obesity, with reduced fibrosis. While Hh signaling inhibition has been associated with a better NAFLD prognosis, further studies are required to evaluate the long-term effects of mutations affecting this pathway. Lay summary: Non-alcoholic fatty liver disease (NAFLD) is characterized by excess fat deposition in the liver predominantly due to high calorie intake and a sedentary lifestyle. NAFLD progression is usually accompanied by activation of the Sonic hedgehog (SHH) pathway leading to fibrous

  2. Human response to combined indoor environment exposures

    DEFF Research Database (Denmark)

    Toftum, Jørn

    2002-01-01

    Most thermal comfort standards and guidelines presume sedentary, light activity and a neutral overall thermal sensation when predicting local thermal discomfort. In addition, current standards specify criteria for separate aspects of the indoor environment, e.g. thermal climate, air quality...... or noise, with only little consideration of possible interactions between the different types of exposure. The studies summarized in this article found a clear impact of activity and overall thermal sensation on human sensitivity to air movement, whereas no interaction effects of exposure to several local...... thermal discomfort factors were observed. Limited evidence was found of significant interactions between different aspects of the indoor environment. Only for the effect of air temperature and air humidity on sensory air quality were well-estabished relationships available....

  3. A radiopharmacological study without human radiation exposure

    International Nuclear Information System (INIS)

    Loew, D.; Graul, E.H.; Kunkel, R.

    1984-01-01

    The development, study and control of new drugs today is hardly conceivable without nuclear medicine studies. Nuclear physicians on ethical commissions bear great responsibility in the planning and execution of such studies. In order to protect subjects and patients those nuclear techniques are therefore to be welcome which do not include exposure to radiation. Nuclear techniques used in in-vitro diagnostics (RIA) and the determination of naturally occurring nuclides incorporated in the human body belong to this category. With the aid of a clinico-pharmacological study of a new combination of diuretics it is shown that both methods supply valuable pharmacodynamic evidence. (orig.) [de

  4. Coal seam gas water: potential hazards and exposure pathways in Queensland.

    Science.gov (United States)

    Navi, Maryam; Skelly, Chris; Taulis, Mauricio; Nasiri, Shahram

    2015-01-01

    The extraction of coal seam gas (CSG) produces large volumes of potentially contaminated water. It has raised concerns about the environmental health impacts of the co-produced CSG water. In this paper, we review CSG water contaminants and their potential health effects in the context of exposure pathways in Queensland's CSG basins. The hazardous substances associated with CSG water in Queensland include fluoride, boron, lead and benzene. The exposure pathways for CSG water are (1) water used for municipal purposes; (2) recreational water activities in rivers; (3) occupational exposures; (4) water extracted from contaminated aquifers; and (5) indirect exposure through the food chain. We recommend mapping of exposure pathways into communities in CSG regions to determine the potentially exposed populations in Queensland. Future efforts to monitor chemicals of concern and consolidate them into a central database will build the necessary capability to undertake a much needed environmental health impact assessment.

  5. Aggregate exposure pathways in support of risk assessment

    Science.gov (United States)

    Over time, risk assessment has shifted from establishing relationships between exposure to a single chemical and a resulting adverse health outcome, to evaluating multiple chemicals and disease outcomes simultaneously. As a result, there is an increasing need to better understand...

  6. Framework for Multi-Pathway Cumulative Exposure for Comparative Assessments

    DEFF Research Database (Denmark)

    McKone, Tom; Fantke, Peter

    2016-01-01

    in comparative risk assessment, life-cycle assessment (LCA), and chemical alternatives assessment (CAA), multimedia fate and exposure models synthesize information about partitioning, reaction, and intermedia-transport properties of chemicals in a representative (local to regional) or generic (continental...

  7. DEGAS: de novo discovery of dysregulated pathways in human diseases.

    Directory of Open Access Journals (Sweden)

    Igor Ulitsky

    Full Text Available BACKGROUND: Molecular studies of the human disease transcriptome typically involve a search for genes whose expression is significantly dysregulated in sick individuals compared to healthy controls. Recent studies have found that only a small number of the genes in human disease-related pathways show consistent dysregulation in sick individuals. However, those studies found that some pathway genes are affected in most sick individuals, but genes can differ among individuals. While a pathway is usually defined as a set of genes known to share a specific function, pathway boundaries are frequently difficult to assign, and methods that rely on such definition cannot discover novel pathways. Protein interaction networks can potentially be used to overcome these problems. METHODOLOGY/PRINCIPAL FINDINGS: We present DEGAS (DysrEgulated Gene set Analysis via Subnetworks, a method for identifying connected gene subnetworks significantly enriched for genes that are dysregulated in specimens of a disease. We applied DEGAS to seven human diseases and obtained statistically significant results that appear to home in on compact pathways enriched with hallmarks of the diseases. In Parkinson's disease, we provide novel evidence for involvement of mRNA splicing, cell proliferation, and the 14-3-3 complex in the disease progression. DEGAS is available as part of the MATISSE software package (http://acgt.cs.tau.ac.il/matisse. CONCLUSIONS/SIGNIFICANCE: The subnetworks identified by DEGAS can provide a signature of the disease potentially useful for diagnosis, pinpoint possible pathways affected by the disease, and suggest targets for drug intervention.

  8. Proteomic Assessment of Biochemical Pathways That Are Critical to Nickel-Induced Toxicity Responses in Human Epithelial Cells

    Science.gov (United States)

    Ge, Yue; Bruno, Maribel; Haykal-Coates, Najwa; Wallace, Kathleen; Andrews, Debora; Swank, Adam; Winnik, Witold; Ross, Jeffrey A.

    2016-01-01

    Understanding the mechanisms underlying toxicity initiated by nickel, a ubiquitous environmental contaminant and known human carcinogen is necessary for proper assessment of its risks to human and environment. Among a variety of toxic mechanisms, disruption of protein responses and protein response-based biochemical pathways represents a key mechanism through which nickel induces cytotoxicity and carcinogenesis. To identify protein responses and biochemical pathways that are critical to nickel-induced toxicity responses, we measured cytotoxicity and changes in expression and phosphorylation status of 14 critical biochemical pathway regulators in human BEAS-2B cells exposed to four concentrations of nickel using an integrated proteomic approach. A subset of the pathway regulators, including interleukin-6, and JNK, were found to be linearly correlated with cell viability, and may function as molecular determinants of cytotoxic responses of BEAS-2B cells to nickel exposures. In addition, 128 differentially expressed proteins were identified by two dimensional electrophoresis (2-DE) and mass spectrometry. Principal component analysis, hierarchical cluster analyses, and ingenuity signaling pathway analysis (IPA) identified putative nickel toxicity pathways. Some of the proteins and pathways identified have not previously been linked to nickel toxicity. Based on the consistent results obtained from both ELISA and 2-DE proteomic analysis, we propose a core signaling pathway regulating cytotoxic responses of human BEAS-2B cells to nickel exposures, which integrates a small set of proteins involved in glycolysis and gluconeogenesis pathways, apoptosis, protein degradation, and stress responses including inflammation and oxidative stress. PMID:27626938

  9. Multi-pathway exposure modelling of chemicals in cosmetics with application to shampoo

    DEFF Research Database (Denmark)

    Ernstoff, Alexi S.; Fantke, Peter; Csiszar, Susan A.

    2016-01-01

    We present a novel multi-pathway, mass balance based, fate and exposure model compatible with life cycle and high-throughput screening assessments of chemicals in cosmetic products. The exposures through product use as well as post-use emissions and environmental media were quantified based...

  10. Multi-pathway exposure modelling of chemicals in cosmetics with application to shampoo

    Science.gov (United States)

    We present a novel multi-pathway, mass balance based, fate and exposure model compatible with life cycle and high-throughput screening assessments of chemicals in cosmetic products. The exposures through product use as well as post-use emissions and environmental media were quant...

  11. Human Exposure and Health Effects of Inorganic and Elemental Mercury

    Science.gov (United States)

    Zheng, Wei

    2012-01-01

    Mercury is a toxic and non-essential metal in the human body. Mercury is ubiquitously distributed in the environment, present in natural products, and exists extensively in items encountered in daily life. There are three forms of mercury, i.e., elemental (or metallic) mercury, inorganic mercury compounds, and organic mercury compounds. This review examines the toxicity of elemental mercury and inorganic mercury compounds. Inorganic mercury compounds are water soluble with a bioavailability of 7% to 15% after ingestion; they are also irritants and cause gastrointestinal symptoms. Upon entering the body, inorganic mercury compounds are accumulated mainly in the kidneys and produce kidney damage. In contrast, human exposure to elemental mercury is mainly by inhalation, followed by rapid absorption and distribution in all major organs. Elemental mercury from ingestion is poorly absorbed with a bioavailability of less than 0.01%. The primary target organs of elemental mercury are the brain and kidney. Elemental mercury is lipid soluble and can cross the blood-brain barrier, while inorganic mercury compounds are not lipid soluble, rendering them unable to cross the blood-brain barrier. Elemental mercury may also enter the brain from the nasal cavity through the olfactory pathway. The blood mercury is a useful biomarker after short-term and high-level exposure, whereas the urine mercury is the ideal biomarker for long-term exposure to both elemental and inorganic mercury, and also as a good indicator of body burden. This review discusses the common sources of mercury exposure, skin lightening products containing mercury and mercury release from dental amalgam filling, two issues that happen in daily life, bear significant public health importance, and yet undergo extensive debate on their safety. PMID:23230464

  12. Hedgehog pathway as a potential treatment target in human cholangiocarcinoma.

    Science.gov (United States)

    Riedlinger, Dorothee; Bahra, Marcus; Boas-Knoop, Sabine; Lippert, Steffen; Bradtmöller, Maren; Guse, Katrin; Seehofer, Daniel; Bova, Roberta; Sauer, Igor M; Neuhaus, Peter; Koch, Arend; Kamphues, Carsten

    2014-08-01

    Innovative treatment concepts targeting essential signaling pathways may offer new chances for patients suffering from cholangiocarcinoma (CCC). For that, we performed a systematic molecular genetic analysis concerning the Hedgehog activity in human CCC samples and analyzed the effect of Hh inhibition on CCC cells in vitro and in vivo. Activation of the Hh pathway was analyzed in 50 human CCC samples using quantitative polymerase chain reaction (qPCR). The efficacy of Hh inhibition using cyclopamine and BMS-833923 was evaluated in vitro. In addition, the effect of BMS-833923, alone or in combination with gemcitabine, was analyzed in vivo in a murine subcutaneous xenograft model. Expression analysis revealed a significant activation of the Hh-signaling pathway in nearly 50% of CCCs. Hh inhibition resulted in a significant decrease in cell proliferation of CCC cells. Moreover, a distinct inhibition of tumor growth could be seen as a result of a combined therapy with BMS-833923 and gemcitabine in CCC xenografts. The results of our study suggest that the Hh pathway plays a relevant role at least in a subset of human CCC. Inhibition of this pathway may represent a possible treatment option for CCC patients in which the Hh pathway is activated. © 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

  13. Exposure pathways and biological receptors: baseline data for the canyon uranium mine, Coconino County, Arizona

    Science.gov (United States)

    Hinck, Jo E.; Linder, Greg L.; Darrah, Abigail J.; Drost, Charles A.; Duniway, Michael C.; Johnson, Matthew J.; Méndez-Harclerode, Francisca M.; Nowak, Erika M.; Valdez, Ernest W.; van Riper, Charles; Wolff, S.W.

    2014-01-01

    Recent restrictions on uranium mining within the Grand Canyon watershed have drawn attention to scientific data gaps in evaluating the possible effects of ore extraction to human populations as well as wildlife communities in the area. Tissue contaminant concentrations, one of the most basic data requirements to determine exposure, are not available for biota from any historical or active uranium mines in the region. The Canyon Uranium Mine is under development, providing a unique opportunity to characterize concentrations of uranium and other trace elements, as well as radiation levels in biota, found in the vicinity of the mine before ore extraction begins. Our study objectives were to identify contaminants of potential concern and critical contaminant exposure pathways for ecological receptors; conduct biological surveys to understand the local food web and refine the list of target species (ecological receptors) for contaminant analysis; and collect target species for contaminant analysis prior to the initiation of active mining. Contaminants of potential concern were identified as arsenic, cadmium, chromium, copper, lead, mercury, nickel, selenium, thallium, uranium, and zinc for chemical toxicity and uranium and associated radionuclides for radiation. The conceptual exposure model identified ingestion, inhalation, absorption, and dietary transfer (bioaccumulation or bioconcentration) as critical contaminant exposure pathways. The biological survey of plants, invertebrates, amphibians, reptiles, birds, and small mammals is the first to document and provide ecological information on .200 species in and around the mine site; this study also provides critical baseline information about the local food web. Most of the species documented at the mine are common to ponderosa pine Pinus ponderosa and pinyon–juniper Pinus–Juniperus spp. forests in northern Arizona and are not considered to have special conservation status by state or federal agencies; exceptions

  14. Responses of the insulin signaling pathways in the brown adipose tissue of rats following cold exposure.

    Science.gov (United States)

    Wang, Xiaofei; Wahl, Richard

    2014-01-01

    The insulin signaling pathway is critical for the control of blood glucose levels. Brown adipose tissue (BAT) has also been implicated as important in glucose homeostasis. The effect of short-term cold exposure on this pathway in BAT has not been explored. We evaluated the effect of 4 hours of cold exposure on the insulin pathway in the BAT of rats. Whole genomic microarray chips were used to examine the transcripts of the pathway in BAT of rats exposed to 4°C and 22°C for 4 hours. The 4 most significantly altered pathways following 4 hours of cold exposure were the insulin signaling pathway, protein kinase A, PI3K/AKT and ERK/MAPK signaling. The insulin signaling pathway was the most affected. In the documented 142 genes of the insulin pathway, 42 transcripts (29.6%) responded significantly to this cold exposure with the least false discovery rate (Benjamini-Hochberg Multiple Testing: -log10 (p-value)  = 7.18). Twenty-seven genes (64%) were up-regulated, including the insulin receptor (Insr), insulin substrates 1 and 2 (Irs1 and Irs2). Fifteen transcripts (36%) were down-regulated. Multiple transcripts of the primary target and secondary effector targets for the insulin signaling were also up-regulated, including those for carbohydrate metabolism. Using western blotting, we demonstrated that the cold induced higher Irs2, Irs1, and Akt-p protein levels in the BAT than in the BAT of controls maintained at room temperature, and higher Akt-p protein level in the muscle. this study demonstrated that 4 hours of cold exposure stimulated the insulin signaling pathway in the BAT and muscle of overnight fasted rats. This raises the possibility that acute cold stimulation may have potential to improve glucose clearance and insulin sensitivity.

  15. Signaling pathway networks mined from human pituitary adenoma proteomics data

    Directory of Open Access Journals (Sweden)

    Zhan Xianquan

    2010-04-01

    Full Text Available Abstract Background We obtained a series of pituitary adenoma proteomic expression data, including protein-mapping data (111 proteins, comparative proteomic data (56 differentially expressed proteins, and nitroproteomic data (17 nitroproteins. There is a pressing need to clarify the significant signaling pathway networks that derive from those proteins in order to clarify and to better understand the molecular basis of pituitary adenoma pathogenesis and to discover biomarkers. Here, we describe the significant signaling pathway networks that were mined from human pituitary adenoma proteomic data with the Ingenuity pathway analysis system. Methods The Ingenuity pathway analysis system was used to analyze signal pathway networks and canonical pathways from protein-mapping data, comparative proteomic data, adenoma nitroproteomic data, and control nitroproteomic data. A Fisher's exact test was used to test the statistical significance with a significance level of 0.05. Statistical significant results were rationalized within the pituitary adenoma biological system with literature-based bioinformatics analyses. Results For the protein-mapping data, the top pathway networks were related to cancer, cell death, and lipid metabolism; the top canonical toxicity pathways included acute-phase response, oxidative-stress response, oxidative stress, and cell-cycle G2/M transition regulation. For the comparative proteomic data, top pathway networks were related to cancer, endocrine system development and function, and lipid metabolism; the top canonical toxicity pathways included mitochondrial dysfunction, oxidative phosphorylation, oxidative-stress response, and ERK/MAPK signaling. The nitroproteomic data from a pituitary adenoma were related to cancer, cell death, lipid metabolism, and reproductive system disease, and the top canonical toxicity pathways mainly related to p38 MAPK signaling and cell-cycle G2/M transition regulation. Nitroproteins from a

  16. MAPK pathway activation by chronic lead-exposure increases vascular reactivity through oxidative stress/cyclooxygenase-2-dependent pathways

    Energy Technology Data Exchange (ETDEWEB)

    Simões, Maylla Ronacher, E-mail: yllars@hotmail.com [Dept. of Physiological Sciences, Federal University of Espirito Santo, Vitória, ES CEP 29040-091 (Brazil); Department of Pharmacology, Universidad Autonoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid (Spain); Aguado, Andrea [Department of Pharmacology, Universidad Autonoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid (Spain); Fiorim, Jonaína; Silveira, Edna Aparecida; Azevedo, Bruna Fernandes; Toscano, Cindy Medice [Dept. of Physiological Sciences, Federal University of Espirito Santo, Vitória, ES CEP 29040-091 (Brazil); Zhenyukh, Olha; Briones, Ana María [Department of Pharmacology, Universidad Autonoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid (Spain); Alonso, María Jesús [Dept. of Biochemistry, Physiology and Molecular Genetics, Universidad Rey Juan Carlos, Alcorcón (Spain); Vassallo, Dalton Valentim [Dept. of Physiological Sciences, Federal University of Espirito Santo, Vitória, ES CEP 29040-091 (Brazil); Health Science Center of Vitória-EMESCAM, Vitória, ES CEP 29045-402 (Brazil); Salaices, Mercedes, E-mail: mercedes.salaices@uam.es [Department of Pharmacology, Universidad Autonoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid (Spain)

    2015-03-01

    Chronic exposure to low lead concentration produces hypertension; however, the underlying mechanisms remain unclear. We analyzed the role of oxidative stress, cyclooxygenase-2-dependent pathways and MAPK in the vascular alterations induced by chronic lead exposure. Aortas from lead-treated Wistar rats (1st dose: 10 μg/100 g; subsequent doses: 0.125 μg/100 g, intramuscular, 30 days) and cultured aortic vascular smooth muscle cells (VSMCs) from Sprague Dawley rats stimulated with lead (20 μg/dL) were used. Lead blood levels of treated rats attained 21.7 ± 2.38 μg/dL. Lead exposure increased systolic blood pressure and aortic ring contractile response to phenylephrine, reduced acetylcholine-induced relaxation and did not affect sodium nitroprusside relaxation. Endothelium removal and L-NAME left-shifted the response to phenylephrine more in untreated than in lead-treated rats. Apocynin and indomethacin decreased more the response to phenylephrine in treated than in untreated rats. Aortic protein expression of gp91(phox), Cu/Zn-SOD, Mn-SOD and COX-2 increased after lead exposure. In cultured VSMCs lead 1) increased superoxide anion production, NADPH oxidase activity and gene and/or protein levels of NOX-1, NOX-4, Mn-SOD, EC-SOD and COX-2 and 2) activated ERK1/2 and p38 MAPK. Both antioxidants and COX-2 inhibitors normalized superoxide anion production, NADPH oxidase activity and mRNA levels of NOX-1, NOX-4 and COX-2. Blockade of the ERK1/2 and p38 signaling pathways abolished lead-induced NOX-1, NOX-4 and COX-2 expression. Results show that lead activation of the MAPK signaling pathways activates inflammatory proteins such as NADPH oxidase and COX-2, suggesting a reciprocal interplay and contribution to vascular dysfunction as an underlying mechanisms for lead-induced hypertension. - Highlights: • Lead-exposure increases oxidative stress, COX-2 expression and vascular reactivity. • Lead exposure activates MAPK signaling pathway. • ROS and COX-2 activation by

  17. EFFECTS OF ARSENIC EXPOSURE IN HUMAN HEALTH

    Directory of Open Access Journals (Sweden)

    Aline Sueli de Lima Rodrigues

    2008-10-01

    Full Text Available In recent years, ingestion of inorganic arsenic from drinking water has emerged as an important public health concern. It enters drinking water supplies from natural deposits in the earth or from agricultural and industrial practices, mainly the mining. The health consequences of chronic arsenic exposure include increased risk for various forms of cancer and numerous pathologic effects, such as cutaneous effects (hyperpigmentation and hyperkeratoses, gastrointestinal effects, vascular effects, diabetes mellitus, and peripheral neuropathy. This way, this study presents through a critical revision of the literature, the more relevant current aspects on the immunological consequences, carcinogenic and resulting genetics of the human intoxication for arsenic. They were identified and analyzed 50 works published on the subject among the years of 1979 and 2008, being used as main sources LILACS-BIREME MEDLINE/Index Medicus, SciELO and PubMed. The specific Arsênio e saúde humana effects of the intoxication for arsenic about the human health are not still completely elucidated. Thus, is possible that this element affects functions still unknown, becoming important the scientificexploration on the subject.

  18. Chemical form of selenium differentially influences DNA repair pathways following exposure to lead nitrate.

    Science.gov (United States)

    McKelvey, Shauna M; Horgan, Karina A; Murphy, Richard A

    2015-01-01

    Lead, an environmental toxin is known to induce a broad range of physiological and biochemical dysfunctions in humans through a number of mechanisms including the deactivation of antioxidants thus leading to generation of reactive oxygen species (ROS) and subsequent DNA damage. Selenium on the other hand has been proven to play an important role in the protection of cells from free radical damage and oxidative stress, though its effects are thought to be form and dose dependent. As the liver is the primary organ required for metabolite detoxification, HepG2 cells were chosen to assess the protective effects of various selenium compounds following exposure to the genotoxic agent lead nitrate. Initially DNA damage was quantified using a comet assay, gene expression patterns associated with DNA damage and signalling were also examined using PCR arrays and the biological pathways which were most significantly affected by selenium were identified. Interestingly, the organic type selenium compounds (selenium yeast and selenomethionine) conferred protection against lead induced DNA damage in HepG2 cells; this is evident by reduction in the quantity of DNA present in the comet tail of cells cultured in their presence with lead. This trend also followed through the gene expression changes noted in DNA damage pathways analysed. These results were in contrast with those of inorganic sodium selenite which promoted lead induced DNA damage evident in both the comet assay results and the gene expression analysis. Over all this study provided valuable insights into the effects which various selenium compounds had on the DNA damage and signalling pathway indicating the potential for using organic forms of selenium such as selenium enriched yeast to protect against DNA damaging agents. Copyright © 2014 Elsevier GmbH. All rights reserved.

  19. Activation of the lectin pathway of complement in experimental human keratitis with Pseudomonas aeruginosa.

    Science.gov (United States)

    Osthoff, Michael; Brown, Karl D; Kong, David C M; Daniell, Mark; Eisen, Damon P

    2014-01-01

    Pseudomonas aeruginosa (P. aeruginosa) microbial keratitis (MK) is a sight-threatening disease. Previous animal studies have identified an important contribution of the complement system to the clearance of P. aeruginosa infection of the cornea. Mannose-binding lectin (MBL), a pattern recognition receptor of the lectin pathway of complement, has been implicated in the host defense against P. aeruginosa. However, studies addressing the role of the lectin pathway in P. aeruginosa MK are lacking. Hence, we sought to determine the activity of the lectin pathway in human MK caused by P. aeruginosa. Primary human corneal epithelial cells (HCECs) from cadaveric donors were exposed to two different P. aeruginosa strains. Gene expression of interleukin (IL)-6, IL-8, MBL, and other complement proteins was determined by reverse transcription-polymerase chain reaction (RT-PCR) and MBL synthesis by enzyme-linked immunosorbent assay and intracellular flow cytometry. MBL gene expression was not detected in unchallenged HCECs. Exposure of HCECs to P. aeruginosa resulted in rapid induction of the transcriptional expression of MBL, IL-6, and IL-8. In addition, expression of several complement proteins of the classical and lectin pathways, but not the alternative pathway, were upregulated after 5 h of challenge, including MBL-associated serine protease 1. However, MBL protein secretion was not detectable 18 h after challenge with P. aeruginosa. MK due to P. aeruginosa triggers activation of MBL and the lectin pathway of complement. However, the physiologic relevance of this finding is unclear, as corresponding MBL oligomer production was not observed.

  20. Human exposure to soil contaminants in subarctic Ontario, Canada

    Directory of Open Access Journals (Sweden)

    Ellen Stephanie Reyes

    2015-05-01

    Full Text Available Background: Chemical contaminants in the Canadian subarctic present a health risk with exposures primarily occurring via the food consumption. Objective: Characterization of soil contaminants is needed in northern Canada due to increased gardening and agricultural food security initiatives and the presence of known point sources of pollution. Design: A field study was conducted in the western James Bay Region of Ontario, Canada, to examine the concentrations of polychlorinated biphenyls, dichlorodiphenyltrichloroethane and its metabolites (ΣDDT, other organochlorines, and metals/metalloids in potentially contaminated agriculture sites. Methods: Exposure pathways were assessed by comparing the estimated daily intake to acceptable daily intake values. Ninety soil samples were collected at random (grid sampling from 3 plots (A, B, and C in Fort Albany (on the mainland, subarctic Ontario, Canada. The contaminated-soil samples were analysed by gas chromatography with an electron capture detector or inductively coupled plasma mass spectrometer. Results: The range of ΣDDT in 90 soil samples was below the limit of detection to 4.19 mg/kg. From the 3 soil plots analysed, Plot A had the highest ΣDDT mean concentration of 1.12 mg/kg, followed by Plot B and Plot C which had 0.09 and 0.01 mg/kg, respectively. Concentrations of other organic contaminants and metals in the soil samples were below the limit of detection or found in low concentrations in all plots and did not present a human health risk. Conclusions: Exposure analyses showed that the human risk was below regulatory thresholds. However, the ΣDDT concentration in Plot A exceeded soil guidelines set out by the Canadian Council of Ministers of the Environment of 0.7 mg/kg, and thus the land should not be used for agricultural or recreational purposes. Both Plots B and C were below threshold limits, and this land can be used for agricultural purposes.

  1. Pathway of 3-MCPD-induced apoptosis in human embryonic kidney cells.

    Science.gov (United States)

    Ji, Jian; Zhu, Pei; Sun, Chao; Sun, Jiadi; An, Lu; Zhang, Yinzhi; Sun, Xiulan

    2017-01-01

    3-Chloropropane-1,2-diol (3-MCPD) is a heat-produced contaminant formed during the preparation of soy sauce worldwide. The present investigation was conducted to determine the molecular aspects of 3-MCPD toxicity on human embryonic kidney cells (HEK293). Cell viability and apoptosis were assessed in response to exposure to 3-MCPD using the MTT assay and high-content screening (HCS). DNA damage, intracellular reactive oxygen species (ROS) and apoptosis-related proteins were evaluated. Genes related with apoptosis were detected by qPCR-array for further understanding the 3-MCPD induced cell apoptosis signaling pathway. Our results clearly showed that 3-MCPD treatment inhibits cell proliferation and reactive oxygen species generation. qPCR-array indicated that nine apoptotic genes were up-regulated more than 2-fold and six down-regulated more than 2-fold. Genes associated with the mitochondrial apoptotic pathway, especially BCL2 family genes, changed significantly, indicating that the mitochondrial apoptotic pathway is activated. Death receptor pathway-related genes, TNFRSF11B and TNFRSF1A, changed significantly, indicating that the death receptor pathway is also activated, resulting in the inhibition of cell growth and proliferation as well as induction of apoptosis. To sum up, the experiment results indicated that 3-MCPD induced HEK293 cell toxicity through the death receptor pathway and mitochondrial pathway.

  2. Evidence that humans metabolize benzene via two pathways.

    NARCIS (Netherlands)

    Rappaport, S.M.; Kim, S.; Lan, Q.; Vermeulen, R.C.H.; Waidyanatha, S.; Zhang, L.; Li, G.; Yin, S.; Hayes, R.B.; Rothman, N.; Smith, M.T.

    2009-01-01

    BACKGROUND: Recent evidence has shown that humans metabolize benzene more efficiently at environmental air concentrations than at concentrations > 1 ppm. This led us to speculate that an unidentified metabolic pathway was mainly responsible for benzene metabolism at ambient levels. OBJECTIVE: We

  3. Activation of the lectin complement pathway on human renal ...

    African Journals Online (AJOL)

    This study aimed to investigate the roles of high glucose and mannose-binding lectin (MBL) on the activation of the lectin complement pathway (LCP) on human renal glomerular endothelial cells (HRGECs) in vitro. Flow cytometry analysis, immunofluorescence staining and Western blot were used to detect the cell surface ...

  4. [Effects of radiation exposure on human body].

    Science.gov (United States)

    Kamiya, Kenji; Sasatani, Megumi

    2012-03-01

    There are two types of radiation health effect; acute disorder and late on-set disorder. Acute disorder is a deterministic effect that the symptoms appear by exposure above a threshold. Tissues and cells that compose the human body have different radiation sensitivity respectively, and the symptoms appear in order, from highly radiosensitive tissues. The clinical symptoms of acute disorder begin with a decrease in lymphocytes, and then the symptoms appear such as alopecia, skin erythema, hematopoietic damage, gastrointestinal damage, central nervous system damage with increasing radiation dose. Regarding the late on-set disorder, a predominant health effect is the cancer among the symptoms of such as cancer, non-cancer disease and genetic effect. Cancer and genetic effect are recognized as stochastic effects without the threshold. When radiation dose is equal to or more than 100 mSv, it is observed that the cancer risk by radiation exposure increases linearly with an increase in dose. On the other hand, the risk of developing cancer through low-dose radiation exposure, less 100 mSv, has not yet been clarified scientifically. Although uncertainty still remains regarding low level risk estimation, ICRP propound LNT model and conduct radiation protection in accordance with LNT model in the low-dose and low-dose rate radiation from a position of radiation protection. Meanwhile, the mechanism of radiation damage has been gradually clarified. The initial event of radiation-induced diseases is thought to be the damage to genome such as radiation-induced DNA double-strand breaks. Recently, it is clarified that our cells could recognize genome damage and induce the diverse cell response to maintain genome integrity. This phenomenon is called DNA damage response which induces the cell cycle arrest, DNA repair, apoptosis, cell senescence and so on. These responses act in the direction to maintain genome integrity against genome damage, however, the death of large number of

  5. Testing pathways linking exposure to community violence and sexual behaviors among African American youth.

    Science.gov (United States)

    Voisin, Dexter R; Hotton, Anna L; Neilands, Torsten B

    2014-09-01

    Exposure to community violence and HIV sexual risks are two major public health concerns among youth. This study tests various pathways linking exposure to community violence and sexual behaviors among African American adolescents. Using a sample of 563 (61% females) African American youth attending high school we examined whether problematic psychological symptoms, low school engagement, and/or negative perceptions of peer norms about safer sex functioned as pathways linking exposure to community violence and sexual behaviors. Major findings indicated that, for boys, the relationship between exposure to community violence and sexual début and sexual risk behaviors were linked by aggression. In addition, the relationship between exposure to community violence and sexual risk behaviors were linked by negative perceptions of peer attitudes about safer sex. For girls, the relationship between exposure to community violence and sexual début was linked by aggression and negative perceptions of peer attitudes about safer sex. These findings provide support for pathways linking exposure to community violence to sexual behaviors.

  6. Pathway analysis and exposure assessment: MEPAS modeling for nonradiological chemical contaminants at the Hanford Site

    International Nuclear Information System (INIS)

    Blanton, M.L.; Dirkes, R.; Buck, J.; Cooper, A.; Castieton, K.; Glantz, C.

    1995-01-01

    A Chemical Pathway Analysis and Exposure Assessment was performed by the Surface Environmental Surveillance Project (SESP). The SESP monitors air, surface water, sediment, agricultural products, vegetation, soil, and wildlife in order to assess onsite of offsite environmental impacts and offsite human health risk at the Hanford Site. The objectives of this study are (1) determine if a nonradiological chemical monitoring program is warranted for the Hanford Site, (2) ensure that the selection of surveillance parameters such as media, sampling location, and analytes are chosen in a manner that is scientifically sound and cost-efficient, and (3) identify specific nonradiological chemicals of concern (COC) for the Hanford Site. The basis for identification of COC for the Hanford Site was an extensive literature review. The model was also used to predict COC concentrations required onsite to achieve an offsite cancer incidence of 1 E-6 and a hazard quotient of 1.0. This study indicated that nonradiological chemical contamination occurring onsite does not pose a significant offsite human health risk. The highest cancer incidence to the offsite maximally exposed individual from COC was from arsenic (1.76E-1 0); the highest hazard quotient was chromium VI (1.48E-04)

  7. Early androgen exposure and human gender development.

    Science.gov (United States)

    Hines, Melissa; Constantinescu, Mihaela; Spencer, Debra

    2015-01-01

    During early development, testosterone plays an important role in sexual differentiation of the mammalian brain and has enduring influences on behavior. Testosterone exerts these influences at times when the testes are active, as evidenced by higher concentrations of testosterone in developing male than in developing female animals. This article critically reviews the available evidence regarding influences of testosterone on human gender-related development. In humans, testosterone is elevated in males from about weeks 8 to 24 of gestation and then again during early postnatal development. Individuals exposed to atypical concentrations of testosterone or other androgenic hormones prenatally, for example, because of genetic conditions or because their mothers were prescribed hormones during pregnancy, have been consistently found to show increased male-typical juvenile play behavior, alterations in sexual orientation and gender identity (the sense of self as male or female), and increased tendencies to engage in physically aggressive behavior. Studies of other behavioral outcomes following dramatic androgen abnormality prenatally are either too small in their numbers or too inconsistent in their results, to provide similarly conclusive evidence. Studies relating normal variability in testosterone prenatally to subsequent gender-related behavior have produced largely inconsistent results or have yet to be independently replicated. For studies of prenatal exposures in typically developing individuals, testosterone has been measured in single samples of maternal blood or amniotic fluid. These techniques may not be sufficiently powerful to consistently detect influences of testosterone on behavior, particularly in the relatively small samples that have generally been studied. The postnatal surge in testosterone in male infants, sometimes called mini-puberty, may provide a more accessible opportunity for measuring early androgen exposure during typical development. This

  8. Transcriptomic analysis in the developing zebrafish embryo after compound exposure: Individual gene expression and pathway regulation

    Energy Technology Data Exchange (ETDEWEB)

    Hermsen, Sanne A.B., E-mail: Sanne.Hermsen@rivm.nl [Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven (Netherlands); Department of Toxicogenomics, Maastricht University, P.O. Box 616, 6200 MD, Maastricht (Netherlands); Institute for Risk Assessment Sciences (IRAS), Utrecht University, P.O. Box 80.178, 3508 TD, Utrecht (Netherlands); Pronk, Tessa E. [Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven (Netherlands); Department of Toxicogenomics, Maastricht University, P.O. Box 616, 6200 MD, Maastricht (Netherlands); Brandhof, Evert-Jan van den [Centre for Environmental Quality, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven (Netherlands); Ven, Leo T.M. van der [Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven (Netherlands); Piersma, Aldert H. [Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven (Netherlands); Institute for Risk Assessment Sciences (IRAS), Utrecht University, P.O. Box 80.178, 3508 TD, Utrecht (Netherlands)

    2013-10-01

    The zebrafish embryotoxicity test is a promising alternative assay for developmental toxicity. Classically, morphological assessment of the embryos is applied to evaluate the effects of compound exposure. However, by applying differential gene expression analysis the sensitivity and predictability of the test may be increased. For defining gene expression signatures of developmental toxicity, we explored the possibility of using gene expression signatures of compound exposures based on commonly expressed individual genes as well as based on regulated gene pathways. Four developmental toxic compounds were tested in concentration-response design, caffeine, carbamazepine, retinoic acid and valproic acid, and two non-embryotoxic compounds, D-mannitol and saccharin, were included. With transcriptomic analyses we were able to identify commonly expressed genes, which were mostly development related, after exposure to the embryotoxicants. We also identified gene pathways regulated by the embryotoxicants, suggestive of their modes of action. Furthermore, whereas pathways may be regulated by all compounds, individual gene expression within these pathways can differ for each compound. Overall, the present study suggests that the use of individual gene expression signatures as well as pathway regulation may be useful starting points for defining gene biomarkers for predicting embryotoxicity. - Highlights: • The zebrafish embryotoxicity test in combination with transcriptomics was used. • We explored two approaches of defining gene biomarkers for developmental toxicity. • Four compounds in concentration-response design were tested. • We identified commonly expressed individual genes as well as regulated gene pathways. • Both approaches seem suitable starting points for defining gene biomarkers.

  9. Environmental and human exposure as a result of radioactive discharges

    International Nuclear Information System (INIS)

    2010-02-01

    Nuclear accidents can lead to the discharge of radioactive particulates, gases, and liquid effluents into the environment. Effluents are characterized by their composition, duration and by other characteristics which can influence the dispersion of radioactivity in the environment. Populations can be exposed directly or through the contamination of the terrestrial and aquatic environments. Therefore, it is necessary to take into consideration both the environmental contamination pathways and the human contamination pathways through the environment. This document summarizes these different pathways: contamination by atmospheric discharge (surface contamination, surface waters, terrestrial fauna and flora); contamination by liquid discharge; spreading of contaminated areas; human contamination pathways (external irradiation, internal contamination, skin contamination). (J.S.)

  10. Human exposure to bovine polyomavirus: a zoonosis

    Energy Technology Data Exchange (ETDEWEB)

    Parry, J V; Gardner, S D

    1986-01-01

    A competitive-type solid phase radioimmunoassay (RIA) was developed for the detection of antibody to bovine polyomavirus. Comparison of RIA and counter-immunoelectrophoresis (CIE) results on 273 cattle sera indicated that both techniques were detecting antibody of like specificity. Human sera from 256 blood donors, 219 people recently vaccinated against polio, rubella or rabies, 50 immunosuppressed patients and 472 people with various occupational exposure to cattle were tested for antibody to bovine polyomavirus, the foetal rhesus monkey kidney strain, (anti-FRKV) by RIA. Apart from one blood donor and one of 108 rabies vaccinees only those in close contact with cattle possessed anti-FRKV. Compared with 62 per cent seropositive in the natural hosts, cattle, 71 per cent of veterinary surgeons, 50 per cent of cattle farmers, 40 per cent of abattoir workers, 16 per cent of veterinary institute technical staff and 10 per cent of veterinary students were anti-FRKV positive. Our findings indicate that the theoretical hazard of FRKV infection from undetected contamination of current tissue culture derived vaccines may, in practice, be remote. Proposed wider use of primate kidney cells as substrates for new vaccines may increase this risk.

  11. Modeling human exposure to hazardous-waste sites: a question of completeness

    International Nuclear Information System (INIS)

    Daniels, J.I.; McKone, T.E.

    1991-01-01

    In risk analysis, we use human-exposure assessments to translate contaminant sources into quantitative estimates of the amount of contaminant that comes in contact with human-environment boundaries, that is, the lungs, the gastrointestinal tract, and the skin surface of individuals within a specified population. An assessment of intake requires that we determine how much crosses these boundaries. Exposure assessments often rely implicitly in the assumption that exposure can be linked by simple parameters to ambient concentration in air, water, and soil. However, more realistic exposure models require that we abandon such simple assumptions. To link contaminant concentrations in water, air, or soil with potential human intakes, we constrict pathway-exposure factors (PEFs). For each PEF we combine information in environmental partitioning as well as human anatomy, physiology, and patterns into an algebraic term that converts concentrations of contaminants (in mg/L water, mg/m 3 air, and mg/kg soil) into a daily intake per unit body weight in mg/kg-d for a specific rout of exposure such as inhalation, ingestion, or dermal uptake. Using examples involving human exposure to either a radionuclide (tritium, 3 H) or a toxic organic chemical (tetrachloroethylene, PCE) in soil, water, and air, we illustrate the use of PEFs and consider the implications for risk assessment. (au)

  12. Human exposure assessment to environmental chemicals using biomonitoring.

    Science.gov (United States)

    Calafat, Antonia M; Ye, Xiaoyun; Silva, Manori J; Kuklenyik, Zsuzsanna; Needham, Larry L

    2006-02-01

    In modern societies, humans may be exposed to a wide spectrum of environmental chemicals. Although the health significance of this exposure for many chemicals is unknown, studies to investigate the prevalence of exposure are warranted because of the chemicals' potential harmful health effects, as often indicated in animal studies. Three tools have been used to assess exposure: exposure history/questionnaire information, environmental monitoring, and biomonitoring (i.e. measuring concentrations of the chemicals, their metabolites, or their adducts in human specimens). We present an overview on the use of biomonitoring in exposure assessment using phthalates, bisphenol A and other environmental phenols, and perfluorinated chemicals as examples. We discuss some factors relevant for interpreting and understanding biomonitoring data, including selection of both biomarkers of exposure and human matrices, and toxicokinetic information. The use of biomonitoring in human risk assessment is not discussed.

  13. Progress in human exposure assessment for biocidal products

    NARCIS (Netherlands)

    Hemmen, J.J. van

    2004-01-01

    An important shortcoming in our present knowledge required for risk assessment of biocidal products is the assessment of human exposure. This knowledge gap has been filled in a preliminary fashion with the TNsG on human exposure to biocidal products (available from the ECB website). Explicit User

  14. Human exposure assessment: Approaches for chemicals (REACH) and biocides (BPD)

    NARCIS (Netherlands)

    Hemmen, J.J. van; Gerritsen-Ebben, R.

    2008-01-01

    The approaches that are indicated in the various guidance documents for the assessment of human exposure for chemicals and biocides are summarised. This reflects the TNsG (Technical notes for Guidance) version 2: human exposure assessment for biocidal products (1) under the BPD (Biocidal Products

  15. Cadmium osteotoxicity in experimental animals: Mechanisms and relationship to human exposures

    International Nuclear Information System (INIS)

    Bhattacharyya, Maryka H.

    2009-01-01

    Extensive epidemiological studies have recently demonstrated increased cadmium exposure correlating significantly with decreased bone mineral density and increased fracture incidence in humans at lower exposure levels than ever before evaluated. Studies in experimental animals have addressed whether very low concentrations of dietary cadmium can negatively impact the skeleton. This overview evaluates results in experimental animals regarding mechanisms of action on bone and the application of these results to humans. Results demonstrate that long-term dietary exposures in rats, at levels corresponding to environmental exposures in humans, result in increased skeletal fragility and decreased mineral density. Cadmium-induced demineralization begins soon after exposure, within 24 h of an oral dose to mice. In bone culture systems, cadmium at low concentrations acts directly on bone cells to cause both decreases in bone formation and increases in bone resorption, independent of its effects on kidney, intestine, or circulating hormone concentrations. Results from gene expression microarray and gene knock-out mouse models provide insight into mechanisms by which cadmium may affect bone. Application of the results to humans is considered with respect to cigarette smoke exposure pathways and direct vs. indirect effects of cadmium. Clearly, understanding the mechanism(s) by which cadmium causes bone loss in experimental animals will provide insight into its diverse effects in humans. Preventing bone loss is critical to maintaining an active, independent lifestyle, particularly among elderly persons. Identifying environmental factors such as cadmium that contribute to increased fractures in humans is an important undertaking and a first step to prevention.

  16. The Aggregate Exposure Pathway (AEP): A conceptual framework for advancing exposure science research and applications

    Science.gov (United States)

    Historically, risk assessment has relied upon toxicological data to obtain hazard-based reference levels, which are subsequently compared to exposure estimates to determine whether an unacceptable risk to public health may exist. Recent advances in analytical methods, biomarker ...

  17. Pulmonary Ozone Exposure Alters Essential Metabolic Pathways involved in Glucose Homeostasis in the Liver

    Science.gov (United States)

    Pulmonary Ozone Exposure Alters Essential Metabolic Pathways involved in Glucose Homeostasis in the Liver D.B. Johnson, 1 W.O. Ward, 2 V.L. Bass, 2 M.C.J. Schladweiler, 2A.D. Ledbetter, 2 D. Andrews, and U.P. Kodavanti 2 1 Curriculum in Toxicology, UNC School of Medicine, Cha...

  18. A geographically-diverse collection of 418 human gut microbiome pathway genome databases

    KAUST Repository

    Hahn, Aria S.; Altman, Tomer; Konwar, Kishori M.; Hanson, Niels W.; Kim, Dongjae; Relman, David A.; Dill, David L.; Hallam, Steven J.

    2017-01-01

    the Pathway Tools software, empowering researchers and clinicians interested in visualizing and interpreting metabolic pathways encoded by the human gut microbiome. For the first time, GutCyc provides consistent annotations and metabolic pathway predictions

  19. Organophosphate pesticides exposure among farmworkers: pathways and risk of adverse health effects.

    Science.gov (United States)

    Suratman, Suratman; Edwards, John William; Babina, Kateryna

    2015-01-01

    Organophosphate (OP) compounds are the most widely used pesticides with more than 100 OP compounds in use around the world. The high-intensity use of OP pesticides contributes to morbidity and mortality in farmworkers and their families through acute or chronic pesticides-related illnesses. Many factors contributing to adverse health effects have been investigated by researchers to determine pathways of OP-pesticide exposure among farmers in developed and developing countries. Factors like wind/agricultural pesticide drift, mixing and spraying pesticides, use of personal protective equipment (PPE), knowledge, perceptions, washing hands, taking a shower, wearing contaminated clothes, eating, drinking, smoking, and hot weather are common in both groups of countries. Factors including low socioeconomic status areas, workplace conditions, duration of exposure, pesticide safety training, frequency of applying pesticides, spraying against the wind, and reuse of pesticide containers for storage are specific contributors in developing countries, whereas housing conditions, social contextual factors, and mechanical equipment were specific pathways in developed countries. This paper compares existing research in environmental and behavioural exposure modifying factors and biological monitoring between developing and developed countries. The main objective of this review is to explore the current depth of understanding of exposure pathways and factors increasing the risk of exposure potentially leading to adverse health effects specific to each group of countries.

  20. Nitrogen species in drinking water indicate potential exposure pathway for Balkan Endemic Nephropathy

    International Nuclear Information System (INIS)

    Niagolova, Nedialka; McElmurry, Shawn P.; Voice, Thomas C.; Long, David T.; Petropoulos, Evangelos A.; Havezov, Ivan; Chou, Karen; Ganev, Varban

    2005-01-01

    This study explored two hypotheses relating elevated concentrations of nitrogen species in drinking water and the disease Balkan Endemic Nephropathy (BEN). Drinking water samples were collected from a variety of water supplies in both endemic and non-endemic villages in the Vratza and Montana districts of Bulgaria. The majority of well water samples exceeded US drinking water standards for nitrate + nitrite. No statistically significant difference was observed for any of the nitrogen species between villages classified as endemic and non-endemic. Other constituents (sodium, potassium and chloride) known to be indicators of anthropogenic pollution were also found at elevated concentrations and all followed the order wells > springs > taps. This ordering coincides with the proximity of human influences to the water sources. Our results clearly establish an exposure pathway between anthropogenic activity and drinking water supplies, suggesting that the causative agent for BEN could result from surface contamination. - Water in villages affected and unaffected by Balkan Endemic Nephropathy had no significant differences in nitrogen compounds

  1. An approach for assessing human exposures to chemical mixtures in the environment

    International Nuclear Information System (INIS)

    Rice, Glenn; MacDonell, Margaret; Hertzberg, Richard C.; Teuschler, Linda; Picel, Kurt; Butler, Jim; Chang, Young-Soo; Hartmann, Heidi

    2008-01-01

    Humans are exposed daily to multiple chemicals, including incidental exposures to complex chemical mixtures released into the environment and to combinations of chemicals that already co-exist in the environment because of previous releases from various sources. Exposures to chemical mixtures can occur through multiple pathways and across multiple routes. In this paper, we propose an iterative approach for assessing exposures to environmental chemical mixtures; it is similar to single-chemical approaches. Our approach encompasses two elements of the Risk Assessment Paradigm: Problem Formulation and Exposure Assessment. Multiple phases of the assessment occur in each element of the paradigm. During Problem Formulation, analysts identify and characterize the source(s) of the chemical mixture, ensure that dose-response and exposure assessment measures are concordant, and develop a preliminary evaluation of the mixture's fate. During Exposure Assessment, analysts evaluate the fate of the chemicals comprising the mixture using appropriate models and measurement data, characterize the exposure scenario, and estimate human exposure to the mixture. We also describe the utility of grouping the chemicals to be analyzed based on both physical-chemical properties and an understanding of environmental fate. In the article, we also highlight the need for understanding of changes in the mixture composition in the environment due to differential transport, differential degradation, and differential partitioning to other media. The section describes the application of the method to various chemical mixtures, highlighting issues associated with assessing exposures to chemical mixtures in the environment

  2. Carcinogen biomonitoring in human exposures and laboratory research: validation and application to human occupational exposures.

    Science.gov (United States)

    Talaska, Glenn; Maier, Andrew; Henn, Scott; Booth-Jones, Angela; Tsuneoka, Yutaka; Vermeulen, Roel; Schumann, Brenda L

    2002-08-05

    A multiple biomarker approach is required to integrate for metabolism, temporal response and exposure-response kinetics, biological relevance, and positive predictive value. Carcinogen DNA adduct analysis can be used in animal and in vitro studies to detect absorption permutations caused by mixture interactions, and to control metabolic variation when specific CYP450 genes (1A1 or 1A2) are knocked out. These enzymes are not critical to the metabolic activation of model Polycyclic Aromatic Compounds (PAC) and aromatic amines, respectively, as suggested by in vitro analysis. Several human studies have been carried out where multiple biomarkers have been measured. In a study of benzidine workers, the similarities in elimination kinetics between urinary metabolites and mutagenicity is likely responsible for a better correlation between these markers than to BZ-DNA adducts in exfoliated cells. In a study of rubber workers, the relationship between specific departments, urinary 1 HP and DNA adducts in exfoliated cells coincided with the historical urinary bladder cancer risk in these departments; the same relationship did not hold for urinary mutagenicity. In a study of automotive mechanics, biomarkers were used to monitor the effectiveness of exposure interventions. These data reinforce the notion that carcinogen biomarkers are useful to monitor exposure, but that a complementary approaches involving effect and perhaps susceptibility biomarkers is necessary to obtain the necessary information.

  3. Comparative expression pathway analysis of human and canine mammary tumors

    Directory of Open Access Journals (Sweden)

    Marconato Laura

    2009-03-01

    Full Text Available Abstract Background Spontaneous tumors in dog have been demonstrated to share many features with their human counterparts, including relevant molecular targets, histological appearance, genetics, biological behavior and response to conventional treatments. Mammary tumors in dog therefore provide an attractive alternative to more classical mouse models, such as transgenics or xenografts, where the tumour is artificially induced. To assess the extent to which dog tumors represent clinically significant human phenotypes, we performed the first genome-wide comparative analysis of transcriptional changes occurring in mammary tumors of the two species, with particular focus on the molecular pathways involved. Results We analyzed human and dog gene expression data derived from both tumor and normal mammary samples. By analyzing the expression levels of about ten thousand dog/human orthologous genes we observed a significant overlap of genes deregulated in the mammary tumor samples, as compared to their normal counterparts. Pathway analysis of gene expression data revealed a great degree of similarity in the perturbation of many cancer-related pathways, including the 'PI3K/AKT', 'KRAS', 'PTEN', 'WNT-beta catenin' and 'MAPK cascade'. Moreover, we show that the transcriptional relationships between different gene signatures observed in human breast cancer are largely maintained in the canine model, suggesting a close interspecies similarity in the network of cancer signalling circuitries. Conclusion Our data confirm and further strengthen the value of the canine mammary cancer model and open up new perspectives for the evaluation of novel cancer therapeutics and the development of prognostic and diagnostic biomarkers to be used in clinical studies.

  4. REGγ is associated with multiple oncogenic pathways in human cancers

    International Nuclear Information System (INIS)

    He, Jing; Wang, Zhuo; Shi, Tieliu; Zhang, Pei; Chen, Rui; Li, Xiaotao; Cui, Long; Zeng, Yu; Wang, Guangqiang; Zhou, Ping; Yang, Yuanyuan; Ji, Lei; Zhao, Yanyan; Chen, Jiwu

    2012-01-01

    Recent studies suggest a role of the proteasome activator, REGγ, in cancer progression. Since there are limited numbers of known REGγ targets, it is not known which cancers and pathways are associated with REGγ. REGγ protein expressions in four different cancers were investigated by immunohistochemistry (IHC) analysis. Following NCBI Gene Expression Omnibus (GEO) database search, microarray platform validation, differential expressions of REGγ in corresponding cancers were statistically analyzed. Genes highly correlated with REGγ were defined based on Pearson's correlation coefficient. Functional links were estimated by Ingenuity Core analysis. Finally, validation was performed by RT-PCR analysis in established cancer cell lines and IHC in human colon cancer tissues Here, we demonstrate overexpression of REGγ in four different cancer types by micro-tissue array analysis. Using meta-analysis of publicly available microarray databases and biological studies, we verified elevated REGγ gene expression in the four types of cancers and identified genes significantly correlated with REGγ expression, including genes in p53, Myc pathways, and multiple other cancer-related pathways. The predicted correlations were largely consistent with quantitative RT-PCR analysis. This study provides us novel insights in REGγ gene expression profiles and its link to multiple cancer-related pathways in cancers. Our results indicate potentially important pathogenic roles of REGγ in multiple cancer types and implicate REGγ as a putative cancer marker

  5. Exposure to Community Violence and Sexual Behaviors Among African American Youth: Testing Multiple Pathways.

    Science.gov (United States)

    Voisin, Dexter R; Hotton, Anna; Neilands, Torsten

    2018-01-01

    African American youth bear a disproportionate burden of sexually transmitted infections. A growing number of studies document that youth exposure to community violence and sexual behaviors are highly correlated. Despite such growing evidence, only a few studies have empirically tested conceptually driven pathways that may account for such relationships. This study seeks to address that gap by exploring multiple pathways linking exposure to community violence and youth sexual behaviors. Using an existing sample of 563 African American youth attending high school, we examined whether possible links between exposure to community violence and sexual activity, sexual risk behaviors were mediated by aggression, low student-teacher connectedness, and negative peer norms. Major findings indicated indirect relationships between exposures to community violence and both sexual activity and risky sex, mediated by aggression and negative peer norms with no significant differences based on gender or socioeconomic status. Overall findings also indicated a significant indirect effect of aggression to risky sex via negative peer norms and from community violence to risky peer norms via aggression. By illuminating ways that community violence, aggression, peer norms, and sexual behaviors are dynamically interrelated, these findings have significant implications for future research and intervention initiatives aimed at addressing the different pathways.

  6. Cl- transport pathways regulated by Ca++, cAMP, and pH in human fibroblasts

    International Nuclear Information System (INIS)

    Lin, P.; Gruenstein, E.

    1987-01-01

    Under basal conditions Cl - efflux from human fibroblasts occurs with a rate constant of permeability of 0.08 min -1 . 50% of the basal efflux is due to Cl - /anion exchange and is DIDS inhibitable, 25% is due to Na + /K + /Cl - cotransport and is furosemide inhibitable, and 20% is due to an electrically conductive pathway. Increasing intracellular Ca ++ with A23187 stimulates Cl - efflux by 30%. This increase appears to occur entirely via an electrically conducting pathway, but unlike basal Cl - conductance, it is DIDS sensitive. Exposure of the cells to dibutyryl cAMP stimulates Cl - efflux by 15%. They do not yet know whether the cAMP stimulated pathway is electrically conductive, but the stimulation is additive with that caused by elevated Ca ++ suggesting that different pathways are activated. Elevation of intracellular pH by any of several standard methods increases Cl - efflux by as much as 700%. The pH effect appears to be mediated by a Cl - /anion exchange pathway since it is DIDS sensitive and electroneutral. Previous work from this laboratory describing a transient rapid efflux of Cl - followed by a slower efflux phase can now be explained as the result of a transient alkalinization of cells rather than as 2 subcellular Cl - compartments. This alkalinization occurs when cells are transferred from a 5% CO 2 atmosphere during 36 Cl - load to ambient CO 2 for efflux

  7. Environmental chemical exposures and human epigenetics

    Science.gov (United States)

    Hou, Lifang; Zhang, Xiao; Wang, Dong; Baccarelli, Andrea

    2012-01-01

    Every year more than 13 million deaths worldwide are due to environmental pollutants, and approximately 24% of diseases are caused by environmental exposures that might be averted through preventive measures. Rapidly growing evidence has linked environmental pollutants with epigenetic variations, including changes in DNA methylation, histone modifications and microRNAs. Environ mental chemicals and epigenetic changes All of these mechanisms are likely to play important roles in disease aetiology, and their modifications due to environmental pollutants might provide further understanding of disease aetiology, as well as biomarkers reflecting exposures to environmental pollutants and/or predicting the risk of future disease. We summarize the findings on epigenetic alterations related to environmental chemical exposures, and propose mechanisms of action by means of which the exposures may cause such epigenetic changes. We discuss opportunities, challenges and future directions for future epidemiology research in environmental epigenomics. Future investigations are needed to solve methodological and practical challenges, including uncertainties about stability over time of epigenomic changes induced by the environment, tissue specificity of epigenetic alterations, validation of laboratory methods, and adaptation of bioinformatic and biostatistical methods to high-throughput epigenomics. In addition, there are numerous reports of epigenetic modifications arising following exposure to environmental toxicants, but most have not been directly linked to disease endpoints. To complete our discussion, we also briefly summarize the diseases that have been linked to environmental chemicals-related epigenetic changes. PMID:22253299

  8. Vitamin C degradation products and pathways in the human lens.

    Science.gov (United States)

    Nemet, Ina; Monnier, Vincent M

    2011-10-28

    Vitamin C and its degradation products participate in chemical modifications of proteins in vivo through non-enzymatic glycation (Maillard reaction) and formation of different products called advanced glycation end products. Vitamin C levels are particularly high in selected tissues, such as lens, brain and adrenal gland, and its degradation products can inflict substantial protein damage via formation of advanced glycation end products. However, the pathways of in vivo vitamin C degradation are poorly understood. Here we have determined the levels of vitamin C oxidation and degradation products dehydroascorbic acid, 2,3-diketogulonic acid, 3-deoxythreosone, xylosone, and threosone in the human lens using o-phenylenediamine to trap both free and protein-bound adducts. In the protein-free fraction and water-soluble proteins (WSP), all five listed degradation products were identified. Dehydroascorbic acid, 2,3-diketogulonic acid, and 3-deoxythreosone were the major products in the protein-free fraction, whereas in the WSP, 3-deoxythreosone was the most abundant measured dicarbonyl. In addition, 3-deoxythreosone in WSP showed positive linear correlation with age (p degradation product bound to human lens proteins provides in vivo evidence for the non-oxidative pathway of dehydroascorbate degradation into erythrulose as a major pathway for vitamin C degradation in vivo.

  9. The fanconi anemia pathway limits human papillomavirus replication.

    Science.gov (United States)

    Hoskins, Elizabeth E; Morreale, Richard J; Werner, Stephen P; Higginbotham, Jennifer M; Laimins, Laimonis A; Lambert, Paul F; Brown, Darron R; Gillison, Maura L; Nuovo, Gerard J; Witte, David P; Kim, Mi-Ok; Davies, Stella M; Mehta, Parinda A; Butsch Kovacic, Melinda; Wikenheiser-Brokamp, Kathryn A; Wells, Susanne I

    2012-08-01

    High-risk human papillomaviruses (HPVs) deregulate epidermal differentiation and cause anogenital and head and neck squamous cell carcinomas (SCCs). The E7 gene is considered the predominant viral oncogene and drives proliferation and genome instability. While the implementation of routine screens has greatly reduced the incidence of cervical cancers which are almost exclusively HPV positive, the proportion of HPV-positive head and neck SCCs is on the rise. High levels of HPV oncogene expression and genome load are linked to disease progression, but genetic risk factors that regulate oncogene abundance and/or genome amplification remain poorly understood. Fanconi anemia (FA) is a genome instability syndrome characterized at least in part by extreme susceptibility to SCCs. FA results from mutations in one of 15 genes in the FA pathway, whose protein products assemble in the nucleus and play important roles in DNA damage repair. We report here that loss of FA pathway components FANCA and FANCD2 stimulates E7 protein accumulation in human keratinocytes and causes increased epithelial proliferation and basal cell layer expansion in the HPV-positive epidermis. Additionally, FANCD2 loss stimulates HPV genome amplification in differentiating cells, demonstrating that the intact FA pathway functions to restrict the HPV life cycle. These findings raise the possibility that FA genes suppress HPV infection and disease and suggest possible mechanism(s) for reported associations of HPV with an FA cohort in Brazil and for allelic variation of FA genes with HPV persistence in the general population.

  10. Wood smoke in a controlled exposure experiment with human volunteers

    DEFF Research Database (Denmark)

    Riddervold, Ingunn Skogstad; Bønløkke, Jakob Hjort; Mølhave, Lars

    2011-01-01

    Exposure to wood smoke in the general population is increasing and concurrently, also our awareness. This article describes a wood-smoke generating system for studying human exposure to wood smoke and symptoms related to this exposure. Twenty nonsmoking atopic human participants with normal lung...... function and normal bronchial reactivity were randomly exposed for 3h at three different exposure conditions; clean filtered air (control exposure) and wood smoke with a characteristic particulate matter (PM) concentration of 200 µg/m3 (low) and 400 µg/m3 (high) under controlled environmental conditions.......0007), “irritative body perceptions” (p = 0.0127), “psychological/neurological effects” (p = 0.0075) and “weak inflammatory responses” (p = 0.0003). Furthermore, significant effects (p = 0.0192) on self-reported general mucosa irritation were found. In conclusion, exposure to wood smoke affected symptom rating...

  11. A changing climate: impacts on human exposures to O3 using ...

    Science.gov (United States)

    Predicting the impacts of changing climate on human exposure to air pollution requires future scenarios that account for changes in ambient pollutant concentrations, population sizes and distributions, and housing stocks. An integrated methodology to model changes in human exposures due to these impacts was developed by linking climate, air quality, land-use, and human exposure models. This methodology was then applied to characterize changes in predicted human exposures to O3 under multiple future scenarios. Regional climate projections for the U.S. were developed by downscaling global circulation model (GCM) scenarios for three of the Intergovernmental Panel on Climate Change’s (IPCC’s) Representative Concentration Pathways (RCPs) using the Weather Research and Forecasting (WRF) model. The regional climate results were in turn used to generate air quality (concentration) projections using the Community Multiscale Air Quality (CMAQ) model. For each of the climate change scenarios, future U.S. census-tract level population distributions from the Integrated Climate and Land Use Scenarios (ICLUS) model for four future scenarios based on the IPCC’s Special Report on Emissions Scenarios (SRES) storylines were used. These climate, air quality, and population projections were used as inputs to EPA’s Air Pollutants Exposure (APEX) model for 12 U.S. cities. Probability density functions show changes in the population distribution of 8 h maximum daily O3 exposur

  12. Probabilistic integrated risk assessment of human exposure risk to environmental bisphenol A pollution sources.

    Science.gov (United States)

    Fu, Keng-Yen; Cheng, Yi-Hsien; Chio, Chia-Pin; Liao, Chung-Min

    2016-10-01

    Environmental bisphenol A (BPA) exposure has been linked to a variety of adverse health effects such as developmental and reproductive issues. However, establishing a clear association between BPA and the likelihood of human health is complex yet fundamentally uncertain. The purpose of this study was to assess the potential exposure risks from environmental BPA among Chinese population based on five human health outcomes, namely immune response, uterotrophic assay, cardiovascular disease (CVD), diabetes, and behavior change. We addressed these health concerns by using a stochastic integrated risk assessment approach. The BPA dose-dependent likelihood of effects was reconstructed by a series of Hill models based on animal models or epidemiological data. We developed a physiologically based pharmacokinetic (PBPK) model that allows estimation of urinary BPA concentration from external exposures. Here we showed that the daily average exposure concentrations of BPA and urinary BPA estimates were consistent with the published data. We found that BPA exposures were less likely to pose significant risks for infants (0-1 year) and adults (male and female >20 years) with human long-term BPA susceptibility in relation to multiple exposure pathways, and for informing the public of the negligible magnitude of environmental BPA pollution impacts on human health.

  13. Human exposure limits to hypergolic fuels

    Science.gov (United States)

    Garcia, H. D.; James, J. T.; Limero, T. F.

    1992-01-01

    Over the past four decades, many studies have been conducted on the toxicities of the rocket propellants hydrazine (HZ) and monomethylhydrazine (MH). Numerous technical challenges have made it difficult to unambiguously interpret the results of these studies, and there is considerable divergence between results obtained by different investigators on the inhalation concentrations (MAC's) for each toxic effect inducible by exposure to hypergolic fuels in spacecraft atmospheres, NASA undertook a critical review of published and unpublished investigations on the toxicities of these compounds. The current state of the art practices for similar studies. While many questions remain unanswered, MAC's were determined using the best available data for a variety of toxic endpoints for potential continuous exposure durations ranging from 1 hour to 180 days. Spacecraft MAC's (SMAC's) were set for each compound based on the most sensitive toxic endpoint at each exposure duration.

  14. Sizewell nuclear power station: investigation of radiation exposure pathways from liquid effluents. Local habits survey 1981

    International Nuclear Information System (INIS)

    Leonard, D.R.P.; Smith, B.D.

    1982-01-01

    A habits and consumption survey to review radiation exposure pathways due to liquid effluents released from the CEGB Sizewell site is described. It is relevant to both the Sizewell A and proposed Sizewell B nuclear power stations. The main objectives are to provide input data to a radiological assessment by means of identifying critical groups and to provide data for guidance in a review of environmental monitoring programmes. The way in which data for the different pathways should be combined in order to aid the subsequent radiological assessment is discussed. Recommendations are made for adjustments to the present monitoring programmes. (U.K.)

  15. Dynamics of the transcriptome response of cultured human embryonic stem cells to ionizing radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Sokolov, Mykyta V., E-mail: sokolovm@mail.nih.gov [Nuclear Medicine Division, Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892 (United States); Panyutin, Irina V., E-mail: ipanyutinv@mail.nih.gov [Nuclear Medicine Division, Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892 (United States); Panyutin, Igor G., E-mail: igorp@helix.nih.gov [Nuclear Medicine Division, Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892 (United States); Neumann, Ronald D., E-mail: rneumann@mail.nih.gov [Nuclear Medicine Division, Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892 (United States)

    2011-05-10

    One of the key consequences of exposure of human cells to genotoxic agents is the activation of DNA damage responses (DDR). While the mechanisms underpinning DDR in fully differentiated somatic human cells have been studied extensively, molecular signaling events and pathways involved in DDR in pluripotent human embryonic stem cells (hESC) remain largely unexplored. We studied changes in the human genome-wide transcriptome of H9 hESC line following exposures to 1 Gy of gamma-radiation at 2 h and 16 h post-irradiation. Quantitative real-time PCR was performed to verify the expression data for a subset of genes. In parallel, the cell growth, DDR kinetics, and expression of pluripotency markers in irradiated hESC were monitored. The changes in gene expression in hESC after exposure to ionizing radiation (IR) are substantially different from those observed in somatic human cell lines. Gene expression patterns at 2 h post-IR showed almost an exclusively p53-dependent, predominantly pro-apoptotic, signature with a total of only 30 up-regulated genes. In contrast, the gene expression patterns at 16 h post-IR showed 354 differentially expressed genes, mostly involved in pro-survival pathways, such as increased expression of metallothioneins, ubiquitin cycle, and general metabolism signaling. Cell growth data paralleled trends in gene expression changes. DDR in hESC followed the kinetics reported for human somatic differentiated cells. The expression of pluripotency markers characteristic of undifferentiated hESC was not affected by exposure to IR during the time course of our analysis. Our data on dynamics of transcriptome response of irradiated hESCs may provide a valuable tool to screen for markers of IR exposure of human cells in their most naive state; thus unmasking the key elements of DDR; at the same time, avoiding the complexity of interpreting distinct cell type-dependent genotoxic stress responses of terminally differentiated cells.

  16. Dynamics of the transcriptome response of cultured human embryonic stem cells to ionizing radiation exposure

    International Nuclear Information System (INIS)

    Sokolov, Mykyta V.; Panyutin, Irina V.; Panyutin, Igor G.; Neumann, Ronald D.

    2011-01-01

    One of the key consequences of exposure of human cells to genotoxic agents is the activation of DNA damage responses (DDR). While the mechanisms underpinning DDR in fully differentiated somatic human cells have been studied extensively, molecular signaling events and pathways involved in DDR in pluripotent human embryonic stem cells (hESC) remain largely unexplored. We studied changes in the human genome-wide transcriptome of H9 hESC line following exposures to 1 Gy of gamma-radiation at 2 h and 16 h post-irradiation. Quantitative real-time PCR was performed to verify the expression data for a subset of genes. In parallel, the cell growth, DDR kinetics, and expression of pluripotency markers in irradiated hESC were monitored. The changes in gene expression in hESC after exposure to ionizing radiation (IR) are substantially different from those observed in somatic human cell lines. Gene expression patterns at 2 h post-IR showed almost an exclusively p53-dependent, predominantly pro-apoptotic, signature with a total of only 30 up-regulated genes. In contrast, the gene expression patterns at 16 h post-IR showed 354 differentially expressed genes, mostly involved in pro-survival pathways, such as increased expression of metallothioneins, ubiquitin cycle, and general metabolism signaling. Cell growth data paralleled trends in gene expression changes. DDR in hESC followed the kinetics reported for human somatic differentiated cells. The expression of pluripotency markers characteristic of undifferentiated hESC was not affected by exposure to IR during the time course of our analysis. Our data on dynamics of transcriptome response of irradiated hESCs may provide a valuable tool to screen for markers of IR exposure of human cells in their most naive state; thus unmasking the key elements of DDR; at the same time, avoiding the complexity of interpreting distinct cell type-dependent genotoxic stress responses of terminally differentiated cells.

  17. Human exposure to polybrominated diphenyl ethers at production area, China.

    Science.gov (United States)

    Jin, Jun; Wang, Ying; Yang, Congqiao; Hu, Jicheng; Liu, Weizhi; Cui, Jian

    2010-05-01

    The concentrations of polybrominated diphenyl ethers (PBDEs) were detected in air and aquatic products in PBDEs production areas which are located at the south coast area of Laizhou Bay, Shandong province, China in this study. Concentrations of SigmaPBDEs in the air ranged from 0.47 ng/m3 to 161 ng/m3. In aquatic products, concentrations of SigmaPBDEs ranged from 2.7 ng/g wet weight to 42 ng/g wet weight. The mean dietary intake of SigmaPBDEs via aquatic products consumption in this study was 218 ng/day. Daily intake of SigmaPBDEs via inhalation in this study was 612 ng for men and 455 ng for women. With a contribution of 80%, BDE-209 was predominant in the total intake. Dietary intake and breathing inhalation contributed 29 and 71%, respectively, to the total PBDEs intake. The results indicate that breathing inhalation also plays a very significant pathway for the population of the PBDEs production area. Compared with similar studies in other countries, human exposure to PBDEs via diet and inhalation in this study was the highest in the world. Copyright (c) 2010 SETAC.

  18. Human Health Effects Associated with Exposure to Toxic Cyanobacteria

    Science.gov (United States)

    Reports of toxic cyanobacteria blooms are increasing worldwide. Warming and eutrophic surface water systems support the development of blooms. We examine the evidence for adverse human health effects associated with exposure to toxic blooms in drinking water, recreational water a...

  19. EVALUATION OF A PERSONAL NEPHELOMETER FOR HUMAN EXPOSURE MONITORING

    Science.gov (United States)

    Current particulate matter (PM) exposure studies are using continuous personal nephelometers (pDR-1000, MIE, Inc.) to measure human exposure to PM. The personal nephelometer is a passive sampler which uses light scattering technology to measure particles ranging in size from 0....

  20. Knowledge of human immunodeficiency virus post-exposure ...

    African Journals Online (AJOL)

    2011-05-21

    May 21, 2011 ... Appropriate post-exposure prophylaxis is an integral part of prevention, control and workplace safety. This study was undertaken to assess the level of knowledge of post-exposure prophylaxis (PEP) against human immunodeficiency virus (HIV) among doctors in Federal Medical Centre, Gombe, Nigeria.

  1. Biomonitoring human exposure to environmental carcinogenic chemicals

    DEFF Research Database (Denmark)

    Farmer, P.B.; Sepai, O.; Lawrence, R.

    1996-01-01

    for detecting carcinogen-induced damage to DNA and proteins, and subsequent biological effects. These methods were validated with the occupational exposures, which showed evidence of DNA and/or protein and/or chromosome damage in workers in a coke oven plant, garage workers exposed to diesel exhaust and workers...

  2. Uncertain quantities in estimating radiation exposure from former landfill sites: groundwater pathway

    International Nuclear Information System (INIS)

    Kistinger, S.

    2005-01-01

    With regard to the title of the closed meeting, ''Realistic determination of radiation exposure'', we state that generic estimates can by definition never be realistic, but that it is their purpose to be conservative. However this still leaves us with the question of how conservative a generic dose estimate must be and how the existing variability or indeterminacy of reality should be taken into account. This paper presents various methods for dealing with this indeterminacy in generic dose estimates. The example used for this purpose is a simplified model for the determination of the potential radiation exposure caused by a former landfill site via the water pathway

  3. Neuroimmune Pathways in Alcohol Consumption: Evidence from Behavioral and Genetic Studies in Rodents and Humans

    Science.gov (United States)

    Robinson, Gizelle; Most, Dana; Ferguson, Laura B.; Mayfield, Jody; Harris, R. Adron; Blednov, Yuri A.

    2014-01-01

    Immune or brain proinflammatory signaling has been linked to some of the behavioral effects of alcohol. Immune signaling appears to regulate voluntary ethanol intake in rodent models, and ethanol intake activates the immune system in multiple models. This bidirectional link raises the possibility that consumption increases immune signaling, which in turn further increases consumption in a feed-forward cycle. Data from animal and human studies provide overlapping support for the involvement of immune-related genes and proteins in alcohol action, and combining animal and human data is a promising approach to systematically evaluate and nominate relevant pathways. Based on rodent models, neuroimmune pathways may represent unexplored, nontraditional targets for medication development to reduce alcohol consumption and prevent relapse. Peroxisome proliferator-activated receptor agonists are one class of anti-inflammatory medications that demonstrate antiaddictive properties for alcohol and other drugs of abuse. Expression of immune-related genes is altered in animals and humans following chronic alcohol exposure, and the regulatory influences of specific mRNAs, microRNAs, and activated cell types are areas of intense study. Ultimately, the use of multiple datasets combined with behavioral validation will be needed to link specific neuroimmune pathways to addiction vulnerability. PMID:25175860

  4. Human exposure to emissions from building materials

    DEFF Research Database (Denmark)

    Kjærgaard, S.; Hauschildt, P.; Pejtersen, Jan

    1999-01-01

    found on peak flow, eye foam formation, tear fluid cells, or conjunctival epithelial damage. Among subjective evaluations only sound intensity rating was significant. A correlation was found between acute nose irritation rating and change in nasal volume.Conclusions. The findings indicate physiological......Objectives. Reactions to emissions from building matrials were studied in a climate chamber as part of an intervention study in an office building. New and existing flooring materials were compared with regard to comfort and health.Methods. Twenty subjects were exposed four times for six hours...... respectively to clean air, to emissions from linoleum, from carpet, and from an alternative new vinyl. Measurements of objective and subjective effects were made.Results. Tear film stability decreased after exposure to linoleum. The nasal volume decreased near-significantly for all exposures. No effects were...

  5. Titanium dioxide nanoparticles activate IL8-related inflammatory pathways in human colonic epithelial Caco-2 cells

    Science.gov (United States)

    Krüger, Kristin; Cossais, François; Neve, Horst; Klempt, Martin

    2014-05-01

    Nanosized titanium dioxide (TiO2) particles are widely used as food additive or coating material in products of the food and pharmaceutical industry. Studies on various cell lines have shown that TiO2 nanoparticles (NPs) induced the inflammatory response and cytotoxicity. However, the influences of TiO2 NPs' exposure on inflammatory pathways in intestinal epithelial cells and their differentiation have not been investigated so far. This study demonstrates that TiO2 NPs with particle sizes ranging between 5 and 10 nm do not affect enterocyte differentiation but cause an activation of inflammatory pathways in the human colon adenocarcinoma cell line Caco-2. 5 and 10 nm NPs' exposures transiently induce the expression of ICAM1, CCL20, COX2 and IL8, as determined by quantitative PCR, whereas larger particles (490 nm) do not. Further, using nuclear factor (NF)-κB reporter gene assays, we show that NP-induced IL8 mRNA expression occurs, in part, through activation of NF-κB and p38 mitogen-activated protein kinase pathways.

  6. Human Health and Exposure to Electromagnetic Radiation

    Science.gov (United States)

    1992-07-01

    passed through volunteers from electrodes attached to their heads and bodies while they were subjected to a series of psychological tests (Bonnell et...al, 1985; Stollery, 1986). The pattern of current was equivalent to that produced by exposure to a 36 kV m- 1 field at 50 Hz. The psychological tests ...Silverman, 1977; Lilienfeld et al, 1978; Stopps and Janischewsky, 1979; Knave et al, 1979; Robinette et al, 1980; Marsh et al, 1982; Silverman, 1985

  7. Natural radiation exposure modified by human activities

    International Nuclear Information System (INIS)

    Fujimoto, Kenzo

    1995-01-01

    We are now living in the radiation environment modified by our technology. It is usually called 'Technologically Enhanced Natural Radiation' and have been discussed in the UNSCEAR Reports as an important source of exposure. The terrestrial radionuclide concentrations as well as the intensity of cosmic rays are considered to have been constant after our ancestors came down from trees and started walking on their two feet. However, we have been changing our environment to be more comfortable for our life and consequently ambient radiation levels are nomore what used to be. In this paper exposures due to natural radiation modified by our following activities are discussed: housing, balneology, cave excursion, mountain climbing, skiing, swimming, smoking and usage of mineral water, well water, coal, natural gas, phosphate rocks and minerals. In the ICRP Publication No. 39, it is clearly mentioned that even natural radiation should be controlled as far as it is controllable. We have to pay more attention to our activities not to enhance the exposure due to unnecessary, avoidable radiation. (author)

  8. Pathways and Subcellular Compartmentation of NAD Biosynthesis in Human Cells

    Science.gov (United States)

    Nikiforov, Andrey; Dölle, Christian; Niere, Marc; Ziegler, Mathias

    2011-01-01

    NAD is a vital redox carrier, and its degradation is a key element of important regulatory pathways. NAD-mediated functions are compartmentalized and have to be fueled by specific biosynthetic routes. However, little is known about the different pathways, their subcellular distribution, and regulation in human cells. In particular, the route(s) to generate mitochondrial NAD, the largest subcellular pool, is still unknown. To visualize organellar NAD changes in cells, we targeted poly(ADP-ribose) polymerase activity into the mitochondrial matrix. This activity synthesized immunodetectable poly(ADP-ribose) depending on mitochondrial NAD availability. Based on this novel detector system, detailed subcellular enzyme localizations, and pharmacological inhibitors, we identified extracellular NAD precursors, their cytosolic conversions, and the pathway of mitochondrial NAD generation. Our results demonstrate that, besides nicotinamide and nicotinic acid, only the corresponding nucleosides readily enter the cells. Nucleotides (e.g. NAD and NMN) undergo extracellular degradation resulting in the formation of permeable precursors. These precursors can all be converted to cytosolic and mitochondrial NAD. For mitochondrial NAD synthesis, precursors are converted to NMN in the cytosol. When taken up into the organelles, NMN (together with ATP) serves as substrate of NMNAT3 to form NAD. NMNAT3 was conclusively localized to the mitochondrial matrix and is the only known enzyme of NAD synthesis residing within these organelles. We thus present a comprehensive dissection of mammalian NAD biosynthesis, the groundwork to understand regulation of NAD-mediated processes, and the organismal homeostasis of this fundamental molecule. PMID:21504897

  9. A comprehensive assessment of human exposure to phthalates from environmental media and food in Tianjin, China.

    Science.gov (United States)

    Ji, Yaqin; Wang, Fumei; Zhang, Leibo; Shan, Chunyan; Bai, Zhipeng; Sun, Zengrong; Liu, Lingling; Shen, Boxiong

    2014-08-30

    A total of 448 samples including foodstuffs (rice, steamed bun, vegetables, meat, poultry, fish, milk and fruits), ambient PM10, drinking water, soil, indoor PM10 and indoor dust samples from Tianjin were obtained to determine the distribution of six priority phthalates (PAEs) and assess the human exposure to them. The results indicated that DBP and DEHP were the most frequently detected PAEs in these samples. The concentrations of PAEs in environmental media were higher than those in food. We estimated the daily intake (DI) of PAEs via ingestion, inhalation and dermal absorption from five sources (food, water, air, dust and soil). Dietary intake was the main exposure source to DEP, BBP, DEHP and DOP, whereas water ingestion/absorption was the major source of exposure to DBP, DEHP and DOP. Although food and water were the overwhelmingly predominant sources of PAEs intake by Tianjin population, contaminated air was another important source of DMP, DEP and DBP contributing to up to 45% of the exposure. The results of this study will help in understanding the major pathways of human exposure to PAEs. These findings also suggest that human exposure to phthalate esters via the environment should not be overlooked. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Relative significance of natural irradiation vs all human exposures

    International Nuclear Information System (INIS)

    Jammet, H.

    1985-01-01

    A review is made of the fundamentals allowing to quantitatively express the importance of the various sources of human exposure by an individual or collective approach. Following a summary of the components of normal exposure to natural sources, the various human actions at the origin of enhanced exposure are studied: 1) those modifying the relationship between natural sources and man (dwelling conditions, coal burning, geothermal energy production, exploitation of phosphate rock); 2) those creating new artificial sources (nuclear explosions in the atmosphere, nuclear power production, medical use of radiation and radionuclides). The effective dose equivalent commitments for these sources are compared with those necessarily involved by continuous normal exposure to the natural sources of exposure [fr

  11. Human health risks and socio-economic perspectives of arsenic exposure in Bangladesh: A scoping review.

    Science.gov (United States)

    Rahman, M Azizur; Rahman, A; Khan, M Zaved Kaiser; Renzaho, Andre M N

    2018-04-15

    Arsenic contamination of drinking water, which can occur naturally or because of human activities such as mining, is the single most important public health issue in Bangladesh. Fifty out of the 64 districts in the country have arsenic concentration of groundwater exceeding 50µgL -1 , the Bangladeshi threshold, affecting 35-77 million people or 21-48% of the total population. Chronic arsenic exposure through drinking water and other dietary sources is an important public health issue worldwide affecting hundreds of millions of people. Consequently, arsenic poisoning has attracted the attention of researchers and has been profiled extensively in the literature. Most of the literature has focused on characterising arsenic poisoning and factors associated with it. However, studies examining the socio-economic aspects of chronic exposure of arsenic through either drinking water or foods remain underexplored. The objectives of this paper are (i) to review arsenic exposure pathways to humans; (ii) to summarise public health impacts of chronic arsenic exposure; and (iii) to examine socio-economic implications and consequences of arsenicosis with a focus on Bangladesh. This scoping review evaluates the contributions of different exposure pathways by analysing arsenic concentrations in dietary and non-dietary sources. The socio-economic consequences of arsenicosis disease in Bangladesh are discussed in this review by considering food habits, nutritional status, socio-economic conditions, and socio-cultural behaviours of the people of the country. The pathways of arsenic exposure in Bangladesh include drinking water, various plant foods and non-dietary sources such as soil. Arsenic affected people are often abandoned by the society, lose their jobs and get divorced and are forced to live a sub-standard life. The fragile public health system in Bangladesh has been burdened by the management of thousands of arsenicosis victims in Bangladesh. Copyright © 2017 Elsevier Inc

  12. Transitions in pathways of human development and carbon emissions

    International Nuclear Information System (INIS)

    Lamb, W F; Bows-Larkin, A; Wood, F R; Steinberger, J K; Peters, G P; Roberts, J T

    2014-01-01

    Countries are known to follow diverse pathways of life expectancy and carbon emissions, but little is known about factors driving these dynamics. In this letter we estimate the cross-sectional economic, demographic and geographic drivers of consumption-based carbon emissions. Using clustering techniques, countries are grouped according to their drivers, and analysed with respect to a criteria of one tonne of carbon emissions per capita and a life expectancy over 70 years (Goldemberg’s Corner). Five clusters of countries are identified with distinct drivers and highly differentiated outcomes of life expectancy and carbon emissions. Representatives from four clusters intersect within Goldemberg’s Corner, suggesting diverse combinations of drivers may still lead to sustainable outcomes, presenting many countries with an opportunity to follow a pathway towards low-carbon human development. By contrast, within Goldemberg’s Corner, there are no countries from the core, wealthy consuming nations. These results reaffirm the need to address economic inequalities within international agreements for climate mitigation, but acknowledge plausible and accessible examples of low-carbon human development for countries that share similar underlying drivers of carbon emissions. In addition, we note differences in drivers between models of territorial and consumption-based carbon emissions, and discuss interesting exceptions to the drivers-based cluster analysis. (paper)

  13. Cadmium exposure pathways in a population living near a battery plant

    International Nuclear Information System (INIS)

    Hellstroem, Lennart; Persson, Bodil; Brudin, Lars; Grawe, Kierstin Petersson; Oborn, Ingrid; Jaerup, Lars

    2007-01-01

    Objectives: The objectives of the present study were to assess the relative impact of different pathways of environmental cadmium (Cd) exposure and to evaluate the contribution from locally produced vegetables and root crops to the total dietary intake of Cd. Methods: Cadmium in urine was determined for 492 individuals living near a closed down battery factory in Sweden. For each individual we created an environmental exposure-index based on Cd emissions to ambient air and number of years living at various distances from the plant. This information as well as dietary data were collected via questionnaires. Samples of soil, carrots and/or potatoes were collected from 37 gardens and analysed for Cd concentration. Results: Eating homegrown vegetables/potatoes, environmental Cd-exposure-index, female gender, age above 30 years and smoking more than one pack of cigarettes daily for at least 10 years were found to be significantly associated with increased urine concentrations of Cd (UCd > 1.0 nmol/mmol creatinine). We found a statistically significant relation between Cd in urine and environmental Cd-exposure-index in persons eating homegrown vegetables/potatoes regularly. Cd concentrations in homegrown carrots, potatoes and in garden soil were highest in the area closest to the factory. Daily consumption of potatoes and vegetables cultivated in the vicinity of the closed battery factory was estimated to increase Cd intake by 18-38%. Conclusion: The present study shows that consumption of locally grown vegetables and root crops was an important exposure pathway, in subjects living near a nickel-cadmium battery plant, whereas direct exposure via ambient air was less important

  14. Multi-pathway exposure modeling of chemicals in cosmetics with application to shampoo.

    Science.gov (United States)

    Ernstoff, Alexi S; Fantke, Peter; Csiszar, Susan A; Henderson, Andrew D; Chung, Susie; Jolliet, Olivier

    2016-01-01

    We present a novel multi-pathway, mass balance based, fate and exposure model compatible with life cycle and high-throughput screening assessments of chemicals in cosmetic products. The exposures through product use as well as post-use emissions and environmental media were quantified based on the chemical mass originally applied via a product, multiplied by the product intake fractions (PiF, the fraction of a chemical in a product that is taken in by exposed persons) to yield intake rates. The average PiFs for the evaluated chemicals in shampoo ranged from 3×10(-4) up to 0.3 for rapidly absorbed ingredients. Average intake rates ranged between nano- and micrograms per kilogram bodyweight per day; the order of chemical prioritization was strongly affected by the ingredient concentration in shampoo. Dermal intake and inhalation (for 20% of the evaluated chemicals) during use dominated exposure, while the skin permeation coefficient dominated the estimated uncertainties. The fraction of chemical taken in by a shampoo user often exceeded, by orders of magnitude, the aggregated fraction taken in by the population through post-use environmental emissions. Chemicals with relatively high octanol-water partitioning and/or volatility, and low molecular weight tended to have higher use stage exposure. Chemicals with low intakes during use (<1%) and subsequent high post-use emissions, however, may yield comparable intake for a member of the general population. The presented PiF based framework offers a novel and critical advancement for life cycle assessments and high-throughput exposure screening of chemicals in cosmetic products demonstrating the importance of consistent consideration of near- and far-field multi-pathway exposures. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Human population exposure to cosmic radiation

    International Nuclear Information System (INIS)

    Bouville, A.; Lowder, W.M.

    1988-01-01

    Critical evaluations of existing data on cosmic radiation in the atmosphere and in interplanetary space have been carried out in order to estimate the exposure of the world's population to this important component of natural background radiation. Data on population distribution and mean terrain heights on a 1 x 1 degree grid have been folded in to estimate regional and global dose distributions. The per caput annual dose equivalent at ground altitudes is estimated to be 270 μSv from charged particles and 50 μSv from neutrons. More than 100 million people receive more than 1 mSv in a year, and two million in excess of 5 mSv. Aircraft flight crews and frequent flyers receive an additional annual dose equivalent in the order of 1 mSv, though the global per caput annual dose equivalent from airplane flights is only about 1 μSv. Future space travellers on extended missions are likely to receive dose equivalents in the range 0.11 Sv, with the possibility of higher doses at relatively high dose rates from unusually large solar flares. These results indicate a critical need for a better understanding of the biological significance of chronic neutron and heavy charged particle exposure. (author)

  16. Consolidated Human Activity Database (CHAD) for use in human exposure and health studies and predictive models

    Science.gov (United States)

    EPA scientists have compiled detailed data on human behavior from 22 separate exposure and time-use studies into CHAD. The database includes more than 54,000 individual study days of detailed human behavior.

  17. Exposure to Human Immunodeficiency Disease. What Precautions ...

    African Journals Online (AJOL)

    Background: The Human Immunodeficiency Virus (HIV) epidemic is more pronounced in sub-Saharan Africa. The ever-increasing prevalence of HIV infection and the continued improvement in clinical management has increased the likelihood of these patients being managed by healthcare workers. The aim of the review ...

  18. Post exposure prophylaxis against human immunodeficiency virus ...

    African Journals Online (AJOL)

    2015-11-23

    Nov 23, 2015 ... Abstract: Objective: To deter- mine the level of awareness, knowledge and practice of human immunodeficiency virus post ex- posure prophylaxis (HIV PEP) among paediatricians in Nigeria. Methodology: The study was a cross sectional questionnaire- based survey conducted among paediatrcians that ...

  19. High Throughput Heuristics for Prioritizing Human Exposure to ...

    Science.gov (United States)

    The risk posed to human health by any of the thousands of untested anthropogenic chemicals in our environment is a function of both the potential hazard presented by the chemical, and the possibility of being exposed. Without the capacity to make quantitative, albeit uncertain, forecasts of exposure, the putative risk of adverse health effect from a chemical cannot be evaluated. We used Bayesian methodology to infer ranges of exposure intakes that are consistent with biomarkers of chemical exposures identified in urine samples from the U.S. population by the National Health and Nutrition Examination Survey (NHANES). We perform linear regression on inferred exposure for demographic subsets of NHANES demarked by age, gender, and weight using high throughput chemical descriptors gleaned from databases and chemical structure-based calculators. We find that five of these descriptors are capable of explaining roughly 50% of the variability across chemicals for all the demographic groups examined, including children aged 6-11. For the thousands of chemicals with no other source of information, this approach allows rapid and efficient prediction of average exposure intake of environmental chemicals. The methods described by this manuscript provide a highly improved methodology for HTS of human exposure to environmental chemicals. The manuscript includes a ranking of 7785 environmental chemicals with respect to potential human exposure, including most of the Tox21 in vit

  20. Editor's Highlight: Hydroxyurea Exposure Activates the P53 Signaling Pathway in Murine Organogenesis-Stage Embryos.

    Science.gov (United States)

    El Husseini, Nazem; Schlisser, Ava E; Hales, Barbara F

    2016-08-01

    Hydroxyurea, an anticancer agent and potent teratogen, induces oxidative stress and activates a DNA damage response pathway in the gestation day (GD) 9 mouse embryo. To delineate the stress response pathways activated by this drug, we investigated the effect of hydroxyurea exposure on the transcriptome of GD 9 embryos. Timed pregnant CD-1 mice were treated with saline or hydroxyurea (400 mg/kg or 600 mg/kg) on GD 9; embryonic gene and protein expression were examined 3 h later. Microarray analysis revealed that the expression of 1346 probe sets changed significantly in embryos exposed to hydroxyurea compared with controls; the P53 signaling pathway was highly affected. In addition, P53 related family members, P63 and P73, were predicted to be activated and had common and unique downstream targets. Western blot analysis revealed that active phospho-P53 was significantly increased in drug-exposed embryos; confocal microscopy showed that the translocation of phospho-P53 to the nucleus was widespread in the embryo. Furthermore, qRT-PCR showed that the expression of P53-regulated genes (Cdkn1A, Fas, and Trp53inp1) was significantly upregulated in hydroxyurea-exposed embryos; the concentration of the redox sensitive P53INP1 protein was also increased in a hydroxyurea dose-dependent fashion. Thus, hydroxyurea elicits a significant effect on the transcriptome of the organogenesis stage murine embryo, activating several key developmental signaling pathways related to DNA damage and oxidative stress. We propose that the P53 pathway plays a central role in the embryonic stress response and the developmental outcome after teratogen exposure. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. Model for screening-level assessment of near-field human exposure to neutral organic chemicals released indoors.

    Science.gov (United States)

    Zhang, Xianming; Arnot, Jon A; Wania, Frank

    2014-10-21

    Screening organic chemicals for hazard and risk to human health requires near-field human exposure models that can be readily parametrized with available data. The integration of a model of human exposure, uptake, and bioaccumulation into an indoor mass balance model provides a quantitative framework linking emissions in indoor environments with human intake rates (iRs), intake fractions (iFs) and steady-state concentrations in humans (C) through consideration of dermal permeation, inhalation, and nondietary ingestion exposure pathways. Parameterized based on representative indoor and adult human characteristics, the model is applied here to 40 chemicals of relevance in the context of human exposure assessment. Intake fractions and human concentrations (C(U)) calculated with the model based on a unit emission rate to air for these 40 chemicals span 2 and 5 orders of magnitude, respectively. Differences in priority ranking based on either iF or C(U) can be attributed to the absorption, biotransformation and elimination processes within the human body. The model is further applied to a large data set of hypothetical chemicals representative of many in-use chemicals to show how the dominant exposure pathways, iF and C(U) change as a function of chemical properties and to illustrate the capacity of the model for high-throughput screening. These simulations provide hypotheses for the combination of chemical properties that may result in high exposure and internal dose. The model is further exploited to highlight the role human contaminant uptake plays in the overall fate of certain chemicals indoors and consequently human exposure.

  2. Neurotrophin receptors expression and JNK pathway activation in human astrocytomas

    Directory of Open Access Journals (Sweden)

    Maraziotis Theodore

    2007-10-01

    Full Text Available Abstract Background Neurotrophins are growth factors that regulate cell growth, differentiation and apoptosis in the nervous system. Their diverse actions are mediated through two different transmembrane – receptor signaling systems: Trk receptor tyrosine kinases (TrkA, TrkB, TrkC and p75NTR neurotrophin receptor. Trk receptors promote cell survival and differentiation while p75NTR induces, in most cases, the activity of JNK-p53-Bax apoptosis pathway or suppresses intracellular survival signaling cascades. Robust Trk activation blocks p75NTR -induced apoptosis by suppressing the JNK-p53-Bax pathway. The aim of this exploratory study was to investigate the expression levels of neurotrophin receptors, Trks and p75NTR, and the activation of JNK pathway in human astrocytomas and in adjacent non-neoplastic brain tissue. Methods Formalin-fixed paraffin-embedded serial sections from 33 supratentorial astrocytomas (5 diffuse fibrillary astrocytomas, WHO grade II; 6 anaplastic astrocytomas, WHO grade III; 22 glioblastomas multiforme, WHO grade IV were immunostained following microwave pretreatment. Polyclonal antibodies against TrkA, TrkB, TrkC and monoclonal antibodies against p75NTR and phosphorylated forms of JNK (pJNK and c-Jun (pc-Jun were used. The labeling index (LI, defined as the percentage of positive (labeled cells out of the total number of tumor cells counted, was determined. Results Moderate to strong, granular cytoplasmic immunoreactivity for TrkA, TrkB and TrkC receptors was detected in greater than or equal to 10% of tumor cells in the majority of tumors independently of grade; on the contrary, p75NTR receptor expression was found in a small percentage of tumor cells (~1% in some tumors. The endothelium of tumor capillaries showed conspicuous immunoreactivity for TrkB receptor. Trk immunoreactivity seemed to be localized in some neurons and astrocytes in non-neoplastic tissue. Phosphorylated forms of JNK (pJNK and c-Jun (pc-Jun were

  3. Neurotrophin receptors expression and JNK pathway activation in human astrocytomas

    International Nuclear Information System (INIS)

    Assimakopoulou, Martha; Kondyli, Maria; Gatzounis, George; Maraziotis, Theodore; Varakis, John

    2007-01-01

    Neurotrophins are growth factors that regulate cell growth, differentiation and apoptosis in the nervous system. Their diverse actions are mediated through two different transmembrane – receptor signaling systems: Trk receptor tyrosine kinases (TrkA, TrkB, TrkC) and p75 NTR neurotrophin receptor. Trk receptors promote cell survival and differentiation while p75 NTR induces, in most cases, the activity of JNK-p53-Bax apoptosis pathway or suppresses intracellular survival signaling cascades. Robust Trk activation blocks p75 NTR -induced apoptosis by suppressing the JNK-p53-Bax pathway. The aim of this exploratory study was to investigate the expression levels of neurotrophin receptors, Trks and p75 NTR , and the activation of JNK pathway in human astrocytomas and in adjacent non-neoplastic brain tissue. Formalin-fixed paraffin-embedded serial sections from 33 supratentorial astrocytomas (5 diffuse fibrillary astrocytomas, WHO grade II; 6 anaplastic astrocytomas, WHO grade III; 22 glioblastomas multiforme, WHO grade IV) were immunostained following microwave pretreatment. Polyclonal antibodies against TrkA, TrkB, TrkC and monoclonal antibodies against p75 NTR and phosphorylated forms of JNK (pJNK) and c-Jun (pc-Jun) were used. The labeling index (LI), defined as the percentage of positive (labeled) cells out of the total number of tumor cells counted, was determined. Moderate to strong, granular cytoplasmic immunoreactivity for TrkA, TrkB and TrkC receptors was detected in greater than or equal to 10% of tumor cells in the majority of tumors independently of grade; on the contrary, p75 NTR receptor expression was found in a small percentage of tumor cells (~1%) in some tumors. The endothelium of tumor capillaries showed conspicuous immunoreactivity for TrkB receptor. Trk immunoreactivity seemed to be localized in some neurons and astrocytes in non-neoplastic tissue. Phosphorylated forms of JNK (pJNK) and c-Jun (pc-Jun) were significantly co-expressed in a tumor

  4. Pathway modeling of microarray data: A case study of pathway activity changes in the testis following in utero exposure to dibutyl phthalate (DBP)

    International Nuclear Information System (INIS)

    Ovacik, Meric A.; Sen, Banalata; Euling, Susan Y.; Gaido, Kevin W.; Ierapetritou, Marianthi G.; Androulakis, Ioannis P.

    2013-01-01

    Pathway activity level analysis, the approach pursued in this study, focuses on all genes that are known to be members of metabolic and signaling pathways as defined by the KEGG database. The pathway activity level analysis entails singular value decomposition (SVD) of the expression data of the genes constituting a given pathway. We explore an extension of the pathway activity methodology for application to time-course microarray data. We show that pathway analysis enhances our ability to detect biologically relevant changes in pathway activity using synthetic data. As a case study, we apply the pathway activity level formulation coupled with significance analysis to microarray data from two different rat testes exposed in utero to Dibutyl Phthalate (DBP). In utero DBP exposure in the rat results in developmental toxicity of a number of male reproductive organs, including the testes. One well-characterized mode of action for DBP and the male reproductive developmental effects is the repression of expression of genes involved in cholesterol transport, steroid biosynthesis and testosterone synthesis that lead to a decreased fetal testicular testosterone. Previous analyses of DBP testes microarray data focused on either individual gene expression changes or changes in the expression of specific genes that are hypothesized, or known, to be important in testicular development and testosterone synthesis. However, a pathway analysis may inform whether there are additional affected pathways that could inform additional modes of action linked to DBP developmental toxicity. We show that Pathway activity analysis may be considered for a more comprehensive analysis of microarray data

  5. Pathway modeling of microarray data: A case study of pathway activity changes in the testis following in utero exposure to dibutyl phthalate (DBP)

    Energy Technology Data Exchange (ETDEWEB)

    Ovacik, Meric A. [Chemical and Biochemical Engineering Department, Rutgers University, Piscataway, NJ 08854 (United States); Sen, Banalata [National Center for Environmental Assessment, U.S. Environmental Protection Agency, Research Triangle Park, NC 27709 (United States); Euling, Susan Y. [National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC 20460 (United States); Gaido, Kevin W. [U.S. Food and Drug Administration, Center for Veterinary Medicine, Office of New Animal Drug Evaluation, Division of Human Food Safety, Rockville, MD 20855 (United States); Ierapetritou, Marianthi G. [Chemical and Biochemical Engineering Department, Rutgers University, Piscataway, NJ 08854 (United States); Androulakis, Ioannis P., E-mail: yannis@rci.rutgers.edu [Chemical and Biochemical Engineering Department, Rutgers University, Piscataway, NJ 08854 (United States); Biomedical Engineering Department, Rutgers University, NJ 08854 (United States)

    2013-09-15

    Pathway activity level analysis, the approach pursued in this study, focuses on all genes that are known to be members of metabolic and signaling pathways as defined by the KEGG database. The pathway activity level analysis entails singular value decomposition (SVD) of the expression data of the genes constituting a given pathway. We explore an extension of the pathway activity methodology for application to time-course microarray data. We show that pathway analysis enhances our ability to detect biologically relevant changes in pathway activity using synthetic data. As a case study, we apply the pathway activity level formulation coupled with significance analysis to microarray data from two different rat testes exposed in utero to Dibutyl Phthalate (DBP). In utero DBP exposure in the rat results in developmental toxicity of a number of male reproductive organs, including the testes. One well-characterized mode of action for DBP and the male reproductive developmental effects is the repression of expression of genes involved in cholesterol transport, steroid biosynthesis and testosterone synthesis that lead to a decreased fetal testicular testosterone. Previous analyses of DBP testes microarray data focused on either individual gene expression changes or changes in the expression of specific genes that are hypothesized, or known, to be important in testicular development and testosterone synthesis. However, a pathway analysis may inform whether there are additional affected pathways that could inform additional modes of action linked to DBP developmental toxicity. We show that Pathway activity analysis may be considered for a more comprehensive analysis of microarray data.

  6. Human exposure to bisphenol A by biomonitoring: Methods, results and assessment of environmental exposures

    International Nuclear Information System (INIS)

    Dekant, Wolfgang; Voelkel, Wolfgang

    2008-01-01

    Human exposure to bisphenol A is controversially discussed. This review critically assesses methods for biomonitoring of bisphenol A exposures and reported concentrations of bisphenol A in blood and urine of non-occupationally ('environmentally') exposed humans. From the many methods published to assess bisphenol A concentrations in biological media, mass spectrometry-based methods are considered most appropriate due to high sensitivity, selectivity and precision. In human blood, based on the known toxicokinetics of bisphenol A in humans, the expected very low concentrations of bisphenol A due to rapid biotransformation and the very rapid excretion result in severe limitations in the use of reported blood levels of bisphenol A for exposure assessment. Due to the rapid and complete excretion of orally administered bisphenol A, urine samples are considered as the appropriate body fluid for bisphenol A exposure assessment. In urine samples from several cohorts, bisphenol A (as glucuronide) was present in average concentrations in the range of 1-3 μg/L suggesting that daily human exposure to bisphenol A is below 6 μg per person (< 0.1 μg/kg bw/day) for the majority of the population

  7. Lead remediation and changes in human lead exposure: some physiological and biokinetic dimensions.

    Science.gov (United States)

    Mushak, Paul

    2003-02-15

    This paper presents a qualitative and quantitative analysis of the various aspects of lead remediation effectiveness with particular reference to human health risk assessment. One of the key elements of lead remediation efforts at such sites as those under the Superfund program deals with populations at elevated exposure and toxicity risk in the proximity of, or at, the site of remediation, especially remediation workers, workers at other tasks on sites that were remediated down to some action level of lead concentration in soils, and groups at risk in nearby communities. A second element has to do with how one measures or models lead exposure changes with special reference to baseline and post-remediation conditions. Various biomarkers of lead exposure can be employed, but their use requires detailed knowledge of what results using each means. The most commonly used approach is measurement of blood lead (Pb-B). Recognized limitations in the use of Pb-B has led to the use of predictive Pb exposure models, which are less vulnerable to the many behavioral, physiological, and environmental parameters that can distort isolated or 'single shot' Pb-B testings. A third aspect covered in this paper presents various physiological factors that affect the methods by which one evaluates Pb remediation effectiveness. Finally, this article offers an integrated look at how lead remediation actions directed at one lead source or pathway affect the total lead exposure picture for human populations at elevated lead exposure and toxicity risk.

  8. Exploring consumer exposure pathways and patterns of use for chemicals in the environment through the Chemical/Product Categories Database

    Science.gov (United States)

    Exploring consumer exposure pathways and patterns of use for chemicals in the environment through the Chemical/Product Categories Database (CPCat) (Presented by: Kathie Dionisio, Sc.D., NERL, US EPA, Research Triangle Park, NC (1/23/2014).

  9. Early brain response to low-dose radiation exposure involves molecular networks and pathways associated with cognitive functions, advanced aging and Alzheimer's disease.

    Science.gov (United States)

    Lowe, Xiu R; Bhattacharya, Sanchita; Marchetti, Francesco; Wyrobek, Andrew J

    2009-01-01

    Understanding the cognitive and behavioral consequences of brain exposures to low-dose ionizing radiation has broad relevance for health risks from medical radiation diagnostic procedures, radiotherapy and environmental nuclear contamination as well as for Earth-orbit and space missions. Analyses of transcriptome profiles of mouse brain tissue after whole-body irradiation showed that low-dose exposures (10 cGy) induced genes not affected by high-dose radiation (2 Gy) and that low-dose genes were associated with unique pathways and functions. The low-dose response had two major components: pathways that are consistently seen across tissues and pathways that were specific for brain tissue. Low-dose genes clustered into a saturated network (P < 10(-53)) containing mostly down-regulated genes involving ion channels, long-term potentiation and depression, vascular damage, etc. We identified nine neural signaling pathways that showed a high degree of concordance in their transcriptional response in mouse brain tissue after low-dose irradiation, in the aging human brain (unirradiated), and in brain tissue from patients with Alzheimer's disease. Mice exposed to high-dose radiation did not show these effects and associations. Our findings indicate that the molecular response of the mouse brain within a few hours after low-dose irradiation involves the down-regulation of neural pathways associated with cognitive dysfunctions that are also down-regulated in normal human aging and Alzheimer's disease.

  10. Early Brain Response to Low-Dose Radiation Exposure Involves Molecular Networks and Pathways Associated with Cognitive Functions, Advanced Aging and Alzheimer's Disease

    International Nuclear Information System (INIS)

    Lowe, Xiu R.; Bhattacharya, Sanchita; Marchetti, Francesco; Wyrobek, Andrew J.

    2008-01-01

    Understanding the cognitive and behavioral consequences of brain exposures to low-dose ionizing radiation has broad relevance for health risks from medical radiation diagnostic procedures, radiotherapy, environmental nuclear contamination, as well as earth orbit and space missions. Analyses of transcriptome profiles of murine brain tissue after whole-body radiation showed that low-dose exposures (10 cGy) induced genes not affected by high dose (2 Gy), and low-dose genes were associated with unique pathways and functions. The low-dose response had two major components: pathways that are consistently seen across tissues, and pathways that were brain tissue specific. Low-dose genes clustered into a saturated network (p -53 ) containing mostly down-regulated genes involving ion channels, long-term potentiation and depression, vascular damage, etc. We identified 9 neural signaling pathways that showed a high degree of concordance in their transcriptional response in mouse brain tissue after low-dose radiation, in the aging human brain (unirradiated), and in brain tissue from patients with Alzheimer's disease. Mice exposed to high-dose radiation did not show these effects and associations. Our findings indicate that the molecular response of the mouse brain within a few hours after low-dose irradiation involves the down-regulation of neural pathways associated with cognitive dysfunctions that are also down regulated in normal human aging and Alzheimer's disease

  11. Early Brain Response to Low-Dose Radiation Exposure Involves Molecular Networks and Pathways Associated with Cognitive Functions, Advanced Aging and Alzheimer's Disease

    Energy Technology Data Exchange (ETDEWEB)

    Lowe, Xiu R; Bhattacharya, Sanchita; Marchetti, Francesco; Wyrobek, Andrew J.

    2008-06-06

    Understanding the cognitive and behavioral consequences of brain exposures to low-dose ionizing radiation has broad relevance for health risks from medical radiation diagnostic procedures, radiotherapy, environmental nuclear contamination, as well as earth orbit and space missions. Analyses of transcriptome profiles of murine brain tissue after whole-body radiation showed that low-dose exposures (10 cGy) induced genes not affected by high dose (2 Gy), and low-dose genes were associated with unique pathways and functions. The low-dose response had two major components: pathways that are consistently seen across tissues, and pathways that were brain tissue specific. Low-dose genes clustered into a saturated network (p < 10{sup -53}) containing mostly down-regulated genes involving ion channels, long-term potentiation and depression, vascular damage, etc. We identified 9 neural signaling pathways that showed a high degree of concordance in their transcriptional response in mouse brain tissue after low-dose radiation, in the aging human brain (unirradiated), and in brain tissue from patients with Alzheimer's disease. Mice exposed to high-dose radiation did not show these effects and associations. Our findings indicate that the molecular response of the mouse brain within a few hours after low-dose irradiation involves the down-regulation of neural pathways associated with cognitive dysfunctions that are also down regulated in normal human aging and Alzheimer's disease.

  12. Acrolein and Human Disease: Untangling the Knotty Exposure Scenarios Accompanying Several Diverse Disorders.

    Science.gov (United States)

    Burcham, Philip C

    2017-01-17

    Acrolein is a highly toxic electrophile that participates in many diseases, yet efforts to delineate its precise mechanistic contributions to specific conditions are complicated by its wide distribution within human environments. This Perspective develops the proposal that due to its mixed status as environmental pollutant, metabolic byproduct, and endotoxicant which forms via ubiquitous pathophysiological processes, many diseases likely involve acrolein released from multiple sources. Although the category boundaries are indistinct, at least four identifiable exposure scenarios are identifiable. First, in some syndromes, such as those accompanying chronic or acute intoxication with smoke, whatever role acrolein plays in disease pathogenesis mainly traces to exogenous sources such as the combustion of tobacco or other organic matter. A second exposure category involves xenobiotics that undergo metabolism within the body to release acrolein. Still other health conditions, however, involve acrolein that forms via several endogenous pathways, some of which are activated upon intoxication with xenobiotics (i.e., Exposure Category 3), while still others accompany direct physical trauma to body tissues (Exposure Category 4). Further complicating efforts to clarify the role of endogenous acrolein in human disease is the likelihood that many such syndromes are complex phenomena that resemble "chemical mixture exposures" by involving multiple toxic substances simultaneously. This Perspective contends that while recent decades have witnessed much progress in describing the deleterious effects of acrolein at the cellular and molecular levels, more work is needed to define the contributions of different acrolein sources to "real-world" health conditions in human subjects.

  13. Developing human health exposure scenarios for petroleum substances under REACH

    Energy Technology Data Exchange (ETDEWEB)

    Carter, M.; De Wilde, P.; Maksimainen, K.; Margary, A.; Money, C.; Pizzella, G.; Svanehav, T.; Tsang, W.; Urbanus, J.; Rohde, A.

    2012-12-15

    This report describes the approaches that were adopted by CONCAWE to prepare the human exposure estimates in the chemical safety assessments of the REACH registration dossiers for petroleum substances based on all applicable regulatory guidance. Separate exposure estimates were developed for workers and for consumers and included inhalation and dermal routes. The complex nature of petroleum substances required various scientifically justified refinements of the regulatory guidance.

  14. Foetal exposure to food and environmental carcinogens in human beings.

    Science.gov (United States)

    Myöhänen, Kirsi; Vähäkangas, Kirsi

    2012-02-01

    Exposure to many different chemicals during pregnancy through maternal circulation is possible. Transplacental transfer of xenobiotics can be demonstrated using human placental perfusion. Also, placental perfusion can give information about the placental kinetics as well as metabolism and accumulation in the placenta because it retains the tissue structure and function. Although human placental perfusion has been used extensively to study the transplacental transfer of drugs, the information on food and environmental carcinogens is much more limited. This review deals with the foetal exposure to food and environmental carcinogens in human beings. In particular, human transplacental transfer of the food carcinogens such as acrylamide, glycidamide and nitrosodimethylamine are in focus. Because these carcinogens are genotoxic, the functional capacity of human placenta to induce DNA adduct formation or metabolize these above mentioned CYP2E1 substrates is of interest in this context. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.

  15. Human Cytomegalovirus: Coordinating Cellular Stress, Signaling, and Metabolic Pathways.

    Science.gov (United States)

    Shenk, Thomas; Alwine, James C

    2014-11-01

    Viruses face a multitude of challenges when they infect a host cell. Cells have evolved innate defenses to protect against pathogens, and an infecting virus may induce a stress response that antagonizes viral replication. Further, the metabolic, oxidative, and cell cycle state may not be conducive to the viral infection. But viruses are fabulous manipulators, inducing host cells to use their own characteristic mechanisms and pathways to provide what the virus needs. This article centers on the manipulation of host cell metabolism by human cytomegalovirus (HCMV). We review the features of the metabolic program instituted by the virus, discuss the mechanisms underlying these dramatic metabolic changes, and consider how the altered program creates a synthetic milieu that favors efficient HCMV replication and spread.

  16. Infectious Entry Pathway Mediated by the Human Endogenous Retrovirus K Envelope Protein.

    Science.gov (United States)

    Robinson, Lindsey R; Whelan, Sean P J

    2016-01-20

    Endogenous retroviruses (ERVs), the majority of which exist as degraded remnants of ancient viruses, comprise approximately 8% of the human genome. The youngest human ERVs (HERVs) belong to the HERV-K(HML-2) subgroup and were endogenized within the past 1 million years. The viral envelope protein (ENV) facilitates the earliest events of endogenization (cellular attachment and entry), and here, we characterize the requirements for HERV-K ENV to mediate infectious cell entry. Cell-cell fusion assays indicate that a minimum of two events are required for fusion, proteolytic processing by furin-like proteases and exposure to acidic pH. We generated an infectious autonomously replicating recombinant vesicular stomatitis virus (VSV) in which the glycoprotein was replaced by HERV-K ENV. HERV-K ENV imparts an endocytic entry pathway that requires dynamin-mediated membrane scission and endosomal acidification but is distinct from clathrin-dependent or macropinocytic uptake pathways. The lack of impediments to the replication of the VSV core in eukaryotic cells allowed us to broadly survey the HERV-K ENV-dictated tropism. Unlike extant betaretroviral envelopes, which impart a narrow species tropism, we found that HERV-K ENV mediates broad tropism encompassing cells from multiple mammalian and nonmammalian species. We conclude that HERV-K ENV dictates an evolutionarily conserved entry pathway and that the restriction of HERV-K to primate genomes reflects downstream stages of the viral replication cycle. Approximately 8% of the human genome is of retroviral origin. While many of those viral genomes have become inactivated, some copies of the most recently endogenized human retrovirus, HERV-K, can encode individual functional proteins. Here, we characterize the envelope protein (ENV) of the virus to define how it mediates infection of cells. We demonstrate that HERV-K ENV undergoes a proteolytic processing step and triggers membrane fusion in response to acidic pH--a strategy

  17. Inhale while Dreaming: Human Exposure to Pollutants while Sleeping

    DEFF Research Database (Denmark)

    Corsi, Richard; Spilak, Michal; Boor, E., Brandon

    2012-01-01

    of indoor pollutants, e.g., flame retardants to isocyanates. As such, there is a need for increased dialogue on this subject, end-point relevant research, and action to reduce exposures to high-risk contaminants for most of humanity. This workshop will involve an opening 5–minute presentation related...... discussion related to practical implications of new findings as well as past studies, geographic variations in emissions from mattresses and beddings, methods for reducing population exposures, and suggestions for future research that has practical endpoints and that can lead to reduced exposures....

  18. Assessment of indirect human exposure to environmental sources of nickel: oral exposure and risk characterization for systemic effects.

    Science.gov (United States)

    De Brouwere, Katleen; Buekers, Jurgen; Cornelis, Christa; Schlekat, Christian E; Oller, Adriana R

    2012-03-01

    This paper describes the indirect human exposure to Ni via the oral route for the regional scale in the EU, together with a method to assess additional local exposure from industrial emissions. The approach fills a gap in the generic REACH guidance which is inadequate for assessing indirect environmental exposure of metals. Estimates of regional scale Ni dietary intake were derived from Ni dietary studies performed in the EU. Typical and Reasonable Worst Case dietary Ni intakes for the general population in the EU were below the oral Derived No Effect Level (DNEL) of Ni sulfate for systemic effects. Estimates for the Ni dietary intake at the local scale take into account the influence of aerial Ni deposition and transfer from soil to crops grown near industrial plants emitting Ni. The additional dietary exposure via this local contribution was small. Despite the use of conservative parameters for these processes, this method may underestimate dietary exposure around older industrial sites because REACH guidance does not account for historical soil contamination. Nevertheless, the method developed here can also be used as a screening tool for community-based risk assessment, as it accounts for historical soil pollution. Nickel exposure via drinking water was derived from databases on Ni tap water quality. A small proportion of the EU population (<5%) is likely to be exposed to tap water exceeding the EU standard (20 μg Ni/l). Taking into account the relative gastrointestinal absorption of Ni from water (30%) versus from solid matrices (5%), water intake constitutes, after dietary intake, the second most important pathway for oral Ni intake. Incidental ingestion of Ni from soil/dust at the regional scale, and also at the local scale, was low in comparison with dietary intake. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. Dietary exposure of 17-alpha ethinylestradiol modulates physiological endpoints and gene signaling pathways in female largemouth bass (Micropterus salmoides).

    Science.gov (United States)

    Colli-Dula, Reyna-Cristina; Martyniuk, Christopher J; Kroll, Kevin J; Prucha, Melinda S; Kozuch, Marianne; Barber, David S; Denslow, Nancy D

    2014-11-01

    17Alpha-ethinylestradiol (EE2), used for birth control in humans, is a potent estrogen that is found in wastewater at low concentrations (ng/l). EE2 has the ability to interfere with the endocrine system of fish, affecting reproduction which can result in population level effects. The objective of this study was to determine if dietary exposure to EE2 would alter gene expression patterns and key pathways in the liver and ovary and whether these could be associated with reproductive endpoints in female largemouth bass during egg development. Female LMB received 70ng EE2/g feed (administered at 1% of body weight) for 60 days. EE2 dietary exposure significantly reduced plasma vitellogenin concentrations by 70%. Hepatosomatic and gonadosomatic indices were also decreased with EE2 feeding by 38.5% and 40%, respectively. Transcriptomic profiling revealed that there were more changes in steady state mRNA levels in the liver compared to the ovary. Genes associated with reproduction were differentially expressed, such as vitellogenin in the liver and aromatase in the gonad. In addition, a set of genes related with oxidative stress (e.g. glutathione reductase and glutathione peroxidase) were identified as altered in the liver and genes associated with the immune system (e.g. complement component 1, and macrophage-inducible C-type lectin) were altered in the gonad. In a follow-up study with 0.2ng EE2/g feed for 60 days, similar phenotypic and gene expression changes were observed that support these findings with the higher concentrations. This study provides new insights into how dietary exposure to EE2 interferes with endocrine signaling pathways in female LMB during a critical period of reproductive oogenesis. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Development of a ECOREA-II code for human exposures from radionuclides through food chain

    International Nuclear Information System (INIS)

    Yoo, D. H.; Choi, Y. H.

    2001-01-01

    The release of radionuclides from nuclear facilities following an accident into air results in human exposures through two pathways. One is direct human exposures by inhalation or dermal absorption of these radionucles. Another is indirect human exposures through food chain which includes intakes of plant products such as rice, vegetables from contaiminated soil and animal products such as meet, milk and eggs feeded by contaminated grasses or plants on the terrestial surface. This study presents efforts of the development of a computer code for the assessment of the indirect human exposure through such food chains. The purpose of ECOREA-II code is to develop appropriate models suitable for a specific soil condition in Korea based on previous experimental efforts and to provide a more user-friendly environment such as GUI for the use of the code. Therefore, the current code, when more fully developed, is expected to increase the understanding of environmental safety assessment of nuclear facilities following an accident and provide a reasonable regulatory guideline with respecte to food safety issues

  1. Developmental pathways from prenatal marijuana exposure to Cannabis Use Disorder in young adulthood.

    Science.gov (United States)

    Sonon, Kristen; Richardson, Gale A; Cornelius, Jack; Kim, Kevin H; Day, Nancy L

    Earlier studies reported an association between prenatal marijuana exposure (PME) and cognitive and behavioral problems in the offspring. A recent publication demonstrated the relation between PME and offspring marijuana use at age 22. There are no reports of the association between PME and Cannabis Use Disorder (CUD) at 22years, the age when use of marijuana and CUD peak. Subjects are from the Maternal Health Practices and Child Development Study, a longitudinal study of PME and other exposures during pregnancy. The cohort of mothers and their offspring has been followed since the fourth prenatal month through 22years of age. A path analysis was conducted on 590 mother-child pairs, representing 77% of the birth cohort, to examine potential pathways from PME to CUD in offspring at 22years of age. There is no direct effect of PME on CUD. There are, however, two indirect pathways from PME to CUD. In the first, the pathway from PME to CUD goes through offspring early age of marijuana onset. In the second, offspring depression at age 10 and early age of marijuana onset predict CUD. Although there is no direct effect of PME on CUD, there are significant indirect pathways from PME to CUD that affect the rate of CUD in the population. Thus, PME, offspring depression, and an early age of marijuana initiation, are significant points for intervention. As marijuana is legalized in more states, the rates of marijuana use will increase significantly, including during pregnancy, and the consequences of the association between PME and CUD will become even more significant from a public health perspective. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Toxicity levels to humans during acute exposure to hydrogen fluoride

    International Nuclear Information System (INIS)

    Halton, D.M.; Dranitsaris, P.; Baynes, C.J.

    1984-11-01

    A literature review was conducted of the acute toxicity of hydrogen fluoride (HF) with emphasis on the effects of inhalation of gaseous HF. The data and findings of the relevant references were summarized under four categories: animal studies, controlled human studies, community exposure and industrial exposure. These were critically reviewed and then lethal concentration-time relationships were developed for humans, corresponding to LCsub(LO), LCsub(10) and LCsub(50) levels. The effects of age, health and other physiological variables on the sensitivity to HF were discussed, as well as antagonistic and synergistic effects with other substances

  3. A dermatotoxicokinetic model of human exposures to jet fuel.

    Science.gov (United States)

    Kim, David; Andersen, Melvin E; Nylander-French, Leena A

    2006-09-01

    Workers, both in the military and the commercial airline industry, are exposed to jet fuel by inhalation and dermal contact. We present a dermatotoxicokinetic (DTK) model that quantifies the absorption, distribution, and elimination of aromatic and aliphatic components of jet fuel following dermal exposures in humans. Kinetic data were obtained from 10 healthy volunteers following a single dose of JP-8 to the forearm over a surface area of 20 cm2. Blood samples were taken before exposure (t = 0 h), after exposure (t = 0.5 h), and every 0.5 h for up to 3.5 h postexposure. The DTK model that best fit the data included five compartments: (1) surface, (2) stratum corneum (SC), (3) viable epidermis, (4) blood, and (5) storage. The DTK model was used to predict blood concentrations of the components of JP-8 based on dermal-exposure measurements made in occupational-exposure settings in order to better understand the toxicokinetic behavior of these compounds. Monte Carlo simulations of dermal exposure and cumulative internal dose demonstrated no overlap among the low-, medium-, and high-exposure groups. The DTK model provides a quantitative understanding of the relationship between the mass of JP-8 components in the SC and the concentrations of each component in the systemic circulation. The model may be used for the development of a toxicokinetic modeling strategy for multiroute exposure to jet fuel.

  4. National Surveillance of Occupational Exposure to the Human Immunodeficiency Virus

    Directory of Open Access Journals (Sweden)

    Maura Ricketts

    1992-01-01

    Full Text Available In September 1985, a prospective study was initiated to monitor the occurrence of occupational exposures to human immunodeficiency virus (HIV-infected blood and body fluids in Canada. This program was coordinated by the Federal Centre for acquired immune deficiency syndrome (AIDS (now the Division of HIV/AIDS Epidemiology at the Laboratory Centre for Disease Control. The objective was to determine the risk to workers of acquiring HIV infection as a result of exposure to HIV-infected blood and other body fluids. To be eligible, a worker must have sustained a documented parenteral, mucous membrane or skin contact exposure to blood or body fluids from an HIV-infected person. A baseline specimen was collected within a week of the exposure and then at six weeks, 12 weeks, six months and 12 months. Information concerning the type of exposure, precautions used and post exposure treatment was submitted to the Federal Centre for AIDS on standard data collection forms. All information was anonymous, identified only by a code number. Guidelines for counselling an exposed employee were provided with enrollment material. As of July 29, 1991, 414 employees have been included in the study. Two hundred and thirty-seven of the 414 exposures (57% were needlestick injuries of which 167 (70% were sustained by nurses. Other exposures consisted of open wound contamination, eye splashes, scalpel wounds and skin contact with blood and body fluids. To date, there have been no seroconversions among workers enrolled in the surveillance program.

  5. Anthropogenic materials and products containing natural radionuclides. Pt. 1. Survey of the major exposure pathways

    International Nuclear Information System (INIS)

    Becker, D.E.; Reichelt, A.

    1991-06-01

    Knowledge of the possible exposure pathways permits to perform an overall assessment of the radiation doses and qualities affecting the population, as well as their inter-relations: A catalogue was established of products, raw materials and waste materials containing natural radioactivity that are processed, produced or dumped in Bavaria and that contribute above negligible level to the radiation exposure of the population and to occupational radiation doses. A literature study rounds up the information on anthropogenic sources containing natural radioactivity and thus representing a radiation source generally to be considered for assessments. Some of these sources are discussed in more detail, indicating their radiological significance for the population and the environment in Bavaria. (Orig./DG) [de

  6. Pathways of human development and carbon emissions embodied in trade

    Science.gov (United States)

    Steinberger, Julia K.; Timmons Roberts, J.; Peters, Glen P.; Baiocchi, Giovanni

    2012-02-01

    It has long been assumed that human development depends on economic growth, that national economic expansion in turn requires greater energy use and, therefore, increased greenhouse-gas emissions. These interdependences are the topic of current research. Scarcely explored, however, is the impact of international trade: although some nations develop socio-economically and import high-embodied-carbon products, it is likely that carbon-exporting countries gain significantly fewer benefits. Here, we use new consumption-based measures of national carbon emissions to explore how the relationship between human development and carbon changes when we adjust national emission rates for trade. Without such adjustment of emissions, some nations seem to be getting far better development `bang' for the carbon `buck' than others, who are showing scant gains for disproportionate shares of global emissions. Adjusting for the transfer of emissions through trade explains many of these outliers, but shows that further socio-economic benefits are accruing to carbon-importing rather than carbon-exporting countries. We also find that high life expectancies are compatible with low carbon emissions but high incomes are not. Finally, we see that, despite strong international trends, there is no deterministic industrial development trajectory: there is great diversity in pathways, and national histories do not necessarily follow the global trends.

  7. Disposition pathways and pharmacokinetics of herbal medicines in humans.

    Science.gov (United States)

    He, S-M; Li, C G; Liu, J-P; Chan, E; Duan, W; Zhou, S-F

    2010-01-01

    Pharmacokinetic studies have become an integral part of modern drug development, but these studies are not regulatory needs for herbal remedies. This paper updates our current knowledge on the disposition pathways and pharmacokinetic properties of commonly used herbal medicines in humans. To retrieve relevant data, the authors have searched through computer-based literatures by full text search in Medline (via Pubmed), ScienceDirect, Current Contents Connect (ISI), Cochrance Library, CINAHL (EBSCO), CrossRef Search and Embase (all from inception to May 2010). Many herbal compounds undergo Phase I and/or Phase II metabolism in vivo, with cytochrome P450s (CYPs) and uridine diphosphate glucuronosyltransferases (UGTs) playing a major role. Some herbal ingredients are substrates of P-glycoprotein (P-gp) which is highly expressed in the intestine, liver, brain and kidney. As such, the activities of these drug metabolizing enzymes and drug transporters are determining factors for the in vivo bioavailability, disposition and distribution of herbal remedies. There are increasing pharmacokinetic studies of herbal remedies, but these studies are mainly focused on a small number of herbal remedies including St John's wort, milk thistle, sculcap, curcumin, echinacea, ginseng, ginkgo, and ginger. The pharmacokinetic data of a small number of purified herbal ingredients, including anthocyanins, berberine, catechins, curcumin, lutein and quercetin, are available. For the majority of herbal remedies used in folk medicines, data on their disposition and biological fate in humans are lacking or in paucity. For a herbal medicine, the pharmacological effect is achieved when the bioactive agents or the metabolites reach and sustain proper levels at their sites of action. Both the dose levels and fates of active components in the body govern their target-site concentrations after administration of an herbal remedy. In this regard, a safe and optimal use of herbal medicines requires a

  8. Evaluation of the soil-to-indoor air exposure pathway at petroleum contaminated sites

    Energy Technology Data Exchange (ETDEWEB)

    Kindzierski, W. B. [Alberta Univ., Edmonton, AB (Canada). Dept. of Civil Engineering

    1997-12-31

    Results of two approaches for evaluating human exposure to benzene inside a former gasoline station converted into a strip mall were discussed. Using passive air sampling, benzene levels inside the mall were evaluated. It was found that contrary to expectations the levels inside the mall were lower than the average levels in Canadian homes. The second approach, i.e. modeling of soil vapour entry, confirmed the findings of the passive air test by showing that incremental exposure conditions for mall workers was no worse than what they receive by inhalation in their own homes. 14 refs., 2 figs.

  9. Evaluation of the soil-to-indoor air exposure pathway at petroleum contaminated sites

    International Nuclear Information System (INIS)

    Kindzierski, W. B.

    1997-01-01

    Results of two approaches for evaluating human exposure to benzene inside a former gasoline station converted into a strip mall were discussed. Using passive air sampling, benzene levels inside the mall were evaluated. It was found that contrary to expectations the levels inside the mall were lower than the average levels in Canadian homes. The second approach, i.e. modeling of soil vapour entry, confirmed the findings of the passive air test by showing that incremental exposure conditions for mall workers was no worse than what they receive by inhalation in their own homes. 14 refs., 2 figs

  10. Modeling The Inhalation Exposure Pathway In Performance Assessment Of Geologic Radioactive Waste Repository At Yucca Mountain

    International Nuclear Information System (INIS)

    M.A. Wasiolek

    2006-01-01

    Inhalation exposure pathway modeling has recently been investigated as one of the tasks of the BIOPROTA Project (BIOPROTA 2005). BIOPROTA was set up to address the key uncertainties in long term assessments of contaminant releases into the environment arising from radioactive waste disposal. Participants of this international Project include national authorities and agencies, both regulators and operators, with responsibility for achieving safe and acceptable radioactive waste management. The objective of the inhalation task was to investigate the calculation of doses arising from inhalation of particles suspended from soils within which long-lived radionuclides, particularly alpha emitters, had accumulated. It was recognized that site-specific conditions influence the choice of conceptual model and input parameter values. Therefore, one of the goals of the task was to identify the circumstances in which different processes included in specific inhalation exposure pathway models were important. This paper discusses evaluation of processes and modeling assumptions specific to the proposed repository at Yucca Mountain as compared to the typical approaches and other models developed for different assessments and project specific contexts. Inhalation of suspended particulates that originate from contaminated soil is an important exposure pathway, particularly for exposure to actinides such as uranium, neptunium and plutonium. Radionuclide accumulation in surface soil arises from irrigation of soil with contaminated water over many years. The level of radionuclide concentration in surface soil depends on the assumed duration of irrigation. Irrigation duration is one of the parameters used on biosphere models and it depends on a specific assessment context. It is one of the parameters addressed in this paper from the point of view of assessment context for the proposed repository at Yucca Mountain. The preferred model for the assessment of inhalation exposure uses

  11. Low Dose Cadmium Inhibits Proliferation of Human Renal Mesangial Cells via Activation of the JNK Pathway

    Science.gov (United States)

    Chen, Xiaocui; Li, Jing; Cheng, Zuowang; Xu, Yinghua; Wang, Xia; Li, Xiaorui; Xu, Dongmei; Kapron, Carolyn M.; Liu, Ju

    2016-01-01

    Cadmium (Cd) is a heavy metal and environmental pollutant. The kidney is the principal target organ of Cd exposure. Previously, we found that low concentration of Cd damages the integrity of the glomerular filtration barrier. However, little is known about the effects of Cd on renal mesangial cells, which provide structural support for the glomerular capillary loops and regulate intraglomerular blood flow. In this study, human renal mesangial cells (HRMCs) were cultured in the presence of serum and treated with 4 μM Cd. We found that Cd activates the c-Jun N-terminal kinase (JNK) pathway, and increases the protein levels of c-Jun and c-Fos. Cd treatment also induces a decrease in proliferation and an increase in apoptosis of HRMCs, but only the decrease in HRMC proliferation was reversed by pretreatment with SP600125, an inhibitor of the JNK pathway. In addition, Cd does not change the expression of α-smooth muscle actin and platelet-derived growth factor receptor-β, the markers of mesangial cells, or the alignment of the filamentous actin (F-actin) cytoskeleton of HRMCs. Our data indicate that the JNK pathway mediates the inhibitory effects of Cd on HRMC proliferation. PMID:27739415

  12. Integrating population dynamics into mapping human exposure to seismic hazard

    Directory of Open Access Journals (Sweden)

    S. Freire

    2012-11-01

    Full Text Available Disaster risk is not fully characterized without taking into account vulnerability and population exposure. Assessment of earthquake risk in urban areas would benefit from considering the variation of population distribution at more detailed spatial and temporal scales, and from a more explicit integration of this improved demographic data with existing seismic hazard maps. In the present work, "intelligent" dasymetric mapping is used to model population dynamics at high spatial resolution in order to benefit the analysis of spatio-temporal exposure to earthquake hazard in a metropolitan area. These night- and daytime-specific population densities are then classified and combined with seismic intensity levels to derive new spatially-explicit four-class-composite maps of human exposure. The presented approach enables a more thorough assessment of population exposure to earthquake hazard. Results show that there are significantly more people potentially at risk in the daytime period, demonstrating the shifting nature of population exposure in the daily cycle and the need to move beyond conventional residence-based demographic data sources to improve risk analyses. The proposed fine-scale maps of human exposure to seismic intensity are mainly aimed at benefiting visualization and communication of earthquake risk, but can be valuable in all phases of the disaster management process where knowledge of population densities is relevant for decision-making.

  13. Assessment of human dietary exposure to arsenic through rice.

    Science.gov (United States)

    Davis, Matthew A; Signes-Pastor, Antonio J; Argos, Maria; Slaughter, Francis; Pendergrast, Claire; Punshon, Tracy; Gossai, Anala; Ahsan, Habibul; Karagas, Margaret R

    2017-05-15

    Rice accumulates 10-fold higher inorganic arsenic (i-As), an established human carcinogen, than other grains. This review summarizes epidemiologic studies that examined the association between rice consumption and biomarkers of arsenic exposure. After reviewing the literature we identified 20 studies, among them included 18 observational and 2 human experimental studies that reported on associations between rice consumption and an arsenic biomarker. Among individuals not exposed to contaminated water, rice is a source of i-As exposure - rice consumption has been consistently related to arsenic biomarkers, and the relationship has been clearly demonstrated in experimental studies. Early-life i-As exposure is of particular concern due to its association with lifelong adverse health outcomes. Maternal rice consumption during pregnancy also has been associated with infant toenail total arsenic concentrations indicating that dietary exposure during pregnancy results in fetal exposure. Thus, the collective evidence indicates that rice is an independent source of arsenic exposure in populations around the world and highlights the importance of investigating its affect on health. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  14. Human exposure to cyanotoxins and their effects on health.

    Science.gov (United States)

    Drobac, Damjana; Tokodi, Nada; Simeunović, Jelica; Baltić, Vladimir; Stanić, Dina; Svirčev, Zorica

    2013-06-01

    Cyanotoxins are secondary metabolites produced by cyanobacteria. They pose a threat to human health and the environment. This review summarises the existing data on human exposure to cyanotoxins through drinking water, recreational activities (e.g., swimming, canoeing or bathing), the aquatic food web, terrestrial plants, food supplements, and haemodialysis. Furthermore, it discusses the tolerable daily intake and guideline values for cyanotoxins (especially microcystins) as well as the need to implement risk management measures via national and international legislation.

  15. Review of the chronic exposure pathways models in MACCS [MELCOR Accident Consequence Code System] and several other well-known probabilistic risk assessment models

    International Nuclear Information System (INIS)

    Tveten, U.

    1990-06-01

    The purpose of this report is to document the results of the work performed by the author in connection with the following task, performed for US Nuclear Regulatory Commission, (USNRC) Office of Nuclear Regulatory Research, Division of Systems Research: MACCS Chronic Exposure Pathway Models: Review the chronic exposure pathway models implemented in the MELCOR Accident Consequence Code System (MACCS) and compare those models to the chronic exposure pathway models implemented in similar codes developed in countries that are members of the OECD. The chronic exposures concerned are via: the terrestrial food pathways, the water pathways, the long-term groundshine pathway, and the inhalation of resuspended radionuclides pathway. The USNRC has indicated during discussions of the task that the major effort should be spent on the terrestrial food pathways. There is one chapter for each of the categories of chronic exposure pathways listed above

  16. Involvement of the kynurenine pathway in human glioma pathophysiology.

    Directory of Open Access Journals (Sweden)

    Seray Adams

    Full Text Available The kynurenine pathway (KP is the principal route of L-tryptophan (TRP catabolism leading to the production of kynurenine (KYN, the neuroprotectants, kynurenic acid (KYNA and picolinic acid (PIC, the excitotoxin, quinolinic acid (QUIN and the essential pyridine nucleotide, nicotinamide adenine dinucleotide (NAD(+. The enzymes indoleamine 2,3-dioxygenase-1 (IDO-1, indoleamine 2,3-dioxygenase-2 (IDO-2 and tryptophan 2,3-dioxygenase (TDO-2 initiate the first step of the KP. IDO-1 and TDO-2 induction in tumors are crucial mechanisms implicated to play pivotal roles in suppressing anti-tumor immunity. Here, we report the first comprehensive characterisation of the KP in 1 cultured human glioma cells and 2 plasma from patients with glioblastoma (GBM. Our data revealed that interferon-gamma (IFN-γ stimulation significantly potentiated the expression of the KP enzymes, IDO-1 IDO-2, kynureninase (KYNU, kynurenine hydroxylase (KMO and significantly down-regulated 2-amino-3-carboxymuconate semialdehyde decarboxylase (ACMSD and kynurenine aminotransferase-I (KAT-I expression in cultured human glioma cells. This significantly increased KP activity but significantly lowered the KYNA/KYN neuroprotective ratio in human cultured glioma cells. KP activation (KYN/TRP was significantly higher, whereas the concentrations of the neuroreactive KP metabolites TRP, KYNA, QUIN and PIC and the KYNA/KYN ratio were significantly lower in GBM patient plasma (n = 18 compared to controls. These results provide further evidence for the involvement of the KP in glioma pathophysiology and highlight a potential role of KP products as novel and highly attractive therapeutic targets to evaluate for the treatment of brain tumors, aimed at restoring anti-tumor immunity and reducing the capacity for malignant cells to produce NAD(+, which is necessary for energy production and DNA repair.

  17. Human reproductive system disturbances and pesticide exposure in Brazil

    Directory of Open Access Journals (Sweden)

    Koifman Sergio

    2002-01-01

    Full Text Available The observation of reproductive disturbances in humans and in the wildlife has been reported in the last decade in different countries. Exposure to different chemicals possibly acting in the endocrine system or endocrine disruptors, including pesticides, has been a hypothesis raised to explain the observed changes. This paper aimed to present results of an epidemiological ecologic study carried out to explore population data on pesticides exposure in selected Brazilian states in the eighties and human reproductive outcomes in the nineties. Pearson correlation coefficients were ascertained between available data pesticides sales in eleven states in Brazil in 1985 and selected further reproductive outcomes or their surrogates. Moderate to high correlations were observed to infertility, testis, breast, prostate and ovarian cancer mortality. Despite the restrains of ecologic studies to establish cause-effect relationships, the observed results are in agreement with evidence supporting a possible association between pesticides exposure and the analyzed reproductive outcomes.

  18. Assessing Sources of Human Methylmercury Exposure Using Stable Mercury Isotopes

    DEFF Research Database (Denmark)

    Li, Miling; Sherman, Laura S; Blum, Joel D

    2014-01-01

    Seafood consumption is the primary route of methylmercury (MeHg) exposure for most populations. Inherent uncertainties in dietary survey data point to the need for an empirical tool to confirm exposure sources. We therefore explore the utility of Hg stable isotope ratios in human hair as a new...... method for discerning MeHg exposure sources. We characterized Hg isotope fractionation between humans and their diets using hair samples from Faroese whalers exposed to MeHg predominantly from pilot whales. We observed an increase of 1.75‰ in δ(202)Hg values between pilot whale muscle tissue and Faroese...... whalers' hair but no mass-independent fractionation. We found a similar offset in δ(202)Hg between consumed seafood and hair samples from Gulf of Mexico recreational anglers who are exposed to lower levels of MeHg from a variety of seafood sources. An isotope mixing model was used to estimate individual...

  19. The causes and consequences of human exposure to ionising radiation

    International Nuclear Information System (INIS)

    Clarke, R.H.

    1991-01-01

    Few phenomena cause as much concern in developed countries as human exposure to artificial sources of radiation, and yet there are more potent threats to health: natural radiation is more pervasive and exposures more substantial; common practices such as smoking and drinking are more detrimental. Developing countries may be more anxious to establish radiological procedures than radiological protection. This paper gives the ranges of exposure to which people are subjected from natural and artificial sources which should help to put all doses in perspective. The relationship between dose and risk is established and used to show that exposures to radiation leak to low levels of risk. Finally, the new recommendations of ICRP for the control of radiation risk are presented. (Author)

  20. Assessment of Nicotine Exposure From Active Human Cigarette Smoking Time

    Directory of Open Access Journals (Sweden)

    Cahours Xavier

    2017-09-01

    Full Text Available The burning of a cigarette is a series of consecutive sequences of both passive and active burnings when a smoking cycle is applied to the cigarette. A previous study, using a smoking machine, showed that cigarette nicotine yields are dependent linearly on the difference between the time of smouldering (passive burning and the time of smoking (active burning. It is predicted that the smoker’s nicotine yield increases when the intensity of smoking increases, i.e., when the time to smoke a cigarette (smoking time decreases. Note that observations made on machines might not be comparable to human behaviours. The aim of this study was to determine whether nicotine mouth-level exposure could be predicted through measurement of human smoking time. A smoking behaviour study was conducted to compare human smoking nicotine yields obtained from both filter tip analysis and the cigarette burning time model. Results showed that smokers’ exposure to the smoke depends essentially on the speed at which the cigarette is smoked. An increase in human smoking intensity, resulting in a decrease in smoking time, generates an increase in smoke exposure, whatever the puff number, puff duration, puff volume and filter ventilation (open or blocked. The association of a machine smoking yield with a corresponding smoking time, and the time taken by a consumer to smoke the cigarette would provide information on the exposure to smoke constituents in a simple and effective manner.

  1. Traditional goat husbandry may substantially contribute to human toxoplasmosis exposure

    Science.gov (United States)

    Raising goats in settings that are highly contaminated with oocysts of Toxoplasma gondii may contribute significantly to human exposure to this zoonotic parasite. Increasing consumption of young goats in Romania, where goats are typically reared in backyards that are also home to cats (the definitiv...

  2. Spatial Analysis of Human Exposure and Vulnerability to Coastal ...

    African Journals Online (AJOL)

    Disasters in coastal cities have shown an ever-increasing frequency of occurrence. Population growth and urbanisation have increased the vulnerability of properties and societies in coastal flood-prone areas. Analysis of human exposure and vulnerability is one of the main strategies used to determine the necessary ...

  3. Radiation exposure and radiation hazards of human population. Pt. 1

    International Nuclear Information System (INIS)

    Jacobi, W.

    1982-01-01

    The present Part I provides a survey on the various sources of natural and artificial radiation exposure of human population. Furthermore, biological radiation effects and radiation damages are surveyed. In an appendix, radiation types, radiation doses, and radiation dose units are explained. (orig./GSCH) [de

  4. Human health risk assessment related to cyanotoxins exposure.

    Science.gov (United States)

    Funari, Enzo; Testai, Emanuela

    2008-01-01

    This review focuses on the risk assessment associated with human exposure to cyanotoxins, secondary metabolites of an ubiquitous group of photosynthetic procariota. Cyanobacteria occur especially in eutrophic inland and coastal surface waters, where under favorable conditions they attain high densities and may form blooms and scums. Cyanotoxins can be grouped according to their biological effects into hepatotoxins, neurotoxins, cytotoxins, and toxins with irritating potential, also acting on the gastrointestinal system. The chemical and toxicological properties of the main cyanotoxins, relevant for the evaluation of possible risks for human health, are presented. Humans may be exposed to cyanotoxins via several routes, with the oral one being by far the most important, occurring by ingesting contaminated drinking water, food, some dietary supplements, or water during recreational activities. Acute and short-term toxic effects have been associated in humans with exposure to high levels of cyanotoxins in drinking and bathing waters. However, the chronic exposure to low cyanotoxin levels remains a critical issue. This article identifies the actual risky exposure scenarios, provides toxicologically derived reference values, and discusses open issues and research needs.

  5. Biocides Steering Group on human exposure assessment: A preliminary report

    NARCIS (Netherlands)

    Hemmen, J.J. van

    1999-01-01

    In a project granted by DG XI of the European Commission, it is attempted to collate experimental and theoretical data on human (workers and consumers) exposure assessment to biocidal products, and to outline the methodology for sampling and measurement. On the basis of the available evidence,

  6. Human exposure to endocrine disrupting chemicals: effects on the male and female reproductive systems.

    Science.gov (United States)

    Sifakis, Stavros; Androutsopoulos, Vasilis P; Tsatsakis, Aristeidis M; Spandidos, Demetrios A

    2017-04-01

    Endocrine disrupting chemicals (EDCs) comprise a group of chemical compounds that have been examined extensively due to the potential harmful effects in the health of human populations. During the past decades, particular focus has been given to the harmful effects of EDCs to the reproductive system. The estimation of human exposure to EDCs can be broadly categorized into occupational and environmental exposure, and has been a major challenge due to the structural diversity of the chemicals that are derived by many different sources at doses below the limit of detection used by conventional methodologies. Animal and in vitro studies have supported the conclusion that endocrine disrupting chemicals affect the hormone dependent pathways responsible for male and female gonadal development, either through direct interaction with hormone receptors or via epigenetic and cell-cycle regulatory modes of action. In human populations, the majority of the studies point towards an association between exposure to EDCs and male and/or female reproduction system disorders, such as infertility, endometriosis, breast cancer, testicular cancer, poor sperm quality and/or function. Despite promising discoveries, a causal relationship between the reproductive disorders and exposure to specific toxicants is yet to be established, due to the complexity of the clinical protocols used, the degree of occupational or environmental exposure, the determination of the variables measured and the sample size of the subjects examined. Future studies should focus on a uniform system of examining human populations with regard to the exposure to specific EDCs and the direct effect on the reproductive system. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Organic UV filters exposure induces the production of inflammatory cytokines in human macrophages.

    Science.gov (United States)

    Ao, Junjie; Yuan, Tao; Gao, Li; Yu, Xiaodan; Zhao, Xiaodong; Tian, Ying; Ding, Wenjin; Ma, Yuning; Shen, Zhemin

    2018-09-01

    Organic ultraviolet (UV) filters, found in many personal care products, are considered emerging contaminants due to growing concerns about potential long-term deleterious effects. We investigated the immunomodulatory effects of four commonly used organic UV filters (2-hydroxy-4-methoxybenzophenone, BP-3; 4-methylbenzylidene camphor, 4-MBC; 2-ethylhexyl 4-methoxycinnamate, EHMC; and butyl-methoxydibenzoylmethane, BDM) on human macrophages. Our results indicated that exposure to these four UV filters significantly increased the production of various inflammatory cytokines in macrophages, particular tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). After exposure to the UV filters, a significant 1.1-1.5 fold increase were found in TNF-α and IL-6 mRNA expression. In addition, both the p38 MAPK and the NF-κB signaling pathways were enhanced 2 to 10 times in terms of phosphorylation after exposure to the UV filters, suggesting that these pathways are involved in the release of TNF-α and IL-6. Molecular docking analysis predicted that all four UV filter molecules would efficiently bind transforming growth factor beta-activated kinase 1 (TAK1), which is responsible for the activation of the p38 MAPK and NF-κB pathways. Our results therefore demonstrate that exposure to the four organic UV filters investigated may alter human immune system function. It provides new clue for the development of asthma or allergic diseases in terms of the environmental pollutants. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Assessment of exposure pathways connected with construction and operation of concrete bridge reinforced with very low level radioactive steel

    International Nuclear Information System (INIS)

    Panik, M.; Necas, V.

    2012-01-01

    Large amount of low level radioactive material arises during decommissioning of nuclear power plants. Material mostly comprises metal scrap and concrete ruble. Paper deals with recycling and reuse of metal scrap and its utilization as part of reinforcement of concrete bridges under the conditional release concept. Radiation exposure originating in very low level reinforcement steel consists of several exposure pathways. Short-term radiation impact is represented mostly by external exposure pathway and it is relevant to the construction workers and users of the bridge. Long-term radiation impacts on inhabitants living near finished bridge and it is divided into inhalation and ingestion of radionuclides-internal exposure pathways. Radiation impact caused by utilization of very low level radioactive waste was calculated using simulation software VISIPLAN 3D ALARA and GOLDSIM. Results of calculations provide fair summary of possibilities of utilization of conditionally released steel as reinforcement of concrete bridges. (Authors)

  9. Human Bronchial Epithelial Cell Response to Heavy Particle Exposure

    Science.gov (United States)

    Story, Michael; Ding, Liang-Hao; Minna, John; Park, Seong-mi; Peyton, Michael; Larsen, Jill

    2012-07-01

    A battery of non-oncogenically immortalized human bronchial epithelial cells (HBECs) are being used to examine the molecular changes that lead to lung carcinogenesis after exposure to heavy particles found in the free space environment. The goal is to ultimately identify biomarkers of radioresponse that can be used for prediction of carcinogenic risk for fatal lung cancer. Our initial studies have focused on the cell line HBEC3 KT and the isogenic variant HBEC3 KTR53, which overexpresses the RASv12 mutant and where p53 has been knocked down by shRNA, and is considered to be a more oncogenically progressed variant. We have previously described the response of HBEC3 KT at the cellular and molecular level, however, the focus here is on the rate of cellular transformation after HZE radiation exposure and the molecular changes in transformed cells. When comparing the two cell lines we find that there is a maximum rate of cellular transformation at 0.25 Gy when cells are exposed to 1 GeV Fe particles, and, for the HBEC3 KTR53 there are multiple pathways upregulated that promote anchorage independent growth including the mTOR pathway, the TGF-1 pathway, RhoA signaling and the ERK/MAPK pathway as early as 2 weeks after radiation. This does not occur in the HBEC3 KT cell line. Transformed HBEC3 KT cells do not show any morphologic or phenotypic changes when grown as cell cultures. HBEC3 KTR53 cells on the other hand show substantial changes in morphology from a cobblestone epithelial appearance to a mesenchymal appearance with a lack of contact inhibition. This epithelial to mesenchymal change in morphology is accompanied by the expression of vimentin and a reduction in the expression of E-cadherin, which are hallmarks of epithelial to mesenchymal transition. Interestingly, for HBEC3 KT transformed cells there are no mutations in the p53 gene, 2 of 15 clones were found to be heterozygous for the RASV12 mutation, and 3 of 15 clones expressed high levels of BigH3, a TGFB

  10. Acute Noise Exposure Is Associated With Intrinsic Apoptosis in Murine Central Auditory Pathway

    Directory of Open Access Journals (Sweden)

    Moritz Gröschel

    2018-05-01

    Full Text Available Noise that is capable of inducing the hearing loss (NIHL has a strong impact on the inner ear structures and causes early and most obvious pathophysiological changes in the auditory periphery. Several studies indicated that intrinsic apoptotic cell death mechanisms are the key factors inducing cellular degeneration immediately after noise exposure and are maintained for days or even weeks. In addition, studies demonstrated several changes in the central auditory system following noise exposure, consistent with early apoptosis-related pathologies. To clarify the underlying mechanisms, the present study focused on the noise-induced gene and protein expression of the pro-apoptotic protease activating factor-1 (APAF1 and the anti-apoptotic B-cell lymphoma 2 related protein a1a (BCL2A1A in the cochlear nucleus (CN, inferior colliculus (IC and auditory cortex (AC of the murine central auditory pathway. The expression of Bcl2a1a mRNA was upregulated immediately after trauma in all tissues investigated, whereas the protein levels were significantly reduced at least in the auditory brainstem. Conversely, acute noise has decreased the expression of Apaf1 gene along the auditory pathway. The changes in APAF1 protein level were not statistically significant. It is tempting to speculate that the acoustic overstimulation leads to mitochondrial dysfunction and induction of apoptosis by regulation of proapoptotic and antiapoptotic proteins. The inverse expression pattern on the mRNA level of both genes might reflect a protective response to decrease cellular damage. Our results indicate the immediate presence of intrinsic apoptosis following noise trauma. This, in turn, may significantly contribute to the development of central structural deficits. Auditory pathway-specific inhibition of intrinsic apoptosis could be a therapeutic approach for the treatment of acute (noise-induced hearing loss to prevent irreversible neuronal injury in auditory brain structures

  11. ERK-dependent and -independent pathways trigger human neural progenitor cell migration

    International Nuclear Information System (INIS)

    Moors, Michaela; Cline, Jason E.; Abel, Josef; Fritsche, Ellen

    2007-01-01

    Besides differentiation and apoptosis, cell migration is a basic process in brain development in which neural cells migrate several centimeters within the developing brain before reaching their proper positions and forming the right connections. For identifying signaling events that control neural migration and are therefore potential targets of chemicals to disturb normal brain development, we developed a human neurosphere-based migration assay based on normal human neural progenitor (NHNP) cells, in which the distance is measured that cells wander over time. Applying this assay, we investigated the role of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) in the regulation of NHNP cell migration. Exposure to model substances like ethanol or phorbol 12-myristate 13-acetate (PMA) revealed a correlation between ERK1/2 activation and cell migration. The participation of phospho-(P-) ERK1/2 was confirmed by exposure of the cells to the MEK inhibitor PD98059, which directly prohibits ERK1/2 phosphorylation and inhibited cell migration. We identified protein kinase C (PKC) and epidermal growth factor receptor (EGFR) as upstream signaling kinases governing ERK1/2 activation, thereby controlling NHNP cell migration. Additionally, treatments with src kinase inhibitors led to a diminished cell migration without affecting ERK1/2 phosphorylation. Based on these results, we postulate that migration of NHNP cells is controlled via ERK1/2-dependent and -independent pathways

  12. Human Bisphenol A Exposure and the “Diabesity Phenotype”

    Science.gov (United States)

    Leone, Alessandro; Battezzati, Alberto

    2015-01-01

    Bisphenol A (BPA), a known endocrine disruptor, is a food contaminant suspected of being a contributing factor to the present-day increase in obesity, diabetes, and cardiovascular disease. This issue is of increasing interest in the field of diabetes research and has become a matter of concern for regulatory agencies and food industries. Recently, the number of studies involving BPA has increased exponentially, but there are still many gaps in the knowledge of the relationship between actual BPA exposure and cardiometabolic risk and of the modalities of food intake exposure, all of which prevents sound judgments concerning the risks to human health. This review focuses on the association between human exposure to BPA and obesity, thyroid function, diabetes, insulin resistance, metabolic syndrome, cardiovascular diseases, and BPA content in food. Many cross-sectional studies support, sometimes contradictorily, an adverse effect of BPA exposure on obesity, diabetes, and cardiovascular diseases. Few prospective studies support an adverse effect of BPA exposure on such pathologies. Moreover, no intervention studies have been conducted to evaluate the causality of such associations. This is mainly due to lack of an appropriate database of BPA content in foods, thus hindering any estimation of the usual dietary BPA intake. PMID:26858585

  13. Pathways, levels and trends of population exposure after the Chernobyl accident

    International Nuclear Information System (INIS)

    Balonov, M.; Jacob, P.; Likhtarev, D.; Minenko, V.

    1996-01-01

    In this paper main regularities of the long-term exposure of the population of former USSR after the Chernobyl accident are described. Influence of some natural, human and social factors on the forming of external and internal dose in the rural and urban population was studied in the most contaminated regions of Belarus, Russia and Ukraine during 1986-1994. Radioecological processes of I, Cs and Sr nuclides migration in biosphere influencing the processes of population dose formation are considered. The model of their intake in human body was developed and validated by large-scaled measurements of the human body content. The model of external exposure of different population groups was developed and confirmed by the series of individual external dose measurements with thermoluminescent dosemeters. General dosimetric characteristics of the population exposure are given along with some samples of accumulated external and internal effective doses in inhabitants of contaminated areas in 1986-1995. Forecast of the external and internal population effective dose is given for the period of 70 years after the accident

  14. Study of Arachidonic Acid Pathway in Human Bladder Tumor

    Directory of Open Access Journals (Sweden)

    Masahide Matsuyama

    2009-12-01

    Full Text Available Recent epidemiological studies and animal experiments have demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs reduce the incidence of colorectal carcinoma. Cyclooxygenase (COX is the principal target of NSAIDs. COX is the first oxidase in the process of prostaglandin production from arachidonic acid. COX enzyme may be involved in the initiation and/or the promotion of tumorigenesis due to NSAIDs inhibition of COX. Lipoxygenase (LOX is also an initial enzyme in the pathway for producing leukotrienes from arachidonic acid. Similar to COX, LOX enzyme may also be involved in the initiation and/or promotion of tumorigenesis. Peroxisome proliferator activator-receptor (PPAR-γ is a ligand-activated transcriptional factor belonging to the steroid receptor superfamily. PPAR-γ plays a role in both adipocyte differentiation and tumorigenesis. PPAR-γ is one target for cell growth modulation of NSAIDs. In this review, we report the expression of COX-2, LOX and PPAR-γ in human bladder tumor tissues as well as the effects of COX-2 and LOX inhibitors and PPAR-γ ligand.

  15. Study of Arachidonic Acid Pathway in Human Bladder Tumor

    Directory of Open Access Journals (Sweden)

    Masahide Matsuyama

    2009-01-01

    Full Text Available Recent epidemiological studies and animal experiments have demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs reduce the incidence of colorectal carcinoma. Cyclooxygenase (COX is the principal target of NSAIDs. COX is the first oxidase in the process of prostaglandin production from arachidonic acid. COX enzyme may be involved in the initiation and/or the promotion of tumorigenesis due to NSAIDs inhibition of COX. Lipoxygenase (LOX is also an initial enzyme in the pathway for producing leukotrienes from arachidonic acid. Similar to COX, LOX enzyme may also be involved in the initiation and/or promotion of tumorigenesis. Peroxisome proliferator activator-receptor (PPAR-γ is a ligand-activated transcriptional factor belonging to the steroid receptor superfamily. PPAR-γ plays a role in both adipocyte differentiation and tumorigenesis. PPAR-γ is one target for cell growth modulation of NSAIDs. In this review, we report the expression of COX-2, LOX and PPAR-γ in human bladder tumor tissues as well as the effects of COX-2 and LOX inhibitors and PPAR-γ ligand.

  16. EVALUATION OF EMF EXPOSURE OF MOBILE PHONES ON HUMAN HEAD

    Directory of Open Access Journals (Sweden)

    N. I. Vtornikova

    2017-01-01

    Full Text Available Introduction. Mobile phones are worldwide spread nowadays. Smartphones penetration is growing year after year. Numerous studies indicate the negative effect of EMF exposure of these devices on humans. Therefore, it is important to study the peculiarities of their influence on the target organ-the brain. It is important for solving this problem to find out the real situation of the distribution of energy flux density (EFD of EMF exposure near the front panel of the apparatus.The aim of the study is to determine and compare EMF exposure from smartphones and classic mobile phones on human head.Material and methods. The original method patented in the Russian Federation was used in this study. The used original measuring setup is also patented, developed and assembled by the authors of the study. The object of the study was classical mobile phones and smartphones widespread at the time of work.Results. We got the graphic of matrices of distribution of energy flux density (EFD of EMF exposure in the plane against the front panel of 10 apparatus corresponding to the topography of a human head. The study revealed peculiarities of this distribution in smartphones and the classic mobile phones and got the values of energy flux density (EFD of EMF exposure in the investigated devices acting primarily on the brain.Conclusions. The design of smartphones and mobile phones determines the overall picture of distribution of EFD of EMF exposure in the plane against the front panel for devices of a particular type. This picture must be taken into account when planning epidemiological and experimental studies to obtain comparable results. Progress in the development of mobile communication technologies has led to an increase in the electromagnetic load on users of modern devices.

  17. GLI3 Links Environmental Arsenic Exposure and Human Fetal Growth

    Directory of Open Access Journals (Sweden)

    Emily F. Winterbottom

    2015-06-01

    Full Text Available Although considerable evidence suggests that in utero arsenic exposure affects children's health, these data are mainly from areas of the world where groundwater arsenic levels far exceed the World Health Organization limit of 10 μg/L. We, and others, have found that more common levels of in utero arsenic exposure may also impact children's health. However, the underlying molecular mechanisms are poorly understood. To address this issue, we analyzed the expression of key developmental genes in fetal placenta in a birth cohort of women using unregulated water supplies in a US region with elevated groundwater arsenic. We identified several genes whose expression associated with maternal arsenic exposure in a fetal sex-specific manner. In particular, expression of the HEDGEHOG pathway component, GLI3, in female placentae was both negatively associated with arsenic exposure and positively associated with infant birth weight. This suggests that modulation of GLI3 in the fetal placenta, and perhaps in other fetal tissues, contributes to arsenic's detrimental effects on fetal growth. We showed previously that arsenic-exposed NIH3T3 cells have reduced GLI3 repressor protein. Together, these studies identify GLI3 as a key signaling node that is affected by arsenic, mediating a subset of its effects on developmental signaling and fetal health.

  18. Ozone exposure increases respiratory epithelial permeability in humans

    International Nuclear Information System (INIS)

    Kehrl, H.R.; Vincent, L.M.; Kowalsky, R.J.; Horstman, D.H.; O'Neil, J.J.; McCartney, W.H.; Bromberg, P.A.

    1987-01-01

    Ozone is a respiratory irritant that has been shown to cause an increase in the permeability of the respiratory epithelium in animals. We used inhaled aerosolized /sup 99m/Tc-labeled diethylene triamine pentacetic acid (/sup 99m/Tc-DTPA) to investigate whether human respiratory epithelial permeability is similarly affected by exposure to ozone. In a randomized, crossover double-blinded study, 8 healthy, nonsmoking young men were exposed for 2 h to purified air and 0.4 ppm ozone while performing intermittent high intensity treadmill exercise (minute ventilation = 66.8 L/min). SRaw and FVC were measured before and at the end of exposures. Seventy-five minutes after the exposures, the pulmonary clearance of /sup 99m/Tc-DTPA was measured by sequential posterior lung imaging with a computer-assisted gamma camera. Ozone exposure caused respiratory symptoms in all 8 subjects and was associated with a 14 +/- 2.8% (mean +/- SEM) decrement in FVC (p less than 0.001) and a 71 +/- 22% increase in SRaw (p = 0.04). Compared with the air exposure day, 7 of the 8 subjects showed increased /sup 99m/Tc-DTPA clearance after the ozone exposure, with the mean value increasing from 0.59 +/- 0.08 to 1.75 +/- 0.43%/min (p = 0.03). These data show that ozone exposure sufficient to produce decrements in the pulmonary function of human subjects also causes an increase in /sup 99m/Tc-DTPA clearance

  19. Biocides Steering Group on human exposure assessment: a preliminary report.

    Science.gov (United States)

    van Hemmen, J J

    1999-06-30

    In a project granted by DG XI of the European Commission, it is attempted to collate experimental and theoretical data on human (workers and consumers) exposure assessment to biocidal products, and to outline the methodology for sampling and measurement. On the basis of the available evidence, approaches are presented for the exposure assessment to be used for estimation of risks in authorization procedures under the recently accepted Directive 98/8/EC. Gaps in knowledge are indicated, making it possible to study the issues involved in a comprehensive and cost-effective way. Some recommendations are given on how to best do this. The current project has been detailed in a final report.

  20. ASSESSING CHILDREN'S EXPOSURES TO PESTICIDES: AN IMPORTANT APPLICATION OF THE STOCHASTIC HUMAN EXPOSURE AND DOSE SIMULATION MODEL (SHEDS)

    Science.gov (United States)

    Accurately quantifying human exposures and doses of various populations to environmental pollutants is critical for the Agency to assess and manage human health risks. For example, the Food Quality Protection Act of 1996 (FQPA) requires EPA to consider aggregate human exposure ...

  1. Naphthalene distributions and human exposure in Southern California

    Science.gov (United States)

    Lu, Rong; Wu, Jun; Turco, Richard P.; Winer, Arthur M.; Atkinson, Roger; Arey, Janet; Paulson, Suzanne E.; Lurmann, Fred W.; Miguel, Antonio H.; Eiguren-Fernandez, Arantzazu

    The regional distribution of, and human exposure to, naphthalene are investigated for Southern California. A comprehensive approach is taken in which advanced models are linked for the first time to quantify population exposure to the emissions of naphthalene throughout Southern California. Naphthalene is the simplest and most abundant of the polycyclic aromatic hydrocarbons found in polluted urban environments, and has been detected in both outdoor and indoor air samples. Exposure to high concentrations of naphthalene may have adverse health effects, possibly causing cancer in humans. Among the significant emission sources are volatilization from naphthalene-containing products, petroleum refining, and combustion of fossil fuels and wood. Gasoline and diesel engine exhaust, with related vaporization from fuels, are found to contribute roughly half of the daily total naphthalene burden in Southern California. As part of this study, the emission inventory for naphthalene has been verified against new field measurements of the naphthalene-to-benzene ratio in a busy traffic tunnel in Los Angeles, supporting the modeling work carried out here. The Surface Meteorology and Ozone Generation (SMOG) airshed model is used to compute the spatial and temporal distributions of naphthalene and its photooxidation products in Southern California. The present simulations reveal a high degree of spatial variability in the concentrations of naphthalene-related species, with large diurnal and seasonal variations as well. Peak naphthalene concentrations are estimated to occur in the early morning hours in the winter season. The naphthalene concentration estimates obtained from the SMOG model are employed in the Regional Human Exposure (REHEX) model to calculate population exposure statistics. Results show average hourly naphthalene exposures in Southern California under summer and winter conditions of 270 and 430 ng m -3, respectively. Exposure to significantly higher concentrations

  2. An Embryonic Growth Pathway is Reactivated in Human Prostate Cancer

    National Research Council Canada - National Science Library

    Bushman, Wade

    2005-01-01

    .... This research postulates that prostate cancer cells commandeer this normal epithelial-mesenchymal signaling pathway to recruit stromal cells to support abnormal tumor growth and tests the hypothesis...

  3. An Embryonic Growth Pathway is Reactivated in Human Prostate Cancer

    National Research Council Canada - National Science Library

    Bushman, Wade

    2003-01-01

    .... This research postulates that prostate cancer cells commandeer this normal epithelial-mesenchymal signaling pathway to recruit stromal cells to support abnormal tumor growth and tests the hypothesis...

  4. Human Physiological Responses to Acute and Chronic Cold Exposure

    Science.gov (United States)

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

    2001-01-01

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

  5. Climate change impacts on human exposures to air pollution ...

    Science.gov (United States)

    This is an abstract for a presentations at the Annual Conference of the International Society on Exposure Science and Environmental Epidemiology. This presentation will serve as an introduction to the symposium. As we consider the potential health impacts of a warming planet, the relationships between climate change and air pollutants become increasingly important to understand. These relationships are complex and highly variable, causing a variety of environmental impacts at local, regional and global scales. Human exposures and health impacts for air pollutants have the potential to be altered by changes in climate through multiple factors that drive population exposures to these pollutants. Research on this topic will provide both state and local governments with the tools and scientific knowledge base to undertake any necessary adaptation of the air pollution regulations and/or public health management systems in the face of climate change.

  6. Human B cells fail to secrete type I interferons upon cytoplasmic DNA exposure.

    Science.gov (United States)

    Gram, Anna M; Sun, Chenglong; Landman, Sanne L; Oosenbrug, Timo; Koppejan, Hester J; Kwakkenbos, Mark J; Hoeben, Rob C; Paludan, Søren R; Ressing, Maaike E

    2017-11-01

    Most cells are believed to be capable of producing type I interferons (IFN I) as part of an innate immune response against, for instance, viral infections. In macrophages, IFN I is potently induced upon cytoplasmic exposure to foreign nucleic acids. Infection of these cells with herpesviruses leads to triggering of the DNA sensors interferon-inducible protein 16 (IFI16) and cyclic GMP-AMP (cGAMP) synthase (cGAS). Thereby, the stimulator of interferon genes (STING) and the downstream molecules TANK-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3) are sequentially activated culminating in IFN I secretion. Human gamma-herpesviruses, such as Epstein-Barr virus (EBV), exploit B cells as a reservoir for persistent infection. In this study, we investigated whether human B cells, similar to macrophages, engage the cytoplasmic DNA sensing pathway to induce an innate immune response. We found that the B cells fail to secrete IFN I upon cytoplasmic DNA exposure, although they express the DNA sensors cGAS and IFI16 and the signaling components TBK1 and IRF3. In primary human B lymphocytes and EBV-negative B cell lines, this deficiency is explained by a lack of detectable levels of the central adaptor protein STING. In contrast, EBV-transformed B cell lines did express STING, yet both these lines as well as STING-reconstituted EBV-negative B cells did not produce IFN I upon dsDNA or cGAMP stimulation. Our combined data show that the cytoplasmic DNA sensing pathway is dysfunctional in human B cells. This exemplifies that certain cell types cannot induce IFN I in response to cytoplasmic DNA exposure providing a potential niche for viral persistence. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Assessment of genetic risk for human exposure to radiation

    International Nuclear Information System (INIS)

    Sevcenko, V.A.; Rubanovic, A.V.

    2002-01-01

    Full text: The methodology of assessing the genetic risk of radiation exposure is based on the concept of 'hitting the target' in development of which N.V. Timofeeff-Ressovsky has played and important role. To predict genetic risk posed by irradiation, the U N Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) has worked out direct and indirect methods of assessment, extrapolation, integral and palpitation criteria of risk analysis that together permit calculating the risk from human exposure on the basis of data obtained for mice. Based on the reports of UNSCEAR for the period from 1958 to 2001 the paper presents a retrospective analysis of the use of direct methods and the doubling dose method for quantitative determination of the genetic risk of human exposure expressed as different hereditary diseases. As early as 1962 UNSCEAR estimated the doubling dose (a dose causing as many mutations as those occurring spontaneously during one generation) at 1 Gy for cases of exposure to ionizing radiations with low LET at a low dose rate and this value was confirmed in the next UNSCEAR reports up to now. For cases of acute irradiation the doubling dose was estimated at 0,3-0,4 Gy for the period under review. The paper considers the evolution of the concepts of human natural hereditary variability which is a basis for assessing the risk of exposure by the doubling dose method. The level of human natural genetic variability per 1 000 000 newborns is estimated at 738 000 hereditary diseases including mendelian, chromosomal and multifactorial ones. The greatest difficulties in assessing the doubling dose value were found to occur in the case of multifactorial diseases the pheno typical expression of which depends on mutational events in polygenic systems and on numerous environmental factors. The introduction in calculations of the potential recoverability correction factor (RPCF) made it possible to assess the genetic risk taking into account this class of

  8. Potential pathways by which maternal second-hand smoke exposure during pregnancy causes full-term low birth weight.

    Science.gov (United States)

    Niu, Zhongzheng; Xie, Chuanbo; Wen, Xiaozhong; Tian, Fuying; Yuan, Shixin; Jia, Deqin; Chen, Wei-Qing

    2016-04-29

    It is well documented that maternal exposure to second-hand smoke (SHS) during pregnancy causes low birth weight (LBW), but its mechanism remains unknown. This study explored the potential pathways. We enrolled 195 pregnant women who delivered full-term LBW newborns, and 195 who delivered full-term normal birth weight newborns as the controls. After controlling for maternal age, education level, family income, pre-pregnant body mass index, newborn gender and gestational age, logistic regression analysis revealed that LBW was significantly and positively associated with maternal exposure to SHS during pregnancy, lower placental weight, TNF-α and IL-1β, and that SHS exposure was significantly associated with lower placental weight, TNF-α and IL-1β. Structural equation modelling identified two plausible pathways by which maternal exposure to SHS during pregnancy might cause LBW. First, SHS exposure induced the elevation of TNF-α, which might directly increase the risk of LBW by transmission across the placenta. Second, SHS exposure first increased maternal secretion of IL-1β and TNF-α, which then triggered the secretion of VCAM-1; both TNF-α and VCAM-1 were significantly associated with lower placental weight, thus increasing the risk of LBW. In conclusion, maternal exposure to SHS during pregnancy may lead to LBW through the potential pathways of maternal inflammation and lower placental weight.

  9. Particle size fractionation and human exposure of polybrominated diphenyl ethers in indoor dust from Chicago.

    Science.gov (United States)

    Wei, Hua; Turyk, Mary; Cali, Salvatore; Dorevitch, Samuel; Erdal, Serap; Li, An

    2009-11-01

    The objective of this study was to investigate the concentration level, the mass distribution based on dust particle size, and the associated human exposure of polybrominated diphenyl ethers (PBDEs) in indoor dust. The total concentration of 13 PBDEs Sigma(13)(BDEs) was found to be 500-6,944 ng/g in indoor dusts, 4,000 ng/g in car interior dust, 260-300 ng/g in outdoor ambient air particles, 30 ng/g in carpet fibers, and as high as 0.5% in carpet padding. Selected dust samples were fractionated based on particle size, and over 80% of the Sigma(13)BDEs were associated with particles exposure of Americans to PBDEs via hand-to-mouth transfer of house dust was estimated under the central tendency exposure and reasonable maximum exposure scenarios. The results suggest that ingestion of PBDE-laden house dust via hand-to-mouth contact is likely a significant exposure pathway, especially for children.

  10. The “CROMa” Project: A Care Pathway for Clinical Management of Patients with Bisphosphonate Exposure

    Directory of Open Access Journals (Sweden)

    Mauro Capocci

    2014-01-01

    Full Text Available Aim. To describe 7 years of activity of “CROMa” (Coordination of Research on Osteonecrosis of the Jaws project of “Sapienza” University of Rome. Materials and Methods. A preventive and therapeutic care pathway was created for patients with bisphosphonates (BPs exposure. Demographic, social, behavioural, pharmacological, and clinical variables were registered in a dedicated database. Results. In the project, 502 patients, 403 females and 99 males, were observed. Bone pathologies were 79% osteometabolic diseases (OMD and 21% metastatic cancer (CA. Females were 90% in OMD group and 41% in CA. BP administration was 54% oral, 31% IV, and 11% IM; 89% of BPs were amino-BP and 11% non-amino-BP. Consistently with bone pathology (OMD/CA, alendronate appears to be prevalent for OMD (40% relative, while zoledronate was indicated in 92% of CA patients. Out of 502 cases collected, 28 BRONJ were detected: 17 of them were related to IV BP treatment. Preventive oral assessment was required for 50% of CA patients and by 4% of OMD patients. Conclusions. The proposed care pathway protocols for BP exposed patients appeared to be useful to meet treatment and preventive needs, in both oncological and osteometabolic diseases patients. Patients’ and physicians’ prevention awareness can be the starting point of a multilevel prevention system.

  11. Ecological and human exposure assessment to PBDEs in Adige River.

    Science.gov (United States)

    Giulivo, Monica; Suciu, Nicoleta Alina; Eljarrat, Ethel; Gatti, Marina; Capri, Ettore; Barcelo, Damia

    2018-07-01

    The interest for environmental issues and the concern resulting from the potential exposure to contaminants were the starting point to develop methodologies in order to evaluate the consequences that those might have over both the environment and human health. Considering the feature of POPs, including PBDEs, such as bioaccumulation, biomagnification, long-range transport and adverse effects even long time after exposure, risk assessment of POPs requires specific approaches and tools. In this particular context, the MERLIN-Expo tool was used to assess the aquatic environmental exposure of Adige River to PBDEs and the accumulation of PBDEs in humans through the consumption of possible contaminated local aquatic food. The aquatic food web models provided as output of the deterministic simulation the time trend of concentrations for twenty years of BDE-47 and total PBDEs, expressed using the physico-chemical properties of BDE-47, in aquatic organisms of the food web of Adige River. For BDE-47, the highest accumulated concentrations were detected for two benthic species: Thymallus thymallus and Squalius cephalus whereas the lowest concentrations were obtained for the pelagic specie Salmo trutta marmoratus. The trend obtained for the total PBDEs, calculated using the physico-chemical properties of BDE-47, follows the one of BDE-47. For human exposure, different BDE-47 and total PBDEs concentration trends between children, adolescent, adults and elderly were observed, probably correlated with the human intake of fish products in the daily diet and the ability to metabolize these contaminants. In detail, for the adolescents, adults and elderly a continuous accumulation of the target contaminants during the simulation's years was observed, whereas for children a plateau at the end of the simulation period was perceived. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Human exposure to static magnetic fields and basic precautions

    International Nuclear Information System (INIS)

    Vulevic, B.

    1999-01-01

    The development of new technologies using the static magnetic fields and their application in the last several years has increased the possibility of higher human exposure to such fields what has raised an issue of potential adverse health effects. The object of this work is to point, on the basis of the past knowledge, to the significance of the problem and therefore to contribute to its popularization. (author)

  13. A short review on human exposure to and tissue distribution of per- and polyfluoroalkyl substances (PFASs).

    Science.gov (United States)

    Jian, Jun-Meng; Chen, Da; Han, Fu-Juan; Guo, Ying; Zeng, Lixi; Lu, Xingwen; Wang, Fei

    2018-09-15

    PFASs are widely distributed in natural and living environment and can enter human bodies via different routes. Many studies have reported that PFASs may be associated with human diseases, such as urine acid and thyroid diseases. In this study, we reviewed PFAS levels in human bodies reported in past seven years, including blood, urine, milk, and tissues (hair and nails). Most studies focused on human blood. Blood type, spatiality, human age, and gender were found to have a strong relationship with PFAS levels in blood samples. The PFAS distribution in urine samples was reported to be associated with the chain length of PFASs and human gender. Urinary excretion was found to be an important pathway of PFAS elimination. PFAS levels in human milk might be affected by various factors, such as mothers' age, dietary habit, parity of mothers and the interval of interpregnancy. Data in hair and nails remain very limited, but these matrices offer a non-invasive approach to evaluate human exposure to PFASs. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Exposure pathways and health effects associated with chemical and radiological toxicity of natural uranium: a review.

    Science.gov (United States)

    Brugge, Doug; de Lemos, Jamie L; Oldmixon, Beth

    2005-01-01

    Natural uranium exposure derives from the mining, milling, and processing of uranium ore, as well as from ingestion of groundwater that is naturally contaminated with uranium. Ingestion and inhalation are the primary routes of entry into the body. Absorption of uranium from the lungs or digestive track is typically low but can vary depending on compound specific solubility. From the blood, two-thirds of the uranium is excreted in urine over the first 24 hours and up to 80% to 90% of uranium deposited in the bone leaves the body within 1.5 years. The primary health outcomes of concern documented with respect to uranium are renal, developmental, reproductive, diminished bone growth, and DNA damage. The reported health effects derive from experimental animal studies and human epidemiology. The Lowest Observed Adverse Effect Level (LOAEL) derived from animal studies is 50 microg/m3 for inhalation and 60 ug/kg body weight/day for ingestion. The current respiratory standard of the Occupational Safety and Health Administration (OSHA), 50 microg/m3, affords no margin of safety. Considering the safety factors for species and individual variation, the ingestion LOAEL corresponds to the daily consumption set by the World Health Organization Drinking Water Standard at 2 microg/L. Based on economic considerations, the United States Environmental Protection Agency maximum contaminant level is 30 microg/L. Further research is needed, with particular attention on the impact of uranium on indigenous populations, on routes of exposure in communities near uranium sites, on the combined exposures present at many uranium sites, on human developmental defects, and on health effects at or below established exposure standards.

  15. Internal exposure dynamics drive the Adverse Outcome Pathways of synthetic glucocorticoids in fish

    Science.gov (United States)

    Margiotta-Casaluci, Luigi; Owen, Stewart F.; Huerta, Belinda; Rodríguez-Mozaz, Sara; Kugathas, Subramanian; Barceló, Damià; Rand-Weaver, Mariann; Sumpter, John P.

    2016-02-01

    The Adverse Outcome Pathway (AOP) framework represents a valuable conceptual tool to systematically integrate existing toxicological knowledge from a mechanistic perspective to facilitate predictions of chemical-induced effects across species. However, its application for decision-making requires the transition from qualitative to quantitative AOP (qAOP). Here we used a fish model and the synthetic glucocorticoid beclomethasone dipropionate (BDP) to investigate the role of chemical-specific properties, pharmacokinetics, and internal exposure dynamics in the development of qAOPs. We generated a qAOP network based on drug plasma concentrations and focused on immunodepression, skin androgenisation, disruption of gluconeogenesis and reproductive performance. We showed that internal exposure dynamics and chemical-specific properties influence the development of qAOPs and their predictive power. Comparing the effects of two different glucocorticoids, we highlight how relatively similar in vitro hazard-based indicators can lead to different in vivo risk. This discrepancy can be predicted by their different uptake potential, pharmacokinetic (PK) and pharmacodynamic (PD) profiles. We recommend that the development phase of qAOPs should include the application of species-species uptake and physiologically-based PK/PD models. This integration will significantly enhance the predictive power, enabling a more accurate assessment of the risk and the reliable transferability of qAOPs across chemicals.

  16. Human exposure, biomarkers, and fate of organotins in the environment.

    Science.gov (United States)

    Okoro, Hussein K; Fatoki, Olalekan S; Adekola, Folahan A; Ximba, Bhekumusa J; Snyman, Reinette G; Opeolu, Beatrice

    2011-01-01

    Organotin compounds result from the addition of organic moieties to inorganic tin.Thus, one or more tin-carbon bonds exist in each organotin molecule. The organo-tin compounds are ubiquitous in the environment. Organotin compounds have many uses, including those as fungicides and stabilizers in plastics, among others in industry. The widespread use of organotins as antifouling agents in boat paints has resulted in pollution of freshwater and marine ecosystems. The presence of organotin compounds in freshwater and marine ecosystems is now understood to be a threat, because of the amounts found in water and the toxicity of some organotin compounds to aquatic organisms, and perhaps to humans as well. Organotin com-pounds are regarded by many to be global pollutants of a stature similar to biphenyl,mercury, and the polychlorinated dibenzodioxins. This stature results from the high toxicity, persistence, bioaccumulation, and endocrine disruptive features of even very low levels of selected organotin compounds.Efforts by selected governmental agencies and others have been undertaken to find a global solution to organotin pollution. France was the first country to ban the use of the organotins in 1980. This occurred before the international maritime organization (IMO) called for a global treaty to ban the application of tributyltin (TBT)-based paints. In this chapter, we review the organotin compounds with emphasis on the human exposure, fate, and distribution of them in the environment. The widespread use of the organotins and their high stability have led to contamination of some aquatic ecosystems. As a result, residues of the organotins may reach humans via food consumption. Notwithstanding the risk of human exposure, only limited data are available on the levels at which the organotins exist in foodstuffs consumed by humans. Moreover, the response of marine species to the organotins, such as TBT, has not been thoroughly investigated. Therefore, more data on the

  17. Solubility of indium-tin oxide in simulated lung and gastric fluids: Pathways for human intake.

    Science.gov (United States)

    Andersen, Jens Christian Østergård; Cropp, Alastair; Paradise, Diane Caroline

    2017-02-01

    From being a metal with very limited natural distribution, indium (In) has recently become disseminated throughout the human society. Little is known of how In compounds behave in the natural environment, but recent medical studies link exposure to In compounds to elevated risk of respiratory disorders. Animal tests suggest that exposure may lead to more widespread damage in the body, notably the liver, kidneys and spleen. In this paper, we investigate the solubility of the most widely used In compound, indium-tin oxide (ITO) in simulated lung and gastric fluids in order to better understand the potential pathways for metals to be introduced into the bloodstream. Our results show significant potential for release of In and tin (Sn) in the deep parts of the lungs (artificial lysosomal fluid) and digestive tract, while the solubility in the upper parts of the lungs (the respiratory tract or tracheobronchial tree) is very low. Our study confirms that ITO is likely to remain as solid particles in the upper parts of the lungs, but that particles are likely to slowly dissolve in the deep lungs. Considering the prolonged residence time of inhaled particles in the deep lung, this environment is likely to provide the major route for uptake of In and Sn from inhaled ITO nano- and microparticles. Although dissolution through digestion may also lead to some uptake, the much shorter residence time is likely to lead to much lower risk of uptake. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  18. Kynurenine Pathway Metabolites in Humans: Disease and Healthy States

    Directory of Open Access Journals (Sweden)

    Yiquan Chen

    2009-01-01

    Full Text Available Tryptophan is an essential amino acid that can be metabolised through different pathways, a major route being the kynurenine pathway. The first enzyme of the pathway, indoleamine-2,3-dioxygenase, is strongly stimulated by inflammatory molecules, particularly interferon gamma. Thus, the kynurenine pathway is often systematically up-regulated when the immune response is activated. The biological significance is that 1 the depletion of tryptophan and generation of kynurenines play a key modulatory role in the immune response; and 2 some of the kynurenines, such as quinolinic acid, 3-hydroxykynurenine and kynurenic acid, are neuroactive. The kynurenine pathway has been demonstrated to be involved in many diseases and disorders, including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, AIDS dementia complex, malaria, cancer, depression and schizophrenia, where imbalances in tryptophan and kynurenines have been found. This review compiles most of these studies and provides an overview of how the kynurenine pathway might be contributing to disease development, and the concentrations of tryptophan and kynurenines in the serum, cerebrospinal fluid and brain tissues in control and patient subjects.

  19. Health risk assessment of various metal(loid)s via multiple exposure pathways on children living near a typical lead-acid battery plant, China

    International Nuclear Information System (INIS)

    Cao, Suzhen; Duan, Xiaoli; Zhao, Xiuge; Wang, Beibei; Ma, Jin; Fan, Delong; Sun, Chengye; He, Bin; Wei, Fusheng; Jiang, Guibin

    2015-01-01

    Manufacture of lead-acid batteries is of widespread interest because of its emissions of heavy metals and metalloids into environment, harming environmental quality and consequently causing detrimental effects on human health. In this study, exposure pathways and health risks of children to heavy metal(loid)s (Pb, Cd, As, etc) were investigated based on field sampling and questionnaire. Pb was one of the most abundant elements in children's blood, with an elevated blood lead level of 12.45 μg dL −1 . Soil/dust and food were heavily polluted by targeted metal(loid)s. Food ingestion accounted for more than 80% of the total exposure for most metal(loid)s. The non-cancer risks to children were 3–10 times higher than the acceptable level of 1, while the cancer risks were 5–200 times higher than the maximum acceptable level of 1.0 × 10 −4 . The study emphasized the significance of effective environmental management, particularly to ensure food security near battery facilities. - Highlights: • The health risks of children living around a typical lead-acid battery was analyzed. • The exposure pathways of children to 12 heavy metal(loid)s were assessed. • Courtyard soil and indoor dust and duplicate food were contaminated by metal(loid)s. • Food ingestion was the major pathway for children's exposure to most metal(loid)s. • Higher potentially non-cancer and cancer risks happened to the local children. - The children living around a typical lead-acid battery plant suffered from serious health risks, which mainly attributed to food ingestion and air inhalation exposure

  20. Human performance analysis of industrial radiography radiation exposure events

    International Nuclear Information System (INIS)

    Reece, W.J.; Hill, S.G.

    1995-01-01

    A set of radiation overexposure event reports were reviewed as part of a program to examine human performance in industrial radiography for the US Nuclear Regulatory Commission. Incident records for a seven year period were retrieved from an event database. Ninety-five exposure events were initially categorized and sorted for further analysis. Descriptive models were applied to a subset of severe overexposure events. Modeling included: (1) operational sequence tables to outline the key human actions and interactions with equipment, (2) human reliability event trees, (3) an application of an information processing failures model, and (4) an extrapolated use of the error influences and effects diagram. Results of the modeling analyses provided insights into the industrial radiography task and suggested areas for further action and study to decrease overexposures

  1. Major national human biomonitoring programs in chemical exposure assessment

    Directory of Open Access Journals (Sweden)

    Judy Choi

    2015-07-01

    Full Text Available Human biomonitoring (HBM programs have been established in several countries around the world in order to monitor the levels of chemical exposures in the general population and qualify health risk assessment of national and international interest. Study design, population, sample collection, and chemical analysis must be considered when comparing and interpreting the results. In this review, the objectives and brief descriptions of the major national HBM programs in North America, Europe, and Asia are provided. Similarities and differences observed from a comparative analysis among these programs, including the stratification of data according to age, sex, socioeconomic background, etc. as well as the identification of chemical exposure associated with food intake, are discussed. Overall, although there are some discrepancies in the study designs among the reviewed national HBM programs, results from the programs can provide useful information such as chemical levels found within the general population of a country that can be compared. Furthermore, the results can be used by regulatory authorities or the government to enforce legislations in order to reduce the exposure of chemicals into the human body.

  2. The Human Exposure Potential from Propylene Releases to the Environment

    Directory of Open Access Journals (Sweden)

    David A. Morgott

    2018-01-01

    Full Text Available A detailed literature search was performed to assess the sources, magnitudes and extent of human inhalation exposure to propylene. Exposure evaluations were performed at both the community and occupational levels for those living or working in different environments. The results revealed a multitude of pyrogenic, biogenic and anthropogenic emission sources. Pyrogenic sources, including biomass burning and fossil fuel combustion, appear to be the primary contributors to atmospheric propylene. Despite a very short atmospheric lifetime, measurable levels could be detected in highly remote locations as a result of biogenic release. The indoor/outdoor ratio for propylene has been shown to range from about 2 to 3 in non-smoking homes, which indicates that residential sources may be the largest contributor to the overall exposure for those not occupationally exposed. In homes where smoking takes place, the levels may be up to thirty times higher than non-smoking residences. Atmospheric levels in most rural regions are typically below 2 ppbv, whereas the values in urban levels are much more variable ranging as high as 10 ppbv. Somewhat elevated propylene exposures may also occur in the workplace; especially for firefighters or refinery plant operators who may encounter levels up to about 10 ppmv.

  3. Development of human exposure standards for radio frequency fields

    International Nuclear Information System (INIS)

    Lin, James C.

    2000-01-01

    Historical aspects of the problem of developing human exposure standards for radio frequency (RF) electromagnetic fields are discussed. It is shown that biological effects and health implications of radiofrequency (RF) electromagnetic fields have been a subject of scientific investigation for more than 50 years. It has become a focus of attention because of the expanded use of RF radiation in the frequency range between 300 MHz and 6 GHz for wireless communication over the past decade. Another cause for the attention is the uncertainty of some observed responses and lack of understanding of the mechanism of interaction of RF electromagnetic fields with biological systems. At present, considerable efforts are devoted to developing and revising RF exposure standards. Each of these efforts should aim to make explicit the philosophy and process by which they reason and decide guidelines for deeming exposure as safe. Furthermore, the reconciliation of philosophies of protection will definitely be an asset, in practice, to those interested in international harmonization of RF exposure standards [ru

  4. Quantifying human exposure to air pollution - moving from static monitoring to spatio-temporally resolved personal exposure assessment

    DEFF Research Database (Denmark)

    Steinle, Susanne; Reis, Stefan; Sabel, Clive E

    2013-01-01

    exposure studies to accurately assess human health risks. ? We discuss potential and shortcomings of methods and tools with a focus on how their development influences study design. ? We propose a novel conceptual model for integrated health impact assessment of human exposure to air pollutants. ? We......Quantifying human exposure to air pollutants is a challenging task. Ambient concentrations of air pollutants at potentially harmful levels are ubiquitous in urban areas and subject to high spatial and temporal variability. At the same time, every individual has unique activity-patterns. Exposure...... results from multifaceted relationships and interactions between environmental and human systems, adding complexity to the assessment process. Traditionally, approaches to quantify human exposure have relied on pollutant concentrations from fixed air quality network sites and static population...

  5. Human Fanconi anemia monoubiquitination pathway promotes homologous DNA repair.

    Science.gov (United States)

    Nakanishi, Koji; Yang, Yun-Gui; Pierce, Andrew J; Taniguchi, Toshiyasu; Digweed, Martin; D'Andrea, Alan D; Wang, Zhao-Qi; Jasin, Maria

    2005-01-25

    Fanconi anemia (FA) is a recessive disorder characterized by congenital abnormalities, progressive bone-marrow failure, and cancer susceptibility. Cells from FA patients are hypersensitive to agents that produce DNA crosslinks and, after treatment with these agents, have pronounced chromosome breakage and other cytogenetic abnormalities. Eight FANC genes have been cloned, and the encoded proteins interact in a common cellular pathway. DNA-damaging agents activate the monoubiquitination of FANCD2, resulting in its targeting to nuclear foci that also contain BRCA1 and BRCA2/FANCD1, proteins involved in homology-directed DNA repair. Given the interaction of the FANC proteins with BRCA1 and BRCA2, we tested whether cells from FA patients (groups A, G, and D2) and mouse Fanca-/- cells with a targeted mutation are impaired for this repair pathway. We find that both the upstream (FANCA and FANCG) and downstream (FANCD2) FA pathway components promote homology-directed repair of chromosomal double-strand breaks (DSBs). The FANCD2 monoubiquitination site is critical for normal levels of repair, whereas the ATM phosphorylation site is not. The defect in these cells, however, is mild, differentiating them from BRCA1 and BRCA2 mutant cells. Surprisingly, we provide evidence that these proteins, like BRCA1 but unlike BRCA2, promote a second DSB repair pathway involving homology, i.e., single-strand annealing. These results suggest an early role for the FANC proteins in homologous DSB repair pathway choice.

  6. Relative biological effectiveness if alpha radiation for human lung exposure

    International Nuclear Information System (INIS)

    Yarmoshenko, I.; Kirdin, I.; Zhukovsky, M.

    2006-01-01

    estimates for cases of indoor radon alpha exposure and exposure to implanted plutonium can be seen. Difference in biological effectiveness of inhaled radon and implanted plutonium may appear due to different distribution of short-lived radon progeny and long lived plutonium within lung tissues. Low RBE value for alpha particle exposures of human lung tissues may be a reason of known inconsistency of dose conversion factors for radon estimates based on dosimetric and epidemiologic approaches. (authors)

  7. Human cerebral venous outflow pathway depends on posture and central venous pressure

    DEFF Research Database (Denmark)

    Gisolf, J; van Lieshout, J J; van Heusden, K

    2004-01-01

    Internal jugular veins are the major cerebral venous outflow pathway in supine humans. In upright humans the positioning of these veins above heart level causes them to collapse. An alternative cerebral outflow pathway is the vertebral venous plexus. We set out to determine the effect of posture...... and during a Valsalva manoeuvre in both body positions, correlate highly with model simulation of the jugular cross-sectional area (R(2) = 0.97). The results suggest that the cerebral venous flow distribution depends on posture and CVP: in supine humans the internal jugular veins are the primary pathway...

  8. Human convective boundary layer and its impact on personal exposure

    DEFF Research Database (Denmark)

    Licina, Dusan

    generated by heat sources are gaining more prominent influence in space airflow formation and on the indoor environment overall. In such spaces with low air supply velocity, air mixing is minimized and the pollution emitted from localized indoor sources is non-uniformly distributed. The large spatial......People spend most of their time indoors and they are constantly exposed to pollution that affects their health, comfort and productivity. Due to strong economic and environmental pressures to reduce building energy consumption, low air velocity design is gaining popularity; hence buoyancy flows...... in inaccurate exposure prediction. This highlights the importance of a detailed understanding of the complex air movements that take place in the vicinity of the human body and their impact on personal exposure. The two objectives of the present work are: (i) to examine the extent to which the room air...

  9. Pre-exposure Prophylaxis Against Human Immunodeficiency Virus

    Directory of Open Access Journals (Sweden)

    Güle ÇINAR

    2018-03-01

    Full Text Available According to the Center for Disease Control and Prevention (CDC, there were 2.1 million new human immunodeficiency virus (HIV cases reported worldwide in 2015, which shows that siginificant work needs to be done to prevent the transmission of HIV. Research to date has focused mainly on high-risk men who have sex with men, but many women around the world are also at a high risk for HIV transmissions. In studies conducted, the incidence of HIV infection in high-risk individuals decreases over 90% when high-risk individuals use pre-exposure prophylaxis (PreP HIV, tenofovir disoproxil fumarate-emtricitabine (TDF-FTC safely. Current data and studies on pre-exposure prophylaxis were discussed in this review.

  10. Genes and pathways underlying susceptibility to impaired lung function in the context of environmental tobacco smoke exposure

    NARCIS (Netherlands)

    K. de Jong (Kim); J.M. Vonk (Judith); M. Imboden (Medea); L. Lahousse (Lies); A. Hofman (Albert); G.G. Brusselle (Guy); N.M. Probst-Hensch (Nicole M.); D.S. Postma (Dirkje); H.M. Boezen (Marike)

    2017-01-01

    textabstractBackground: Studies aiming to assess genetic susceptibility for impaired lung function levels upon exposure to environmental tobacco smoke (ETS) have thus far focused on candidate-genes selected based on a-priori knowledge of potentially relevant biological pathways, such as glutathione

  11. Dosimetry Methods for Human Exposure to Non-Ionising Radiation

    International Nuclear Information System (INIS)

    Poljak, D.; Sarolic, A.; Doric, V.; Peratta, C.; Peratta, A.

    2011-01-01

    The paper deals with human exposure to electromagnetic fields from extremely low frequencies (ELF) to GSM frequencies. The problem requires (1) the assessment of external field generated by electromagnetic interference (EMI) source at a given frequency (incident field dosimetry) and then (2) the assessment of corresponding fields induced inside the human body (internal field dosimetry). Several methods used in theoretical and experimental dosimetry are discussed within this work. Theoretical dosimetry models at low frequencies are based on quasistatic approaches, while analyses at higher frequencies use the full-wave models. Experimental techniques involve near and far field measurement. Human exposure to power lines, transformer substations, power line communication (PLC) systems, Radio Frequency Identification (RFID) antennas and GSM base station antenna systems is analyzed. The results o are compared to the exposure limits proposed by relevant safety guidelines. Theoretical incident dosimetry used in this paper is based on the set of Pocklington integro-differential equations for the calculation of the current distribution and subsequently radiated field from power lines. Experimental incident dosimetry techniques involve measurement techniques of fields radiated by RFID antennas and GSM base station antennas. First example set of numerical results is related to the internal dosimetry of realistic well-grounded body model exposed to vertical component of the electric field E = 10 kV/m generated by high voltage power line. The results obtained via the HNA model exceed the ICNIRP basic restrictions for public exposure (2 mA/m 2 ) in knee (8.6 mA/m 2 ) and neck (9.8 mA/m 2 ) and for occupational exposure (10 mA/m 2 ) in ankle (32 mA/m 2 ). In the case of a conceptual model of a realistic human body inside a transformer substation room touching a control panel at the potential φ0 = 400 V and with two scenarios for dry-air between worker's hand and panel, the values

  12. Legacy and emerging brominated flame retardants in China: A review on food and human milk contamination, human dietary exposure and risk assessment.

    Science.gov (United States)

    Shi, Zhixiong; Zhang, Lei; Li, Jingguang; Wu, Yongning

    2018-05-01

    Brominated flame retardants (BFRs) are a large group of widely used chemicals, which have been produced and used since 1970s. As a consequence of substantial and long-term usage, BFRs have been found to be ubiquitous in humans, wildlife, and abiotic matrices around the world. Although several reports have reviewed BFRs contamination in general, none have focused specifically on foods and human milk, and the corresponding dietary exposure. Foods (including human milk) have long been recognized as a major pathway of BFRs intake for non-occupationally exposed persons. This review summarizes most available BFRs data in foods and human milk from China in recent years, and emphasizes several specific aspects, i.e., contamination levels of legacy and emerging BFRs, dietary exposure assessment and related health concerns, comparison between various BFRs, and temporal changes in BFRs contamination. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Analyses of human exposures to alpha-emitting radionuclides from nuclear fuel cycles

    International Nuclear Information System (INIS)

    Cuddihy, R.G.; McClellan, R.O.; Griffith, W.C.; Hoover, M.D.

    1977-01-01

    Human populations may potentially be exposed to alpha-emitting radionuclides released to the environment from a variety of activities associated with nuclear fuel cycles. Generally, the most important exposure pathway is by way of inhalation. This can occur soon after release of these substances or after they have been deposited on ground surfaces and resuspended with soil particles. Estimating the potential magnitude of these exposures is usually done through the use of mathematical models accounting for the dispersion of the released material through the environment and its uptake by people living near the nuclear facilities. Studies described in this paper suggest that these exposures can probably be estimated within a factor of 10 based upon our previous experience with measured human organ levels of other trace metals taken up from the environment. It should also be noted that variability among individuals within the population may result in a few percent accumulating more than 10 times the geometric mean of the internal organ radionuclide burdens

  14. Case definitions for human poisonings postulated to palytoxins exposure.

    Science.gov (United States)

    Tubaro, A; Durando, P; Del Favero, G; Ansaldi, F; Icardi, G; Deeds, J R; Sosa, S

    2011-03-01

    A series of case reports and anecdotal references describe the adverse effects on human health ascribed to the marine toxin palytoxin (PLTX) after different exposure routes. They include poisonings after oral intake of contaminated seafood, but also inhalation and cutaneous/systemic exposures after direct contact with aerosolized seawater during Ostreopsis blooms and/or through maintaining aquaria containing cnidarian zoanthids. The symptoms commonly recorded during PLTX intoxication are general malaise and weakness, associated with myalgia, respiratory effects, impairment of the neuromuscular apparatus and abnormalities in cardiac function. Systemic symptoms are often recorded together with local damages whose intensity varies according to the route and length of exposure. Gastrointestinal malaise or respiratory distress is common for oral and inhalational exposure, respectively. In addition, irritant properties of PLTX probably account for the inflammatory reactions typical of cutaneous and inhalational contact. Unfortunately, the toxin identification and/or quantification are often incomplete or missing and cases of poisoning are indirectly ascribed to PLTXs, according only to symptoms, anamnesis and environmental/epidemiological investigations (i.e. zoanthid handling or ingestion of particular seafood). Based on the available literature, we suggest a "case definition of PLTX poisonings" according to the main exposure routes, and, we propose the main symptoms to be checked, as well as, hemato-clinical analysis to be carried out. We also suggest the performance of specific analyses both on biological specimens of patients, as well as, on the contaminated materials responsible for the poisoning. A standardized protocol for data collection could provide a more rapid and reliable diagnosis of palytoxin-poisoning, but also the collection of necessary data for the risk assessment for this family of toxins. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Prenatal Exposure to Progesterone Affects Sexual Orientation in Humans.

    Science.gov (United States)

    Reinisch, June M; Mortensen, Erik Lykke; Sanders, Stephanie A

    2017-07-01

    Prenatal sex hormone levels affect physical and behavioral sexual differentiation in animals and humans. Although prenatal hormones are theorized to influence sexual orientation in humans, evidence is sparse. Sexual orientation variables for 34 prenatally progesterone-exposed subjects (17 males and 17 females) were compared to matched controls (M age = 23.2 years). A case-control double-blind design was used drawing on existing data from the US/Denmark Prenatal Development Project. Index cases were exposed to lutocyclin (bioidentical progesterone = C 21 H 30 O 2 ; M W : 314.46) and no other hormonal preparation. Controls were matched on 14 physical, medical, and socioeconomic variables. A structured interview conducted by a psychologist and self-administered questionnaires were used to collect data on sexual orientation, self-identification, attraction to the same and other sex, and history of sexual behavior with each sex. Compared to the unexposed, fewer exposed males and females identified as heterosexual and more of them reported histories of same-sex sexual behavior, attraction to the same or both sexes, and scored higher on attraction to males. Measures of heterosexual behavior and scores on attraction to females did not differ significantly by exposure. We conclude that, regardless of sex, exposure appeared to be associated with higher rates of bisexuality. Prenatal progesterone may be an underappreciated epigenetic factor in human sexual and psychosexual development and, in light of the current prevalence of progesterone treatment during pregnancy for a variety of pregnancy complications, warrants further investigation. These data on the effects of prenatal exposure to exogenous progesterone also suggest a potential role for natural early perturbations in progesterone levels in the development of sexual orientation.

  16. Chronic copper exposure causes spatial memory impairment, selective loss of hippocampal synaptic proteins, and activation of PKR/eIF2α pathway in mice.

    Science.gov (United States)

    Ma, Quan; Ying, Ming; Sui, Xiaojing; Zhang, Huimin; Huang, Haiyan; Yang, Linqing; Huang, Xinfeng; Zhuang, Zhixiong; Liu, Jianjun; Yang, Xifei

    2015-01-01

    Copper is an essential element for human growth and development; however, excessive intake of copper could contribute to neurotoxicity. Here we show that chronic exposure to copper in drinking water impaired spatial memory with simultaneous selective loss of hippocampal pre-synaptic protein synapsin 1, and post-synaptic density protein (PSD)-93/95 in mice. Copper exposure was shown to elevate the levels of nitrotyrosine and 8-hydroxydeoxyguanosine (8-OHdG) in hippocampus, two markers of oxidative stress. Concurrently, we also found that copper exposure activated double stranded RNA-dependent protein kinase (PKR) as evidenced by increased ratio of phosphorylated PKR at Thr451 and total PKR and increased the phosphorylation of its downstream signaling molecule eukaryotic initiation factor 2α (eIF2α) at Ser51 in hippocampus. Consistent with activation of PKR/eIF2α signaling pathway which was shown to mediate synaptic deficit and cognitive impairment, the levels of activating transcription factor 4 (ATF-4), a downstream signaling molecule of eIF2α and a repressor of CREB-mediated gene expression, were significantly increased, while the activity of cAMP response elements binding protein (CREB) was inactivated as suggested by decreased phosphorylation of CREB at Ser133 by copper exposure. In addition, the expression of the pro-apoptotic target molecule C/EBP homology protein (CHOP) of ATF-4 was upregulated and hippocampal neuronal apoptosis was induced by copper exposure. Taken together, we propose that chronic copper exposure might cause spatial memory impairment, selective loss of synaptic proteins, and neuronal apoptosis through the mechanisms involving activation of PKR/eIF2α signaling pathway.

  17. Environmentally relevant concentrations of di(2-ethylhexyl)phthalate exposure alter larval growth and locomotion in medaka fish via multiple pathways.

    Science.gov (United States)

    Yang, Wen-Kai; Chiang, Li-Fen; Tan, Shi-Wei; Chen, Pei-Jen

    2018-06-01

    Di(2-ethylhexyl)phthalate (DEHP) is a commonly used plasticizer, with evidence of ubiquitous human exposure and widespread occurrence in the aquatic environment. It is an emerging environmental pollutant with regulatory priority; however, most studies have focused on the toxicity of DEHP related to endocrine disruption and reproduction in mammals. The ecotoxicological impact of phthalates (e.g., DEHP) on early life stages of fish under environmentally relevant concentrations of chronic exposure remains unclear. In this study, 7-day post-hatching fry of medaka fish (Oryzias latipes) underwent 21-day continuous exposure to DEHP solutions at 20, 100 and 200 μg/L to assess the effects on fish development and locomotion and related toxic mechanisms. Larval mortality was low with DEHP (20-200 μg/L) within 21 days, but such exposure significantly reduced fish body weight and length and altered swimming behavior. At 21 days, DEHP exposure resulted in specific patterns of larval locomotion (e.g., increased maximum velocity and absolute turn angle) and dose-dependently increased the mRNA expression of acetylcholinesterase (ache) but did not alter AChE activity. Transcriptional expression of antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase and peroxisome proliferation-activated receptor and retinoid X receptor genes was significantly suppressed with 21-day DEHP exposure (20-200 μg/L), with marginal alteration in reactive oxygen species levels and antioxidant activities within the dosing period. As well, DEHP altered the mRNA expression of p53-regulated apoptosis pathways, such as upregulated p53, p21 and bcl-2 and downregulated caspase-3 expression, with increased enzymatic activity of caspase-3 in larvae. Our results suggest that toxic mechanisms of waterborne DEHP altered fish growth and locomotion likely via a combined effect of oxidative stress, neurotoxicity and apoptosis pathways. Copyright © 2018

  18. Effects of electromagnetic fields exposure on plasma hormonal and inflammatory pathway biomarkers in male workers of a power plant

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Zhaopin; Fei, Ying; Liu, Hui [Zhejiang Univ., Hangzhou (China). Dept. of Epidemiology and Health Statistics; Zhejiang Univ., Hangzhou (China). Chronic Disease Research Inst.; and others

    2016-01-15

    The potential health risks of electromagnetic fields (EMFs) have currently raised considerable public concerns. The aim of this study was to evaluate the effects of EMF exposure on levels of plasma hormonal and inflammatory pathway biomarkers in male workers of an electric power plant. Seventy-seven male workers with high occupational EMF exposure and 77 male controls with low exposure, matched by age, were selected from a cross-sectional study. Moreover, high EMF exposure group was with walkie-talkies usage and exposed to power frequency EMF at the work places for a longer duration than control group. A questionnaire was applied to obtain relevant information, including sociodemographic characteristics, lifestyle factors, and EMF exposures. Plasma levels of testosterone, estradiol, melatonin, NF-KB, heat-shock protein (HSP) 70, HSP27, and TET1 were determined by an enzyme-linked immunosorbent assay. EMF exposure group had statistically significantly lower levels of testosterone (β = -0.3 nmol/L, P = 0.015), testosterone/estradiol (T/E2) ratio (β = -15.6, P = 0.037), and NF-KB (β = -20.8 ng/L, P = 0.045) than control group. Moreover, joint effects between occupational EMF exposure and employment duration, mobile phone fees, years of mobile phone usage, and electric fees on levels of testosterone and T/E2 ratio were observed. Nevertheless, no statistically significant associations of EMF exposures with plasma estradiol, melatonin, HSP70, HSP27, and TET1 were found. The findings showed that chronic exposure to EMF could decrease male plasma testosterone and T/E2 ratio, and it might possibly affect reproductive functions in males. No significant associations of EMF exposure with inflammatory pathway biomarkers were found.

  19. 'Omics analysis of low dose acetaminophen intake demonstrates novel response pathways in humans

    Energy Technology Data Exchange (ETDEWEB)

    Jetten, Marlon J.A.; Gaj, Stan [Department of Toxicogenomics, Maastricht University, Universitiessingel 50 6229 ER Maastricht (Netherlands); Ruiz-Aracama, Ainhoa [RIKILT, Institute of Food Safety, Wageningen UR, PO Box 230, 6700 AE, Wageningen (Netherlands); Kok, Theo M. de [Department of Toxicogenomics, Maastricht University, Universitiessingel 50 6229 ER Maastricht (Netherlands); Delft, Joost H.M. van, E-mail: j.vandelft@maastrichtuniversity.nl [Department of Toxicogenomics, Maastricht University, Universitiessingel 50 6229 ER Maastricht (Netherlands); Lommen, Arjen [RIKILT, Institute of Food Safety, Wageningen UR, PO Box 230, 6700 AE, Wageningen (Netherlands); Someren, Eugene P. van [Research Group Microbiology and Systems Biology, TNO, PO Box 360 3700 AJ Zeist (Netherlands); Jennen, Danyel G.J.; Claessen, Sandra M. [Department of Toxicogenomics, Maastricht University, Universitiessingel 50 6229 ER Maastricht (Netherlands); Peijnenburg, Ad A.C.M. [RIKILT, Institute of Food Safety, Wageningen UR, PO Box 230, 6700 AE, Wageningen (Netherlands); Stierum, Rob H. [Research Group Microbiology and Systems Biology, TNO, PO Box 360 3700 AJ Zeist (Netherlands); Kleinjans, Jos C.S. [Department of Toxicogenomics, Maastricht University, Universitiessingel 50 6229 ER Maastricht (Netherlands)

    2012-03-15

    Acetaminophen is the primary cause of acute liver toxicity in Europe/USA, which led the FDA to reconsider recommendations concerning safe acetaminophen dosage/use. Unfortunately, the current tests for liver toxicity are no ideal predictive markers for liver injury, i.e. they only measure acetaminophen exposure after profound liver toxicity has already occurred. Furthermore, these tests do not provide mechanistic information. Here, 'omics techniques (global analysis of metabolomic/gene-expression responses) may provide additional insight. To better understand acetaminophen-induced responses at low doses, we evaluated the effects of (sub-)therapeutic acetaminophen doses on metabolite formation and global gene-expression changes (including, for the first time, full-genome human miRNA expression changes) in blood/urine samples from healthy human volunteers. Many known and several new acetaminophen-metabolites were detected, in particular in relation to hepatotoxicity-linked, oxidative metabolism of acetaminophen. Transcriptomic changes indicated immune-modulating effects (2 g dose) and oxidative stress responses (4 g dose). For the first time, effects of acetaminophen on full-genome human miRNA expression have been considered and confirmed the findings on mRNA level. 'Omics techniques outperformed clinical chemistry tests and revealed novel response pathways to acetaminophen in humans. Although no definitive conclusion about potential immunotoxic effects of acetaminophen can be drawn from this study, there are clear indications that the immune system is triggered even after intake of low doses of acetaminophen. Also, oxidative stress-related gene responses, similar to those seen after high dose acetaminophen exposure, suggest the occurrence of possible pre-toxic effects of therapeutic acetaminophen doses. Possibly, these effects are related to dose-dependent increases in levels of hepatotoxicity-related metabolites. -- Highlights: ► 'Omics techniques

  20. 'Omics analysis of low dose acetaminophen intake demonstrates novel response pathways in humans

    International Nuclear Information System (INIS)

    Jetten, Marlon J.A.; Gaj, Stan; Ruiz-Aracama, Ainhoa; Kok, Theo M. de; Delft, Joost H.M. van; Lommen, Arjen; Someren, Eugene P. van; Jennen, Danyel G.J.; Claessen, Sandra M.; Peijnenburg, Ad A.C.M.; Stierum, Rob H.; Kleinjans, Jos C.S.

    2012-01-01

    Acetaminophen is the primary cause of acute liver toxicity in Europe/USA, which led the FDA to reconsider recommendations concerning safe acetaminophen dosage/use. Unfortunately, the current tests for liver toxicity are no ideal predictive markers for liver injury, i.e. they only measure acetaminophen exposure after profound liver toxicity has already occurred. Furthermore, these tests do not provide mechanistic information. Here, 'omics techniques (global analysis of metabolomic/gene-expression responses) may provide additional insight. To better understand acetaminophen-induced responses at low doses, we evaluated the effects of (sub-)therapeutic acetaminophen doses on metabolite formation and global gene-expression changes (including, for the first time, full-genome human miRNA expression changes) in blood/urine samples from healthy human volunteers. Many known and several new acetaminophen-metabolites were detected, in particular in relation to hepatotoxicity-linked, oxidative metabolism of acetaminophen. Transcriptomic changes indicated immune-modulating effects (2 g dose) and oxidative stress responses (4 g dose). For the first time, effects of acetaminophen on full-genome human miRNA expression have been considered and confirmed the findings on mRNA level. 'Omics techniques outperformed clinical chemistry tests and revealed novel response pathways to acetaminophen in humans. Although no definitive conclusion about potential immunotoxic effects of acetaminophen can be drawn from this study, there are clear indications that the immune system is triggered even after intake of low doses of acetaminophen. Also, oxidative stress-related gene responses, similar to those seen after high dose acetaminophen exposure, suggest the occurrence of possible pre-toxic effects of therapeutic acetaminophen doses. Possibly, these effects are related to dose-dependent increases in levels of hepatotoxicity-related metabolites. -- Highlights: ► 'Omics techniques outperformed

  1. Exposure to atrazine affects the expression of key genes in metabolic pathways integral to energy homeostasis in Xenopus laevis tadpoles.

    Science.gov (United States)

    Zaya, Renee M; Amini, Zakariya; Whitaker, Ashley S; Ide, Charles F

    2011-08-01

    In our laboratory, Xenopus laevis tadpoles exposed throughout development to 200 or 400 μg/L atrazine, concentrations reported to periodically occur in puddles, vernal ponds and runoff soon after application, were smaller and had smaller fat bodies (the tadpole's lipid storage organ) than controls. It was hypothesized that these changes were due to atrazine-related perturbations of energy homeostasis. To investigate this hypothesis, selected metabolic responses to exposure at the transcriptional and biochemical levels in atrazine-exposed tadpoles were measured. DNA microarray technology was used to determine which metabolic pathways were affected after developmental exposure to 400 μg/L atrazine. From these data, genes representative of the affected pathways were selected for assay using quantitative real time polymerase chain reaction (qRT-PCR) to measure changes in expression during a 2-week exposure to 400 μg/L. Finally, ATP levels were measured from tadpoles both early in and at termination of exposure to 200 and 400 μg/L. Microarray analysis revealed significant differential gene expression in metabolic pathways involved with energy homeostasis. Pathways with increased transcription were associated with the conversion of lipids and proteins into energy. Pathways with decreased transcription were associated with carbohydrate metabolism, fat storage, and protein synthesis. Using qRT-PCR, changes in gene expression indicative of an early stress response to atrazine were noted. Exposed tadpoles had significant decreases in acyl-CoA dehydrogenase (AD) and glucocorticoid receptor protein (GR) mRNA after 24 h of exposure, and near-significant (p=0.07) increases in peroxisome proliferator-activated receptor β (PPAR-β) mRNA by 72 h. Decreases in AD suggested decreases in fatty acid β-oxidation while decreases in GR may have been a receptor desensitization response to a glucocorticoid surge. Involvement of PPAR-β, an energy homeostasis regulatory molecule, also

  2. Exposure to atrazine affects the expression of key genes in metabolic pathways integral to energy homeostasis in Xenopus laevis tadpoles

    International Nuclear Information System (INIS)

    Zaya, Renee M.; Amini, Zakariya; Whitaker, Ashley S.; Ide, Charles F.

    2011-01-01

    In our laboratory, Xenopus laevis tadpoles exposed throughout development to 200 or 400 μg/L atrazine, concentrations reported to periodically occur in puddles, vernal ponds and runoff soon after application, were smaller and had smaller fat bodies (the tadpole's lipid storage organ) than controls. It was hypothesized that these changes were due to atrazine-related perturbations of energy homeostasis. To investigate this hypothesis, selected metabolic responses to exposure at the transcriptional and biochemical levels in atrazine-exposed tadpoles were measured. DNA microarray technology was used to determine which metabolic pathways were affected after developmental exposure to 400 μg/L atrazine. From these data, genes representative of the affected pathways were selected for assay using quantitative real time polymerase chain reaction (qRT-PCR) to measure changes in expression during a 2-week exposure to 400 μg/L. Finally, ATP levels were measured from tadpoles both early in and at termination of exposure to 200 and 400 μg/L. Microarray analysis revealed significant differential gene expression in metabolic pathways involved with energy homeostasis. Pathways with increased transcription were associated with the conversion of lipids and proteins into energy. Pathways with decreased transcription were associated with carbohydrate metabolism, fat storage, and protein synthesis. Using qRT-PCR, changes in gene expression indicative of an early stress response to atrazine were noted. Exposed tadpoles had significant decreases in acyl-CoA dehydrogenase (AD) and glucocorticoid receptor protein (GR) mRNA after 24 h of exposure, and near-significant (p = 0.07) increases in peroxisome proliferator-activated receptor β (PPAR-β) mRNA by 72 h. Decreases in AD suggested decreases in fatty acid β-oxidation while decreases in GR may have been a receptor desensitization response to a glucocorticoid surge. Involvement of PPAR-β, an energy homeostasis regulatory molecule

  3. Exposure to atrazine affects the expression of key genes in metabolic pathways integral to energy homeostasis in Xenopus laevis tadpoles

    Energy Technology Data Exchange (ETDEWEB)

    Zaya, Renee M., E-mail: renee.zaya@wmich.edu [Great Lakes Environmental and Molecular Sciences Center, Department of Biological Sciences, 3425 Wood Hall, Western Michigan University, 1903 West Michigan Avenue, Kalamazoo, MI 49008 (United States); Amini, Zakariya, E-mail: zakariya.amini@wmich.edu [Great Lakes Environmental and Molecular Sciences Center, Department of Biological Sciences, 3425 Wood Hall, Western Michigan University, 1903 West Michigan Avenue, Kalamazoo, MI 49008 (United States); Whitaker, Ashley S., E-mail: ashley.s.whitaker@wmich.edu [Great Lakes Environmental and Molecular Sciences Center, Department of Biological Sciences, 3425 Wood Hall, Western Michigan University, 1903 West Michigan Avenue, Kalamazoo, MI 49008 (United States); Ide, Charles F., E-mail: charles.ide@wmich.edu [Great Lakes Environmental and Molecular Sciences Center, Department of Biological Sciences, 3425 Wood Hall, Western Michigan University, 1903 West Michigan Avenue, Kalamazoo, MI 49008 (United States)

    2011-08-15

    In our laboratory, Xenopus laevis tadpoles exposed throughout development to 200 or 400 {mu}g/L atrazine, concentrations reported to periodically occur in puddles, vernal ponds and runoff soon after application, were smaller and had smaller fat bodies (the tadpole's lipid storage organ) than controls. It was hypothesized that these changes were due to atrazine-related perturbations of energy homeostasis. To investigate this hypothesis, selected metabolic responses to exposure at the transcriptional and biochemical levels in atrazine-exposed tadpoles were measured. DNA microarray technology was used to determine which metabolic pathways were affected after developmental exposure to 400 {mu}g/L atrazine. From these data, genes representative of the affected pathways were selected for assay using quantitative real time polymerase chain reaction (qRT-PCR) to measure changes in expression during a 2-week exposure to 400 {mu}g/L. Finally, ATP levels were measured from tadpoles both early in and at termination of exposure to 200 and 400 {mu}g/L. Microarray analysis revealed significant differential gene expression in metabolic pathways involved with energy homeostasis. Pathways with increased transcription were associated with the conversion of lipids and proteins into energy. Pathways with decreased transcription were associated with carbohydrate metabolism, fat storage, and protein synthesis. Using qRT-PCR, changes in gene expression indicative of an early stress response to atrazine were noted. Exposed tadpoles had significant decreases in acyl-CoA dehydrogenase (AD) and glucocorticoid receptor protein (GR) mRNA after 24 h of exposure, and near-significant (p = 0.07) increases in peroxisome proliferator-activated receptor {beta} (PPAR-{beta}) mRNA by 72 h. Decreases in AD suggested decreases in fatty acid {beta}-oxidation while decreases in GR may have been a receptor desensitization response to a glucocorticoid surge. Involvement of PPAR-{beta}, an energy

  4. Phthalate exposure through different pathways and allergic sensitization in preschool children with asthma, allergic rhinoconjunctivitis and atopic dermatitis

    DEFF Research Database (Denmark)

    Bekö, Gabriel; Callesen, Michael; Weschler, Charles J.

    2015-01-01

    Studies in rodents indicate that phthalates can function as adjuvants, increasing the potency of allergens. Meanwhile, epidemiological studies have produced inconsistent findings regarding relationships between phthalate exposures and allergic disease in humans. The present study examined phthala...

  5. Prolonged Particulate Hexavalent Chromium Exposure Suppresses Homologous Recombination Repair in Human Lung Cells.

    Science.gov (United States)

    Browning, Cynthia L; Qin, Qin; Kelly, Deborah F; Prakash, Rohit; Vanoli, Fabio; Jasin, Maria; Wise, John Pierce

    2016-09-01

    Genomic instability is one of the primary models of carcinogenesis and a feature of almost all cancers. Homologous recombination (HR) repair protects against genomic instability by maintaining high genomic fidelity during the repair of DNA double strand breaks. The defining step of HR repair is the formation of the Rad51 nucleofilament, which facilitates the search for a homologous sequence and invasion of the template DNA strand. Particulate hexavalent chromium (Cr(VI)), a human lung carcinogen, induces DNA double strand breaks and chromosome instability. Since the loss of HR repair increases Cr(VI)-induced chromosome instability, we investigated the effect of extended Cr(VI) exposure on HR repair. We show acute (24 h) Cr(VI) exposure induces a normal HR repair response. In contrast, prolonged (120 h) exposure to particulate Cr(VI) inhibited HR repair and Rad51 nucleofilament formation. Prolonged Cr(VI) exposure had a profound effect on Rad51, evidenced by reduced protein levels and Rad51 mislocalization to the cytoplasm. The response of proteins involved in Rad51 nuclear import and nucleofilament formation displayed varying responses to prolonged Cr(VI) exposure. BRCA2 formed nuclear foci after prolonged Cr(VI) exposure, while Rad51C foci formation was suppressed. These results suggest that particulate Cr(VI), a major chemical carcinogen, inhibits HR repair by targeting Rad51, causing DNA double strand breaks to be repaired by a low fidelity, Rad51-independent repair pathway. These results further enhance our understanding of the underlying mechanism of Cr(VI)-induced chromosome instability and thus, carcinogenesis. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. DEPOSITION DISTRICUTION AMONG THE PARALLEL PATHWAYS IN THE HUMAN LUNG CONDUCTING AIRWAY STRUCTURE.

    Science.gov (United States)

    DEPOSITION DISTRIBUTION AMONG THE PARALLEL PATHWAYS IN THE HUMAN LUNG CONDUCTING AIRWAY STRUCTURE. Chong S. Kim*, USEPA National Health and Environmental Effects Research Lab. RTP, NC 27711; Z. Zhang and C. Kleinstreuer, Department of Mechanical and Aerospace Engineering, North C...

  7. Inhibition of plasmin activity by tranexamic acid does not influence inflammatory pathways during human endotoxemia

    NARCIS (Netherlands)

    Renckens, Rosemarijn; Weijer, Sebastiaan; de Vos, Alex F.; Pater, Jennie M.; Meijers, Joost C.; Hack, C. Erik; Levi, Marcel; van der Poll, Tom

    2004-01-01

    Objective - Plasmin activates several proinflammatory pathways at the cellular level in vitro. Lipopolysaccharide (LPS) administration to healthy humans results in a rapid generation of plasmin activity, accompanied by activation of a number of inflammatory systems. Methods and Results - To

  8. Resistance to asbestos-induced apoptosis with continuous exposure to crocidolite on a human T cell

    Energy Technology Data Exchange (ETDEWEB)

    Maeda, Megumi [Department of Biofunctional Chemistry, Graduate School of Natural Science and Technology, Okayama University, 1-1-1 Tsushima-Naka, Okayama 700-8530 (Japan); Department of Hygiene, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192 (Japan); Yamamoto, Shoko [Department of Hygiene, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192 (Japan); Chen, Ying [Division of Pneumoconiosis, School of Public Health, China Medical University, 92 North 2nd, Heping District, Shenyang 110001 (China); Kumagai-Takei, Naoko [Department of Hygiene, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192 (Japan); Hayashi, Hiroaki [Department of Hygiene, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192 (Japan); Department of Dermatology, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192 (Japan); Matsuzaki, Hidenori; Lee, Suni; Hatayama, Tamayo; Miyahara, Naomi; Katoh, Minako [Department of Hygiene, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192 (Japan); Hiratsuka, Juni-ichi [Department of Radiation Oncology, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192 (Japan); Nishimura, Yasumitsu [Department of Hygiene, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192 (Japan); Otsuki, Takemi, E-mail: takemi@med.kawasaki-m.ac.jp [Department of Hygiene, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192 (Japan)

    2012-07-01

    We have been investigating the immunological effects of asbestos. The establishment of a low-dose and continuously exposed human T cell line, HTLV-1 immortalized MT-2, to chrysotile (CB) revealed reduction of CXCR3 chemokine receptor and production of IFN-{gamma} that caused a decline of tumor immunity. These effects were coupled with upregulation of IL-10, TGF-{beta}, and BCL-2 in asbestos-exposed patients. To observe the immunological effects of crocidolite (CR) on human T cells, a trial to establish a low-dose and continuously exposed model was conducted and compared with a previously reported CB-exposed model (MT-2CB). Transient exposure of MT-2 original cells to CB or CR induced a similar level of apoptosis and growth inhibition. The establishment of a continuously exposed subline to CR (MT-2CR) revealed resistance against CR-induced apoptosis and upregulation of the BCL-2/BAX ratio similar to that recorded for MT-2CB. Both sublines showed reduced production of IFN-{gamma}, TNF-{alpha}, and IL-6 with increased IL-10. cDNA microarray with network/pathway analyses focusing on transcription factors revealed that many similar factors related to cell proliferation were involved following continuous exposure to asbestos in both MT-2CB and MT-2CR. These results indicate that both CB and CR fibers affect human T cells with similar degrees even though the carcinogenic activity of these substances differs due to their chemical and physical forms. Trials to identify early detection markers for asbestos exposure or the occurrence of asbestos-inducing malignancies using these findings may lead to the development of clinical tools for asbestos-related diseases and chemoprevention that modifies the reduced tumor immunity. - Highlights: Black-Right-Pointing-Pointer Comparison of effects of chrysotile and crocidolite on human T cell was done. Black-Right-Pointing-Pointer Both fibers caused apoptosis of T cells by transient exposure. Black-Right-Pointing-Pointer T cells

  9. Human Embryonic Stem Cell Responses to Ionizing Radiation Exposures: Current State of Knowledge and Future Challenges

    Directory of Open Access Journals (Sweden)

    Mykyta V. Sokolov

    2012-01-01

    Full Text Available Human embryonic stem cells, which are derived from the inner cell mass of the blastocyst, have become an object of intense study over the last decade. They possess two unique properties that distinguish them from many other cell types: (i the ability to self-renew indefinitely in culture under permissive conditions, and (ii the pluripotency, defined as the capability of giving rise to all cell types of embryonic lineage under the guidance of the appropriate developmental cues. The focus of many recent efforts has been on the elucidating the signaling pathways and molecular networks operating in human embryonic stem cells. These cells hold great promise in cell-based regenerative therapies, disease modeling, drug screening and testing, assessing genotoxic and mutagenic risks associated with exposures to a variety of environmental factors, and so forth. Ionizing radiation is ubiquitous in nature, and it is widely used in diagnostic and therapeutic procedures in medicine. In this paper, our goal is to summarize the recent progress in understanding how human embryonic stem cells respond to ionizing radiation exposures, using novel methodologies based on “omics” approaches, and to provide a critical discussion of what remains unknown; thus proposing a roadmap for the future research in this area.

  10. Gene expression profiling to identify potentially relevant disease outcomes and support human health risk assessment for carbon black nanoparticle exposure.

    Science.gov (United States)

    Bourdon, Julie A; Williams, Andrew; Kuo, Byron; Moffat, Ivy; White, Paul A; Halappanavar, Sabina; Vogel, Ulla; Wallin, Håkan; Yauk, Carole L

    2013-01-07

    New approaches are urgently needed to evaluate potential hazards posed by exposure to nanomaterials. Gene expression profiling provides information on potential modes of action and human relevance, and tools have recently become available for pathway-based quantitative risk assessment. The objective of this study was to use toxicogenomics in the context of human health risk assessment. We explore the utility of toxicogenomics in risk assessment, using published gene expression data from C57BL/6 mice exposed to 18, 54 and 162 μg Printex 90 carbon black nanoparticles (CBNP). Analysis of CBNP-perturbed pathways, networks and transcription factors revealed concomitant changes in predicted phenotypes (e.g., pulmonary inflammation and genotoxicity), that correlated with dose and time. Benchmark doses (BMDs) for apical endpoints were comparable to minimum BMDs for relevant pathway-specific expression changes. Comparison to inflammatory lung disease models (i.e., allergic airway inflammation, bacterial infection and tissue injury and fibrosis) and human disease profiles revealed that induced gene expression changes in Printex 90 exposed mice were similar to those typical for pulmonary injury and fibrosis. Very similar fibrotic pathways were perturbed in CBNP-exposed mice and human fibrosis disease models. Our synthesis demonstrates how toxicogenomic profiles may be used in human health risk assessment of nanoparticles and constitutes an important step forward in the ultimate recognition of toxicogenomic endpoints in human health risk. As our knowledge of molecular pathways, dose-response characteristics and relevance to human disease continues to grow, we anticipate that toxicogenomics will become increasingly useful in assessing chemical toxicities and in human health risk assessment. Crown Copyright © 2012. Published by Elsevier Ireland Ltd. All rights reserved.

  11. Apoptosis induction in human lymphocytes after in vitro exposure to cobalt/hard metal compounds

    International Nuclear Information System (INIS)

    Boeck, M. de; Decordier, I.; Lombaert, N.; Cundari, E.; Kirsch-Volders, M.; Lison, D.

    2001-01-01

    Full text: An increased risk of lung cancer is associated with occupational exposure to mixtures of cobalt metal (Co) and tungsten carbide (WC) particles, but apparently not when exposure is to cobalt alone. The mechanism for this increased cancer risk is not fully understood. The evaluation of the in vitro genotoxic effects in lymphocytes exposed to varying cobalt species demonstrated that the WC-Co hard metal mixture is more genotoxic (DNA damage, chromosome/genome mutations) than metallic Co alone. WC alone was not genotoxic. Thus, WC-Co represents a specific (geno)toxic entity. In order to assess the survival of human lymphocytes after in vitro exposure to metallic Co, CoCl 2 , WC and the WC-Co mixture, two apoptosis/necrosis detection methods were applied (annexin V staining and flow cytometry). Annexin-V staining of early apoptotic cells demonstrated a dose- and time dependent induction of apoptosis by metallic Co, CoCl 2 , WC and the WC-Co mixture. The time course of the process varied according to the metal species tested. Metallic Co and CoCl 2 caused a gradually increasing frequency of apoptotic cells with time (up to 24 h). WC-induced apoptosis displayed a typical 6 hour peak, which was not the case for the WC-Co mixture or for Co. Apoptosis induction by the WC-Co mixture was intermediate between that induced by Co and WC separately. Analysis of propidium iodide stained cells by flow cytometry was performed as a later marker for apoptosis induction. Preliminary data indicate similar tendencies of apoptosis induction as those detected by annexin-V. Identification of the apoptotic pathway triggered by the metal compounds was studied by inhibition of the ceramide-apoptosis pathway by fumonisin causing reduction of apoptosis induction for all compounds, but strongest after 6 hour exposure to WC. The use of specific caspase inhibitors will allow to further elucidate the different pathways involved. The current data demonstrating in vitro the apoptosis

  12. Apoptosis induction in human lymphocytes after in vitro exposure to cobalt/hard metal compounds

    Energy Technology Data Exchange (ETDEWEB)

    Boeck, M de; Decordier, I; Lombaert, N; Cundari, E; Kirsch-Volders, M [Vrije Universiteit Brussel, Laboratorium voor Cellulaire Genetica, Brussel (Belgium); Lison, D [Universite catholique de Louvain, Unite de Toxicologie industrielle et Medecine du Travail, Bruxelles (Belgium)

    2001-07-01

    Full text: An increased risk of lung cancer is associated with occupational exposure to mixtures of cobalt metal (Co) and tungsten carbide (WC) particles, but apparently not when exposure is to cobalt alone. The mechanism for this increased cancer risk is not fully understood. The evaluation of the in vitro genotoxic effects in lymphocytes exposed to varying cobalt species demonstrated that the WC-Co hard metal mixture is more genotoxic (DNA damage, chromosome/genome mutations) than metallic Co alone. WC alone was not genotoxic. Thus, WC-Co represents a specific (geno)toxic entity. In order to assess the survival of human lymphocytes after in vitro exposure to metallic Co, CoCl{sub 2}, WC and the WC-Co mixture, two apoptosis/necrosis detection methods were applied (annexin V staining and flow cytometry). Annexin-V staining of early apoptotic cells demonstrated a dose- and time dependent induction of apoptosis by metallic Co, CoCl{sub 2}, WC and the WC-Co mixture. The time course of the process varied according to the metal species tested. Metallic Co and CoCl{sub 2} caused a gradually increasing frequency of apoptotic cells with time (up to 24 h). WC-induced apoptosis displayed a typical 6 hour peak, which was not the case for the WC-Co mixture or for Co. Apoptosis induction by the WC-Co mixture was intermediate between that induced by Co and WC separately. Analysis of propidium iodide stained cells by flow cytometry was performed as a later marker for apoptosis induction. Preliminary data indicate similar tendencies of apoptosis induction as those detected by annexin-V. Identification of the apoptotic pathway triggered by the metal compounds was studied by inhibition of the ceramide-apoptosis pathway by fumonisin causing reduction of apoptosis induction for all compounds, but strongest after 6 hour exposure to WC. The use of specific caspase inhibitors will allow to further elucidate the different pathways involved. The current data demonstrating in vitro the

  13. Vitamin C Degradation Products and Pathways in the Human Lens*

    OpenAIRE

    Nemet, Ina; Monnier, Vincent M.

    2011-01-01

    Vitamin C and its degradation products participate in chemical modifications of proteins in vivo through non-enzymatic glycation (Maillard reaction) and formation of different products called advanced glycation end products. Vitamin C levels are particularly high in selected tissues, such as lens, brain and adrenal gland, and its degradation products can inflict substantial protein damage via formation of advanced glycation end products. However, the pathways of in vivo vitamin C degradation ...

  14. Natural and anthropogenic radiation exposure of humans in Germany

    International Nuclear Information System (INIS)

    Koelzer, Winfried

    2016-12-01

    The contribution on natural and anthropogenic radiation exposure in Germany covers the following issues: (1) natural radiation exposure: external radiation exposure - cosmic and terrestric radiation, internal radiation exposure - primordial and cosmogenic radionuclides; radiation exposure due to sola neutrinos and geo-neutrinos. (2) Anthropogenic radiation exposure: radiation exposure in medicine, radioactivity in industrial products, radiation exposure during flights, radiation exposure due to nuclear facilities, radiation exposure due to fossil energy carriers in power generation, radiation exposure due to nuclear explosions, radiation exposure due to nuclear accidents. (3) Occupational radiation exposure in Germany: radiation monitoring with personal dosimeters in medicine and industry, dose surveillance of the aviation personal, working places with increases radiation exposure by natural radiation sources.

  15. Retinoblastoma pathway defects show differential ability to activate the constitutive DNA damage response in human tumorigenesis

    DEFF Research Database (Denmark)

    Tort, F.; Bartkova, J.; Sehested, M.

    2006-01-01

    culture models with differential defects of retinoblastoma pathway components, as overexpression of cyclin D1 or lack of p16(Ink4a), either alone or combined, did not elicit detectable DDR. In contrast, inactivation of pRb, the key component of the pathway, activated the DDR in cultured human or mouse...... with their hierarchical positions along the retinoblastoma pathway. Our data provide new insights into oncogene-evoked DDR in human tumorigenesis, with potential implications for individualized management of tumors with elevated cyclin D1 versus cyclin E, due to their distinct clinical variables and biological behavior....

  16. E-Cigarette Vapor Induces an Apoptotic Response in Human Gingival Epithelial Cells Through the Caspase-3 Pathway.

    Science.gov (United States)

    Rouabhia, Mahmoud; Park, Hyun Jin; Semlali, Abdelhabib; Zakrzewski, Andrew; Chmielewski, Witold; Chakir, Jamila

    2017-06-01

    Electronic cigarettes represent an increasingly significant proportion of today's consumable tobacco products. E-cigarettes contain several chemicals which may promote oral diseases. The aim of this study was to investigate the effect of e-cigarette vapor on human gingival epithelial cells. Results show that e-cigarette vapor altered the morphology of cells from small cuboidal form to large undefined shapes. Both single and multiple exposures to e-cigarette vapor led to a bulky morphology with large faint nuclei and an enlarged cytoplasm. E-cigarette vapor also increased L-lactate dehydrogenase (LDH) activity in the targeted cells. This activity was greater with repeated exposures. Furthermore, e-cigarette vapor increased apoptotic/necrotic epithelial cell percentages compared to that observed in the control. Epithelial cell apoptosis was confirmed by TUNEL assay showing that exposure to e-cigarette vapor increased apoptotic cell numbers, particularly after two and three exposures. This negative effect involved the caspase-3 pathway, the activity of which was greater with repeated exposure and which decreased following the use of caspase-3 inhibitor. The adverse effects of e-cigarette vapor on gingival epithelial cells may lead to dysregulated gingival cell function and result in oral disease. J. Cell. Physiol. 232: 1539-1547, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. Assessment of human exposure to environmental sources of nickel in Europe: Inhalation exposure.

    Science.gov (United States)

    Buekers, Jurgen; De Brouwere, Katleen; Lefebvre, Wouter; Willems, Hanny; Vandenbroele, Marleen; Van Sprang, Patrick; Eliat-Eliat, Maxime; Hicks, Keegan; Schlekat, Christian E; Oller, Adriana R

    2015-07-15

    The paper describes the inhalation nickel (Ni) exposure of humans via the environment for the regional scale in the EU, together with a tiered approach for assessing additional local exposure from industrial emissions. The approach was designed, in the context of REACH, for the purpose of assessing and controlling emissions and air quality in the neighbourhood of Ni producers and downstream users. Two Derived No Effect Level (DNEL) values for chronic inhalation exposure to total Ni in PM10 (20 and 60ngNi/m(3)) were considered. The value of 20ngNi/m(3) is the current EU air quality guidance value. The value of 60ngNi/m(3) is derived here based on recently published Ni data (Oller et al., 2014). Both values are protective for respiratory toxicity and carcinogenicity but differ in the application of toxicokinetic adjustments and cancer threshold considerations. Estimates of air Ni concentrations at the European regional scale were derived from the database of the European Environment Agency. The 50th and 90th percentile regional exposures were below both DNEL values. To assess REACH compliance at the local scale, measured ambient air data are preferred but are often unavailable. A tiered approach for the use of modelled ambient air concentrations was developed, starting with the application of the default EUSES model and progressing to more sophisticated models. As an example, the tiered approach was applied to 33 EU Ni sulphate producers' and downstream users' sites. Applying the EUSES model demonstrates compliance with a DNEL of 60ngNi/m(3) for the majority of sites, while the value of the refined modelling is demonstrated when a DNEL of 20ngNi/m(3) is considered. The proposed approach, applicable to metals in general, can be used in the context of REACH, for refining the risk characterisation and guiding the selection of risk management measures. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. A geographically-diverse collection of 418 human gut microbiome pathway genome databases

    KAUST Repository

    Hahn, Aria S.

    2017-04-11

    Advances in high-throughput sequencing are reshaping how we perceive microbial communities inhabiting the human body, with implications for therapeutic interventions. Several large-scale datasets derived from hundreds of human microbiome samples sourced from multiple studies are now publicly available. However, idiosyncratic data processing methods between studies introduce systematic differences that confound comparative analyses. To overcome these challenges, we developed GutCyc, a compendium of environmental pathway genome databases (ePGDBs) constructed from 418 assembled human microbiome datasets using MetaPathways, enabling reproducible functional metagenomic annotation. We also generated metabolic network reconstructions for each metagenome using the Pathway Tools software, empowering researchers and clinicians interested in visualizing and interpreting metabolic pathways encoded by the human gut microbiome. For the first time, GutCyc provides consistent annotations and metabolic pathway predictions, making possible comparative community analyses between health and disease states in inflammatory bowel disease, Crohn’s disease, and type 2 diabetes. GutCyc data products are searchable online, or may be downloaded and explored locally using MetaPathways and Pathway Tools.

  19. Leveraging human genetic and adverse outcome pathway (AOP) data to inform susceptibility in human health risk assessment

    Science.gov (United States)

    Estimation of susceptibility differences in human health risk assessment (HHRA) has been challenged by a lack of available susceptibility and variability data after exposure to a specific environmental chemical or pharmaceutical. With the increasingly large number of available da...

  20. A Workflow to Investigate Exposure and Pharmacokinetic Influences on High-Throughput in Vitro Chemical Screening Based on Adverse Outcome Pathways

    Science.gov (United States)

    Phillips, Martin B.; Leonard, Jeremy A.; Grulke, Christopher M.; Chang, Daniel T.; Edwards, Stephen W.; Brooks, Raina; Goldsmith, Michael-Rock; El-Masri, Hisham; Tan, Yu-Mei

    2015-01-01

    Background Adverse outcome pathways (AOPs) link adverse effects in individuals or populations to a molecular initiating event (MIE) that can be quantified using in vitro methods. Practical application of AOPs in chemical-specific risk assessment requires incorporation of knowledge on exposure, along with absorption, distribution, metabolism, and excretion (ADME) properties of chemicals. Objectives We developed a conceptual workflow to examine exposure and ADME properties in relation to an MIE. The utility of this workflow was evaluated using a previously established AOP, acetylcholinesterase (AChE) inhibition. Methods Thirty chemicals found to inhibit human AChE in the ToxCast™ assay were examined with respect to their exposure, absorption potential, and ability to cross the blood–brain barrier (BBB). Structures of active chemicals were compared against structures of 1,029 inactive chemicals to detect possible parent compounds that might have active metabolites. Results Application of the workflow screened 10 “low-priority” chemicals of 30 active chemicals. Fifty-two of the 1,029 inactive chemicals exhibited a similarity threshold of ≥ 75% with their nearest active neighbors. Of these 52 compounds, 30 were excluded due to poor absorption or distribution. The remaining 22 compounds may inhibit AChE in vivo either directly or as a result of metabolic activation. Conclusions The incorporation of exposure and ADME properties into the conceptual workflow eliminated 10 “low-priority” chemicals that may otherwise have undergone additional, resource-consuming analyses. Our workflow also increased confidence in interpretation of in vitro results by identifying possible “false negatives.” Citation Phillips MB, Leonard JA, Grulke CM, Chang DT, Edwards SW, Brooks R, Goldsmith MR, El-Masri H, Tan YM. 2016. A workflow to investigate exposure and pharmacokinetic influences on high-throughput in vitro chemical screening based on adverse outcome pathways. Environ

  1. Asymmetry of radial and symmetry of tangential neuronal migration pathways in developing human fetal brains

    Directory of Open Access Journals (Sweden)

    Yuta eMiyazaki

    2016-01-01

    Full Text Available AbstractThe radial and tangential neural migration pathways are two major neuronal migration streams in humans that are critical during corticogenesis. Corticogenesis is a complex process of neuronal proliferation that is followed by neuronal migration and the formation of axonal connections. Existing histological assessments of these two neuronal migration pathways have limitations inherent to microscopic studies and are confined to small anatomic regions of interest. Thus, little evidence is available about their three-dimensional fiber pathways and development throughout the entire brain. In this study, we imaged and analyzed radial and tangential migration pathways in the whole human brain using high-angular resolution diffusion MR imaging (HARDI tractography. We imaged ten fixed, postmortem fetal (17 gestational weeks (GW, 18 GW, 19 GW, three 20 GW, three 21 GW and 22 GW and eight in vivo newborn (two 30 GW, 34 GW, 35 GW and four 40 GW brains with no neurological/pathological conditions. We statistically compared the volume of the left and right radial and tangential migration pathways, and the volume of the radial migration pathways of the anterior and posterior regions of the brain. In specimens 22 GW or younger, the volume of radial migration pathways of the left hemisphere was significantly larger than that of the right hemisphere. The volume of posterior radial migration pathways was also larger when compared to the anterior pathways in specimens 22 GW or younger. In contrast, no significant differences were observed in the radial migration pathways of brains older than 22 GW. Moreover, our study did not identify any significant differences in volumetric laterality in the tangential migration pathways. These results suggest that these two neuronal migration pathways develop and regress differently, and radial neuronal migration varies regionally based on hemispheric and anterior-posterior laterality, potentially explaining regional

  2. Effects of bifenthrin exposure on the estrogenic and dopaminergic pathways in zebrafish embryos and juveniles.

    Science.gov (United States)

    Bertotto, Luísa Becker; Richards, Jaben; Gan, Jay; Volz, David Christopher; Schlenk, Daniel

    2018-01-01

    Bifenthrin is a pyrethroid insecticide used in urban and agricultural applications. Previous studies have shown that environmentally relevant (ng/L) concentrations of bifenthrin increased plasma concentrations of 17β-estradiol (E2) and altered the expression of dopaminergic pathway components. The dopaminergic neurons can indirectly regulate E2 biosynthesis, suggesting that bifenthrin may disrupt the hypothalamic-pituitary-gonadal (HPG) axis. Because embryos do not have a complete HPG axis, the hypothesis that bifenthrin impairs dopamine regulation was tested in embryonic and 1-mo-old juvenile zebrafish (Danio rerio) with exposure to measured concentrations of 0.34 and 3.1 µg/L bifenthrin for 96 h. Quantitative reverse transcriptase polymerase chain reaction was used to investigate transcripts of tyrosine hydroxylase (TH), dopamine receptor 1 (DR1) and 2A (DR2A), dopamine active transporter (DAT), estrogen receptor α (ERα), ERβ1, ERβ2, luteinizing hormone β (LHβ), follicle-stimulating hormone β (FSHβ), vitellogenin (VTG), cytochrome P450 cyp19a1a, and cyp19a1b. Levels of E2 were measured by enzyme-linked immunosorbent assay (ELISA). Dopamine and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) concentrations were measured by liquid chromatrography-tandem mass spectrometry (LC-MS/MS). Significant decreases in TH and DR1 transcripts and HVA levels, as well as ratios of HVA/dopamine and HVA+DOPAC/dopamine, in zebrafish embryos were observed after bifenthrin treatment. In juveniles, a significant increase in the expression of ERβ1 and the DOPAC to dopamine ratio was noted. These results show a possible antiestrogenic effect of bifenthrin in embryos, and estrogenicity in juveniles, indicating life-stage-dependent toxicity in developing fish. Environ Toxicol Chem 2018;37:236-246. © 2017 SETAC. © 2017 SETAC.

  3. Screening of ovarian steroidogenic pathway in Ciona intestinalis and its modulation after tributyltin exposure

    International Nuclear Information System (INIS)

    Cangialosi, Maria Vittoria; Puccia, Egidio; Mazzola, Antonio; Mansueto, Valentina; Arukwe, Augustine

    2010-01-01

    In this study, we have identified several ovarian steroids in Ciona with high similarity to vertebrate steroids and showed that cholesterol, corticosterone, dehydroepiandrosterone, estrone, estradiol-17β, testosterone, pregnenolone, progesterone, have identical molecular spectra with vertebrate steroids. In addition, we have studied the effects of an endocrine disruptor (tributyltin: TBT) on these sex hormones and their precursors, ovarian morphology, and gene expression of some key enzymes in steroidogenic pathway in the ovary of Ciona. Ovarian specimens were cultured in vitro using different concentrations of TBT (10 -5 , 10 -4 and 10 -3 M). Ethanol was used as solvent control. Gene expression analysis was performed for adrenodoxin (ADREN) and adrenodoxin reductase (ADOX) (mediators of acute steroidogenesis) and 17β-hydroxysteroid dehydrogenase (17β-HSD). These transcripts were detected and measured by quantitative (real-time) polymerase chain reaction (qPCR). Sex steroids and their precursors were identified and quantified by a gas chromatography-mass spectroscopy (GC-MS) method. Exposure of Ciona ovaries to TBT produced modulations (either increased or decreased) of sterols and sex steroid levels, whereas no significant differences in ADREN, ADOX or 17β-HSD mRNA expression patterns were observed. Histological analysis shows that TBT produced several modifications on Ciona ovarian morphology that includes irregular outline of nuclear membrane, less compacted cytoplasm, in addition to test and granulosa cells that were detached from the oocyte membrane. Given that the ascidians represent very simple experimental models for the study of endocrine disruption by environmental contaminants, our findings provide excellent models for multiple identification and quantification of sex steroid and their precursors in biological samples exposed to endocrine-disrupting chemicals and for direct extrapolation of such effects across taxonomic groups and phyla. In addition

  4. Methylmercury degradation and exposure pathways in streams and wetlands impacted by historical mining

    Energy Technology Data Exchange (ETDEWEB)

    Donovan, Patrick M., E-mail: pmdon@umich.edu [University of Michigan, Department of Earth and Environmental Sciences, 1100 N., University Ave., Ann Arbor, MI 48109 (United States); Blum, Joel D. [University of Michigan, Department of Earth and Environmental Sciences, 1100 N., University Ave., Ann Arbor, MI 48109 (United States); Singer, Michael Bliss [University of St Andrews, Department of Earth and Environmental Sciences, North St., St. Andrews, KY16 9AL (United Kingdom); Earth Research Institute, University of California Santa Barbara, Santa Barbara, CA, 91306 (United States); Marvin-DiPasquale, Mark [U.S. Geological Survey, Menlo Park, CA (United States); Tsui, Martin T.K. [Department of Biology, University of North Carolina at Greensboro, Greensboro, NC 27402 (United States)

    2016-10-15

    Monomethyl mercury (MMHg) and total mercury (THg) concentrations and Hg stable isotope ratios (δ{sup 202}Hg and Δ{sup 199}Hg) were measured in sediment and aquatic organisms from Cache Creek (California Coast Range) and Yolo Bypass (Sacramento Valley). Cache Creek sediment had a large range in THg (87 to 3870 ng/g) and δ{sup 202}Hg (− 1.69 to − 0.20‰) reflecting the heterogeneity of Hg mining sources in sediment. The δ{sup 202}Hg of Yolo Bypass wetland sediment suggests a mixture of high and low THg sediment sources. Relationships between %MMHg (the percent ratio of MMHg to THg) and Hg isotope values (δ{sup 202}Hg and Δ{sup 199}Hg) in fish and macroinvertebrates were used to identify and estimate the isotopic composition of MMHg. Deviation from linear relationships was found between %MMHg and Hg isotope values, which is indicative of the bioaccumulation of isotopically distinct pools of MMHg. The isotopic composition of pre-photodegraded MMHg (i.e., subtracting fractionation from photochemical reactions) was estimated and contrasting relationships were observed between the estimated δ{sup 202}Hg of pre-photodegraded MMHg and sediment IHg. Cache Creek had mass dependent fractionation (MDF; δ{sup 202}Hg) of at least − 0.4‰ whereas Yolo Bypass had MDF of + 0.2 to + 0.5‰. This result supports the hypothesis that Hg isotope fractionation between IHg and MMHg observed in rivers (− MDF) is unique compared to + MDF observed in non-flowing water environments such as wetlands, lakes, and the coastal ocean. - Highlights: • Mercury isotope ratios were measured in sediment and biota from Central California. • The isotopic composition of MMHg was estimated in streams and wetlands. • Mercury isotopes suggest multiple exposure pathways in these habitats. • Mass dependent fractionation between IHg and MMHg is different in streams.

  5. Methylmercury degradation and exposure pathways in streams and wetlands impacted by historical mining

    International Nuclear Information System (INIS)

    Donovan, Patrick M.; Blum, Joel D.; Singer, Michael Bliss; Marvin-DiPasquale, Mark; Tsui, Martin T.K.

    2016-01-01

    Monomethyl mercury (MMHg) and total mercury (THg) concentrations and Hg stable isotope ratios (δ"2"0"2Hg and Δ"1"9"9Hg) were measured in sediment and aquatic organisms from Cache Creek (California Coast Range) and Yolo Bypass (Sacramento Valley). Cache Creek sediment had a large range in THg (87 to 3870 ng/g) and δ"2"0"2Hg (− 1.69 to − 0.20‰) reflecting the heterogeneity of Hg mining sources in sediment. The δ"2"0"2Hg of Yolo Bypass wetland sediment suggests a mixture of high and low THg sediment sources. Relationships between %MMHg (the percent ratio of MMHg to THg) and Hg isotope values (δ"2"0"2Hg and Δ"1"9"9Hg) in fish and macroinvertebrates were used to identify and estimate the isotopic composition of MMHg. Deviation from linear relationships was found between %MMHg and Hg isotope values, which is indicative of the bioaccumulation of isotopically distinct pools of MMHg. The isotopic composition of pre-photodegraded MMHg (i.e., subtracting fractionation from photochemical reactions) was estimated and contrasting relationships were observed between the estimated δ"2"0"2Hg of pre-photodegraded MMHg and sediment IHg. Cache Creek had mass dependent fractionation (MDF; δ"2"0"2Hg) of at least − 0.4‰ whereas Yolo Bypass had MDF of + 0.2 to + 0.5‰. This result supports the hypothesis that Hg isotope fractionation between IHg and MMHg observed in rivers (− MDF) is unique compared to + MDF observed in non-flowing water environments such as wetlands, lakes, and the coastal ocean. - Highlights: • Mercury isotope ratios were measured in sediment and biota from Central California. • The isotopic composition of MMHg was estimated in streams and wetlands. • Mercury isotopes suggest multiple exposure pathways in these habitats. • Mass dependent fractionation between IHg and MMHg is different in streams.

  6. The ADMA/DDAH/NO pathway in human vein endothelial cells exposed to arsenite.

    Science.gov (United States)

    Osorio-Yáñez, Citlalli; Chin-Chan, Miguel; Sánchez-Peña, Luz C; Atzatzi-Aguilar, Octavio G; Olivares-Reyes, Jesus A; Segovia, José; Del Razo, Luz M

    2017-08-01

    Inorganic arsenic (iAs) exposure is related to cardiovascular disease, which is characterized by endothelial dysfunction and nitric oxide (NO) depletion. The mechanisms underlying NO depletion as related to iAs exposure are not fully understood. The endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine (ADMA), might be a molecular target of iAs. ADMA concentrations are regulated by proteins involved in its synthesis (arginine methyl transferase 1 [PRMT-1]) and degradation (dimethylarginine dimethylaminohydrolase [DDAH]). Both, ADMA and NO are susceptible to oxidative stress. We aimed to determine the ADMA/DDAH/NO pathway in human vein endothelial cells (HUVEC-CS) exposed to arsenite. We exposed HUVEC-CS cells to 1, 2.5 and 5μM of arsenite for 24h. We proved that arsenite at 5μM was able to decrease NO levels with an associated increase in ADMA and depletion of l-arginine in HUVEC-CS cells. We also found a decrease in DDAH-1 protein expression with 5μM of arsenite compared to the control group. However, we did not observe significant differences in PRMT-1 protein expression at any of the concentrations of arsenite employed. Finally, arsenite (2.5 and 5μM) increased NADPH oxidase 4 protein levels compared with the control group. We conclude that ADMA, l-arginine and DDAH are involved in NO depletion produced by arsenite, and that the mechanism is related to oxidative stress. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Human Exposure Model (HEM): A modular, web-based application to characterize near-field chemical exposures and releases

    Science.gov (United States)

    The U.S. EPA’s Chemical Safety and Sustainability research program is developing the Human Exposure Model (HEM) to assess near-field exposures to chemicals that occur in various populations over the entire life cycle of a consumer product. The model will be implemented as a...

  8. Human platelet lysate versus minoxidil stimulates hair growth by activating anagen promoting signaling pathways.

    Science.gov (United States)

    Dastan, Maryam; Najafzadeh, Nowruz; Abedelahi, Ali; Sarvi, Mohammadreza; Niapour, Ali

    2016-12-01

    Minoxidil and human platelet lysate (HPL) are commonly used to treat patients with hair loss. However, the roles of HPL versus minoxidil in hair follicle biology largely remain unknown. Here, we hypothesized that bulge and dermal papilla (DP) cells may express specific genes, including Kras, Erk, Akt, Shh and β-catenin after exposure to minoxidil or HPL. The mouse hair follicles were isolated on day 10 after depilation and bulge or DP regions were dissected. The bulge and DP cells were cultured for 14days in DMEM/F12 medium. Then, the cells were treated with 100μM minoxidil and 10% HPL for 10 days. Nuclear morphology was identified using DAPi staining. Reverse transcriptase and real-time polymerase chain reaction (PCR) analysis were also performed to examine the expression of Kras, Erk, Akt, Shh and β-catenin mRNA levels in the treated bulge and DP regions after organ culture. Here, we found that minoxidil influences bulge and DP cell survival (Pminoxidil treatment in both bulge and DP cells. HPL mediated Erk upregulation in both bulge and DP cells (Pminoxidil-treated bulge cells. In contrast, the expression of β-cateinin and Shh in the DP cells was not meaningfully increased after treatment with HPL. Our results suggest that minoxidil and HPL can promote hair growth by activating the main anagen inducing signaling pathways. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  9. Relative importance of different exposure routes of heavy metals for humans living near a municipal solid waste incinerator

    International Nuclear Information System (INIS)

    Li, Tong; Wan, Yi; Ben, Yujie; Fan, Senrong; Hu, Jianying

    2017-01-01

    The potential health effects of toxic chemicals (e.g. heavy metals) emitted by municipal solid waste incinerators (MSWIs) are of great concern to local residents, however there have been few studies on the contributions of different exposure pathways and their subsequent effects on the body burden of residents living near MSWIs. In this study, multiple exposure routes of heavy metals including Pb, Cr, Cd and Mn were assessed by investigating the metals in foods (such as vegetables, crops, meats and fruits etc.), drinking water, ambient air and soil collected surrounding an MSWI in Shenzhen, south China. Vegetable ingestion played the most important role in the total average daily dose of Pb and Cr, and cereals were the key exposure routes for Mn and Cd. Compound-specific contaminations were observed in the investigated areas, with Pb and Cr present in the surrounding environment, having accumulated to relatively high levels in the local vegetables, and the intake of contaminated vegetable foods greatly influencing the body burden of Pb and Cr. Consistently, significantly high blood concentrations of Pb and Cr were detected in the local residents compared to a referenced population, and a lack of significant differences was found for Cd and Mn. The results possibly suggested that emission of MSWI influenced the external exposure doses of the major pathways of Pb and Cr in this study, and resulted in the different body burden of metals in humans living near a MSWI. MSWI-local food-humans is an important exposure pathway for residents living near MSWI, and thus should not be neglected in developing future strategies and policies to prevent the high risks suffered by residents living near MSWIs. - Highlights: • Vegetable and cereal ingestion were the main contributors to exposure of Pb/Cr and Mn/Cd, respectively. • Concentrations of Pb/Cr in vegetables grown near MSWI were significantly higher. • Blood concentrations of Pb/Cr in populations near MSWI were

  10. Effect of nickel and iron co-exposure on human lung cells

    International Nuclear Information System (INIS)

    Salnikow, Konstantin; Li Xiaomei; Lippmann, Morton

    2004-01-01

    Exposure to ambient air particulate matter (PM) is associated with increased mortality and morbidity in susceptible populations. The epidemiological data also suggest a relationship between PM air pollution and impairment of cardiopulmonary function. The mechanisms that may be responsible for these effects are not fully understood and are likely related to perturbations of cellular and molecular functions. One type of PM, residual oil fly ash (ROFA), is of particular interest. ROFA does not contain much organic material, but does contain relatively high quantities of transition metals, predominantly nickel, vanadium, and iron, as well as black carbon and sulfates. In this study, we investigated the effect of two metals (iron and nickel) on the induction of 'hypoxia-like' stress and the production of interleukins (ILs) in minimally transformed human airway epithelial cells (1HAEo - ). We found that exposure to soluble nickel sulfate results in the induction of hypoxia-inducible genes and IL-8 production by the 1HAEo - cells. The simultaneous addition of iron in either ferric or ferrous form and nickel completely inhibited IL-8 production and had no effect on 'hypoxia-like' stress caused by nickel, suggesting the existence of two different pathways for the induction 'hypoxia-like' stress and IL-8 production. The effect of nickel was not related to the blocking of iron entry into cells since the level of intracellular iron was not affected by co-exposure with nickel. The obtained data indicate that nickel can induce different signaling pathways with or without interference with iron metabolism. Our observations suggest that in some cases the excess of iron in PM can cancel the effects of nickel

  11. A Margin-of-Exposure Approach to Assessment of Noncancer Risks of Dioxins Based on Human Exposure and Response Data

    OpenAIRE

    Aylward, Lesa L.; Goodman, Julie E.; Charnley, Gail; Rhomberg, Lorenz R.

    2008-01-01

    Background Risk assessment of human environmental exposure to polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/PCDFs) and other dioxin-like compounds is complicated by several factors, including limitations in measuring intakes because of the low concentrations of these compounds in foods and the environment and interspecies differences in pharmacokinetics and responses. Objectives We examined the feasibility of relying directly on human studies of exposure and potential responses to...

  12. Sun Exposure and Its Effects on Human Health: Mechanisms through Which Sun Exposure Could Reduce the Risk of Developing Obesity and Cardiometabolic Dysfunction

    Science.gov (United States)

    Fleury, Naomi; Geldenhuys, Sian; Gorman, Shelley

    2016-01-01

    Obesity is a significant burden on global healthcare due to its high prevalence and associations with chronic health conditions. In our animal studies, ongoing exposure to low dose ultraviolet radiation (UVR, found in sunlight) reduced weight gain and the development of signs of cardiometabolic dysfunction in mice fed a high fat diet. These observations suggest that regular exposure to safe levels of sunlight could be an effective means of reducing the burden of obesity. However, there is limited knowledge around the nature of associations between sun exposure and the development of obesity and cardiometabolic dysfunction, and we do not know if sun exposure (independent of outdoor activity) affects the metabolic processes that determine obesity in humans. In addition, excessive sun exposure has strong associations with a number of negative health consequences such as skin cancer. This means it is very important to “get the balance right” to ensure that we receive benefits without increasing harm. In this review, we detail the evidence around the cardiometabolic protective effects of UVR and suggest mechanistic pathways through which UVR could be beneficial. PMID:27727191

  13. MAPK signaling pathway regulates cerebrovascular receptor expression in human cerebral arteries

    DEFF Research Database (Denmark)

    Ansar, Saema; Eftekhari, Sajedeh; Waldsee, Roya

    2013-01-01

    if the upregulation of contractile cerebrovascular receptors after 48 h of organ culture of human cerebral arteries involves MAPK pathways and if it can be prevented by a MEK1/2 inhibitor. Human cerebral arteries were obtained from patients undergoing intracranial tumor surgery. The vessels were divided into ring...

  14. Comparison of the DOE and the EPA risk assessment methodologies and default parameters for the air exposure pathway

    International Nuclear Information System (INIS)

    Tan, Z.; Eckart, R.

    1993-01-01

    The U.S. Department of Energy (DOE) and the U.S. Environmental Protection Agency (EPA) each publish radiological health effects risk assessment methodologies. Those methodologies are in the form of computer program models or extensive documentation. This research paper compares the significant differences between the DOE and EPA methodologies and default parameters for the important air exposure pathway. The purpose of this analysis was to determine the fundamental differences in methodology and parameter values between the DOE and the EPA. This study reviewed the parameter values and default values that are utilized in the air exposure pathway and revealed the significant differences in risk assessment results when default values are used in the analysis of an actual site. The study details the sources and the magnitude of the parameter departures between the DOE and the EPA methodologies and their impact on dose or risk

  15. Human exposure to ionizing radiation for medical reasons

    International Nuclear Information System (INIS)

    Thomas, R.H.; Busick, D.D.

    1977-01-01

    The central issue in this debate is not whether there is a threshold dose below which deleterious effects in humans occur nor whether the dose-effect relationship is linear or curvilinear. The central issue is whether there is merit in a continuing effort to reduce radiation exposures to patients no matter at what level. This should be determined by a careful balancing of potential risks against expected benefits. It is this element of risk-benefit analysis that is absent in Morgan's philosophy. A good example of the changing nature on the risk-benefit balance is that of the use of mass radiography programs to diagnose tuberculosis. Before the Second World War this disease was a terrible scourge of the poor who could ill-afford adequate medical care. The use of mass radiography programs have played a large part in the elimination of this disease

  16. Survival of human lymphocytes after exposure to densely ionizing radiations

    International Nuclear Information System (INIS)

    Madhvanath, U.; Raju, M.R.; Kelly, L.S.

    1976-01-01

    Interphase death of human blood lymphocytes cultured in vitro was studied after exposure to 60 Co gamma rays and to accelerated ions of 1 H, 4 He, 7 Li, 11 B, 12 C, 20 Ne, 40 Ar, and π - meson beam under aerobic conditions. Exposures were also conducted under hypoxic conditions with 60 Co gamma rays, 4 He, 7 Li, and 12 C ion beams. Time course of interphase death was followed for 6 days after irradiation. Percent survivals were determined by using the trypan blue exclusion method. Survival curves at 5 days postirradiation were exponential for all radiations studied. These observations indicate that the production of interphase death of lymphocytes by densely ionizing radiations follows a pattern similar to that observed with colony-forming mammalian cells. However, the reproductive capacity of the latter cells is impaired with maximum effectiveness at energy densities associated with 220 keV/μm for the beam conditions used in this investigation. The much lower energy densities required to kill a lymphocyte suggest that a sensitive structure other than DNA may be responsible for the production of lymphocyte death, perhaps the membranes. The calculated inactivation cross sections for high-LET radiations above 650 keV/μm yielded values larger than the actual cell dimensions. It appears that contributions from delta rays become appreciable in this system at these LET's

  17. Multiplexed activity-based protein profiling of the human pathogen Aspergillus fumigatus reveals large functional changes upon exposure to human serum.

    Science.gov (United States)

    Wiedner, Susan D; Burnum, Kristin E; Pederson, LeeAnna M; Anderson, Lindsey N; Fortuin, Suereta; Chauvigné-Hines, Lacie M; Shukla, Anil K; Ansong, Charles; Panisko, Ellen A; Smith, Richard D; Wright, Aaron T

    2012-09-28

    Environmental adaptability is critical for survival of the fungal human pathogen Aspergillus fumigatus in the immunocompromised host lung. We hypothesized that exposure of the fungal pathogen to human serum would lead to significant alterations to the organism's physiology, including metabolic activity and stress response. Shifts in functional pathway and corresponding enzyme reactivity of A. fumigatus upon exposure to the human host may represent much needed prognostic indicators of fungal infection. To address this, we employed a multiplexed activity-based protein profiling (ABPP) approach coupled to quantitative mass spectrometry-based proteomics to measure broad enzyme reactivity of the fungus cultured with and without human serum. ABPP showed a shift from aerobic respiration to ethanol fermentation and utilization over time in the presence of human serum, which was not observed in serum-free culture. Our approach provides direct insight into this pathogen's ability to survive, adapt, and proliferate. Additionally, our multiplexed ABPP approach captured a broad swath of enzyme reactivity and functional pathways and provides a method for rapid assessment of the A. fumigatus response to external stimuli.

  18. Multiplexed Activity-based Protein Profiling of the Human Pathogen Aspergillus fumigatus Reveals Large Functional Changes upon Exposure to Human Serum*

    Science.gov (United States)

    Wiedner, Susan D.; Burnum, Kristin E.; Pederson, LeeAnna M.; Anderson, Lindsey N.; Fortuin, Suereta; Chauvigné-Hines, Lacie M.; Shukla, Anil K.; Ansong, Charles; Panisko, Ellen A.; Smith, Richard D.; Wright, Aaron T.

    2012-01-01

    Environmental adaptability is critical for survival of the fungal human pathogen Aspergillus fumigatus in the immunocompromised host lung. We hypothesized that exposure of the fungal pathogen to human serum would lead to significant alterations to the organism's physiology, including metabolic activity and stress response. Shifts in functional pathway and corresponding enzyme reactivity of A. fumigatus upon exposure to the human host may represent much needed prognostic indicators of fungal infection. To address this, we employed a multiplexed activity-based protein profiling (ABPP) approach coupled to quantitative mass spectrometry-based proteomics to measure broad enzyme reactivity of the fungus cultured with and without human serum. ABPP showed a shift from aerobic respiration to ethanol fermentation and utilization over time in the presence of human serum, which was not observed in serum-free culture. Our approach provides direct insight into this pathogen's ability to survive, adapt, and proliferate. Additionally, our multiplexed ABPP approach captured a broad swath of enzyme reactivity and functional pathways and provides a method for rapid assessment of the A. fumigatus response to external stimuli. PMID:22865858

  19. Multiple Drug Transport Pathways through Human P-Glycoprotein.

    Science.gov (United States)

    McCormick, James W; Vogel, Pia D; Wise, John G

    2015-07-21

    P-Glycoprotein (P-gp) is a plasma membrane efflux pump that is commonly associated with therapy resistances in cancers and infectious diseases. P-gp can lower the intracellular concentrations of many drugs to subtherapeutic levels by translocating them out of the cell. Because of the broad range of substrates transported by P-gp, overexpression of P-gp causes multidrug resistance. We reported previously on dynamic transitions of P-gp as it moved through conformations based on crystal structures of homologous ABCB1 proteins using in silico targeted molecular dynamics techniques. We expanded these studies here by docking transport substrates to drug binding sites of P-gp in conformations open to the cytoplasm, followed by cycling the pump through conformations that opened to the extracellular space. We observed reproducible transport of two substrates, daunorubicin and verapamil, by an average of 11-12 Å through the plane of the membrane as P-gp progressed through a catalytic cycle. Methylpyrophosphate, a ligand that should not be transported by P-gp, did not show this movement through P-gp. Drug binding to either of two subsites on P-gp appeared to determine the initial pathway used for drug movement through the membrane. The specific side-chain interactions with drugs within each pathway seemed to be, at least in part, stochastic. The docking and transport properties of a P-gp inhibitor, tariquidar, were also studied. A mechanism of inhibition by tariquidar that involves stabilization of an outward open conformation with tariquidar bound in intracellular loops or at the drug binding domain of P-gp is presented.

  20. Multiple Drug Transport Pathways through human P-Glycoprotein(†)

    Science.gov (United States)

    McCormick, James W.; Vogel, Pia D.; Wise, John G.

    2015-01-01

    P-glycoprotein (P-gp) is a plasma membrane efflux pump that is commonly associated with therapy resistances in cancers and infectious diseases. P-gp can lower the intracellular concentrations of many drugs to subtherapeutic levels by translocating them out of the cell. Because of the broad range of substrates transported by P-gp, overexpression of P-gp causes multidrug resistance. We reported previously on dynamic transitions of P-gp as it moved through conformations based on crystal structures of homologous ABCB1 proteins using in silico targeted molecular dynamics techniques. We expanded these studies here by docking transport substrates to drug binding sites of P-gp in conformations open to the cytoplasm, followed by cycling the pump through conformations that opened to the extracellular space. We observed reproducible transport of two substrates, daunorubicin and verapamil, by an average of 11 to 12 Å through the plane of the membrane as P-gp progressed through a catalytic cycle. Methyl-pyrophosphate, a ligand that should not be transported by P-gp, did not show this movement through P-gp. Drug binding to either of two subsites on P-gp appeared to determine the initial pathway used for drug movement through the membrane. The specific side-chain interactions with drugs within each pathway seemed to be, at least in part, stochastic. The docking and transport properties of a P-gp inhibitor, tariquidar, were also studied. A mechanism of inhibition by tariquidar is presented that involves stabilization of an outward open conformation with tariquidar bound in intracellular loops or at the drug binding domain of P-gp. PMID:26125482

  1. Diosgenin induces apoptosis in IGF-1-stimulated human thyrocytes through two caspase-dependent pathways

    International Nuclear Information System (INIS)

    Mu, Shumin; Tian, Xingsong; Ruan, Yongwei; Liu, Yuantao; Bian, Dezhi; Ma, Chunyan; Yu, Chunxiao; Feng, Mei; Wang, Furong; Gao, Ling; Zhao, Jia-jun

    2012-01-01

    Highlights: ► Diosgenin induces apoptosis in IGF-1-treated thyrocytes through two caspase pathways. ► Diosgenin inhibits FLIP and activates caspase-8 in FAS related-pathway. ► Diosgenin increases ROS, regulates the ratio of Bax/Bcl-2 in mitochondrial pathway. -- Abstract: Insulin-like growth factor-1 (IGF-1) is a growth factor of the thyroid that has been shown in our previous study to possess proliferative and antiapoptotic effects in FRTL-5 cell lines through the upregulation of cyclin D and Fas-associated death domain-like interleukin-1-converting enzyme (FLICE)-inhibitory protein (FLIP). Diosgenin, a natural steroid sapogenin from plants, has been shown to induce apoptosis in many cell lines, with the exception of thyroid cells. In this report, we investigated the apoptotic effect and mechanism of diosgenin in IGF-1-stimulated primary human thyrocytes. Primary human thyrocytes were preincubated with or without IGF-1 for 24 h and subsequently exposed to varying concentrations of diosgenin for different times. We found that diosgenin induced apoptosis in human thyrocytes pretreated with IGF-1 in a dose-dependent manner through the activation of caspase cascades. Moreover, diosgenin inhibited FLIP and activated caspase-8 in the FAS-related apoptotic pathway. Diosgenin increased the production of ROS, regulated the balance of Bax and Bcl-2 and cleaved caspase-9 in the mitochondrial apoptotic pathway. These results indicate that diosgenin induces apoptosis in IGF-1-stimulated primary human thyrocytes through two caspase-dependent pathways.

  2. Multiple successional pathways in human-modified tropical landscapes

    NARCIS (Netherlands)

    Arroyo-Rodríguez, Víctor; Melo, Felipe P.L.; Martínez-Ramos, Miguel; Bongers, Frans; Chazdon, Robin L.; Meave, Jorge A.; Norden, Natalia; Santos, Bráulio A.; Leal, Inara R.; Tabarelli, Marcelo

    2017-01-01

    Old-growth tropical forests are being extensively deforested and fragmented worldwide. Yet forest recovery through succession has led to an expansion of secondary forests in human-modified tropical landscapes (HMTLs). Secondary forests thus emerge as a potential repository for tropical

  3. Neuroanatomical pathways for thyroid hormone feedback in the human hypothalamus

    NARCIS (Netherlands)

    Alkemade, Anneke; Friesema, Edith C.; Unmehopa, Unga A.; Fabriek, Babs O.; Kuiper, George G.; Leonard, Jack L.; Wiersinga, Wilmar M.; Swaab, Dick F.; Visser, Theo J.; Fliers, Eric

    2005-01-01

    Context: Recent findings point to an increasing number of hypothalamic proteins involved in the central regulation of thyroid hormone feedback. The functional neuroanatomy of these proteins in the human hypothalamus is largely unknown at present. Objective: The aim of this study was to report the

  4. The Aggregate Exposure Pathway (AEP): A conceptual framework for advancing exposure science research and transforming risk assessment

    Science.gov (United States)

    Recent advances in analytical methods, biomarker discovery, cell-based assay development, computational tools, sensor/monitor, and omics technology have enabled new streams of exposure and toxicity data to be generated at higher volumes and speed. These new data offer the opport...

  5. Using Information on Exposure to Characterizing Risks to Human Health from Concurrent Exposures to Multiple Chemicals

    NARCIS (Netherlands)

    Mr Price, PSP

    2012-01-01

    This thesis explores the concept of using exposure information to understand, organize, and manage the risks associated with cumulative exposures to chemicals (exposures to multiple chemicals from multiple sources). The issue of cumulative exposures was identified in more than 30 years ago, but in

  6. Estimating the human exposure to chemical substances and radiation. Definition report

    International Nuclear Information System (INIS)

    Vermeire, T.G.; Van Veen, M.P.

    1995-06-01

    This report aims at boosting the human exposure assessment activities of the RIVM with regard to chemical substances and radiation. It is the result of thorough discussions with RIVM-experts. The report starts with an overview of past developments in the area of human exposure assessment at the RIVM and continues describing recent projects. Major developments outside the Institute are also discussed. An attempt is made to harmonize definitions which are relevant for exposure assessment, i.e. definitions on exposure, intake, uptake and dose. Important gaps in the human exposure assessment work at the RIVM are identified, leading to proposals for future work. 2 figs., 31 refs., 3 appendices

  7. The recovery of the human organism after radiation exposure

    International Nuclear Information System (INIS)

    Gerber, G.B.

    1976-01-01

    The repair of radiation damage in the human organism is reviewed. A distinction is made between the single repair steps, first the molecular repair of sublethal damage during the periods of 30 min to 2 h and several days to months, second the substitution of the whole cells during a period of reproduction which is specific for the kind and persistence of the cells. One example is the radiosensitive stem cell with a reproduction rate of 40% and a redoublication time of 10 d at 100 rads and the very low reproduction rate of 1% with redoublication time of 7 d after a dose of 400 rads. 5 rads seems to be acceptable for systems with recovery and repeated exposure, single doses normally should not exceed 25 rads, not 100 rads/d for to save human life, and not a total dose of 500 rads. About 20% of irradiation damage is not repaired and leads to late effects, for example the induction of tumors, the shortening of life span and an increase in embryonic mortality. The author recommends the acceptance of a radiation dose leading to 20 additional cases of leucemia in the whole population of Germany and an increase of tumor frequency of 1%. The shortening of life span should not exceed 0,5%. The equivalent residual dose (ERD) can be calculated by the following equation: ERD = last effective dose minus 5 rads x number of days. (AJ) [de

  8. Toward a Psychology of Human Agency: Pathways and Reflections.

    Science.gov (United States)

    Bandura, Albert

    2018-03-01

    Social cognitive theory is founded on an agentic perspective. This article reviews the core features of human agency and the individual, proxy, and collective forms in which it is exercised. Agency operates through a triadic codetermination process of causation. Knowledge from this line of theorizing is widely applied to effect individual and social change, including worldwide applications that address some of the most urgent global problems.

  9. Arachidonic Acid Metabolism Pathway Is Not Only Dominant in Metabolic Modulation but Associated With Phenotypic Variation After Acute Hypoxia Exposure

    Directory of Open Access Journals (Sweden)

    Chang Liu

    2018-03-01

    Full Text Available Background: The modulation of arachidonic acid (AA metabolism pathway is identified in metabolic alterations after hypoxia exposure, but its biological function is controversial. We aimed at integrating plasma metabolomic and transcriptomic approaches to systematically explore the roles of the AA metabolism pathway in response to acute hypoxia using an acute mountain sickness (AMS model.Methods: Blood samples were obtained from 53 enrolled subjects before and after exposure to high altitude. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and RNA sequencing were separately performed for metabolomic and transcriptomic profiling, respectively. Influential modules comprising essential metabolites and genes were identified by weighted gene co-expression network analysis (WGCNA after integrating metabolic information with phenotypic and transcriptomic datasets, respectively.Results: Enrolled subjects exhibited diverse response manners to hypoxia. Combined with obviously altered heart rate, oxygen saturation, hemoglobin, and Lake Louise Score (LLS, metabolomic profiling detected that 36 metabolites were highly related to clinical features in hypoxia responses, out of which 27 were upregulated and nine were downregulated, and could be mapped to AA metabolism pathway significantly. Integrated analysis of metabolomic and transcriptomic data revealed that these dominant molecules showed remarkable association with genes in gas transport incapacitation and disorders of hemoglobin metabolism pathways, such as ALAS2, HEMGN. After detailed description of AA metabolism pathway, we found that the molecules of 15-d-PGJ2, PGA2, PGE2, 12-O-3-OH-LTB4, LTD4, LTE4 were significantly up-regulated after hypoxia stimuli, and increased in those with poor response manner to hypoxia particularly. Further analysis in another cohort showed that genes in AA metabolism pathway such as PTGES, PTGS1, GGT1, TBAS1 et al. were excessively

  10. Quantifying human exposure to air pollution--moving from static monitoring to spatio-temporally resolved personal exposure assessment.

    Science.gov (United States)

    Steinle, Susanne; Reis, Stefan; Sabel, Clive Eric

    2013-01-15

    Quantifying human exposure to air pollutants is a challenging task. Ambient concentrations of air pollutants at potentially harmful levels are ubiquitous in urban areas and subject to high spatial and temporal variability. At the same time, every individual has unique activity-patterns. Exposure results from multifaceted relationships and interactions between environmental and human systems, adding complexity to the assessment process. Traditionally, approaches to quantify human exposure have relied on pollutant concentrations from fixed air quality network sites and static population distributions. New developments in sensor technology now enable us to monitor personal exposure to air pollutants directly while people are moving through their activity spaces and varying concentration fields. The literature review on which this paper is based on reflects recent developments in the assessment of human exposure to air pollution. This includes the discussion of methodologies and concepts, and the elaboration of approaches and study designs applied in the field. We identify shortcomings of current approaches and discuss future research needs. We close by proposing a novel conceptual model for the integrated assessment of human exposure to air pollutants taking into account latest technological capabilities and contextual information. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Silencing of the pentose phosphate pathway genes influences DNA replication in human fibroblasts.

    Science.gov (United States)

    Fornalewicz, Karolina; Wieczorek, Aneta; Węgrzyn, Grzegorz; Łyżeń, Robert

    2017-11-30

    Previous reports and our recently published data indicated that some enzymes of glycolysis and the tricarboxylic acid cycle can affect the genome replication process by changing either the efficiency or timing of DNA synthesis in human normal cells. Both these pathways are connected with the pentose phosphate pathway (PPP pathway). The PPP pathway supports cell growth by generating energy and precursors for nucleotides and amino acids. Therefore, we asked if silencing of genes coding for enzymes involved in the pentose phosphate pathway may also affect the control of DNA replication in human fibroblasts. Particular genes coding for PPP pathway enzymes were partially silenced with specific siRNAs. Such cells remained viable. We found that silencing of the H6PD, PRPS1, RPE genes caused less efficient enterance to the S phase and decrease in efficiency of DNA synthesis. On the other hand, in cells treated with siRNA against G6PD, RBKS and TALDO genes, the fraction of cells entering the S phase was increased. However, only in the case of G6PD and TALDO, the ratio of BrdU incorporation to DNA was significantly changed. The presented results together with our previously published studies illustrate the complexity of the influence of genes coding for central carbon metabolism on the control of DNA replication in human fibroblasts, and indicate which of them are especially important in this process. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Human exposure to piroplasms in Central and Northern Italy

    Directory of Open Access Journals (Sweden)

    Simona Gabrielli

    2014-03-01

    Full Text Available A serosurvey has been conducted in Northern and Central Italy to investigate the presence in humans of antibodies against zoonotic Babesia and Theileria species. The study focused on a total of 432 volunteers, of which 290 were persistently exposed to tick bites because of their jobs (forester employees, livestock keepers, veterinary practitioners, farmers and hunters and 142 resident in the same area less frequently exposed. An indirect fluorescent antibody test (IFAT for humans was used to detect antibodies to Babesia microti, IFAT tests for veterinary use were modified to detect reactivity to Babesia bovis, Babesia canis and Theileria equi. A laboratory-derived ELISA was employed to detect antibodies to Babesia divergens. Both reactive and 10 negative sera were analysed against plasmodial antigens to evaluate possible aspecificity. A high reactivity to piroplasm antigens was found, showing significant difference between the sera of the two groups of volunteers (24% vs 7.0%; p<0.001. No cross-reactivity was observed, while each professional group showed reactivity that would fit with the professional risk exposure. In particular, a high reactivity to B. microti and B. divergens antigens was observed in foresters and hunters (32% and 12%, respectively. This is the first report on the human seroreactivity to piroplasms in Italy; it also provides additional epidemiological information on these tick-borne zoonoses in Europe. Our findings suggest the possible occurrence of piroplasm infections in Italy and alert physicians to consider these otherwise neglected parasitic diseases when dealing with any febrile illness, especially in subjects exposed to tick bites.

  13. DNA-Related Pathways Defective in Human Premature Aging

    OpenAIRE

    Bohr, Vilhelm A.

    2002-01-01

    One of the major issues in studies on aging is the choice of biological model system. The human premature aging disorders represent excellent model systems for the study of the normal aging process, which occurs at a much earlier stage in life in these individuals than in normals. The patients with premature aging also get the age associated diseases at an early stage in life, and thus age associated disease can be studied as well. It is thus of great interest to understand the molecular path...

  14. 3'-5' RNA degradation pathways in human cells

    DEFF Research Database (Denmark)

    Lubas, Michal Szymon

    RNA synthesis and degradation are key steps in the regulation of gene expression in all living organisms. During the course of his PhD studies, Michal Lubas centred his research on the nuclear and cytoplasmic RNA turnover of both noncoding and coding RNAs in human cells. His proteomic studies...... revealed the interaction network of the main 3'-5' RNA degradation machinery – the RNA exosome complex. One of the key findings was the identification and characterisation of the Nuclear Exosome Targeting (NEXT) complex, important for nuclear functions of the exosome. Michal Lubas also studied the role...

  15. Identification of Biomarkers of Exposure to FTOHs and PAPs in Humans Using a Targeted and Nontargeted Analysis Approach.

    Science.gov (United States)

    Dagnino, Sonia; Strynar, Mark J; McMahen, Rebecca L; Lau, Christopher S; Ball, Carol; Garantziotis, Stavros; Webster, Thomas F; McClean, Michael D; Lindstrom, Andrew B

    2016-09-20

    Although historic perfluorinated compounds are currently under scrutiny and growing regulatory control in the world, little is known about human exposure to other polyfluorinated compounds presently in use. Fluorotelomer alcohols (FTOHs) and polyfluoroalkyl phosphate esters (PAPs) are known to degrade to terminal perfluorinated acids and toxic reactive intermediates through metabolic pathways. Therefore, it is important to characterize their human exposure by the identification of unique biomarkers. With the use of liquid chromatography-mass spectrometry-time-of-flight analysis (LC-MS-TOF), we developed a workflow for the identification of metabolites for the 8:2 FTOH and 8:2 diPAP. Analysis of serum and urine of dosed rats indicated the 8:2 FTOH-sulfate and the 8:2 diPAP as potential biomarkers. These compounds, as well as 25 other fluorinated compounds and metabolites, were analyzed in human serum and urine samples from the general population (n = 100) and office workers (n = 30). The 8:2 FTOH-sulfate was measured for the first time in human samples in 5 to 10% of the serum samples, ranging from 50 to 80 pg/mL. The 8:2 diPAP was measured in 58% of the samples, ranging from 100 to 800 pg/mL. This study indicates the FTOH-sulfate conjugate as a biomarker of exposure to FTOHs and PAPs in humans.

  16. Biomarkers of exposure in environment-wide association studies - Opportunities to decode the exposome using human biomonitoring data.

    Science.gov (United States)

    Steckling, Nadine; Gotti, Alberto; Bose-O'Reilly, Stephan; Chapizanis, Dimitris; Costopoulou, Danae; De Vocht, Frank; Garí, Mercè; Grimalt, Joan O; Heath, Ester; Hiscock, Rosemary; Jagodic, Marta; Karakitsios, Spyros P; Kedikoglou, Kleopatra; Kosjek, Tina; Leondiadis, Leondios; Maggos, Thomas; Mazej, Darja; Polańska, Kinga; Povey, Andrew; Rovira, Joaquim; Schoierer, Julia; Schuhmacher, Marta; Špirić, Zdravko; Stajnko, Anja; Stierum, Rob; Tratnik, Janja Snoj; Vassiliadou, Irene; Annesi-Maesano, Isabella; Horvat, Milena; Sarigiannis, Dimosthenis A

    2018-07-01

    The European Union's 7th Framework Programme (EU's FP7) project HEALS - Health and Environment-wide Associations based on Large Population Surveys - aims a refinement of the methodology to elucidate the human exposome. Human biomonitoring (HBM) provides a valuable tool for understanding the magnitude of human exposure from all pathways and sources. However, availability of specific biomarkers of exposure (BoE) is limited. The objective was to summarize the availability of BoEs for a broad range of environmental stressors and exposure determinants and corresponding reference and exposure limit values and biomonitoring equivalents useful for unraveling the exposome using the framework of environment-wide association studies (EWAS). In a face-to-face group discussion, scope, content, and structure of the HEALS deliverable "Guidelines for appropriate BoE selection for EWAS studies" were determined. An expert-driven, distributed, narrative review process involving around 30 individuals of the HEALS consortium made it possible to include extensive information targeted towards the specific characteristics of various environmental stressors and exposure determinants. From the resulting 265 page report, targeted information about BoE, corresponding reference values (e.g., 95th percentile or measures of central tendency), exposure limit values (e.g., the German HBM I and II values) and biomonitoring equivalents (BEs) were summarized and updated. 64 individual biological, chemical, physical, psychological and social environmental stressors or exposure determinants were included to fulfil the requirements of EWAS. The list of available BoEs is extensive with a number of 135; however, 12 of the stressors and exposure determinants considered do not leave any measurable specific substance in accessible body specimens. Opportunities to estimate the internal exposure stressors not (yet) detectable in human specimens were discussed. Data about internal exposures are useful to decode

  17. Developmental fluoride exposure influenced rat's splenic development and cell cycle via disruption of the ERK signal pathway.

    Science.gov (United States)

    Ma, Yanqin; Zhang, Kankan; Ren, Fengjun; Wang, Jundong

    2017-11-01

    Excessive fluoride exposure has been reported to cause damage to spleen. Neonatal period is characterized by rapid proliferation and differentiation of lymphocyte in the spleen. Children may be more sensitive to the toxicity of fluoride compared to the adults. The aim of this study was to investigate the effects of postnatal exposure (from neonatal period to early adulthood) to fluoride on the development of spleen on a regular basis and the underlying signal pathway. Results showed a marked decrease in spleen weight index and altered morphology in the spleen of fluoride-treated group on PND-84, which reflected fluoride inhibition of the development of spleen. Fluoride exposure induced cell cycle arrest of splenocytes and decreased the mRNA expression of IL-2, which indicated compromised baseline lymphocyte proliferation in the spleen. Time course research from 3-wk-of-age until 12-wk-of-age showed an adverse and cumulative impact of fluoride on the development of spleen. In view of the key role of MAPK/ERK pathway in lymphocyte development, Raf-1/MEK-1/ERK-2/c-fos mRNA expression and ERK/p-ERK protein expression were detected. Results showed despite a transitory increase in mRNA expression from PND-42 to PND-63 in fluoride-treated group, the expression of these genes on PND-84 decreased significantly compared with PND-42 or PND-63. NaF significantly inhibited the phosphorylation of ERK protein on PND-84. Taken together, these results emphasized the vital role of ERK pathway in the interfered development of spleen induced by a high dose of fluoride exposure in rats. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Gene expression analysis in human osteoblasts exposed to dexamethasone identifies altered developmental pathways as putative drivers of osteoporosis

    Directory of Open Access Journals (Sweden)

    Sadlier Denise M

    2007-02-01

    Full Text Available Abstract Background Osteoporosis, a disease of decreased bone mineral density represents a significant and growing burden in the western world. Aging population structure and therapeutic use of glucocorticoids have contributed in no small way to the increase in the incidence of this disease. Despite substantial investigative efforts over the last number of years the exact molecular mechanism underpinning the initiation and progression of osteoporosis remain to be elucidated. This has meant that no significant advances in therapeutic strategies have emerged, with joint replacement surgery being the mainstay of treatment. Methods In this study we have used an integrated genomics profiling and computational biology based strategy to identify the key osteoblast genes and gene clusters whose expression is altered in response to dexamethasone exposure. Primary human osteoblasts were exposed to dexamethasone in vitro and microarray based transcriptome profiling completed. Results These studies identified approximately 500 osteoblast genes whose expression was altered. Functional characterization of the transcriptome identified developmental networks as being reactivated with 106 development associated genes found to be differentially regulated. Pathway reconstruction revealed coordinate alteration of members of the WNT signaling pathway, including frizzled-2, frizzled-7, DKK1 and WNT5B, whose differential expression in this setting was confirmed by real time PCR. Conclusion The WNT pathway is a key regulator of skeletogenesis as well as differentiation of bone cells. Reactivation of this pathway may lead to altered osteoblast activity resulting in decreased bone mineral density, the pathological hallmark of osteoporosis. The data herein lend weight to the hypothesis that alterations in developmental pathways drive the initiation and progression of osteoporosis.

  19. Candidate gene biodosimeters of mice and human exposure to ionizing radiation by quantitative reverse transcription polymerase chain reaction

    Directory of Open Access Journals (Sweden)

    Hamed Rezaeejam

    2015-01-01

    Full Text Available Understanding of cellular responses to ionizing radiation (IR is essential for the development of predictive markers useful for assessing human exposure. Biological markers of exposure to IR in human populations are of great interest for assessing normal tissue injury in radiation oncology and for biodosimetry in nuclear incidents and accidental radiation exposures. Traditional radiation exposure biomarkers based on cytogenetic assays (biodosimetry, are time-consuming and do not provide results fast enough and requires highly trained personnel for scoring. Hence, the development of rapid biodosimetry methods is one of the highest priorities. Exposure of cells to IR activates multiple signal transduction pathways, which result in complex alterations in gene-expression. Real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR has become the benchmark for the detection and quantification of RNA targets and is being utilized increasingly in monitoring the specific genes with more accurately and sensitively. This review evaluates the RT-qPCR as a biodosimetry method and we investigated the papers from 2000 up to now, which identified the genes-expression related the DNA repair, cell cycle checkpoint, and apoptosis induced by ionization radiation in peripheral blood and determined as biodosimeters. In conclusion, it could be say that RT-qPCR technique for determining the specific genes as biodosimeters could be a fully quantitative reliable and sensitive method. Furthermore, the results of the current review will help the researchers to recognize the most expressed genes induced by ionization radiation.

  20. Relationship between Human Aging Muscle and Oxidative System Pathway

    Directory of Open Access Journals (Sweden)

    Enrico Doria

    2012-01-01

    Full Text Available Ageing is a complex process that in muscle is usually associated with a decrease in mass, strength, and velocity of contraction. One of the most striking effects of ageing on muscle is known as sarcopenia. This inevitable biological process is characterized by a general decline in the physiological and biochemical functions of the major systems. At the cellular level, aging is caused by a progressive decline in mitochondrial function that results in the accumulation of reactive oxygen species (ROS generated by the addition of a single electron to the oxygen molecule. The aging process is characterized by an imbalance between an increase in the production of reactive oxygen species in the organism and the antioxidant defences as a whole. The goal of this review is to examine the results of existing studies on oxidative stress in aging human skeletal muscles, taking into account different physiological factors (sex, fibre composition, muscle type, and function.

  1. The Health Impacts of Energy Policy Pathways in Ulaanbaatar, Mongolia: A Total Exposure Assessment

    Science.gov (United States)

    Hill, L. A.; Damdinsuren, Y.; Olkhanud, P. B.; Smith, K. R.; Turner, J. R.; Edwards, R.; Odsuren, M.; Ochir, C.

    2015-12-01

    Ulaanbaatar is home to nearly half of Mongolia's 2.8 million residents. The city's rapid growth, frigid winters, valley topography, and reliance on coal-fired stoves have led to some of the worst winter pollution levels in the world. To better understand this issue, we modeled integrated PM2.5exposures and related health impacts for various city-wide heating policies through 2024. This assessment is one of the first to employ a total exposure approach and results of the 2014 Comparative Risk Assessments of the Global Burden of Disease Project (CRA/GBD) in a policy-relevant energy study. Emissions related to heating, traffic, and power generation were considered under Business as Usual, Moderate Improvement, and Max Improvement scenarios. Calibrated outdoor models were combined with indoor models, local infiltration and time activity estimates, and demographic projections to estimate PM2.5exposures in 2014 and 2024. Indoor exposures were assigned by heating type, home type, and smoking status; outdoor exposures were assigned through geocoding. Population average annual exposures were calculated and applied to local disease rates and integrated exposure-response curves (2014 CRA/GBD) to arrive at annual projections of premature deaths and DALYs. We estimate 2014 annual average exposures at 68 μg/m3, dictated almost exclusively by indoor winter exposures. Under current trends, annual exposures increase 10% to 75 μg/m3 in 2024. This is in stark contrast to the moderate and max improvement scenarios, which lead to 2024 annual exposures that are 31%, and 68% lower, respectively. Under the Moderate scenario, 2024 per capita annual DALY and death burdens drop 26% and 22%, respectively, from 2014 levels. Under the Max scenario, 2024 per capita annual DALY and death burdens drop 71% and 66%, respectively, from 2014. SHS becomes a major contributor as emissions from other sectors decrease. Reductions are dominated by cardiovascular and lower respiratory diseases in children.

  2. ASSESSING HUMAN EXPOSURE TO GRASS POLLEN IN DENMARK

    DEFF Research Database (Denmark)

    Peel, Robert George; Hertel, Ole; Herbert, Rob

    Objectives: Exposure to pollen is typically assessed using data collected at fixed roof-top monitoring stations, which give a general picture of airborne pollen concentrations over a wide region. Actual exposure levels can be obtained through personal exposure monitoring. This is typically done u...

  3. AGE-RELATED TOXICITY PATHWAY ANALYSIS IN BROWN NORWAY RAT BRAIN FOLLOWING ACUTE TOLUENE EXPOSURE

    Science.gov (United States)

    The influence of aging on susceptibility to environmental exposures is poorly understood. To investigate-the contribution of different life stages on response to toxicants, we examined the effects of an acute exposure to the volatile organic compound, toluene (0.0 or 1.0 g/kg), i...

  4. A changing climate: impacts on human exposures to O3 using an integrated modeling methodology

    Science.gov (United States)

    Predicting the impacts of changing climate on human exposure to air pollution requires future scenarios that account for changes in ambient pollutant concentrations, population sizes and distributions, and housing stocks. An integrated methodology to model changes in human exposu...

  5. Pathways Regulating Spheroid Formation of Human Follicular Thyroid Cancer Cells under Simulated Microgravity Conditions: A Genetic Approach

    Directory of Open Access Journals (Sweden)

    Stefan Riwaldt

    2016-04-01

    Full Text Available Microgravity induces three-dimensional (3D growth in numerous cell types. Despite substantial efforts to clarify the underlying mechanisms for spheroid formation, the precise molecular pathways are still not known. The principal aim of this paper is to compare static 1g-control cells with spheroid forming (MCS and spheroid non-forming (AD thyroid cancer cells cultured in the same flask under simulated microgravity conditions. We investigated the morphology and gene expression patterns in human follicular thyroid cancer cells (UCLA RO82-W-1 cell line after a 24 h-exposure on the Random Positioning Machine (RPM and focused on 3D growth signaling processes. After 24 h, spheroid formation was observed in RPM-cultures together with alterations in the F-actin cytoskeleton. qPCR indicated more changes in gene expression in MCS than in AD cells. Of the 24 genes analyzed VEGFA, VEGFD, MSN, and MMP3 were upregulated in MCS compared to 1g-controls, whereas ACTB, ACTA2, KRT8, TUBB, EZR, RDX, PRKCA, CAV1, MMP9, PAI1, CTGF, MCP1 were downregulated. A pathway analysis revealed that the upregulated genes code for proteins, which promote 3D growth (angiogenesis and prevent excessive accumulation of extracellular proteins, while genes coding for structural proteins are downregulated. Pathways regulating the strength/rigidity of cytoskeletal proteins, the amount of extracellular proteins, and 3D growth may be involved in MCS formation.

  6. Repeated allergen exposure reduce early phase airway response and leukotriene release despite upregulation of 5-lipoxygenase pathways

    Directory of Open Access Journals (Sweden)

    Cui Zhi-Hua

    2012-03-01

    Full Text Available Abstract Background Allergen induced early phase airway response and airway plasma exudation are predominantly mediated by inflammatory mast cell mediators including histamine, cysteinyl leukotrienes (cysLTs and thromboxane A2 (TXA2. The aim of the present study was to evaluate whether repeated allergen exposure affects early phase airway response to allergen challenge. Methods A trimellitic anhydride (TMA sensitized guinea pig model was used to investigate the effects of low dose repeated allergen exposure on cholinergic airway responsiveness, early phase airway response and plasma exudation, as well as local airway production of mast cell derived cysteinyl leukotrienes and thromboxane B2 (TXB2 after allergen challenge. Results Repeated low dose allergen exposure increased cholinergic airway responsiveness. In contrast, early phase airway response and plasma exudation in response to a high-dose allergen challenge were strongly attenuated after repeated low dose allergen exposure. Inhibition of the airway response was unspecific to exposed allergen and independent of histamine receptor blocking. Furthermore, a significant reduction of cysteinyl leukotrienes and TXB2 was found in the airways of animals repeatedly exposed to a low dose allergen. However, in vitro stimulation of airway tissue from animals repeatedly exposed to a low dose allergen with arachidonic acid and calcium ionophore (A23187 induced production of cysteinyl leukotrienes and TXB2, suggesting enhanced activity of 5-lipoxygenase and cyclooxygenase pathways. Conclusions The inhibition of the early phase airway response, cysteinyl leukotriene and TXB2 production after repeated allergen exposure may result from unresponsive effector cells.

  7. Cytotoxicity and inflammation in human alveolar epithelial cells following exposure to occupational levels of gold and silver nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Bachand, George D., E-mail: gdbacha@sandia.gov [Sandia National Laboratories, Center for Integrated Nanotechnologies (United States); Allen, Amy [Sandia National Laboratories, Department of Analytical Science (United States); Bachand, Marlene [Sandia National Laboratories, Department of Nanobiology (United States); Achyuthan, Komandoor E. [Sandia National Laboratories, Department of Biosensors and Nanomaterials (United States); Seagrave, Jean Clare [Lovelace Respiratory Research Institute, Applied Life Science and Toxicology Division (United States); Brozik, Susan M. [Sandia National Laboratories, Department of Biosensors and Nanomaterials (United States)

    2012-10-15

    While inhalation represents one of the most likely routes of exposure, the toxicity and response of nanoparticles at concentrations expected from such an exposure are not well understood. Here we characterized the in vitro response of human A549 adenocarcinomic alveolar epithelial cells following exposure to gold (AuNP) and silver (AgNP) nanoparticles at levels approximating an occupational exposure. Changes in neither oxidative stress nor cytotoxicity were significantly affected by exposure to AgNPs and AuNPs, regardless of NP type (Ag vs. Au), concentration, surface ligand (citrate or tannic acid), or size. An inflammatory response was, however, observed in response to 20 nm AgNPs and 20 nm AuNPs, where significant differences in the release of interleukin (IL)-8 but not IL-6 were observed. Additional data demonstrated that increased IL-8 secretion was strongly dependent on both nanoparticle size and concentration. Overall these data suggest that, while not acutely toxic, occupational exposure to AuNPs and AgNPs may trigger a significant inflammatory response in alveolar epithelium. Moreover, the differential responses in IL-8 and IL-6 secretion suggest that NPs may induce a response pathway that is distinct from those commonly elicited by allergens and pathogens.

  8. Axon guidance pathways served as common targets for human speech/language evolution and related disorders.

    Science.gov (United States)

    Lei, Huimeng; Yan, Zhangming; Sun, Xiaohong; Zhang, Yue; Wang, Jianhong; Ma, Caihong; Xu, Qunyuan; Wang, Rui; Jarvis, Erich D; Sun, Zhirong

    2017-11-01

    Human and several nonhuman species share the rare ability of modifying acoustic and/or syntactic features of sounds produced, i.e. vocal learning, which is the important neurobiological and behavioral substrate of human speech/language. This convergent trait was suggested to be associated with significant genomic convergence and best manifested at the ROBO-SLIT axon guidance pathway. Here we verified the significance of such genomic convergence and assessed its functional relevance to human speech/language using human genetic variation data. In normal human populations, we found the affected amino acid sites were well fixed and accompanied with significantly more associated protein-coding SNPs in the same genes than the rest genes. Diseased individuals with speech/language disorders have significant more low frequency protein coding SNPs but they preferentially occurred outside the affected genes. Such patients' SNPs were enriched in several functional categories including two axon guidance pathways (mediated by netrin and semaphorin) that interact with ROBO-SLITs. Four of the six patients have homozygous missense SNPs on PRAME gene family, one youngest gene family in human lineage, which possibly acts upon retinoic acid receptor signaling, similarly as FOXP2, to modulate axon guidance. Taken together, we suggest the axon guidance pathways (e.g. ROBO-SLIT, PRAME gene family) served as common targets for human speech/language evolution and related disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. The development of a methodology to assess population doses from multiple sources and exposure pathways of radioactivity

    International Nuclear Information System (INIS)

    Hancox, J.; Stansby, S.; Thorne, M.

    2002-01-01

    The Environment Agency (EA) has new duties in accordance with the Basic Safety Standards Directive under which it is required to ensure that doses to individuals received from exposure to anthropogenic sources of radioactivity are within defined limits. In order to assess compliance with these requirements, the EA needs to assess the doses to members of the most highly exposed population groups ('critical' groups) from all relevant potential sources of anthropogenic radioactivity and all relevant potential exposure pathways to such radioactivity. The EA has identified a need to develop a methodology for the retrospective assessment of effective doses from multiple sources of radioactive materials and exposure pathways associated with those sources. Under contract to the EA, AEA Technology has undertaken the development of a suitable methodology as part of EA R and D Project P3-070. The methodology developed under this research project has been designed to support the EA in meeting its obligations under the Euratom Basic Safety Standards Directive and is consistent with UK and international approaches to radiation dosimetry and radiological protection. The development and trial application of the methodology is described in this report

  10. Integrated Assessment of Shallow-Aquifer Vulnerability to Multiple Contaminants and Drinking-Water Exposure Pathways in Holliston, Massachusetts

    Directory of Open Access Journals (Sweden)

    Birgit Claus Henn

    2017-12-01

    Full Text Available Half of U.S. drinking water comes from aquifers, and very shallow ones (<20 feet to water table are especially vulnerable to anthropogenic contamination. We present the case of Holliston, a Boston, Massachusetts suburb that draws its drinking water from very shallow aquifers, and where metals and solvents have been reported in groundwater. Community concerns focus on water discolored by naturally occurring manganese (Mn, despite reports stating regulatory aesthetic compliance. Epidemiologic studies suggest Mn is a potentially toxic element (PTE for children exposed by the drinking-water pathway at levels near the regulatory aesthetic level. We designed an integrated, community-based project: five sites were profiled for contaminant releases; service areas for wells were modeled; and the capture zone for one vulnerable well was estimated. Manganese, mercury, and trichloroethylene are among 20 contaminants of interest. Findings show that past and/or current exposures to multiple contaminants in drinking water are plausible, satisfying the criteria for complete exposure pathways. This case questions the adequacy of aquifer protection and monitoring regulations, and highlights the need for integrated assessment of multiple contaminants, associated exposures and health risks. It posits that community-researcher partnerships are essential for understanding and solving complex problems.

  11. Environmental, health, and safety decision making for naturally occurring radioactive materials in producing operations using pathway exposure analysis

    International Nuclear Information System (INIS)

    Miller, H.T.; Cook, L.M.

    1991-01-01

    A number of health and safety issues have arisen because of the occurrence of NORM, naturally occurring radioactive materials of the 226 radium and 228 radium decay chains, in production operations. Issues such as risk to workers or the general public, disposal of contaminated production fluids, disposal of NORM removed in cleaning equipment and tubing, and procedures to follow in well rework, equipment decontamination and other types of maintenance must be addressed. This paper describes the application of a procedural aid to decision making known as pathway exposure analysis to these issues. The procedure examines the radiation exposure of individuals and population groups by calculating the dose from each exposure route and pathway. The sum of these is used to calculate the overall risk to the individual or the group. This method can be used to examine management and procedural options to identify the option offering the smallest risk. Risk information coupled with cost estimates then permits management maximum utilization of its available resources

  12. Different routes, same pathways: Molecular mechanisms under silver ion and nanoparticle exposures in the soil sentinel Eisenia fetida

    International Nuclear Information System (INIS)

    Novo, Marta; Lahive, Elma; Díez-Ortiz, María; Matzke, Marianne; Morgan, Andrew J.; Spurgeon, David J.; Svendsen, Claus; Kille, Peter

    2015-01-01

    Use of nanotechnology products is increasing; with silver (Ag) nanoparticles particularly widely used. A key uncertainty surrounding the risk assessment of AgNPs is whether their effects are driven through the same mechanism of action that underlies the toxic effects of Ag ions. We present the first full transcriptome study of the effects of Ag ions and NPs in an ecotoxicological model soil invertebrate, the earthworm Eisenia fetida. Gene expression analyses indicated similar mechanisms for both silver forms with toxicity being exerted through pathways related to ribosome function, sugar and protein metabolism, molecular stress, disruption of energy production and histones. The main difference seen between Ag ions and NPs was associated with potential toxicokinetic effects related to cellular internalisation and communication, with pathways related to endocytosis and cilia being significantly enriched. These results point to a common final toxicodynamic response, but initial internalisation driven by different exposure routes and toxicokinetic mechanisms. - Highlights: • Molecular effects underlying Ag ions and NPs exposure were studied in Eisenia fetida. • Full transcriptomic study of a genetically characterised lineage. • NPs and ions presented a similar toxicodynamic response. • Internalisation of the two Ag forms by different toxicokinetic mechanisms. - Transcriptomic analyses after exposure of earthworms to silver NPs or ions showed a final common toxicodynamic response, but internalisation by different toxicokinetic mechanisms

  13. BAD-mediated apoptotic pathway is associated with human cancer development.

    Science.gov (United States)

    Stickles, Xiaomang B; Marchion, Douglas C; Bicaku, Elona; Al Sawah, Entidhar; Abbasi, Forough; Xiong, Yin; Bou Zgheib, Nadim; Boac, Bernadette M; Orr, Brian C; Judson, Patricia L; Berry, Amy; Hakam, Ardeshir; Wenham, Robert M; Apte, Sachin M; Berglund, Anders E; Lancaster, Johnathan M

    2015-04-01

    The malignant transformation of normal cells is caused in part by aberrant gene expression disrupting the regulation of cell proliferation, apoptosis, senescence and DNA repair. Evidence suggests that the Bcl-2 antagonist of cell death (BAD)-mediated apoptotic pathway influences cancer chemoresistance. In the present study, we explored the role of the BAD-mediated apoptotic pathway in the development and progression of cancer. Using principal component analysis to derive a numeric score representing pathway expression, we evaluated clinico-genomic datasets (n=427) from corresponding normal, pre-invasive and invasive cancers of different types, such as ovarian, endometrial, breast and colon cancers in order to determine the associations between the BAD-mediated apoptotic pathway and cancer development. Immunofluorescence was used to compare the expression levels of phosphorylated BAD [pBAD (serine-112, -136 and -155)] in immortalized normal and invasive ovarian, colon and breast cancer cells. The expression of the BAD-mediated apoptotic pathway phosphatase, PP2C, was evaluated by RT-qPCR in the normal and ovarian cancer tissue samples. The growth-promoting effects of pBAD protein levels in the immortalized normal and cancer cells were assessed using siRNA depletion experiments with MTS assays. The expression of the BAD-mediated apoptotic pathway was associated with the development and/or progression of ovarian (n=106, pBAD-mediated apoptotic pathway is thus associated with the development of human cancers likely influenced by the protein levels of pBAD.

  14. Oxygen entry through multiple pathways in T-state human hemoglobin.

    Science.gov (United States)

    Takayanagi, Masayoshi; Kurisaki, Ikuo; Nagaoka, Masataka

    2013-05-23

    The heme oxygen (O2) binding site of human hemoglobin (HbA) is buried in the interior of the protein, and there is a debate over the O2 entry pathways from solvent to the binding site. As a first step to understand HbA O2 binding process at the atomic level, we detected all significant multiple O2 entry pathways from solvent to the binding site in the α and β subunits of the T-state tetramer HbA by utilizing ensemble molecular dynamics (MD) simulation. By executing 128 independent 8 ns MD trajectories in O2-rich aqueous solvent, we simulated the O2 entry processes and obtained 141 and 425 O2 entry events in the α and β subunits of HbA, respectively. We developed the intrinsic pathway identification by clustering method to achieve a persuasive visualization of the multiple entry pathways including both the shapes and relative importance of each pathway. The rate constants of O2 entry estimated from the MD simulations correspond to the experimentally observed values, suggesting that O2 ligands enter the binding site through multiple pathways. The obtained multiple pathway map can be utilized for future detailed analysis of HbA O2 binding process.

  15. Multiple intracellular signaling pathways orchestrate adipocytic differentiation of human bone marrow stromal stem cells

    DEFF Research Database (Denmark)

    Ayesh Hafez Ali, Dalia; Abuelreich, Sarah; Alkeraishan, Nora

    2018-01-01

    during adipocyte differentiation of human bone marrow stromal (mesenchymal) stem cells (hMSCs) and identified 2,589 up-regulated and 2,583 down-regulated mRNA transcripts. Pathway analysis on the up-regulated gene list untraveled enrichment in multiple signaling pathways including insulin receptor......Bone marrow adipocyte formation plays a role in bone homeostasis and whole body energy metabolism. However, the transcriptional landscape and signaling pathways associated with adipocyte lineage commitment and maturation are not fully delineated. Thus, we performed global gene expression profiling...... signaling, focal Adhesion, metapathway biotransformation, a number of metabolic pathways e.g. selenium metabolism, Benzo(a)pyrene metabolism, fatty acid, triacylglycerol, ketone body metabolism, tryptophan metabolism, and catalytic cycle of mammalian flavin-containing monooxygenase (FMOs). On the other hand...

  16. Oocyte exposure to ZnO nanoparticles inhibits early embryonic development through the γ-H2AX and NF-κB signaling pathways.

    Science.gov (United States)

    Liu, Jing; Zhao, Yong; Ge, Wei; Zhang, Pengfei; Liu, Xinqi; Zhang, Weidong; Hao, Yanan; Yu, Shuai; Li, Lan; Chu, Meiqiang; Min, Lingjiang; Zhang, Hongfu; Shen, Wei

    2017-06-27

    The impacts of zinc oxide nanoparticles on embryonic development following oocyte stage exposure are unknown and the underlying mechanisms are sparsely understood. In the current investigation, intact nanoparticles were detected in ovarian tissue in vivo and cultured cells in vitro under zinc oxide nanoparticles treatment. Zinc oxide nanoparticles exposure during the oocyte stage inhibited embryonic development. Notably, in vitro culture data closely matched in vivo embryonic data, in that the impairments caused by Zinc oxide nanoparticles treatment passed through cell generations; and both gamma-H2AX and NF-kappaB pathways were involved in zinc oxide nanoparticles caused embryo-toxicity. Copper oxide and silicon dioxide nanoparticles have been used to confirm that particles are important for the toxicity of zinc oxide nanoparticles. The toxic effects of zinc oxide nanoparticles emanate from both intact nanoparticles and Zn2+. Our investigation along with others suggests that zinc oxide nanoparticles are toxic to the female reproductive system [ovaries (oocytes)] and subsequently embryo-toxic and that precaution should be taken regarding human exposure to their everyday use.

  17. HExpoChem: a systems biology resource to explore human exposure to chemicals

    DEFF Research Database (Denmark)

    Taboureau, Olivier; Jacobsen, Ulrik Plesner; Kalhauge, Christian Gram

    2013-01-01

    of computational biology approaches are needed to assess the health risks of chemical exposure. Here we present HExpoChem, a tool based on environmental chemicals and their bioactivities on human proteins with the objective of aiding the qualitative exploration of human exposure to chemicals. The chemical...

  18. Exposure to perfluorinated compounds and human semen quality in Arctic and European populations

    DEFF Research Database (Denmark)

    Toft, G; Jönsson, B A G; Lindh, C H

    2012-01-01

    Perfluorinated compounds (PFCs) have been suspected to adversely affect human reproductive health. The aim of this study was to investigate the associations between PFC exposure and male semen quality.......Perfluorinated compounds (PFCs) have been suspected to adversely affect human reproductive health. The aim of this study was to investigate the associations between PFC exposure and male semen quality....

  19. Bipolar cell gap junctions serve major signaling pathways in the human retina.

    Science.gov (United States)

    Kántor, Orsolya; Varga, Alexandra; Nitschke, Roland; Naumann, Angela; Énzsöly, Anna; Lukáts, Ákos; Szabó, Arnold; Németh, János; Völgyi, Béla

    2017-08-01

    Connexin36 (Cx36) constituent gap junctions (GJ) throughout the brain connect neurons into functional syncytia. In the retina they underlie the transmission, averaging and correlation of signals prior conveying visual information to the brain. This is the first study that describes retinal bipolar cell (BC) GJs in the human inner retina, whose function is enigmatic even in the examined animal models. Furthermore, a number of unique features (e.g. fovea, trichromacy, midget system) necessitate a reexamination of the animal model results in the human retina. Well-preserved postmortem human samples of this study are allowed to identify Cx36 expressing BCs neurochemically. Results reveal that both rod and cone pathway interneurons display strong Cx36 expression. Rod BC inputs to AII amacrine cells (AC) appear in juxtaposition to AII GJs, thus suggesting a strategic AII cell targeting by rod BCs. Cone BCs serving midget, parasol or koniocellular signaling pathways display a wealth of Cx36 expression to form homologously coupled arrays. In addition, they also establish heterologous GJ contacts to serve an exchange of information between parallel signaling streams. Interestingly, a prominent Cx36 expression was exhibited by midget system BCs that appear to maintain intimate contacts with bistratified BCs serving other pathways. These findings suggest that BC GJs in parallel signaling streams serve both an intra- and inter-pathway exchange of signals in the human retina.

  20. Revealing the cerebello-ponto-hypothalamic pathway in the human brain.

    Science.gov (United States)

    Kamali, Arash; Karbasian, Niloofar; Rabiei, Pejman; Cano, Andres; Riascos, Roy F; Tandon, Nitin; Arevalo, Octavio; Ocasio, Laura; Younes, Kyan; Khayat-Khoei, Mahsa; Mirbagheri, Saeedeh; Hasan, Khader M

    2018-04-16

    The cerebellum is shown to be involved in some limbic functions of the human brain such as emotion and affect. The major connection of the cerebellum with the limbic system is known to be through the cerebello-hypothalamic pathways. The consensus is that the projections from the cerebellar nuclei to the limbic system, and particularly the hypothalamus, or from the hypothalamus to the cerebellar nuclei, are through multisynaptic pathways in the bulbar reticular formation. The detailed anatomy of the pathways responsible for mediating these responses, however, is yet to be determined. Diffusion tensor imaging may be helpful in better visualizing the surgical anatomy of the cerebello-ponto-hypothalamic (CPH) pathway. This study aimed to investigate the utility of high-spatial-resolution diffusion tensor tractography for mapping the trajectory of the CPH tract in the human brain. Fifteen healthy adults were studied. We delineated, for the first time, the detailed trajectory of the CPH tract of the human brain in fifteen normal adult subjects using high-spatial-resolution diffusion tensor tractography. We further revealed the close relationship of the CPH tract with the optic tract, temporo-pontine tract, amygdalofugal tract and the fornix in the human brain. Copyright © 2018. Published by Elsevier B.V.

  1. Deregulation of the RB pathway in human testicular germ cell tumours

    DEFF Research Database (Denmark)

    Bartkova, Jirina; Lukas, Claudia; Sørensen, Claus S

    2003-01-01

    Deregulation of the RB pathway is shared by most human malignancies. Components upstream of the retinoblastoma tumour suppressor (pRB), namely the INK4 family of cyclin-dependent kinase (CDK) inhibitors, the D-type cyclins, their partner kinases CDK4/CDK6, and pRB as their critical substrate...

  2. HPIminer: A text mining system for building and visualizing human protein interaction networks and pathways.

    Science.gov (United States)

    Subramani, Suresh; Kalpana, Raja; Monickaraj, Pankaj Moses; Natarajan, Jeyakumar

    2015-04-01

    The knowledge on protein-protein interactions (PPI) and their related pathways are equally important to understand the biological functions of the living cell. Such information on human proteins is highly desirable to understand the mechanism of several diseases such as cancer, diabetes, and Alzheimer's disease. Because much of that information is buried in biomedical literature, an automated text mining system for visualizing human PPI and pathways is highly desirable. In this paper, we present HPIminer, a text mining system for visualizing human protein interactions and pathways from biomedical literature. HPIminer extracts human PPI information and PPI pairs from biomedical literature, and visualize their associated interactions, networks and pathways using two curated databases HPRD and KEGG. To our knowledge, HPIminer is the first system to build interaction networks from literature as well as curated databases. Further, the new interactions mined only from literature and not reported earlier in databases are highlighted as new. A comparative study with other similar tools shows that the resultant network is more informative and provides additional information on interacting proteins and their associated networks. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Connectivity Map-based discovery of parbendazole reveals targetable human osteogenic pathway

    NARCIS (Netherlands)

    A.M. Brum (Andrea M.); J. van de Peppel (Jeroen); C.S. Van Der Leije (Cindy S.); M. Schreuders-Koedam (M.); H.J.M. Eijken (Marco); B.C.J. van der Eerden (Bram); J.P.T.M. van Leeuwen (Hans)

    2015-01-01

    textabstractOsteoporosis is a common skeletal disorder characterized by low bone mass leading to increased bone fragility and fracture susceptibility. In this study, we have identified pathways that stimulate differentiation of bone forming osteoblasts from human mesenchymal stromal cells (hMSCs).

  4. Linking Social Change and Developmental Change: Shifting Pathways of Human Development

    Science.gov (United States)

    Greenfield, Patricia M.

    2009-01-01

    P. M. Greenfield's new theory of social change and human development aims to show how changing sociodemographic ecologies alter cultural values and learning environments and thereby shift developmental pathways. Worldwide sociodemographic trends include movement from rural residence, informal education at home, subsistence economy, and…

  5. Diosgenin induces apoptosis in IGF-1-stimulated human thyrocytes through two caspase-dependent pathways

    Energy Technology Data Exchange (ETDEWEB)

    Mu, Shumin [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Hospital Affiliated to Shandong Traditional Chinese Medicine University, Jinan 250011 (China); Institute of Endocrinology, Shandong Academy of Clinical Medicine, Jinan 250021 (China); Tian, Xingsong; Ruan, Yongwei [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Liu, Yuantao [The Second Hospital of Shandong University, Jinan 250033 (China); Bian, Dezhi [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Jining Medical College, Jining 272013 (China); Ma, Chunyan [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Yu, Chunxiao [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Institute of Endocrinology, Shandong Academy of Clinical Medicine, Jinan 250021 (China); Feng, Mei [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Wang, Furong [Shandong University of Traditional Chinese Medicine, Jinan 250011 (China); Gao, Ling [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Institute of Endocrinology, Shandong Academy of Clinical Medicine, Jinan 250021 (China); Zhao, Jia-jun, E-mail: jjzhao@medmail.com.cn [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Institute of Endocrinology, Shandong Academy of Clinical Medicine, Jinan 250021 (China)

    2012-02-10

    Highlights: Black-Right-Pointing-Pointer Diosgenin induces apoptosis in IGF-1-treated thyrocytes through two caspase pathways. Black-Right-Pointing-Pointer Diosgenin inhibits FLIP and activates caspase-8 in FAS related-pathway. Black-Right-Pointing-Pointer Diosgenin increases ROS, regulates the ratio of Bax/Bcl-2 in mitochondrial pathway. -- Abstract: Insulin-like growth factor-1 (IGF-1) is a growth factor of the thyroid that has been shown in our previous study to possess proliferative and antiapoptotic effects in FRTL-5 cell lines through the upregulation of cyclin D and Fas-associated death domain-like interleukin-1-converting enzyme (FLICE)-inhibitory protein (FLIP). Diosgenin, a natural steroid sapogenin from plants, has been shown to induce apoptosis in many cell lines, with the exception of thyroid cells. In this report, we investigated the apoptotic effect and mechanism of diosgenin in IGF-1-stimulated primary human thyrocytes. Primary human thyrocytes were preincubated with or without IGF-1 for 24 h and subsequently exposed to varying concentrations of diosgenin for different times. We found that diosgenin induced apoptosis in human thyrocytes pretreated with IGF-1 in a dose-dependent manner through the activation of caspase cascades. Moreover, diosgenin inhibited FLIP and activated caspase-8 in the FAS-related apoptotic pathway. Diosgenin increased the production of ROS, regulated the balance of Bax and Bcl-2 and cleaved caspase-9 in the mitochondrial apoptotic pathway. These results indicate that diosgenin induces apoptosis in IGF-1-stimulated primary human thyrocytes through two caspase-dependent pathways.

  6. Quantitative analysis of untreated human nails for monitoring human exposure to heavy metals

    International Nuclear Information System (INIS)

    Sera, Koichiro; Futatsugawa, Shouji; Murao, Satoshi; Clemente, E.

    2002-01-01

    In order to address global environmental issues, a standard-free method developed by ourselves has been successfully applied to various kinds of bio-samples. Especially, a method for untreated hairs has been applied in many polluted areas to study human exposure to toxic elements. In addition to hair, nail is expected to give us valuable information about human exposure to toxic elements. However, the analysis requires relatively large amounts of samples and laborious sample preparation techniques which necessitate internal standards. In this work, we have developed a quantitative method for untreated human-nail analysis based on the standard-free method. It requires neither large amounts of nails nor complicated target preparation procedure. Furthermore, it is perfectly free from any ambiguity in target preparation such as volatilization of certain elements and contamination of the sample during chemical ashing. The optimum conditions of irradiating nail samples are established, and accuracy and reproducibility of the present method are confirmed. It is found that ultrasonic washing in distilled water is effective for many nail samples preventing the loss of elements from the sample. It is also found that elemental concentration in nails strongly depends on their sampling positions. (author)

  7. Cytogenetic adaptive response induced by pre-exposure in human lymphocytes and marrow cells of mice

    International Nuclear Information System (INIS)

    Zhang Lianzhen; Deng Zhicheng

    1993-01-01

    The cytogenetic adaptive response induced by pre-exposure in human lymphocytes and marrow cells of mice were studied. The results of this study showed that human lymphocytes in vitro and mouse marrow cells in vivo can become adapted to low-level irradiation from 3 H-TdR or exposure to a low dose of X-or γ-irradiation, so that they become less sensitive to the chromosomal damage effects of subsequent exposures. (4 tabs.)

  8. Assessing quality and completeness of human transcriptional regulatory pathways on a genome-wide scale

    Directory of Open Access Journals (Sweden)

    Aifantis Iannis

    2011-02-01

    Full Text Available Abstract Background Pathway databases are becoming increasingly important and almost omnipresent in most types of biological and translational research. However, little is known about the quality and completeness of pathways stored in these databases. The present study conducts a comprehensive assessment of transcriptional regulatory pathways in humans for seven well-studied transcription factors: MYC, NOTCH1, BCL6, TP53, AR, STAT1, and RELA. The employed benchmarking methodology first involves integrating genome-wide binding with functional gene expression data to derive direct targets of transcription factors. Then the lists of experimentally obtained direct targets are compared with relevant lists of transcriptional targets from 10 commonly used pathway databases. Results The results of this study show that for the majority of pathway databases, the overlap between experimentally obtained target genes and targets reported in transcriptional regulatory pathway databases is surprisingly small and often is not statistically significant. The only exception is MetaCore pathway database which yields statistically significant intersection with experimental results in 84% cases. Additionally, we suggest that the lists of experimentally derived direct targets obtained in this study can be used to reveal new biological insight in transcriptional regulation and suggest novel putative therapeutic targets in cancer. Conclusions Our study opens a debate on validity of using many popular pathway databases to obtain transcriptional regulatory targets. We conclude that the choice of pathway databases should be informed by solid scientific evidence and rigorous empirical evaluation. Reviewers This article was reviewed by Prof. Wing Hung Wong, Dr. Thiago Motta Venancio (nominated by Dr. L Aravind, and Prof. Geoff J McLachlan.

  9. Methamphetamine exposure triggers apoptosis and autophagy in neuronal cells by activating the C/EBPβ-related signaling pathway.

    Science.gov (United States)

    Xu, Xiang; Huang, Enping; Luo, Baoying; Cai, Dunpeng; Zhao, Xu; Luo, Qin; Jin, Yili; Chen, Ling; Wang, Qi; Liu, Chao; Lin, Zhoumeng; Xie, Wei-Bing; Wang, Huijun

    2018-06-25

    Methamphetamine (Meth) is a widely abused psychoactive drug that primarily damages the nervous system, notably causing dopaminergic neuronal apoptosis. CCAAT-enhancer binding protein (C/EBPβ) is a transcription factor and an important regulator of cell apoptosis and autophagy. Insulin-like growth factor binding protein (IGFBP5) is a proapoptotic factor that mediates Meth-induced neuronal apoptosis, and Trib3 (tribbles pseudokinase 3) is an endoplasmic reticulum (ER) stress-inducible gene involved in autophagic cell death through the mammalian target of rapamycin (mTOR) signaling pathway. To test the hypothesis that C/EBPβ is involved in Meth-induced IGFBP5-mediated neuronal apoptosis and Trib3-mediated neuronal autophagy, we measured the protein expression of C/EBPβ after Meth exposure and evaluated the effects of silencing C/EBPβ, IGFBP5, or Trib3 on Meth-induced apoptosis and autophagy in neuronal cells and in the rat striatum after intrastriatal Meth injection. We found that, at relatively high doses, Meth exposure increased C/EBPβ protein expression, which was accompanied by increased neuronal apoptosis and autophagy; triggered the IGFBP5-mediated, p53-up-regulated modulator of apoptosis (PUMA)-related mitochondrial apoptotic signaling pathway; and stimulated the Trib3-mediated ER stress signaling pathway through the Akt-mTOR signaling axis. We also found that autophagy is an early response to Meth-induced stress upstream of apoptosis and plays a detrimental role in Meth-induced neuronal cell death. These results suggest that Meth exposure induces C/EBPβ expression, which plays an essential role in the neuronal apoptosis and autophagy induced by relatively high doses of Meth; however, relatively low concentrations of Meth did not change the expression of C/EBPβ in vitro. Further studies are needed to elucidate the role of C/EBPβ in low-dose Meth-induced neurotoxicity.-Xu, X., Huang, E., Luo, B., Cai, D., Zhao, X., Luo, Q., Jin, Y., Chen, L., Wang, Q

  10. Human Rights Engagement and Exposure: New Scales to Challenge Social Work Education

    Science.gov (United States)

    McPherson, Jane; Abell, Neil

    2012-01-01

    Objectives: Advancing human rights is a core competency of U.S. social work education; yet, human rights attitudes and behaviors have never been measured in the social work literature. Thus, this article describes the development and initial validation of two scales, Human Rights Engagement in Social Work (HRESW) and Human Rights Exposure in…

  11. Chlorine Isotopic Composition of Perchlorate in Human Urine as a Means of Distinguishing Among Natural and Synthetic Exposure Sources

    Science.gov (United States)

    Poghosyan, Armen; Morel-Espinosa, Maria; Valentín-Blasini, Liza; Blount, Benjamin C.; Ferreccio, Catterina; Steinmaus, Craig M.; Sturchio, Neil C.

    2015-01-01

    Perchlorate (ClO4−) is a ubiquitous environmental contaminant with high human exposure potential; it has both natural and man-made sources in the environment. Natural perchlorate forms in the atmosphere from where it deposits onto the surface of Earth, whereas synthetic perchlorate is manufactured as an oxidant for industrial, aerospace, and military applications. Perchlorate exposure can potentially cause adverse health effects in humans by interfering with the production of thyroid hormones through competitively blocking iodide uptake. To control and reduce perchlorate exposure, the contributions of different sources of perchlorate exposure need to be quantified. Thus, we demonstrate a novel approach for determining the contribution of different perchlorate exposure sources by quantifying stable and radioactive chlorine isotopes of perchlorate extracted from composite urine samples from two distinct populations: one in Atlanta, USA and one in Taltal, Chile (Atacama region). Urinary perchlorate from the Atlanta region resembles indigenous natural perchlorate from the southwestern USA [δ37Cl = +4.1 ± 1.0 ‰; 36Cl/Cl = 1811 (± 136) × 10−15], and urinary perchlorate from the Taltal, Chile region is similar to natural perchlorate in nitrate salt deposits from the Atacama Desert of northern Chile [δ37Cl = −11.0 ± 1.0 ‰; 36Cl/Cl = 254 (± 40) × 10−15]. Neither urinary perchlorate resembled the isotopic pattern found in synthetic perchlorate. These results indicate that natural perchlorate of regional provenance is the dominant exposure source for the two sample populations, and that chlorine isotope ratios provide a robust tool for elucidating perchlorate exposure pathways. PMID:25805252

  12. Reconstruction of human exposure to heavy metals using synchrotron radiation microbeams in prehistoric and modern humans

    International Nuclear Information System (INIS)

    Koizumi, Akio; Azechi, Miki; Shirasawa, Koyo

    2009-01-01

    Teeth can serve as records of environmental exposure to heavy metals during their formation. We applied a new technology - synchrotron radiation microbeams (SRXRF) - for analysis of heavy metals in human permanent teeth in modern and historical samples. Each tooth was cut in half. A longitudinal section 200 μm in thickness was subjected to the determination of the heavy metal content by SRXRF or conventional analytical methods (ICP-MS analysis or reduction-aeration atomic absorption spectrometry). The relative concentrations of Pb, Hg, Cu and Zn measured by SRXRF were translated in concentrations (in g of heavy metal/g of enamel) using calibration curves by the two analytical methods. Concentrations in teeth in the modern females (n=5) were 1.2±0.5 μg/g (n=5) for Pb; 1.7±0.2 ng/g for Hg; 0.9±1.1 μg/g for Cu; 150±24.6 μg/g for Zn. The levels of Pb were highest in the teeth samples obtained from the humans of the Edo era (1603-1868 AD) (0.5-4.0 μg/g, n=4). No trend was observed in this study in the Hg content in teeth during 3,000 years. The concentrations of Cu were highest in teeth of two medieval craftsmen (57.0 and 220 μg/g). The levels of Zn were higher in modern subjects (P<0.05) than those in the Jomon (∼1000 BC) to Edo periods [113.2±27.4 (μg/g, n=11)]. Reconstruction of developmental exposure history to lead in a famous court painter of the Edo period (18th century) revealed high levels of Pb (7.1-22.0 μg/g) in his childhood. SRXRF is useful a method for reconstructing human exposures in very long trends. (author)

  13. A margin-of-exposure approach to assessment of noncancer risks of dioxins based on human exposure and response data.

    Science.gov (United States)

    Aylward, Lesa L; Goodman, Julie E; Charnley, Gail; Rhomberg, Lorenz R

    2008-10-01

    Risk assessment of human environmental exposure to polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/PCDFs) and other dioxin-like compounds is complicated by several factors, including limitations in measuring intakes because of the low concentrations of these compounds in foods and the environment and interspecies differences in pharmacokinetics and responses. We examined the feasibility of relying directly on human studies of exposure and potential responses to PCDD/PCDFs and related compounds in terms of measured lipid-adjusted concentrations to assess margin of exposure (MOE) in a quantitative, benchmark dose (BMD)-based framework using representative exposure and selected response data sets. We characterize estimated central tendency and upper-bound general U.S. population lipid-adjusted concentrations of PCDD/PCDFs from the 1970s and early 2000s based on available data sets. Estimates of benchmark concentrations for three example responses of interest (induction of cytochrome P4501A2 activity, dental anomalies, and neonatal thyroid hormone alterations) were derived based on selected human studies. The exposure data sets indicate that current serum lipid concentrations in young adults are approximately 6- to 7-fold lower than 1970s-era concentrations. Estimated MOEs for each end point based on current serum lipid concentrations range from 100 for dental anomalies-approximately 6-fold greater than would have existed during the 1970s. Human studies of dioxin exposure and outcomes can be used in a BMD framework for quantitative assessments of MOE. Incomplete exposure characterization can complicate the use of such studies in a BMD framework.

  14. Effects of PM2.5 exposure on the Notch signaling pathway and immune imbalance in chronic obstructive pulmonary disease

    International Nuclear Information System (INIS)

    Gu, Xing-yu; Chu, Xu; Zeng, Xiao-Li; Bao, Hai-Rong; Liu, Xiao-Ju

    2017-01-01

    Chronic Obstructive Pulmonary Disease (COPD) is associated with T lymphocytes subset (Th1/Th2, Th17/Treg) imbalance. Notch signaling pathway plays a key role in the development of the adaptive immunity. The immune disorder induced by fine particulate matter (PM2.5) is related to COPD. The aim of this study was to investigate the mechanism by which PM2.5 influences the Notch signaling pathway leading to worsening immune disorder and accelerating COPD development. A COPD mouse model was established by cigarette smoke exposure. PM2.5 exposure was performed by aerosol inhalation. γ-secretase inhibitor (GSI) was given using intraperitoneal injection. Splenic T lymphocytes were purified using a density gradient centrifugation method. CD4 + T lymphocyte subsets (Th1/Th2, Th17/Treg) were detected using flow cytometry. mRNA and proteins of Notch1/2/3/4, Hes1/5, and Hey1 were detected using RT-PCR and Western blot. Serum INF-γ, IL-4, IL-17 and IL-10 concentrations were measured using ELISA. The results showed that in COPD mice Th1% and Th17%, Th1/Th2 and Th17/Treg were increased, and the levels of mRNA and protein in Notch1/2/3/4, Hes1/5, and Hey1 and serum INF-γ and IL-17 concentrations were significantly increased, and Th2%, Treg%, and serum IL-4 and IL-10 concentrations were significantly decreased. COPD Mice have Th1- and Th17-mediated immune disorder, and the Notch signaling pathway is in an overactivated state. PM2.5 promotes the overactivation of the Notch signaling pathway and aggravates the immune disorder of COPD. GSI can partially inhibit the activation of the Notch signaling pathway and alleviate the immune disorder under basal state and the immune disorder of COPD caused by PM2.5. This result suggests that PM2.5 is involved in the immune disorder of mice with COPD by affecting the Notch signaling pathway and that PM2.5 aggravates COPD. - Highlights: • The COPD mice demonstrated Th1 and Th17 dominant immune imbalance. • PM2.5 aggravates the Th1/Th2 and Th

  15. Domain altering SNPs in the human proteome and their impact on signaling pathways.

    Directory of Open Access Journals (Sweden)

    Yichuan Liu

    Full Text Available Single nucleotide polymorphisms (SNPs constitute an important mode of genetic variations observed in the human genome. A small fraction of SNPs, about four thousand out of the ten million, has been associated with genetic disorders and complex diseases. The present study focuses on SNPs that fall on protein domains, 3D structures that facilitate connectivity of proteins in cell signaling and metabolic pathways. We scanned the human proteome using the PROSITE web tool and identified proteins with SNP containing domains. We showed that SNPs that fall on protein domains are highly statistically enriched among SNPs linked to hereditary disorders and complex diseases. Proteins whose domains are dramatically altered by the presence of an SNP are even more likely to be present among proteins linked to hereditary disorders. Proteins with domain-altering SNPs comprise highly connected nodes in cellular pathways such as the focal adhesion, the axon guidance pathway and the autoimmune disease pathways. Statistical enrichment of domain/motif signatures in interacting protein pairs indicates extensive loss of connectivity of cell signaling pathways due to domain-altering SNPs, potentially leading to hereditary disorders.

  16. Diesel exhaust particles increase IL-1β-induced human β-defensin expression via NF-κB-mediated pathway in human lung epithelial cells

    Directory of Open Access Journals (Sweden)

    Lee Chun

    2006-05-01

    Full Text Available Abstract Background Human β-defensin (hBD-2, antimicrobial peptide primarily induced in epithelial cells, is a key factor in the innate immune response of the respiratory tract. Several studies showed increased defensin levels in both inflammatory lung diseases, such as cystic fibrosis, diffuse panbronchiolitis, idiopathic pulmonary fibrosis and acute respiratory distress syndrome, and infectious diseases. Recently, epidemiologic studies have demonstrated acute and serious adverse effects of particulate air pollution on respiratory health, especially in people with pre-existing inflammatory lung disease. To elucidate the effect of diesel exhaust particles (DEP on pulmonary innate immune response, we investigated the hBD-2 and interleukin-8 (IL-8 expression to DEP exposure in interleukin-1 beta (IL-1β-stimulated A549 cells. Results IL-1β markedly up-regulated the hBD-2 promoter activity, and the subsequent DEP exposure increased dose-dependently the expression of hBD-2 and inflammatory cytokine IL-8 at the transcriptional level. In addition, DEP further induced the NF-κB activation in IL-1β-stimulated A549 cells more rapidly than in unstimulated control cells, which was showed by nuclear translocation of p65 NF-κB and degradation of IκB-α. The experiment using two NF-κB inhibitors, PDTC and MG132, confirmed that this increase of hBD-2 expression following DEP exposure was regulated through NF-κB-mediated pathway. Conclusion These results demonstrated that DEP exposure increases the expression of antimicrobial peptide and inflammatory cytokine at the transcriptional level in IL-1β-primed A549 epithelial cells and suggested that the increase is mediated at least partially through NF-κB activation. Therefore, DEP exposure may contribute to enhance the airway-responsiveness especially on the patients suffering from chronic respiratory disease.

  17. Physiological responses to exposure to carbon dioxide and human bioeffluents

    DEFF Research Database (Denmark)

    Zhang, Xiaojing; Wargocki, Pawel; Lian, Zhiwei

    2015-01-01

    Present paper describes physiological responses as a result of exposures to CO2 (between 500 ppm to 3,000 ppm) with and without bioeffluents. Twenty-five subjects participated. They were exposed in the climate chamber for 255 minutes in groups of five at a time. During exposure, they performed di...

  18. Risk of human exposure to polycyclic aromatic hydrocarbons: A case study in Beijing, China

    International Nuclear Information System (INIS)

    Yu, Yanxin; Li, Qi; Wang, Hui; Wang, Bin; Wang, Xilong; Ren, Aiguo; Tao, Shu

    2015-01-01

    Polycyclic aromatic hydrocarbons (PAHs) can cause adverse effects on human health. The relative contributions of their two major intake routes (diet and inhalation) to population PAH exposure are still unclear. We modeled the contributions of diet and inhalation to the overall PAH exposure of the population of Beijing in China, and assessed their human incremental lifetime cancer risks (ILCR) using a Mont Carlo simulation approach. The results showed that diet accounted for about 85% of low-molecular-weight PAH (L-PAH) exposure, while inhalation accounted for approximately 57% of high-molecular-weight PAH (H-PAH) exposure of the Beijing population. Meat and cereals were the main contributors to dietary PAH exposure. Both gaseous- and particulate-phase PAHs contributed to L-PAH exposure through inhalation, whereas exposure to H-PAHs was mostly from the particulate-phase. To reduce the cancer incidence of the Beijing population, more attention should be given to inhaled particulate-phase PAHs with considerable carcinogenic potential. - Highlights: • We modeled the contributions of diet and inhalation to population PAH exposure. • Diet contributed 85% of population exposure to low molecular-weight PAHs. • Inhalation contributed 57% of population exposure to high molecular-weight PAHs. • The PAH exposure level with body-weight adjustment decreased with age increasing. • The population cancer risk of PAH exposure is lower than the serious risk level. - The exposure of the Beijing population to carcinogenic polycyclic aromatic hydrocarbons was mainly from inhaled particulate matter

  19. Pulmonary Inflammatory Responses to Acute Meteorite Dust Exposures - Implications for Human Space Exploration

    Science.gov (United States)

    Harrington, A. D.; McCubbin, F. M.; Vander Kaaden, K. E.; Kaur, J.; Smirnov, A.; Galdanes, K.; Schoonen, M. A. A.; Chen, L. C.; Tsirka, S. E.; Gordon, T.

    2018-01-01

    New initiatives to send humans to Mars within the next few decades are illustrative of the resurgence of interest in space travel. However, as with all exploration, there are risks. The Human Research Roadmap developed by NASA identifies the Risk of Adverse Health and Performance Effects of Celestial Dust Exposure as an area of concern. Extended human exploration will further increase the probability of inadvertent and repeated exposures to celestial dusts.

  20. The U.S. National Health and Nutrition Examination Survey and human exposure to environmental chemicals.

    Science.gov (United States)

    Calafat, Antonia M

    2012-02-01

    Researchers are increasingly interested in using human biomonitoring - the measurement of chemicals, their metabolites or specific reaction products in biological specimens/body fluids - for investigating exposure to environmental chemicals. General population human biomonitoring programs are useful for investigating human exposure to environmental chemicals and an important tool for integrating environment and health. One of these programs, the National Health and Nutrition Examination Survey (NHANES), conducted in the United States is designed to collect data on the health and nutritional status of the noninstitutionalized, civilian U.S. population. NHANES includes a physical examination, collecting a detailed medical history, and collecting biological specimens (i.e., blood and urine). These biological specimens can be used to assess exposure to environmental chemicals. NHANES human biomonitoring data can be used to establish reference ranges for selected chemicals, provide exposure data for risk assessment, and monitor exposure trends. Published by Elsevier GmbH.

  1. TOXICITY PATHWAY ANALYSIS IN AGING BROWN NORWAY RAT BRAIN FOLLOWING ACUTE TOLUENE EXPOSURE

    Science.gov (United States)

    The influence of aging on susceptibility to environmental stressors is poorly understood. To investigate the contribution of different life stages on response to toxicants, we examined the effects of acute exposure by oral gavage of the volatile organic solvent toluene (0.00, 0.3...

  2. Cold Exposure Induces Proliferation of Mature Brown Adipocyte in a ß3-Adrenergic Receptor-Mediated Pathway.

    Science.gov (United States)

    Fukano, Keigo; Okamatsu-Ogura, Yuko; Tsubota, Ayumi; Nio-Kobayashi, Junko; Kimura, Kazuhiro

    2016-01-01

    Hyperplasia of brown adipose tissue (BAT) is a fundamental mechanism for adaptation to survive in the cold environment in rodents. To determine which cell types comprising BAT contribute to tissue hyperplasia, immunohistochemical analysis using a proliferative marker Ki67 was performed on the BAT from 6-week-old C57BL/6J mice housed at 23°C (control) or 10°C (cold) for 5 days. Interestingly, in the control group, the cell proliferative marker Ki67 was detected in the nuclei of uncoupling protein 1-positive mature brown adipocytes (7.2% ± 0.4% of brown adipocyte), as well as in the non-adipocyte stromal-vascular (SV) cells (19.6% ± 2.3% of SV cells), which include preadiopocytes. The percentage of Ki67-positive brown adipocytes increased to 25.6% ± 1.8% at Day 1 after cold exposure and was significantly higher than the non-cold acclimated control until Day 5 (21.8% ± 1.7%). On the other hand, the percentage of Ki67-positive SV cells gradually increased by a cold exposure and peaked to 42.1% ± 8.3% at Day 5. Injection of a ß3-adrenergic receptor (ß3-AR) agonist for continuous 5 days increased the number of Ki67-positive brown adipocytes even at Day 1 but not that of SV cells. In addition, the ß3-AR antagonist, but not ß1-AR antagonist, attenuated the cold exposure-induced increase in the number of Ki67-positive brown adipocytes. These results suggest that mature brown adipocytes proliferate immediately after cold exposure in a ß3-AR-mediated pathway. Thus, proliferation of mature brown adipocytes as well as preadipocytes in SV cells may contribute to cold exposure-induced BAT hyperplasia.

  3. Climate change impacts on human exposures to air pollution

    Science.gov (United States)

    This is an abstract for a presentations at the Annual Conference of the International Society on Exposure Science and Environmental Epidemiology. This presentation will serve as an introduction to the symposium.

  4. Campylobacter fetus infections in humans : exposure and disease

    NARCIS (Netherlands)

    Wagenaar, Jaap A; van Bergen, Marcel A P; Blaser, Martin J; Tauxe, Robert V; Newell, Diane G; van Putten, Jos P M

    Campylobacter fetus can cause intestinal illness and, occasionally, severe systemic infections. Infections mainly affect persons at higher risk, including elderly and immunocompromised individuals and those with occupational exposure to infected animals. Outbreaks are infrequent but have provided

  5. Dosimetric significance of cytogenetic examinations in human accidental over exposures

    International Nuclear Information System (INIS)

    Doloy-Biola, M.T.; Lego, R.; Ducatez, G.; Lepetit, J.; Bourguignon, M.

    1975-01-01

    The damage to 13 workers following accidental exposures was assessed from lymphocyte chromosomal aberrations, and the results compared with those supplied by physical dosimetry and the clinical syndromes [fr

  6. Human dermal absorption of chlorinated organophosphate flame retardants; implications for human exposure

    Energy Technology Data Exchange (ETDEWEB)

    Abou-Elwafa Abdallah, Mohamed, E-mail: mae_abdallah@yahoo.co.uk [Division of Environmental Health and Risk Management, School of Geography, Earth, and Environmental Sciences, University of Birmingham, Birmingham B15 2TT (United Kingdom); Department of Analytical Chemistry, Faculty of Pharmacy, Assiut University, 71526 Assiut (Egypt); Pawar, Gopal; Harrad, Stuart [Division of Environmental Health and Risk Management, School of Geography, Earth, and Environmental Sciences, University of Birmingham, Birmingham B15 2TT (United Kingdom)

    2016-01-15

    Tris-2-chloroethyl phosphate (TCEP), tris (1-chloro-2-propyl) phosphate (TCIPP) and tris-1,3-dichloropropyl phosphate (TDCIPP) are organophosphate flame retardants (PFRs) widely applied in a plethora of consumer products despite their carcinogenic potential. Human dermal absorption of these PFRs is investigated for the first time using human ex vivo skin and EPISKIN™ models. Results of human ex vivo skin experiments revealed 28%, 25% and 13% absorption of the applied dose (500 ng/cm{sup 2}, finite dose) of TCEP, TCIPP and TDCIPP, respectively after 24 h exposure. The EPISKIN™ model showed enhanced permeability values (i.e. weaker barrier), that were respectively 16%, 11% and 9% for TCEP, TCIPP and TDCIPP compared to human ex vivo skin. However, this difference was not significant (P > 0.05). Estimated permeability constants (K{sub p}, cm/h) showed a significant negative correlation with log K{sub ow} for the studied contaminants. The effect of hand-washing on dermal absorption of PFRs was investigated. Washing reduced overall dermal absorption, albeit to varying degrees depending on the physicochemical properties of the target PFRs. Moreover, slight variations of the absorbed dose were observed upon changing the dosing solution from acetone to 20% Tween 80 in water, indicating the potential influence of the dose vehicle on the dermal absorption of PFRs. Finally, estimated dermal uptake of the studied PFRs via contact with indoor dust was higher in UK toddlers (median ΣPFRs = 36 ng/kg bw day) than adults (median ΣPFRs = 4 ng/kg bw day). More research is required to fully elucidate the toxicological implications of such exposure. - Highlights: • Human dermal absorption of PFRs was studied using human ex vivo skin and EPISKIN™. • Absorbed fractions of TCEP, TCIPP and TDCIPP were 28%, 25% and 13% of applied dose. • Permeability constants showed significant negative correlation to log K{sub ow} of PFRs. • Skin washing reduced the overall dermal

  7. Human dermal absorption of chlorinated organophosphate flame retardants; implications for human exposure

    International Nuclear Information System (INIS)

    Abou-Elwafa Abdallah, Mohamed; Pawar, Gopal; Harrad, Stuart

    2016-01-01

    Tris-2-chloroethyl phosphate (TCEP), tris (1-chloro-2-propyl) phosphate (TCIPP) and tris-1,3-dichloropropyl phosphate (TDCIPP) are organophosphate flame retardants (PFRs) widely applied in a plethora of consumer products despite their carcinogenic potential. Human dermal absorption of these PFRs is investigated for the first time using human ex vivo skin and EPISKIN™ models. Results of human ex vivo skin experiments revealed 28%, 25% and 13% absorption of the applied dose (500 ng/cm 2 , finite dose) of TCEP, TCIPP and TDCIPP, respectively after 24 h exposure. The EPISKIN™ model showed enhanced permeability values (i.e. weaker barrier), that were respectively 16%, 11% and 9% for TCEP, TCIPP and TDCIPP compared to human ex vivo skin. However, this difference was not significant (P > 0.05). Estimated permeability constants (K p , cm/h) showed a significant negative correlation with log K ow for the studied contaminants. The effect of hand-washing on dermal absorption of PFRs was investigated. Washing reduced overall dermal absorption, albeit to varying degrees depending on the physicochemical properties of the target PFRs. Moreover, slight variations of the absorbed dose were observed upon changing the dosing solution from acetone to 20% Tween 80 in water, indicating the potential influence of the dose vehicle on the dermal absorption of PFRs. Finally, estimated dermal uptake of the studied PFRs via contact with indoor dust was higher in UK toddlers (median ΣPFRs = 36 ng/kg bw day) than adults (median ΣPFRs = 4 ng/kg bw day). More research is required to fully elucidate the toxicological implications of such exposure. - Highlights: • Human dermal absorption of PFRs was studied using human ex vivo skin and EPISKIN™. • Absorbed fractions of TCEP, TCIPP and TDCIPP were 28%, 25% and 13% of applied dose. • Permeability constants showed significant negative correlation to log K ow of PFRs. • Skin washing reduced the overall dermal absorption of target PFRs

  8. Understanding specificity in metabolic pathways-Structural biology of human nucleotide metabolism

    International Nuclear Information System (INIS)

    Welin, Martin; Nordlund, Paer

    2010-01-01

    Interactions are the foundation of life at the molecular level. In the plethora of activities in the cell, the evolution of enzyme specificity requires the balancing of appropriate substrate affinity with a negative selection, in order to minimize interactions with other potential substrates in the cell. To understand the structural basis for enzyme specificity, the comparison of structural and biochemical data between enzymes within pathways using similar substrates and effectors is valuable. Nucleotide metabolism is one of the largest metabolic pathways in the human cell and is of outstanding therapeutic importance since it activates and catabolises nucleoside based anti-proliferative drugs and serves as a direct target for anti-proliferative drugs. In recent years the structural coverage of the enzymes involved in human nucleotide metabolism has been dramatically improved and is approaching completion. An important factor has been the contribution from the Structural Genomics Consortium (SGC) at Karolinska Institutet, which recently has solved 33 novel structures of enzymes and enzyme domains in human nucleotide metabolism pathways and homologs thereof. In this review we will discuss some of the principles for substrate specificity of enzymes in human nucleotide metabolism illustrated by a selected set of enzyme families where a detailed understanding of the structural determinants for specificity is now emerging.

  9. Phosphoproteomic Analysis Identifies Signaling Pathways Regulated by Curcumin in Human Colon Cancer Cells.

    Science.gov (United States)

    Sato, Tatsuhiro; Higuchi, Yutaka; Shibagaki, Yoshio; Hattori, Seisuke

    2017-09-01

    Curcumin, a major polyphenol of the spice turmeric, acts as a potent chemopreventive and chemotherapeutic agent in several cancer types, including colon cancer. Although various proteins have been shown to be affected by curcumin, how curcumin exerts its anticancer activity is not fully understood. Phosphoproteomic analyses were performed using SW480 and SW620 human colon cancer cells to identify curcumin-affected signaling pathways. Curcumin inhibited the growth of the two cell lines in a dose-dependent manner. Thirty-nine curcumin-regulated phosphoproteins were identified, five of which are involved in cancer signaling pathways. Detailed analyses revealed that the mTORC1 and p53 signaling pathways are main targets of curcumin. Our results provide insight into the molecular mechanisms of the anticancer activities of curcumin and future molecular targets for its clinical application. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  10. Development of steroid signaling pathways during primordial follicle formation in the human fetal ovary.

    Science.gov (United States)

    Fowler, Paul A; Anderson, Richard A; Saunders, Philippa T; Kinnell, Hazel; Mason, J Ian; Evans, Dean B; Bhattacharya, Siladitya; Flannigan, Samantha; Franks, Stephen; Monteiro, Ana; O'Shaughnessy, Peter J

    2011-06-01

    Ovarian primordial follicle formation is critical for subsequent human female fertility. It is likely that steroid, and especially estrogen, signaling is required for this process, but details of the pathways involved are currently lacking. The aim was to identify and characterize key members of the steroid-signaling pathway expressed in the second trimester human fetal ovary. We conducted an observational study of the female fetus, quantifying and localizing steroid-signaling pathway members. The study was conducted at the Universities of Aberdeen, Edinburgh, and Glasgow. Ovaries were collected from 43 morphologically normal human female fetuses from women undergoing elective termination of second trimester pregnancies. We measured mRNA transcript levels and immunolocalized key steroidogenic enzymes and steroid receptors, including those encoded by ESR2, AR, and CYP19A1. Levels of mRNA encoding the steroidogenic apparatus and steroid receptors increased across the second trimester. CYP19A1 transcript increased 4.7-fold during this period with intense immunostaining for CYP19A detected in pregranulosa cells around primordial follicles and somatic cells around oocyte nests. ESR2 was localized primarily to germ cells, but androgen receptor was exclusively expressed in somatic cells. CYP17A1 and HSD3B2 were also localized to oocytes, whereas CYP11A1 was detected in oocytes and some pregranulosa cells. The human fetal ovary expresses the machinery to produce and detect multiple steroid signaling pathways, including estrogenic signaling, with the oocyte acting as a key component. This study provides a step-change in our understanding of local dynamics of steroid hormone signaling during the key period of human primordial follicle formation.

  11. Oxytocin Pathway Genes: Evolutionary Ancient System Impacting on Human Affiliation, Sociality, and Psychopathology.

    Science.gov (United States)

    Feldman, Ruth; Monakhov, Mikhail; Pratt, Maayan; Ebstein, Richard P

    2016-02-01

    Oxytocin (OT), a nonapeptide signaling molecule originating from an ancestral peptide, appears in different variants across all vertebrate and several invertebrate species. Throughout animal evolution, neuropeptidergic signaling has been adapted by organisms for regulating response to rapidly changing environments. The family of OT-like molecules affects both peripheral tissues implicated in reproduction, homeostasis, and energy balance, as well as neuromodulation of social behavior, stress regulation, and associative learning in species ranging from nematodes to humans. After describing the OT-signaling pathway, we review research on the three genes most extensively studied in humans: the OT receptor (OXTR), the structural gene for OT (OXT/neurophysin-I), and CD38. Consistent with the notion that sociality should be studied from the perspective of social life at the species level, we address human social functions in relation to OT-pathway genes, including parenting, empathy, and using social relationships to manage stress. We then describe associations between OT-pathway genes with psychopathologies involving social dysfunctions such as autism, depression, or schizophrenia. Human research particularly underscored the involvement of two OXTR single nucleotide polymorphisms (rs53576, rs2254298) with fewer studies focusing on other OXTR (rs7632287, rs1042778, rs2268494, rs2268490), OXT (rs2740210, rs4813627, rs4813625), and CD38 (rs3796863, rs6449197) single nucleotide polymorphisms. Overall, studies provide evidence for the involvement of OT-pathway genes in human social functions but also suggest that factors such as gender, culture, and early environment often confound attempts to replicate first findings. We conclude by discussing epigenetics, conceptual implications within an evolutionary perspective, and future directions, especially the need to refine phenotypes, carefully characterize early environments, and integrate observations of social behavior across

  12. An introduction to the indirect exposure assessment approach: modeling human exposure using microenvironmental measurements and the recent National Human Activity Pattern Survey.

    Science.gov (United States)

    Klepeis, N E

    1999-01-01

    Indirect exposure approaches offer a feasible and accurate method for estimating population exposures to indoor pollutants, including environmental tobacco smoke (ETS). In an effort to make the indirect exposure assessment approach more accessible to people in the health and risk assessment fields, this paper provides examples using real data from (italic>a(/italic>) a week-long personal carbon monoxide monitoring survey conducted by the author; and (italic>b(/italic>) the 1992 to 1994 National Human Activity Pattern Survey (NHAPS) for the United States. The indirect approach uses measurements of exposures in specific microenvironments (e.g., homes, bars, offices), validated microenvironmental models (based on the mass balance equation), and human activity pattern data obtained from questionnaires to predict frequency distributions of exposure for entire populations. This approach requires fewer resources than the direct approach to exposure assessment, for which the distribution of monitors to a representative sample of a given population is necessary. In the indirect exposure assessment approach, average microenvironmental concentrations are multiplied by the total time spent in each microenvironment to give total integrated exposure. By assuming that the concentrations encountered in each of 10 location categories are the same for different members of the U.S. population (i.e., the NHAPS respondents), the hypothetical contribution that ETS makes to the average 24-hr respirable suspended particle exposure for Americans working their main job is calculated in this paper to be 18 microg/m3. This article is an illustrative review and does not contain an actual exposure assessment or model validation. Images Figure 3 Figure 4 PMID:10350522

  13. Pesticide Flow Analysis to Assess Human Exposure in Greenhouse Flower Production in Colombia

    Directory of Open Access Journals (Sweden)

    Claudia R. Binder

    2013-03-01

    Full Text Available Human exposure assessment tools represent a means for understanding human exposure to pesticides in agricultural activities and managing possible health risks. This paper presents a pesticide flow analysis modeling approach developed to assess human exposure to pesticide use in greenhouse flower crops in Colombia, focusing on dermal and inhalation exposure. This approach is based on the material flow analysis methodology. The transfer coefficients were obtained using the whole body dosimetry method for dermal exposure and the button personal inhalable aerosol sampler for inhalation exposure, using the tracer uranine as a pesticide surrogate. The case study was a greenhouse rose farm in the Bogota Plateau in Colombia. The approach was applied to estimate the exposure to pesticides such as mancozeb, carbendazim, propamocarb hydrochloride, fosetyl, carboxin, thiram, dimethomorph and mandipropamide. We found dermal absorption estimations close to the AOEL reference values for the pesticides carbendazim, mancozeb, thiram and mandipropamide during the study period. In addition, high values of dermal exposure were found on the forearms, hands, chest and legs of study participants, indicating weaknesses in the overlapping areas of the personal protective equipment parts. These results show how the material flow analysis methodology can be applied in the field of human exposure for early recognition of the dispersion of pesticides and support the development of measures to improve operational safety during pesticide management. Furthermore, the model makes it possible to identify the status quo of the health risk faced by workers in the study area.

  14. Characterizing the impact of projected changes in climate and air quality on human exposures to ozone.

    Science.gov (United States)

    Dionisio, Kathie L; Nolte, Christopher G; Spero, Tanya L; Graham, Stephen; Caraway, Nina; Foley, Kristen M; Isaacs, Kristin K

    2017-05-01

    The impact of climate change on human and environmental health is of critical concern. Population exposures to air pollutants both indoors and outdoors are influenced by a wide range of air quality, meteorological, behavioral, and housing-related factors, many of which are also impacted by climate change. An integrated methodology for modeling changes in human exposures to tropospheric ozone (O 3 ) owing to potential future changes in climate and demographics was implemented by linking existing modeling tools for climate, weather, air quality, population distribution, and human exposure. Human exposure results from the Air Pollutants Exposure Model (APEX) for 12 US cities show differences in daily maximum 8-h (DM8H) exposure patterns and levels by sex, age, and city for all scenarios. When climate is held constant and population demographics are varied, minimal difference in O 3 exposures is predicted even with the most extreme demographic change scenario. In contrast, when population is held constant, we see evidence of substantial changes in O 3 exposure for the most extreme change in climate. Similarly, we see increases in the percentage of the population in each city with at least one O 3 exposure exceedance above 60 p.p.b and 70 p.p.b thresholds for future changes in climate. For these climate and population scenarios, the impact of projected changes in climate and air quality on human exposure to O 3 are much larger than the impacts of changing demographics. These results indicate the potential for future changes in O 3 exposure as a result of changes in climate that could impact human health.

  15. Children, computer exposure and musculoskeletal outcomes: the development of pathway models for school and home computer-related musculoskeletal outcomes.

    Science.gov (United States)

    Harris, Courtenay; Straker, Leon; Pollock, Clare; Smith, Anne

    2015-01-01

    Children's computer use is rapidly growing, together with reports of related musculoskeletal outcomes. Models and theories of adult-related risk factors demonstrate multivariate risk factors associated with computer use. Children's use of computers is different from adult's computer use at work. This study developed and tested a child-specific model demonstrating multivariate relationships between musculoskeletal outcomes, computer exposure and child factors. Using pathway modelling, factors such as gender, age, television exposure, computer anxiety, sustained attention (flow), socio-economic status and somatic complaints (headache and stomach pain) were found to have effects on children's reports of musculoskeletal symptoms. The potential for children's computer exposure to follow a dose-response relationship was also evident. Developing a child-related model can assist in understanding risk factors for children's computer use and support the development of recommendations to encourage children to use this valuable resource in educational, recreational and communication environments in a safe and productive manner. Computer use is an important part of children's school and home life. Application of this developed model, that encapsulates related risk factors, enables practitioners, researchers, teachers and parents to develop strategies that assist young people to use information technology for school, home and leisure in a safe and productive manner.

  16. The Activation Pathway of Human Rhodopsin in Comparison to Bovine Rhodopsin*

    Science.gov (United States)

    Kazmin, Roman; Rose, Alexander; Szczepek, Michal; Elgeti, Matthias; Ritter, Eglof; Piechnick, Ronny; Hofmann, Klaus Peter; Scheerer, Patrick; Hildebrand, Peter W.; Bartl, Franz J.

    2015-01-01

    Rhodopsin, the photoreceptor of rod cells, absorbs light to mediate the first step of vision by activating the G protein transducin (Gt). Several human diseases, such as retinitis pigmentosa or congenital night blindness, are linked to rhodopsin malfunctions. Most of the corresponding in vivo studies and structure-function analyses (e.g. based on protein x-ray crystallography or spectroscopy) have been carried out on murine or bovine rhodopsin. Because these rhodopsins differ at several amino acid positions from human rhodopsin, we conducted a comprehensive spectroscopic characterization of human rhodopsin in combination with molecular dynamics simulations. We show by FTIR and UV-visible difference spectroscopy that the light-induced transformations of the early photointermediates are very similar. Significant differences between the pigments appear with formation of the still inactive Meta I state and the transition to active Meta II. However, the conformation of Meta II and its activity toward the G protein are essentially the same, presumably reflecting the evolutionary pressure under which the active state has developed. Altogether, our results show that although the basic activation pathways of human and bovine rhodopsin are similar, structural deviations exist in the inactive conformation and during receptor activation, even between closely related rhodopsins. These differences between the well studied bovine or murine rhodopsins and human rhodopsin have to be taken into account when the influence of point mutations on the activation pathway of human rhodopsin are investigated using the bovine or murine rhodopsin template sequences. PMID:26105054

  17. Curcumin and emodin down-regulate TGF-β signaling pathway in human cervical cancer cells.

    Directory of Open Access Journals (Sweden)

    Pooja Chandrakant Thacker

    Full Text Available Cervical cancer is the major cause of cancer related deaths in women, especially in developing countries and Human Papilloma Virus infection in conjunction with multiple deregulated signaling pathways leads to cervical carcinogenesis. TGF-β signaling in later stages of cancer is known to induce epithelial to mesenchymal transition promoting tumor growth. Phytochemicals, curcumin and emodin, are effective as chemopreventive and chemotherapeutic compounds against several cancers including cervical cancer. The main objective of this work was to study the effect of curcumin and emodin on TGF-β signaling pathway and its functional relevance to growth, migration and invasion in two cervical cancer cell lines, SiHa and HeLa. Since TGF-β and Wnt/β-catenin signaling pathways are known to cross talk having common downstream targets, we analyzed the effect of TGF-β on β-catenin (an important player in Wnt/β-catenin signaling and also studied whether curcumin and emodin modulate them. We observed that curcumin and emodin effectively down regulate TGF-β signaling pathway by decreasing the expression of TGF-β Receptor II, P-Smad3 and Smad4, and also counterbalance the tumorigenic effects of TGF-β by inhibiting the TGF-β-induced migration and invasion. Expression of downstream effectors of TGF-β signaling pathway, cyclinD1, p21 and Pin1, was inhibited along with the down regulation of key mesenchymal markers (Snail and Slug upon curcumin and emodin treatment. Curcumin and emodin were also found to synergistically inhibit cell population and migration in SiHa and HeLa cells. Moreover, we found that TGF-β activates Wnt/β-catenin signaling pathway in HeLa cells, and curcumin and emodin down regulate the pathway by inhibiting β-catenin. Taken together our data provide a mechanistic basis for the use of curcumin and emodin in the treatment of cervical cancer.

  18. Weighing serological evidence of human exposure to animal influenza viruses − A literature review

    NARCIS (Netherlands)

    Sikkema, R.S. (Reina S.); G.S. Freidl (Gudrun); E.I. de Bruin (Esther); M.P.G. Koopmans D.V.M. (Marion)

    2016-01-01

    textabstractAssessing influenza A virus strains circulating in animals and their potential to cross the species barrier and cause human infections is important to improve human influenza surveillance and preparedness. We reviewed studies describing serological evidence of human exposure to animal

  19. Florida Red Tide and Human Health: A Pilot Beach Conditions Reporting System to Minimize Human Exposure

    Science.gov (United States)

    Kirkpatrick, Barbara; Currier, Robert; Nierenberg, Kate; Reich, Andrew; Backer, Lorraine C.; Stumpf, Richard; Fleming, Lora; Kirkpatrick, Gary

    2008-01-01

    pathway for the lifeguards to minimize the amount of time away from their primary duties. Specifically, we provided a Personal Digital Assistant for each of the eight beaches. The portable unit allows the lifeguards to report from their guard tower. The data are transferred via wireless Internet to a website hosted on the Mote Marine Laboratory Sarasota Operations of the Coastal Ocean Observation Laboratories (SO COOL) server. The system has proven to be robust and well received by the public. The system has reported variability from beach to beach and has provided vital information to users to minimize their exposure to toxic marine aerosols. PMID:18501955

  20. Exposure levels, environmental fate modelling and human health risk assessment of lindane in Ghana

    International Nuclear Information System (INIS)

    Adu-Kumi, S.

    2011-01-01

    -HCH which is a known environmental estrogen, was predominant contaminant measured (geometric mean concentrations 4.18 ng g -1 lipid wt. and 4.35 ng g -1 lipid wt. for pooled and individual samples respectively). The levels of Lindane, α-HCH and β-HCH in edible fish (catfish and tilapia) sourced from Lake Bosumtwi and the Weija Lake, were concurrently investigated using HRGC/HRMS. Concentrations of HCHs were found to be generally low (mainly limits of detection) probably reflecting the historical use of Lindane and technical HCH mixtures. Catfish sourced from Lake Volta (purchased from the Madina market) however contained appreciable amounts of Lindane (average concentration of 0.72 ng g -1 lipid wt). Measured values are lower than the maximum acceptable limit for human consumption established by the FAO/WHO (FAO/WHO, 1986). Hence there is no potential health risk from HCHs (Lindane, α-HCH and β-HCH) in fish for the general population of Ghana. Level III and level IV fugacity models were successfully applied to investigate the environmental fate of Lindane in the compartments of air, water, sediment, soil and biota (fish). Model estimates showed that air, water, soil and fish constitute important exposure pathways of Lindane for the general population of Ghana. The estimated total amount of Lindane accumulated in all media at steady-state was 136 tonnes, the soil compartment accounting for ore than 97% of the total accumulation. Time trends in concentration and fluxes simulated in for the period 1959-2020 predicted that less than 1% of the 2002 concentration levels of Lindane in air, water and soil, respectively, will be left in 2020. Finally, health risks associated with the exposure of the general population of Ghana to Lindane via the pathways of air, water, soil, food (or diet) were characterized using the combined field measurements and results of the multi-media environmental fate modelling. Diet (mainly vegetables), soil and to a lesser extent water constituted

  1. Human cerebral venous outflow pathway depends on posture and central venous pressure

    DEFF Research Database (Denmark)

    Gisolf, J; van Lieshout, J J; van Heusden, K

    2004-01-01

    and central venous pressure (CVP) on the distribution of cerebral outflow over the internal jugular veins and the vertebral plexus, using a mathematical model. Input to the model was a data set of beat-to-beat cerebral blood flow velocity and CVP measurements in 10 healthy subjects, during baseline rest......Internal jugular veins are the major cerebral venous outflow pathway in supine humans. In upright humans the positioning of these veins above heart level causes them to collapse. An alternative cerebral outflow pathway is the vertebral venous plexus. We set out to determine the effect of posture...... and a Valsalva manoeuvre in the supine and standing position. The model, consisting of 2 jugular veins, each a chain of 10 units containing nonlinear resistances and capacitors, and a vertebral plexus containing a resistance, showed blood flow mainly through the internal jugular veins in the supine position...

  2. Human immunotoxicologic markers of chemical exposures: preliminary validation studies.

    Science.gov (United States)

    Wartenberg, D; Laskin, D; Kipen, H

    1993-01-01

    The circulating cells of the immune system are sensitive to environmental contaminants, and effects are often manifested as changes in the cell surface differentiation antigens of affected populations of cells, particularly lymphocytes. In this investigation, we explore the likelihood that variation in the expression of the surface markers of immune cells can be used as an index of exposure to toxic chemicals. We recruited 38 healthy New Jersey men to study pesticides effects: 19 orchard farmers (high exposure); 13 berry farmers (low exposure); and 6 hardware store owners (no exposure). Immunophenotyping was performed assaying the following cell surface antigens: CD2, CD4, CD8, CD14, CD20, CD26, CD29, CD45R, CD56, and PMN. Data were analyzed using univariate and multivariate methods. There were no significant differences among the groups with respect to routine medical histories, physical examinations, or routine laboratory parameters. No striking differences between groups were seen in univariate tests. Multivariate tests suggested some differences among groups and limited ability to correctly classify individuals based on immunophenotyping results. Immunophenotyping represents a fruitful area of research for improved exposure classification. Work is needed both on mechanistic understanding of the patterns observed and on the statistical interpretation of these patterns.

  3. Impairment of object recognition memory by maternal bisphenol A exposure is associated with inhibition of Akt and ERK/CREB/BDNF pathway in the male offspring hippocampus.

    Science.gov (United States)

    Wang, Chong; Li, Zhihui; Han, Haijun; Luo, Guangying; Zhou, Bingrui; Wang, Shaolin; Wang, Jundong

    2016-02-03

    Bisphenol A (BPA) is a commonly used endocrine-disrupting chemical used as a component of polycarbonates plastics that has potential adverse effects on human health. Exposure to BPA during development has been implicated in memory deficits, but the mechanism of action underlying the effect is not fully understood. In this study, we investigated the effect of maternal exposure to BPA on object recognition memory and the expressions of proteins important for memory, especially focusing on the ERK/CREB/BDNF pathway. Pregnant Sprague-Dawley female rats were orally treated with either vehicle or BPA (0.05, 0.5, 5 or 50 mg/kg BW/day) during days 9-20 of gestation. Male offspring were tested on postnatal day 21 with the object recognition task. Recognition memory was assessed using the object recognition index (index=the time spent exploring the novel object/(the time spent exploring the novel object+the time spent exploring the familiar object)). In the test session performed 90 min after the training session, BPA-exposed male offspring not only spent more time in exploring the familiar object at the highest dose than the control, but also displayed a significantly decreased the object recognition index at the doses of 0.5, 5 and 50 mg/kg BW/day. During the test session performed 24h after the training session, BPA-treated males did not change the time spent exploring the familiar object, but had a decreased object recognition index at 5 and 50 mg/kg BW/day, when compared to control group. These findings indicate that object recognition memory was susceptible to maternal BPA exposure. Western blot analysis of hippocampi from BPA-treated male offspring revealed a decrease in Akt, phospho-Akt, p44/42 MAPK and phospho-p44/42 MAPK protein levels, compared to controls. In addition, BPA significantly inhibited the levels of phosphorylation of CREB and BDNF in the hippocampus. Our results show that maternal BPA exposure may full impair object recognition memory, and that

  4. Toxicogenomic outcomes predictive of forestomach carcinogenesis following exposure to benzo(a)pyrene: Relevance to human cancer risk

    Energy Technology Data Exchange (ETDEWEB)

    Labib, Sarah, E-mail: Sarah.Labib@hc-sc.gc.ca; Guo, Charles H., E-mail: Charles.Guo@hc-sc.gc.ca; Williams, Andrew, E-mail: Andrew.Williams@hc-sc.gc.ca; Yauk, Carole L., E-mail: Carole.Yauk@hc-sc.gc.ca; White, Paul A., E-mail: Paul.White@hc-sc.gc.ca; Halappanavar, Sabina, E-mail: Sabina.Halappanavar@hc-sc.gc.ca

    2013-12-01

    Forestomach tumors are observed in mice exposed to environmental carcinogens. However, the relevance of this data to humans is controversial because humans lack a forestomach. We hypothesize that an understanding of early molecular changes after exposure to a carcinogen in the forestomach will provide mode-of-action information to evaluate the applicability of forestomach cancers to human cancer risk assessment. In the present study we exposed mice to benzo(a)pyrene (BaP), an environmental carcinogen commonly associated with tumors of the rodent forestomach. Toxicogenomic tools were used to profile gene expression response in the forestomach. Adult Muta™Mouse males were orally exposed to 25, 50, and 75 mg BaP/kg-body-weight/day for 28 consecutive days. The forestomach was collected three days post-exposure. DNA microarrays, real-time RT-qPCR arrays, and protein analyses were employed to characterize responses in the forestomach. Microarray results showed altered expression of 414 genes across all treatment groups (± 1.5 fold; false discovery rate adjusted P ≤ 0.05). Significant downregulation of genes associated with phase II xenobiotic metabolism and increased expression of genes implicated in antigen processing and presentation, immune response, chemotaxis, and keratinocyte differentiation were observed in treated groups in a dose-dependent manner. A systematic comparison of the differentially expressed genes in the forestomach from the present study to differentially expressed genes identified in human diseases including human gastrointestinal tract cancers using the NextBio Human Disease Atlas showed significant commonalities between the two models. Our results provide molecular evidence supporting the use of the mouse forestomach model to evaluate chemically-induced gastrointestinal carcinogenesis in humans. - Highlights: • Benzo(a)pyrene-mediated transcriptomic response in the forestomach was examined. • The immunoproteosome subunits and MHC class I

  5. Novel robust biomarkers for human bladder cancer based on activation of intracellular signaling pathways

    OpenAIRE

    Lezhnina, Ksenia; Kovalchuk, Olga; Zhavoronkov, Alexander A.; Korzinkin, Mikhail B.; Zabolotneva, Anastasia A.; Shegay, Peter V.; Sokov, Dmitry G.; Gaifullin, Nurshat M.; Rusakov, Igor G.; Aliper, Alexander M.; Roumiantsev, Sergey A.; Alekseev, Boris Y.; Borisov, Nikolay M.; Buzdin, Anton A.

    2014-01-01

    We recently proposed a new bioinformatic algorithm called OncoFinder for quantifying the activation of intracellular signaling pathways. It was proved advantageous for minimizing errors of high-throughput gene expression analyses and showed strong potential for identifying new biomarkers. Here, for the first time, we applied OncoFinder for normal and cancerous tissues of the human bladder to identify biomarkers of bladder cancer. Using Illumina HT12v4 microarrays, we profiled gene expression ...

  6. Dose-Dependent Response to 3-Nitrobenzanthrone Exposure in Human Urothelial Cancer Cells.

    Science.gov (United States)

    Pink, Mario; Verma, Nisha; Zerries, Anna; Schmitz-Spanke, Simone

    2017-10-16

    A product of incomplete combustion of diesel fuel, 3-nitrobenzanthrone (3-NBA), has been classified as a cancer-causing substance. It first gained attention as a potential urinary bladder carcinogen due to the presence of its metabolite in urine and formation of DNA adducts. The aim of the present study was to characterize the dose-response relationship of 3-NBA in human urothelial cancer cell line (RT4) exposed to concentrations ranging from 0.0003 μM (environmentally relevant) to 80 μM by utilizing toxicological and metabolomic approaches. We observed that the RT4 cells were capable of bioactivation of 3-NBA within 30 min of exposure. Activity measurements of various enzymes involved in the conversion of 3-NBA in RT4 cells demonstrated NAD(P)H:quinone oxidoreductase (NQO1) as the main contributor for its bioactivation. Moreover, cytotoxicity assessment exhibited an initiation of adaptive mechanisms at low dosages, which diminished at higher doses, indicating that the capacity of these mechanisms no longer suffices, resulting in increased levels of intracellular reactive oxygen species, reduced proliferation, and hyperpolarisation of the mitochondrial membrane. To characterize the underlying mechanisms of this cellular response, the metabolism of 3-NBA and metabolomic changes in the cells were analyzed. The metabolomic analysis of the cells (0.0003, 0.01, 0.08, 10, and 80 μM 3-NBA) showed elevated levels of various antioxidants at low concentrations of 3-NBA. However, at higher exposure concentrations, it appeared that the cells reprogrammed their metabolism to maintain the cell homeostasis via activation of pentose phosphate pathway (PPP).

  7. Distinct Signaling Pathways After Higher or Lower Doses of Radiation in Three Closely Related Human Lymphoblast Cell Lines

    International Nuclear Information System (INIS)

    Lu, T.-P.; Lai, L.-C.; Lin, B.-I.; Chen, L.-H.; Hsiao, T.-H.; Liber, Howard L.; Cook, John A.; Mitchell, James B.; Tsai, M.-H.; Chuang, Eric Y.

    2010-01-01

    Purpose: The tumor suppressor p53 plays an essential role in cellular responses to DNA damage caused by ionizing radiation; therefore, this study aims to further explore the role that p53 plays at different doses of radiation. Materials and Methods: The global cellular responses to higher-dose (10 Gy) and lower dose (iso-survival dose, i.e., the respective D0 levels) radiation were analyzed using microarrays in three human lymphoblast cell lines with different p53 status: TK6 (wild-type p53), NH32 (p53-null), and WTK1 (mutant p53). Total RNAs were extracted from cells harvested at 0, 1, 3, 6, 9, and 24 h after higher and lower dose radiation exposures. Template-based clustering, hierarchical clustering, and principle component analysis were applied to examine the transcriptional profiles. Results: Differential expression profiles between 10 Gy and iso-survival radiation in cells with different p53 status were observed. Moreover, distinct gene expression patterns were exhibited among these three cells after 10 Gy radiation treatment, but similar transcriptional responses were observed in TK6 and NH32 cells treated with iso-survival radiation. Conclusions: After 10 Gy radiation exposure, the p53 signaling pathway played an important role in TK6, whereas the NFkB signaling pathway appeared to replace the role of p53 in WTK1. In contrast, after iso-survival radiation treatment, E2F4 seemed to play a dominant role independent of p53 status. This study dissected the impacts of p53, NFkB and E2F4 in response to higher or lower doses of γ-irradiation.

  8. TCDD Induces the Hypoxia-Inducible Factor (HIF-1α Regulatory Pathway in Human Trophoblastic JAR Cells

    Directory of Open Access Journals (Sweden)

    Tien-Ling Liao

    2014-09-01

    Full Text Available The exposure to dioxin can compromise pregnancy outcomes and increase the risk of preterm births. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD has been demonstrated to induce placental hypoxia at the end of pregnancy in a rat model, and hypoxia has been suggested to be the cause of abnormal trophoblast differentiation and placental insufficiency syndromes. In this study, we demonstrate that the non-hypoxic stimulation of human trophoblastic cells by TCDD strongly increased hypoxia inducible factor-1 alpha (HIF-1α stabilization. TCDD exposure induced the generation of reactive oxygen species (ROS and nitric oxide. TCDD-induced HIF-1α stabilization and Akt phosphorylation was inhibited by pretreatment with wortmannin (a phosphatidylinositol 3-kinase (PI3K inhibitor or N-acetylcysteine (a ROS scavenger. The augmented HIF-1α stabilization by TCDD occurred via the ROS-dependent activation of the PI3K/Akt pathway. Additionally, a significant increase in invasion and metallomatrix protease-9 activity was found in TCDD-treated cells. The gene expression of vascular endothelial growth factor and placental growth factor was induced upon TCDD stimulation, whereas the protein levels of peroxisome proliferator-activated receptor γ (PPARγ, PPARγ coactivator-1α, mitochondrial transcription factor, and uncoupling protein 2 were decreased. Our results indicate that an activated HIF-1α pathway, elicited oxidative stress, and induced metabolic stress contribute to TCDD-induced trophoblastic toxicity. These findings may provide molecular insight into the TCDD-induced impairment of trophoblast function and placental development.

  9. Human Exposure Risk Assessment Due to Heavy Metals in Groundwater by Pollution Index and Multivariate Statistical Methods: A Case Study from South Africa

    OpenAIRE

    Vetrimurugan Elumalai; K. Brindha; Elango Lakshmanan

    2017-01-01

    Heavy metals in surface and groundwater were analysed and their sources were identified using multivariate statistical tools for two towns in South Africa. Human exposure risk through the drinking water pathway was also assessed. Electrical conductivity values showed that groundwater is desirable to permissible for drinking except for six locations. Concentration of aluminium, lead and nickel were above the permissible limit for drinking at all locations. Boron, cadmium, iron and manganese ex...

  10. A probabilistic atlas of human brainstem pathways based on connectome imaging data.

    Science.gov (United States)

    Tang, Yuchun; Sun, Wei; Toga, Arthur W; Ringman, John M; Shi, Yonggang

    2018-04-01

    The brainstem is a critical structure that regulates vital autonomic functions, houses the cranial nerves and their nuclei, relays motor and sensory information between the brain and spinal cord, and modulates cognition, mood, and emotions. As a primary relay center, the fiber pathways of the brainstem include efferent and afferent connections among the cerebral cortex, spinal cord, and cerebellum. While diffusion MRI has been successfully applied to map various brain pathways, its application for the in vivo imaging of the brainstem pathways has been limited due to inadequate resolution and large susceptibility-induced distortion artifacts. With the release of high-resolution data from the Human Connectome Project (HCP), there is increasing interest in mapping human brainstem pathways. Previous works relying on HCP data to study brainstem pathways, however, did not consider the prevalence (>80%) of large distortions in the brainstem even after the application of correction procedures from the HCP-Pipeline. They were also limited in the lack of adequate consideration of subject variability in either fiber pathways or region of interests (ROIs) used for bundle reconstruction. To overcome these limitations, we develop in this work a probabilistic atlas of 23 major brainstem bundles using high-quality HCP data passing rigorous quality control. For the large-scale data from the 500-Subject release of HCP, we conducted extensive quality controls to exclude subjects with severe distortions in the brainstem area. After that, we developed a systematic protocol to manually delineate 1300 ROIs on 20 HCP subjects (10 males; 10 females) for the reconstruction of fiber bundles using tractography techniques. Finally, we leveraged our novel connectome modeling techniques including high order fiber orientation distribution (FOD) reconstruction from multi-shell diffusion imaging and topography-preserving tract filtering algorithms to successfully reconstruct the 23 fiber bundles

  11. Alternative pathways of thromboplastin-dependent activation of human factor X in plasma

    International Nuclear Information System (INIS)

    Marlar, R.A.; Griffin, J.H.

    1981-01-01

    To determine the interrelationships of the major coagulation pathways, the activation of 3H-labeled factor X in normal and various deficient human plasmas was evaluated when clotting was triggered by dilute rabbit or human thromboplastin. Various dilutions of thromboplastin and calcium were added to plasma samples containing 3H-factor X, and the time course of factor X activation was determined. At a 1/250 dilution of rabbit brain thromboplastin, the rate of factor X activation in plasmas deficient in factor VIII or factor IX was 10% of the activation rate of normal plasma or of factor XI deficient plasma. Reconstitution of the deficient plasmas with factors VIII or IX, respectively, reconstituted normal factor X activation. Similar results were obtained when various dilutions of human thromboplastin replaced the rabbit thromboplastin. From these plasma experiments, it is inferred that the dilute thromboplastin-dependent activation of factor X requires factors VII, IX, and VIII. An alternative extrinsic pathway that involves factors IX and VIII may be the physiologic extrinsic pathway and hence help to explain the consistent clinical observations of bleeding diatheses in patients deficient in factors IX or VIII

  12. Simulation of biatrial conduction via different pathways during sinus rhythm with a detailed human atrial model

    Institute of Scientific and Technical Information of China (English)

    Dong-dong DENG; Ying-lan GONG; Guo-fa SHOU; Pei-feng JIAO; Heng-gui ZHANG; Xue-song YE; Ling XIA

    2012-01-01

    In order to better understand biatrial conduction,investigate various conduction pathways,and compare the differences between isotropic and anisotropic conductions in human atria,we present a simulation study of biatrial conduction with known/assumed conduction pathways using a recently developed human atrial model.In addition to known pathways:(1) Bachmann's bundle (BB),(2) limbus of fossa ovalis (LFO),and (3) coronary sinus (CS),we also hypothesize that there exist two fast conduction bundles that connect the crista terminalis (CT),LFO,and CS.Our simulation demonstrates that use of these fast conduction bundles results in a conduction pattern consistent with experimental data.The comparison of isotropic and anisotropoic conductions in the BB case showed that the atrial working muscles had small effect on conduction time and conduction speed,although the conductivities assigned in anisotropic conduction were two to four times higher than the isotropic conduction.In conclusion,we suggest that the hypothesized intercaval bundles play a significant role in the biatrial conduction and that myofiber orientation has larger effects on the conduction system than the atrial working muscles.This study presents readers with new insights into human atrial conduction.

  13. Group B streptococcus activates transcriptomic pathways related to premature birth in human extraplacental membranes in vitro.

    Science.gov (United States)

    Park, Hae-Ryung; Harris, Sean M; Boldenow, Erica; McEachin, Richard C; Sartor, Maureen; Chames, Mark; Loch-Caruso, Rita

    2018-03-01

    Streptococcus agalactiae (group B streptococcus [GBS]) infection in pregnant women is the leading cause of infectious neonatal morbidity and mortality in the United States. Although inflammation during infection has been associated with preterm birth, the contribution of GBS to preterm birth is less certain. Moreover, the early mechanisms by which GBS interacts with the gestational tissue to affect adverse pregnancy outcomes are poorly understood. We hypothesized that short-term GBS inoculation activates pathways related to inflammation and premature birth in human extraplacental membranes. We tested this hypothesis using GBS-inoculated human extraplacental membranes in vitro. In agreement with our hypothesis, a microarray-based transcriptomics analysis of gene expression changes in GBS-inoculated membranes revealed that GBS activated pathways related to inflammation and preterm birth with significant gene expression changes occurring as early as 4 h postinoculation. In addition, pathways related to DNA replication and repair were downregulated with GBS treatment. Conclusions based on our transcriptomics data were further supported by responses of prostaglandin E2 (PGE2), and matrix metalloproteinases 1 (MMP1) and 3 (MMP3), all of which are known to be involved in parturition and premature rupture of membranes. These results support our initial hypothesis and provide new information on molecular targets of GBS infection in human extraplacental membranes.

  14. Presence of insoluble Tau following rotenone exposure ameliorates basic pathways associated with neurodegeneration

    Directory of Open Access Journals (Sweden)

    Rodrigo S. Chaves

    2016-12-01

    Full Text Available Protein aggregation is an important feature of neurodegenerative disorders. In Alzheimer's disease (AD protein aggregates are composed of hyperphosphorylated Tau and amyloid beta peptide (Aβ. Despite the involvement and identification of the molecular composition of these aggregates, their role in AD pathophysiology is not fully understood. However, depositions of these insoluble aggregates are typically reported as pathogenic and toxic for cell homeostasis. New evidences suggest that the deposition of these aggregates is a protective mechanism that preserves cell from toxic insults associated with the early stages of neurodegenerative diseases. To better understand the biological role of the protein aggregation with regard its effects in cellular homeostasis, the present study investigated the role of insoluble Tau and Tau aggregates on crucial cellular parameters such as redox homeostasis, proteasome activity and autophagy in hippocampal cell cultures and hippocampus of aged Lewis rats using a rotenone-induced aggregation model. Neurons were exposed to rotenone in different concentrations and exposure times aiming to determine the interval required for Tau aggregation. Our experimental design allowed us to demonstrate that rotenone exposure induces Tau hyperphosphorylation and aggregation in a concentration and time-dependent manner. Oxidative stress triggered by rotenone exposure was observed with the absence of Tau aggregates and was reduced or absent when Tau aggregates were present. This reduction of oxidative stress along with the presence of insoluble Tau was independent of alterations in antioxidant enzymes activities or cell death. In addition, rotenone induced oxidative stress was mainly associated with decrease in proteasome activity and autophagy flux. Conversely, when insoluble Tau appeared, autophagy turns to be overactivated while proteasome activity remained low. Our studies significantly advance the understanding that Tau

  15. 77 FR 52025 - Notification of a Public Teleconference of the Science Advisory Board; Exposure and Human Health...

    Science.gov (United States)

    2012-08-28

    ... Science Advisory Board; Exposure and Human Health Committee AGENCY: Environmental Protection Agency (EPA... Office announces a public teleconference of the SAB Exposure and Human Health Committee to discuss its... hereby given that the SAB Exposure and Human Health Committee (EHHC) will hold a public teleconference to...

  16. Combined Toxic Exposures and Human Health: Biomarkers of Exposure and Effect

    Directory of Open Access Journals (Sweden)

    Johan Högberg

    2011-02-01

    Full Text Available Procedures for risk assessment of chemical mixtures, combined and cumulative exposures are under development, but the scientific database needs considerable expansion. In particular, there is a lack of knowledge on how to monitor effects of complex exposures, and there are few reviews on biomonitoring complex exposures. In this review we summarize articles in which biomonitoring techniques have been developed and used. Most examples describe techniques for biomonitoring effects which may detect early changes induced by many chemical stressors and which have the potential to accelerate data gathering. Some emphasis is put on endocrine disrupters acting via epigenetic mechanisms and on carcinogens. Solid evidence shows that these groups of chemicals can interact and even produce synergistic effects. They may act during sensitive time windows and biomonitoring their effects in epidemiological studies is a challenging task.

  17. Human exposure to mercury in a compact fluorescent lamp manufacturing area: By food (rice and fish) consumption and occupational exposure

    International Nuclear Information System (INIS)

    Liang, Peng; Feng, Xinbin; Zhang, Chan; Zhang, Jin; Cao, Yucheng; You, Qiongzhi; Leung, Anna Oi Wah; Wong, Ming-Hung; Wu, Sheng-Chun

    2015-01-01

    To investigate human Hg exposure by food consumption and occupation exposure in a compact fluorescent lamp (CFL) manufacturing area, human hair and rice samples were collected from Gaohong town, Zhejiang Province, China. The mean values of total mercury (THg) and methylmercury (MeHg) concentrations in local cultivated rice samples were significantly higher than in commercial rice samples which indicated that CFL manufacturing activities resulted in Hg accumulation in local rice samples. For all of the study participants, significantly higher THg concentrations in human hair were observed in CFL workers compared with other residents. In comparison, MeHg concentrations in human hair of residents whose diet consisted of local cultivated rice were significantly higher than those who consumed commercial rice. These results demonstrated that CFL manufacturing activities resulted in THg accumulation in the hair of CFL workers. However, MeHg in hair were mainly affected by the sources of rice of the residents. - Highlights: • Rice samples were contaminated by Compact fluorescent lamp (CFL) manufacturing. • CFL manufacturing lead to THg accumulation in human hair. • MeHg in human hair were mainly affected by the sources of rice. • MeHg intake from fish consumption was lower than that from rice consumption. • PDI of MeHg by food consumption was below the guidelines for public health concern. - CFL manufacturing activities result in Hg accumulation in local rice samples and hair of CFL workers. However, MeHg in hair were mainly affected by sources of rice

  18. Human health risk assessment of lead from mining activities at semi-arid locations in the context of total lead exposure.

    Science.gov (United States)

    Zheng, Jiajia; Huynh, Trang; Gasparon, Massimo; Ng, Jack; Noller, Barry

    2013-12-01

    Lead from historical mining and mineral processing activities may pose potential human health risks if materials with high concentrations of bioavailable lead minerals are released to the environment. Since the Joint Expert Committee on Food Additives of Food and Agriculture Organization/World Health Organization withdrew the Provisional Tolerable Weekly Intake of lead in 2011, an alternative method was required for lead exposure assessment. This study evaluated the potential lead hazard to young children (0-7 years) from a historical mining location at a semi-arid area using the U.S. EPA Integrated Exposure Uptake Biokinetic (IEUBK) Model, with selected site-specific input data. This study assessed lead exposure via the inhalation pathway for children living in a location affected by lead mining activities and with specific reference to semi-arid conditions and made comparison with the ingestion pathway by using the physiologically based extraction test for gastro-intestinal simulation. Sensitivity analysis for major IEUBK input parameters was conducted. Three groups of input parameters were classified according to the results of predicted blood concentrations. The modelled lead absorption attributed to the inhalation route was lower than 2 % (mean ± SE, 0.9 % ± 0.1 %) of all lead intake routes and was demonstrated as a less significant exposure pathway to children's blood, compared with ingestion. Whilst dermal exposure was negligible, diet and ingestion of soil and dust were the dominant parameters in terms of children's blood lead prediction. The exposure assessment identified the changing role of dietary intake when house lead loadings varied. Recommendations were also made to conduct comprehensive site-specific human health risk assessment in future studies of lead exposure under a semi-arid climate.

  19. Hexachlorobenzene sources, levels and human exposure in the environment of China

    NARCIS (Netherlands)

    Wang, G.; Lu, Y.L.; Han, Jingyi; Luo, W.; Shi, Y.J.; Wang, T.Y.; Sun, Y.M.

    2010-01-01

    This article summarizes the published scientific data on sources, levels and human exposure of hexachlorobenzene (HCB) in China. Potential sources of unintended HCB emission were assessed by production information, emission factors and environmental policies. HCB was observed in various

  20. In vivo plasma concentration for lindane after 6 hour exposure in human skin

    Data.gov (United States)

    U.S. Environmental Protection Agency — Dataset is a time course description of lindane disappearance in blood plasma after dermal exposure in human volunteers. This dataset is associated with the...

  1. Human Health Effects Associated with Exposure to Cyanobacteria and Cyanotoxins: What Do We Know?

    Science.gov (United States)

    The study of environmental health typically focuses on human populations. However, companion animals, livestock and wildlife also experience adverse health effects from environmental pollutants. Animals may experience direct exposure to pollutants unlike people in most ambient ex...

  2. Probabilistic estimation of residential air exchange rates for population-based human exposure modeling

    Science.gov (United States)

    Residential air exchange rates (AERs) are a key determinant in the infiltration of ambient air pollution indoors. Population-based human exposure models using probabilistic approaches to estimate personal exposure to air pollutants have relied on input distributions from AER meas...

  3. A Quantitative ADME-base Tool for Exploring Human Exposure to Consumer Product Ingredients

    Science.gov (United States)

    Exposure to a wide range of chemicals through our daily habits and routines is ubiquitous and largely unavoidable within modern society. The potential for human exposure, however, has not been quantified for the vast majority of chemicals with wide commercial use. Creative advanc...

  4. In Vivo Lipopolysaccharide Exposure of Human Blood Leukocytes Induces Cross-Tolerance to Multiple TLR Ligands

    NARCIS (Netherlands)

    de Vos, Alex F.; Pater, Jennie M.; van den Pangaart, Petra S.; de Kruif, Martijn D.; van 't Veer, Cornelis; van der Poll, Tom

    2009-01-01

    In vitro and in vivo experiments in mice have shown that exposure of cells to the TLR4 ligand LPS induces tolerance toward a second exposure to LPS and induces cross-tolerance to certain other TLR ligands. Recently, we found that LPS tolerance in experimental human endotoxemia and Gram-negative

  5. The Progression of Circadian Phase during Light Exposure in Animals and Humans

    NARCIS (Netherlands)

    Beersma, Domien G. M.; Comas, Marian; Hut, Roelof A.; Gordijn, Marijke C. M.; Rueger, Melanie; Daan, Serge

    Studies in humans and mice revealed that circadian phase shifting effects of light are larger at the beginning of a light exposure interval than during subsequent exposure. Little is known about the dynamics of this response reduction phenomenon. Here the authors propose a method to obtain

  6. Ecological and human health risks arising from exposure to metals in urban soils under different land use in Nigeria.

    Science.gov (United States)

    Iwegbue, Chukwujindu M A; Martincigh, Bice S

    2018-05-01

    The concentrations of eight metals (Cd, Pb, Cr, Ni, Cu, Mn, Zn and Fe) were measured in soils under different land use in an urban environment of the Niger Delta in Nigeria. The aim was to provide information on the potential ecological and human health risks associated with human exposure to metals in these soils. The potential ecological risk due to metals in soils of these land use types falls in the range of low to moderate ecological risk with a significant contribution from Cd. The severity of the individual metals to ecological risk in these land use types followed the order Cd > Pb > Zn > Cu > Ni > Cr > Mn. The non-carcinogenic risk, expressed in terms of the hazard index (HI), arising through exposure to metals through oral, dermal and inhalation pathways, was greater than 1 for children in the majority of the land use types and less than 1 for adults for all land use types. This indicated that there are considerable non-cancer risks arising from childhood exposure to metals in soils of these land use types. The cancer risk values were within acceptable threshold values indicating a negligible cancer risk for both children and adults exposed to metals in these urban soils.

  7. [Exposure pathways to pesticides in schoolchildren in the Province of Talca, Chile].

    Science.gov (United States)

    Muñoz-Quezada, María Teresa; Lucero, Boris; Iglesias, Verónica; Muñoz, María Pía

    2014-01-01

    To describe pesticide concentrations in distinct environmental matrices at two time points (low and high seasons in local agricultural production) and to estimate the association between the presence of pesticide residues in matrices and the use of pesticides in the home with the sociodemographic variables of schoolchildren in the Province of Talca, Chile. A cross-sectional study was conducted in 190 schoolchildren. Families were surveyed about their children's vegetable consumption in school and at home, the use of pesticides in the home, and other sociodemographic variables. Additionally, we measured pesticide residues in vegetables and water consumed by the schoolchildren and in the soil of 14 schools. At both time points, the vegetable matrix had the highest pesticide concentration, both in urban and rural schoolchildren. The most common pesticide residues in vegetables were chlorpyrifos, diphenylamine, pyrimethanil, and thiabendazole. In the home, pyrethroid and organophosphate pesticides were mainly used in summer. Dangerous pesticide residues such as azinphos methyl and dimethoate were found in vegetables consumed by the children in schools and households, and organochlorines were found in the soil in some schools. Pesticide exposure should be limited and the health effects related to pesticide exposure should be assessed in the school population. Copyright © 2013 SESPAS. Published by Elsevier Espana. All rights reserved.

  8. Evaluation of exposure pathways to man from disposal of radioactive materials into sanitary sewer systems

    Energy Technology Data Exchange (ETDEWEB)

    Kennedy, W.E. Jr.; Parkhurst, M.A.; Aaberg, R.L.; Rhoads, K.C.; Hill, R.L.; Martin, J.B. [Pacific Northwest Lab., Richland, WA (United States)

    1992-05-01

    In accordance with 10 CFR 20, the US Nuclear Regulatory Commission (NRC) regulates licensees` discharges of small quantities of radioactive materials into sanitary sewer systems. This generic study was initiated to examine the potential radiological hazard to the public resulting from exposure to radionuclides in sewage sludge during its treatment and disposal. Eleven scenarios were developed to characterize potential exposures to radioactive materials during sewer system operations and sewage sludge treatment and disposal activities and during the extended time frame following sewage sludge disposal. Two sets of deterministic dose calculations were performed; one to evaluate potential doses based on the radionuclides and quantities associated with documented case histories of sewer system contamination and a second, somewhat more conservative set, based on theoretical discharges at the maximum allowable levels for a more comprehensive list of 63 radionuclides. The results of the stochastic uncertainty and sensitivity analysis were also used to develop a collective dose estimate. The collective doses for the various radionuclides and scenarios range from 0.4 person-rem for {sup 137}Cs in Scenario No. 5 (sludge incinerator effluent) to 420 person-rem for {sup 137}Cs in Scenario No. 3 (sewage treatment plant liquid effluent). None of the 22 scenario/radionuclide combinations considered have collective doses greater than 1000 person-rem/yr. However, the total collective dose from these 22 combinations was found to be about 2100 person-rem.

  9. Parent-child drug communication: pathway from parents' ad exposure to youth's marijuana use intention.

    Science.gov (United States)

    Huansuriya, Thipnapa; Siegel, Jason T; Crano, William D

    2014-01-01

    The authors combined the 2-step flow of communication model and the theory of planned behavior to create a framework to evaluate the effectiveness of a set of advertisements from the National Youth Anti-Drug Media Campaign promoting parent-child drug communication. The sample consisted of 1,349 pairs of parents and children who responded to the first and second annual rounds of the National Survey of Parents and Youth, and 1,276 pairs from Rounds 3 and 4. Parents' exposure to the campaign reported at Round 1 was indirectly associated with youth's lowered intentions to use marijuana at Round 2. Ad exposure was associated with positive changes in parental attitudes toward drug communication and perceived social approval of antidrug communications. These two beliefs, along with perceived behavioral control, predicted parents' intentions to discuss drugs with their children. Parental intentions to discuss drugs reported at Round 1 were associated with youth's report of actual drug communication with their parents at Round 2. Frequency and breadth of the topics in parent-child drug communication were associated with less positive attitudes toward marijuana use among youth who spoke with their parents. Together, the child's attitudes toward marijuana use and perceived ability to refuse marijuana use predicted youth's intentions to use marijuana. The proposed model fit well with the data and was replicated in a parallel analysis of the data from Rounds 3 and 4. Implications for future antidrug media campaign efforts are discussed.

  10. Evaluation of exposure pathways to man from disposal of radioactive materials into sanitary sewer systems

    International Nuclear Information System (INIS)

    Kennedy, W.E. Jr.; Parkhurst, M.A.; Aaberg, R.L.; Rhoads, K.C.; Hill, R.L.; Martin, J.B.

    1992-05-01

    In accordance with 10 CFR 20, the US Nuclear Regulatory Commission (NRC) regulates licensees' discharges of small quantities of radioactive materials into sanitary sewer systems. This generic study was initiated to examine the potential radiological hazard to the public resulting from exposure to radionuclides in sewage sludge during its treatment and disposal. Eleven scenarios were developed to characterize potential exposures to radioactive materials during sewer system operations and sewage sludge treatment and disposal activities and during the extended time frame following sewage sludge disposal. Two sets of deterministic dose calculations were performed; one to evaluate potential doses based on the radionuclides and quantities associated with documented case histories of sewer system contamination and a second, somewhat more conservative set, based on theoretical discharges at the maximum allowable levels for a more comprehensive list of 63 radionuclides. The results of the stochastic uncertainty and sensitivity analysis were also used to develop a collective dose estimate. The collective doses for the various radionuclides and scenarios range from 0.4 person-rem for 137 Cs in Scenario No. 5 (sludge incinerator effluent) to 420 person-rem for 137 Cs in Scenario No. 3 (sewage treatment plant liquid effluent). None of the 22 scenario/radionuclide combinations considered have collective doses greater than 1000 person-rem/yr. However, the total collective dose from these 22 combinations was found to be about 2100 person-rem

  11. Separation of uncertainty and interindividual variability in human exposure modeling.

    NARCIS (Netherlands)

    Ragas, A.M.J.; Brouwer, F.P.E.; Buchner, F.L.; Hendriks, H.W.; Huijbregts, M.A.J.

    2009-01-01

    The NORMTOX model predicts the lifetime-averaged exposure to contaminants through multiple environmental media, that is, food, air, soil, drinking and surface water. The model was developed to test the coherence of Dutch environmental quality objectives (EQOs). A set of EQOs is called coherent if

  12. Aquatic Sentinels Forecasting Human Exposure To Emerging Contaminants

    Science.gov (United States)

    Most of us have heard the axiom, “canary in the coal mine”. These melodious exposure indicators - a necessity in U.K. mines well into the 20th century - were especially sensitive to methane and carbon monoxide gases, and would cease singing (and oftentimes die) at le...

  13. Strategies for estimating human exposure to mycotoxins via food

    NARCIS (Netherlands)

    Nijs, De M.; Mengelers, M.J.B.; Boon, P.E.; Heyndrickx, E.; Hoogenboom, L.A.P.; Lopez, P.; Mol, H.G.J.

    2016-01-01

    In this review, five strategies to estimate mycotoxin exposure of a (sub-)population via food, including data collection, are discussed with the aim to identify the added values and limitations of each strategy for risk assessment of these chemicals. The well-established point estimate, observed

  14. Mathematical Models of Human Hematopoiesis Following Acute Radiation Exposure

    Science.gov (United States)

    2014-05-01

    response of 11 subjects from Chernobyl 1986 . . . . . . 104 B.8 Chernobyl case studies: Platelet data . . . . . . . . . . . . . . . . . . . . . . 105 B...9 Chernobyl case studies: Granulocyte data . . . . . . . . . . . . . . . . . . . 106 B.10 Chernobyl case studies: Lymphocyte data...information for use in nuclear disaster preparedness planning. Understanding how biological systems change after radiation exposure provides insight on the

  15. Human health effects of dust exposure in anmial confinement buildings

    NARCIS (Netherlands)

    Iversen, M.; Kirychuk, S.; Drost, H.; Jacobson, L.

    2001-01-01

    Work in swine and poultry units is associated with exposure to significant levels of organic dust and endotoxins with the highest concentrations found in poultry houses, whereas values found in dairy and in cattle farming are much lower. Corresponding to this is an excess of work-related respiratory

  16. Prenatal low-dose methylmercury exposure impairs neurite outgrowth and synaptic protein expression and suppresses TrkA pathway activity and eEF1A1 expression in the rat cerebellum

    Energy Technology Data Exchange (ETDEWEB)

    Fujimura, Masatake, E-mail: fujimura@nimd.go.jp [Department of Basic Medical Sciences, National Institute for Minamata Disease, Kumamoto (Japan); Usuki, Fusako [Department of Clinical Medicine, National Institute for Minamata Disease, Kumamoto (Japan); Cheng, Jinping; Zhao, Wenchang [School of Environmental Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240 (China)

    2016-05-01

    Methylmercury (MeHg) is a highly neurotoxic environmental chemical that can cause developmental impairments. Human fetuses and neonates are particularly susceptible to MeHg toxicity; however, the mechanisms governing its effects in the developing brain are unclear. In the present study, we investigated the effects of prenatal and lactational MeHg exposure on the developing cerebellum in rats. We demonstrated that exposure to 5 ppm MeHg decreased postnatal expression of pre- and postsynaptic proteins, suggesting an impairment in synaptic development. MeHg exposure also reduced neurite outgrowth, as shown by a decrease in the expression of the neurite marker neurofilament H. These changes were not observed in rats exposed to 1 ppm MeHg. In order to define the underlying mechanism, we investigated the effects of MeHg exposure on the tropomyosin receptor kinase (Trk) A pathway, which plays important roles in neuronal differentiation and synapse formation. We demonstrated suppression of the TrkA pathway on gestation day 20 in rats exposed to 5 ppm MeHg. In addition, down-regulation of eukaryotic elongation factor 1A1 (eEF1A1) was observed on postnatal day 1. eEF1A1 knockdown in differentiating PC12 cells impaired neurite outgrowth and synaptic protein expression, similar to the results of MeHg exposure in the cerebellum. These results suggest that suppression of the TrkA pathway and subsequent decreases in eEF1A1 expression induced by prenatal exposure to MeHg may lead to reduced neurite outgrowth and synaptic protein expression in the developing cerebellum. - Highlights: • Prenatal exposure to MeHg decreased postnatal expression of synaptic proteins. • MeHg exposure also reduced neurite outgrowth postnatally. • Suppression of the TrkA pathway and eEF1A1 expression was induced by MeHg exposure. • eEF1A1 knockdown impaired neurite outgrowth and synaptic protein expression.

  17. Prenatal low-dose methylmercury exposure impairs neurite outgrowth and synaptic protein expression and suppresses TrkA pathway activity and eEF1A1 expression in the rat cerebellum

    International Nuclear Information System (INIS)

    Fujimura, Masatake; Usuki, Fusako; Cheng, Jinping; Zhao, Wenchang

    2016-01-01

    Methylmercury (MeHg) is a highly neurotoxic environmental chemical that can cause developmental impairments. Human fetuses and neonates are particularly susceptible to MeHg toxicity; however, the mechanisms governing its effects in the developing brain are unclear. In the present study, we investigated the effects of prenatal and lactational MeHg exposure on the developing cerebellum in rats. We demonstrated that exposure to 5 ppm MeHg decreased postnatal expression of pre- and postsynaptic proteins, suggesting an impairment in synaptic development. MeHg exposure also reduced neurite outgrowth, as shown by a decrease in the expression of the neurite marker neurofilament H. These changes were not observed in rats exposed to 1 ppm MeHg. In order to define the underlying mechanism, we investigated the effects of MeHg exposure on the tropomyosin receptor kinase (Trk) A pathway, which plays important roles in neuronal differentiation and synapse formation. We demonstrated suppression of the TrkA pathway on gestation day 20 in rats exposed to 5 ppm MeHg. In addition, down-regulation of eukaryotic elongation factor 1A1 (eEF1A1) was observed on postnatal day 1. eEF1A1 knockdown in differentiating PC12 cells impaired neurite outgrowth and synaptic protein expression, similar to the results of MeHg exposure in the cerebellum. These results suggest that suppression of the TrkA pathway and subsequent decreases in eEF1A1 expression induced by prenatal exposure to MeHg may lead to reduced neurite outgrowth and synaptic protein expression in the developing cerebellum. - Highlights: • Prenatal exposure to MeHg decreased postnatal expression of synaptic proteins. • MeHg exposure also reduced neurite outgrowth postnatally. • Suppression of the TrkA pathway and eEF1A1 expression was induced by MeHg exposure. • eEF1A1 knockdown impaired neurite outgrowth and synaptic protein expression.

  18. Plasma metabolomics reveal the correlation of metabolic pathways and Prakritis of humans

    Directory of Open Access Journals (Sweden)

    Amey Shirolkar

    2018-04-01

    Full Text Available Background: Ayurveda, an ancient Indian medicinal system, has categorized human body constitutions in three broad constitutional types (prakritis i.e. Vata, Pitta and Kapha. Objectives: Analysis of plasma metabolites and related pathways to classify Prakriti specific dominant marker metabolites and metabolic pathways. Materials and methods: 38 healthy male individuals were assessed for dominant Prakritis and their fasting blood samples were collected. The processed plasma samples were subjected to rapid resolution liquid chromatography–electrospray ionization–quadrupole time of flight mass spectrometry (RRLC–ESI–QTOFMS. Mass profiles were aligned and subjected to multivariate analysis. Results: Partial least square discriminant analysis (PLS-DA model showed 97.87% recognition capability. List of PLS-DA metabolites was subjected to permutative Benjamini–Hochberg false discovery rate (FDR correction and final list of 76 metabolites with p  2.0 was identified. Pathway analysis using metascape and JEPETTO plugins in Cytoscape revealed that steroidal hormone biosynthesis, amino acid, and arachidonic acid metabolism are major pathways varying with different constitution. Biological Go processes analysis showed that aromatic amino acids, sphingolipids, and pyrimidine nucleotides metabolic processes were dominant in kapha type of body constitution. Fat soluble vitamins, cellular amino acid, and androgen biosynthesis process along with branched chain amino acid and glycerolipid catabolic processes were dominant in pitta type individuals. Vata Prakriti was found to have dominant catecholamine, arachidonic acid and hydrogen peroxide metabolomics processes. Conclusion: The neurotransmission and oxidative stress in vata, BCAA catabolic, androgen, xenobiotics metabolic processes in pitta, and aromatic amino acids, sphingolipid, and pyrimidine metabolic process in kapha Prakriti were the dominant marker pathways. Keywords: Ayurveda, Prakriti, Human

  19. Limited infection upon human exposure to a recombinant raccoon pox vaccine vector

    Science.gov (United States)

    Rocke, T.E.; Dein, F.J.; Fuchsberger, M.; Fox, B.C.; Stinchcomb, D.T.; Osorio, J.G.

    2004-01-01

    A laboratory accident resulted in human exposure to a recombinant raccoon poxvirus (RCN) developed as a vaccine vector for antigens of Yersinia pestis for protection of wild rodents (and other animals) against plague. Within 9 days, the patient developed a small blister that healed within 4 weeks. Raccoon poxvirus was cultured from the lesion, and the patient developed antibody to plague antigen (F1) and RCN. This is the first documented case of human exposure to RCN.

  20. Limited infection upon human exposure to a recombinant raccoon pox vaccine vector.

    Science.gov (United States)

    Rocke, Tonie E; Dein, F Joshua; Fuchsberger, Martina; Fox, Barry C; Stinchcomb, Dan T; Osorio, Jorge E

    2004-07-29

    A laboratory accident resulted in human exposure to a recombinant raccoon poxvirus (RCN) developed as a vaccine vector for antigens of Yersinia pestis for protection of wild rodents (and other animals) against plague. Within 9 days, the patient developed a small blister that healed within 4 weeks. Raccoon poxvirus was cultured from the lesion, and the patient developed antibody to plague antigen (F1) and RCN. This is the first documented case of human exposure to RCN.

  1. Hypo-responsiveness of interleukin-8 production in human embryonic epithelial intestine 407 cells independent of NF-κB pathway: New lessons from endotoxin and ribotoxic deoxynivalenol

    International Nuclear Information System (INIS)

    Moon, Yuseok; Yang, Hyun; Park, Seung-Hwan

    2008-01-01

    Mucosal epithelium senses external toxic insults and transmits the danger signals into the epithelial cells in order to activate a broad range of inflammatory responses. However, pre-exposure to the commensal endotoxins can induce inflammatory tolerance and maintain the homeostasis without excessive immune responses. We recently reported that ribotoxin deoxynivalenol (DON) and its derivatives elicited the pro-inflammatory response as the mucosal insults in human epithelial cells. Taking the knowledge into consideration, we tested the hypothesis that endotoxin pre-exposure can attenuate ribotoxin-induced epithelial interleukin-8 (IL-8) production via a tolerance mechanism. Pre-exposure to endotoxin repressed IL-8 release and its gene expression. However, inflammatory tolerance was not mediated by the attenuated NF-κB activation which has been generally recognized as the major mediator of LPS-mediated toll-like receptor (TLR) signaling pathway. Instead, pre-exposure to endotoxin was observed to trigger the delayed induction of peroxisome proliferator-activated receptor gamma (PPAR-γ) which contributed to the diminished IL-8 production in the human epithelial cells. Moreover, endogenous PPAR-γ agonist suppressed toxicant-mediated interleukin-8 production and IL-8 mRNA stability. Taken together, endotoxin induced hypo-production of pro-inflammatory cytokine IL-8 in the human epithelial cells, which was associated with the delayed activation of PPAR-γ expression by pre-existing endotoxin

  2. CONTROLLED EXPOSURES OF HUMAN VOLUNTEERS TO DIESEL ENGINE EXHAUST: BIOMARKERS OF EXPOSURE AND HEALTH OUTCOMES

    Science.gov (United States)

    Combustion of diesel fuel contributes to ambient air pollutant fine particulate matter (PM) and gases. Fine PM exposure has been associated with increased mortality due to adverse cardiac events, and morbidity, such as increased hospitalization for asthma symptoms and lung infect...

  3. Assessment of Relevant Exposure Pathways in Scenario of Reuse of Very Low Level Radioactive Steel in Tunnel Constructions

    International Nuclear Information System (INIS)

    Hrncir, T.; Necas, V.

    2012-01-01

    Decommissioning process and related management of generated radioactive materials during this process became important topics during last several years because of continuously increasing number of nuclear power plant approaching the end of their lifetime. The very low level radioactive waste category includes considerable amount of materials arising from decommissioning. In line with international incentives of optimization of the waste management process, alternative concepts of recycling and reuse of materials are considered. One of these concepts of such optimization is the conditional release of materials with their subsequent recycling and reuse in industrial or nuclear sector. This paper is devoted to an option of recycling and reuse of conditionally released steel in industrial sector, specifically in motorway tunnel constructions. It is assumed that very low level radioactive steel would be released and reused in form of steel reinforcing components, such as steel nets and bars, assembled in primary and secondary lining of motorway tunnel. Assessment of exposure pathways relevant for construction, operation and post-operation period was performed. The computational tool VISIPLAN 3D ALARA was used for calculation of external individual effective dose for personnel constructing the tunnel and for members of the public driving through already built motorway tunnel. The simulation software GOLDSIM was used for the assessment of internal exposure pathways. GOLDSIM environment enables modelling of degradation processes and transport of radionuclides through unsaturated and saturated zone of subsoil. There are international recommendations available for the concept of release of radioactive materials into the environment derived from the principles that the individual effective dose received by critical individual must not exceed some tens of microSv/yr. Dose limits 10 microSv/yr or 50 microSv/yr considering specific conditions are stated in Slovak legislation

  4. Exosomes Derived from Human Bone Marrow Mesenchymal Stem Cells Promote Tumor Growth Through Hedgehog Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Jin Qi

    2017-08-01

    Full Text Available Background/Aims: Mesenchymal stem/stromal cells (MSCs are known to home to sites of tumor microenvironments where they participate in the formation of the tumor microenvironment and to interplay with tumor cells. However, the potential functional effects of MSCs on tumor cell growth are controversial. Here, we, from the view of bone marrow MSC-derived exosomes, study the molecular mechanism of MSCs on the growth of human osteosarcoma and human gastric cancer cells. Methods: MSCs derived from human bone marrow (hBMSCs were isolated and cultured in complete DMEM/F12 supplemented with 10% exosome-depleted fetal bovine serum and 1% penicillin-streptomycin, cell culture supernatants containing exosomes were harvested and exosome purification was performed by ultracentrifugation. Osteosarcoma (MG63 and gastric cancer (SGC7901 cells, respectively, were treated with hBMSC-derived exosomes in the presence or absence of a small molecule inhibitor of Hedgehog pathway. Cell viability was measured by transwell invasion assay, scratch migration assay and CCK-8 test. The expression of the signaling molecules Smoothened, Patched-1, Gli1 and the ligand Shh were tested by western blot and RT-PCR. Results: In this study, we found that hBMSC-derived exosomes promoted MG63 and SGC7901 cell growth through the activation of Hedgehog signaling pathway. Inhibition of Hedgehog signaling pathway significantly suppressed the process of hBMSC-derived exosomes on tumor growth. Conclusion: Our findings demonstrated the new roles of hedgehog signaling pathway in the hBMSCs-derived exosomes induced tumor progression.

  5. Human cerebral venous outflow pathway depends on posture and central venous pressure

    Science.gov (United States)

    Gisolf, J; van Lieshout, J J; van Heusden, K; Pott, F; Stok, W J; Karemaker, J M

    2004-01-01

    Internal jugular veins are the major cerebral venous outflow pathway in supine humans. In upright humans the positioning of these veins above heart level causes them to collapse. An alternative cerebral outflow pathway is the vertebral venous plexus. We set out to determine the effect of posture and central venous pressure (CVP) on the distribution of cerebral outflow over the internal jugular veins and the vertebral plexus, using a mathematical model. Input to the model was a data set of beat-to-beat cerebral blood flow velocity and CVP measurements in 10 healthy subjects, during baseline rest and a Valsalva manoeuvre in the supine and standing position. The model, consisting of 2 jugular veins, each a chain of 10 units containing nonlinear resistances and capacitors, and a vertebral plexus containing a resistance, showed blood flow mainly through the internal jugular veins in the supine position, but mainly through the vertebral plexus in the upright position. A Valsalva manoeuvre while standing completely re-opened the jugular veins. Results of ultrasound imaging of the right internal jugular vein cross-sectional area at the level of the laryngeal prominence in six healthy subjects, before and during a Valsalva manoeuvre in both body positions, correlate highly with model simulation of the jugular cross-sectional area (R2 = 0.97). The results suggest that the cerebral venous flow distribution depends on posture and CVP: in supine humans the internal jugular veins are the primary pathway. The internal jugular veins are collapsed in the standing position and blood is shunted to an alternative venous pathway, but a marked increase in CVP while standing completely re-opens the jugular veins. PMID:15284348

  6. Indicative and complementary effects of human biological indicators for heavy metal exposure assessment.

    Science.gov (United States)

    Xing, Ruiya; Li, Yonghua; Zhang, Biao; Li, Hairong; Liao, Xiaoyong

    2017-10-01

    Although human biological indicators have been widely utilized for biomonitoring environmental pollutants in health exposure assessment, the relationship between internal and external exposure has not yet been adequately established. In this study, we collected and analyzed 61 rice, 56 pepper, and 58 soil samples, together with 107 hair, 107 blood, and 107 urine samples from residents living in selected intensive mining areas in China. Concentrations of most of the four elements considered (Pb, Cd, Hg, and Se) exceeded national standards, implying high exposure risk in the study areas. Regression analysis also revealed a correlation (0.33, P human hair (as well as in human blood); to some extent, Pb content in hair and blood could therefore be used to characterize external Pb exposure. The correlation between Hg in rice and in human hair (up to 0.5, P human hair for Hg exposure. A significant correlation was also noted between concentrations of some elements in different human samples, for example, between Hg in hair and blood (0.641, P assessing heavy metal exposure.

  7. Assessment of human exposure to fumonisin B1

    NARCIS (Netherlands)

    Nijs, M. de; Egmond, H.P. van; Nauta, M.; Rombouts, F.M.; Notermans, S.H.W.

    1998-01-01

    Fumonisin B1 is currently regarded as the most significant mycotoxin produced by Fusarium spp. It has carcinogenic properties and may play a role in the etiology of human esophageal cancer. The human population is exposed to fumonisin B1 primarily by intake of fumonisin B1-contaminated maize. Maize

  8. Identification of molecular candidates and interaction networks via integrative toxicogenomic analysis in a human cell line following low-dose exposure to the carcinogenic metals cadmium and nickel.

    Science.gov (United States)

    Kwon, Jee Young; Weon, Jong-Il; Koedrith, Preeyaporn; Park, Kang-Sik; Kim, Im Soon; Seo, Young Rok

    2013-09-01

    Cadmium and nickel have been classified as carcinogenic to humans by the World Health Organization's International Agency for Research on Cancer. Given their prevalence in the environment, the fact that cadmium and nickel may cause diseases including cancer even at low doses is a cause for concern. However, the exact mechanisms underlying the toxicological effects induced by low-dose exposure to cadmium and nickel remain to be elucidated. Furthermore, it has recently been recognized that integrative analysis of DNA, mRNA and proteins is required to discover biomarkers and signaling networks relevant to human toxicant exposure. In the present study, we examined the deleterious effects of chronic low-dose exposure of either cadmium or nickel on global profiling of DNA copy number variation, mRNA and proteins. Array comparative genomic hybridization, gene expression microarray and functional proteomics were conducted, and a bioinformatics tool, which predicted signaling pathways, was applied to integrate data for each heavy metal separately and together. We found distinctive signaling networks associated with subchronic low-dose exposure to cadmium and nickel, and identified pathways common to both. ACTB, HSP90AA1, HSPA5 and HSPA8, which are key mediators of pathways related to apoptosis, proliferation and neoplastic processes, were key mediators of the same pathways in low-dose nickel and cadmium exposure in particular. CASP-associated signaling pathways involving CASP3, CASP7 and CASP9 were observed in cadmium-exposed cells. We found that HSP90AA1, one of the main modulators, interacted with HIF1A, AR and BCL2 in nickel-exposed cells. Interestingly, we found that HSP90AA1 was involved in the BCL2-associated apoptotic pathway in the nickel-only data, whereas this gene interacted with several genes functioning in CASP-associated apoptotic signaling in the cadmium-only data. Additionally, JUN and FASN were main modulators in nickel-responsive signaling pathways. Our

  9. A systematic review of the human body burden of e-waste exposure in China.

    Science.gov (United States)

    Song, Qingbin; Li, Jinhui

    2014-07-01

    As China is one of the countries facing the most serious pollution and human exposure effects of e-waste in the world, much of the population there is exposed to potentially hazardous substances due to informal e-waste recycling processes. This report reviews recent studies on human exposure to e-waste in China, with particular focus on exposure routes (e.g. dietary intake, inhalation, and soil/dust ingestion) and human body burden markers (e.g. placenta, umbilical cord blood, breast milk, blood, hair, and urine) and assesses the evidence for the association between such e-waste exposure and the human body burden in China. The results suggest that residents in the e-waste exposure areas, located mainly in the three traditional e-waste recycling sites (Taizhou, Guiyu, and Qingyuan), are faced with a potential higher daily intake of these pollutants than residents in the control areas, especially via food ingestion. Moreover, pollutants (PBBs, PBDEs, PCBs, PCDD/Fs, and heavy metals) from the e-waste recycling processes were all detectable in the tissue samples at high levels, showing that they had entered residents' bodies through the environment and dietary exposure. Children and neonates are the groups most sensitive to the human body effects of e-waste exposure. We also recorded plausible outcomes associated with exposure to e-waste, including 7 types of human body burden. Although the data suggest that exposure to e-waste is harmful to health, better designed epidemiological investigations in vulnerable populations, especially neonates and children, are needed to confirm these associations. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Activation of IGF-1 and insulin signaling pathways ameliorate mitochondrial function and energy metabolism in Huntington's Disease human lymphoblasts.

    Science.gov (United States)

    Naia, Luana; Ferreira, I Luísa; Cunha-Oliveira, Teresa; Duarte, Ana I; Ribeiro, Márcio; Rosenstock, Tatiana R; Laço, Mário N; Ribeiro, Maria J; Oliveira, Catarina R; Saudou, Frédéric; Humbert, Sandrine; Rego, A Cristina

    2015-02-01

    Huntington's disease (HD) is an inherited neurodegenerative disease caused by a polyglutamine repeat expansion in the huntingtin protein. Mitochondrial dysfunction associated with energy failure plays an important role in this untreated pathology. In the present work, we used lymphoblasts obtained from HD patients or unaffected parentally related individuals to study the protective role of insulin-like growth factor 1 (IGF-1) versus insulin (at low nM) on signaling and metabolic and mitochondrial functions. Deregulation of intracellular signaling pathways linked to activation of insulin and IGF-1 receptors (IR,IGF-1R), Akt, and ERK was largely restored by IGF-1 and, at a less extent, by insulin in HD human lymphoblasts. Importantly, both neurotrophic factors stimulated huntingtin phosphorylation at Ser421 in HD cells. IGF-1 and insulin also rescued energy levels in HD peripheral cells, as evaluated by increased ATP and phosphocreatine, and decreased lactate levels. Moreover, IGF-1 effectively ameliorated O2 consumption and mitochondrial membrane potential (Δψm) in HD lymphoblasts, which occurred concomitantly with increased levels of cytochrome c. Indeed, constitutive phosphorylation of huntingtin was able to restore the Δψm in lymphoblasts expressing an abnormal expansion of polyglutamines. HD lymphoblasts further exhibited increased intracellular Ca(2+) levels before and after exposure to hydrogen peroxide (H2O2), and decreased mitochondrial Ca(2+) accumulation, being the later recovered by IGF-1 and insulin in HD lymphoblasts pre-exposed to H2O2. In summary, the data support an important role for IR/IGF-1R mediated activation of signaling pathways and improved mitochondrial and metabolic function in HD human lymphoblasts.

  11. Human exposure to herpesvirus B-seropositive macaques, Bali, Indonesia.

    Science.gov (United States)

    Engel, Gregory A; Jones-Engel, Lisa; Schillaci, Michael A; Suaryana, Komang Gde; Putra, Artha; Fuentes, Agustin; Henkel, Richard

    2002-08-01

    Herpesvirus B (Cercopithecine herpesvirus 1) has been implicated as the cause of approximately 40 cases of meningoencephalitis affecting persons in direct or indirect contact with laboratory macaques. However, the threat of herpesvirus B in nonlaboratory settings worldwide remains to be addressed. We investigated the potential for exposure to herpesvirus B in workers at a "monkey forest" (a temple that has become a tourist attraction because of its monkeys) in Bali, Indonesia. In July 2000, 105 workers at the Sangeh Monkey Forest in Central Bali were surveyed about contact with macaques (Macaca fascicularis). Nearly half of those interviewed had either been bitten or scratched by a macaque. Prevalence of injury was higher in those who fed macaques. Serum from 31 of 38 Sangeh macaques contained antibodies to herpesvirus B. We conclude that workers coming into contact with macaques at the Sangeh Monkey Forest are at risk for exposure to herpesvirus B.

  12. Controlled human exposure to indoor air, dust, and ozone; XDOZ

    DEFF Research Database (Denmark)

    Elholm, Grethe; Bønløkke, Jakob; Schlünssen, Vivi

    2017-01-01

    . All participants were subjected to four different exposure scenarios in the climate chamber.Exp. 1: Dust (250 – 300 µg/m3)Exp. 2: Ozone (100 ppb)Exp. 3: Dust (250 – 300 µg/m3) + ozone (100 ppb)Exp. 4: Filtered air (<20µg/m3)The exposure time was 5½ hours for each session.The health effects were...... evaluated at baseline and specific follow-up times in relation to selected respiratory and cardiovascular outcomes, such as; nasal volume, exhaled nitric oxide (FENO), spirometry (FEV1 and FVC), exhaled breath condensate (EBC), nasal lavage, blood samples, EndoPat. Questionnaires were used for assessment...

  13. The human placenta--an alternative for studying foetal exposure

    DEFF Research Database (Denmark)

    Myren, Maja; Mose, Tina; Mathiesen, Line

    2007-01-01

    Pregnant women are daily exposed to a wide selection of foreign substances. Sources are as different as lifestyle factors (smoking, daily care products, alcohol consumption, etc.), maternal medication or occupational/environmental exposures. The placenta provides the link between mother and foetus......, and though its main task is to act as a barrier and transport nutrients and oxygen to the foetus, many foreign compounds are transported across the placenta to some degree and may therefore influence the unborn child. Foetal exposures to environmental and medicinal products may have impact on the growth...... of the foetus (e.g. cigarette smoke) and development of the foetal organs (e.g. methylmercury and thalidomide). The scope of this review is to give insight to the placental anatomy, development and function. Furthermore, the compounds physical properties and the transfer mechanism across the placental barrier...

  14. The Impact of Hedgehog Signaling Pathway on DNA Repair Mechanisms in Human Cancer

    International Nuclear Information System (INIS)

    Meng, Erhong; Hanna, Ann; Samant, Rajeev S.; Shevde, Lalita A.

    2015-01-01

    Defined cellular mechanisms have evolved that recognize and repair DNA to protect the integrity of its structure and sequence when encountering assaults from endogenous and exogenous sources. There are five major DNA repair pathways: mismatch repair, nucleotide excision repair, direct repair, base excision repair and DNA double strand break repair (including non-homologous end joining and homologous recombination repair). Aberrant activation of the Hedgehog (Hh) signaling pathway is a feature of many cancer types. The Hh pathway has been documented to be indispensable for epithelial-mesenchymal transition, invasion and metastasis, cancer stemness, and chemoresistance. The functional transcription activators of the Hh pathway include the GLI proteins. Inhibition of the activity of GLI can interfere with almost all DNA repair types in human cancer, indicating that Hh/GLI functions may play an important role in enabling tumor cells to survive lethal types of DNA damage induced by chemotherapy and radiotherapy. Thus, Hh signaling presents an important therapeutic target to overcome DNA repair-enabled multi-drug resistance and consequently increase chemotherapeutic response in the treatment of cancer

  15. The Impact of Hedgehog Signaling Pathway on DNA Repair Mechanisms in Human Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Erhong; Hanna, Ann; Samant, Rajeev S.; Shevde, Lalita A., E-mail: lsamant@uab.edu [Department of Pathology, Comprehensive Cancer Center, University of Alabama at Birmingham, WTI320D, 1824 6th Avenue South, Birmingham, AL 35233 (United States)

    2015-07-21

    Defined cellular mechanisms have evolved that recognize and repair DNA to protect the integrity of its structure and sequence when encountering assaults from endogenous and exogenous sources. There are five major DNA repair pathways: mismatch repair, nucleotide excision repair, direct repair, base excision repair and DNA double strand break repair (including non-homologous end joining and homologous recombination repair). Aberrant activation of the Hedgehog (Hh) signaling pathway is a feature of many cancer types. The Hh pathway has been documented to be indispensable for epithelial-mesenchymal transition, invasion and metastasis, cancer stemness, and chemoresistance. The functional transcription activators of the Hh pathway include the GLI proteins. Inhibition of the activity of GLI can interfere with almost all DNA repair types in human cancer, indicating that Hh/GLI functions may play an important role in enabling tumor cells to survive lethal types of DNA damage induced by chemotherapy and radiotherapy. Thus, Hh signaling presents an important therapeutic target to overcome DNA repair-enabled multi-drug resistance and consequently increase chemotherapeutic response in the treatment of cancer.

  16. Novel Human Radiation Exposure Biomarker Panel Applicable for Population Triage

    Energy Technology Data Exchange (ETDEWEB)

    Bazan, Jose G. [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Chang, Polly; Balog, Robert; D' Andrea, Annalisa; Shaler, Thomas; Lin, Hua; Lee, Shirley; Harrison, Travis [SRI International, Menlo Park, California (United States); Shura, Lei; Schoen, Lucy; Knox, Susan J. [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Cooper, David E., E-mail: david.cooper@sri.com [SRI International, Menlo Park, California (United States)

    2014-11-01

    Purpose: To identify a panel of radiation-responsive plasma proteins that could be used in a point-of-care biologic dosimeter to detect clinically significant levels of ionizing radiation exposure. Methods and Materials: Patients undergoing preparation for hematopoietic cell transplantation using radiation therapy (RT) with either total lymphoid irradiation or fractionated total body irradiation were eligible. Plasma was examined from patients with potentially confounding conditions and from normal individuals. Each plasma sample was analyzed for a panel of 17 proteins before RT was begun and at several time points after RT exposure. Paired and unpaired t tests between the dose and control groups were performed. Conditional inference trees were constructed based on panels of proteins to compare the non-RT group with the RT group. Results: A total of 151 patients (62 RT, 41 infection, 48 trauma) were enrolled on the study, and the plasma from an additional 24 healthy control individuals was analyzed. In comparison with to control individuals, tenascin-C was upregulated and clusterin was downregulated in patients receiving RT. Salivary amylase was strongly radiation responsive, with upregulation in total body irradiation patients and slight downregulation in total lymphoid irradiation patients compared with control individuals. A panel consisting of these 3 proteins accurately distinguished between irradiated patients and healthy control individuals within 3 days after exposure: 97% accuracy, 0.5% false negative rate, 2% false positive rate. The accuracy was diminished when patients with trauma, infection, or both were included (accuracy, 74%-84%; false positive rate, 14%-33%, false negative rate: 8%-40%). Conclusions: A panel of 3 proteins accurately distinguishes unirradiated healthy donors from those exposed to RT (0.8-9.6 Gy) within 3 days of exposure. These findings have significant implications in terms of triaging individuals in the case of nuclear or other

  17. Lead Exposure Induces Telomere Instability in Human Cells.

    Directory of Open Access Journals (Sweden)

    Géraldine Pottier

    Full Text Available Lead (Pb is an important environmental contaminant due to its widespread use over many centuries. While it affects primarily every organ system of the body, the most pernicious effects of Pb are on the central nervous system leading to cognitive and behavioral modification. Despite decades of research, the mechanisms responsible for Pb toxicity remain poorly understood. Recent work has suggested that Pb exposure may have consequences on chromosomal integrity as it was shown that Pb exposure leads to the generation of γH2Ax foci, a well-established biomarker for DNA double stranded break (DSB formation. As the chromosomal localization of γH2Ax foci plays an important role in determining the molecular mechanism responsible for their formation, we examined the localization of Pb-induced foci with respect to telomeres. Indeed, short or dysfunctional telomeres (uncapped or damaged telomeres may be recognized as DSB by the DNA repair machinery, leading to "telomere-Induced Foci" (TIFs. In the current study, we show that while Pb exposure did not increase intra-chromosomal foci, it significantly induced TIFs, leading in some cases, to chromosomal abnormalities including telomere loss. The evidence suggests that these chromosomal abnormalities are likely due to perturbation of telomere replication, in particular on the lagging DNA strand. We propose a mechanism by which Pb exposure leads to the loss of telomere maintenance. As numerous studies have demonstrated a role for telomere maintenance in brain development and tissue homeostasis, our results suggest a possible mechanism for lead-induced neurotoxicity.

  18. Chromosomal Aberrations in Canine Gliomas Define Candidate Genes and Common Pathways in Dogs and Humans

    Science.gov (United States)

    York, Dan; Higgins, Robert J.; LeCouteur, Richard A.; Joshi, Nikhil; Bannasch, Danika

    2016-01-01

    Spontaneous gliomas in dogs occur at a frequency similar to that in humans and may provide a translational model for therapeutic development and comparative biological investigations. Copy number alterations in 38 canine gliomas, including diffuse astrocytomas, glioblastomas, oligodendrogliomas, and mixed oligoastrocytomas, were defined using an Illumina 170K single nucleotide polymorphism array. Highly recurrent alterations were seen in up to 85% of some tumor types, most notably involving chromosomes 13, 22, and 38, and gliomas clustered into 2 major groups consisting of high-grade IV astrocytomas, or oligodendrogliomas and other tumors. Tumor types were characterized by specific broad and focal chromosomal events including focal loss of the INK4A/B locus in glioblastoma and loss of the RB1 gene and amplification of the PDGFRA gene in oligodendrogliomas. Genes associated with the 3 critical pathways in human high-grade gliomas (TP53, RB1, and RTK/RAS/PI3K) were frequently associated with canine aberrations. Analysis of oligodendrogliomas revealed regions of chromosomal losses syntenic to human 1p involving tumor suppressor genes, such as CDKN2C, as well as genes associated with apoptosis, autophagy, and response to chemotherapy and radiation. Analysis of high frequency chromosomal aberrations with respect to human orthologues may provide insight into both novel and common pathways in gliomagenesis and response to therapy. PMID:27251041

  19. Acute effects of acrolein in human volunteers during controlled exposure.

    Science.gov (United States)

    Dwivedi, Aishwarya M; Johanson, Gunnar; Lorentzen, Johnny C; Palmberg, Lena; Sjögren, Bengt; Ernstgård, Lena

    2015-01-01

    Acrolein is a reactive aldehyde mainly formed by combustion. The critical effect is considered to be irritation of the eyes and airways; however, the scarce data available make it difficult to assess effect levels. The aim of the study was to determine thresholds for acute irritation for acrolein. Nine healthy volunteers of each sex were exposed at six occasions for 2 h at rest to: clean air, 15 ppm ethyl acetate (EA), and 0.05 ppm and 0.1 ppm acrolein with and without EA (15 ppm) to mask the potential influence of odor. Symptoms related to irritation and central nervous system effects were rated on 100-mm Visual Analogue Scales. The ratings of eye irritation were slightly but significantly increased during exposure to acrolein in a dose-dependent manner (p acrolein alone but not during any of the other five exposure conditions. Based on subjective ratings, the present study showed minor eye irritation by exposure to 0.1 ppm acrolein.

  20. Wnt pathway reprogramming during human embryonal carcinoma differentiation and potential for therapeutic targeting

    International Nuclear Information System (INIS)

    Snow, Grace E; Kasper, Allison C; Busch, Alexander M; Schwarz, Elisabeth; Ewings, Katherine E; Bee, Thomas; Spinella, Michael J; Dmitrovsky, Ethan; Freemantle, Sarah J

    2009-01-01

    Testicular germ cell tumors (TGCTs) are classified as seminonas or non-seminomas of which a major subset is embryonal carcinoma (EC) that can differentiate into diverse tissues. The pluripotent nature of human ECs resembles that of embryonic stem (ES) cells. Many Wnt signalling species are regulated during differentiation of TGCT-derived EC cells. This study comprehensively investigated expression profiles of Wnt signalling components regulated during induced differentiation of EC cells and explored the role of key components in maintaining pluripotency. Human embryonal carcinoma cells were stably infected with a lentiviral construct carrying a canonical Wnt responsive reporter to assess Wnt signalling activity following induced differentiation. Cells were differentiated with all-trans retinoic acid (RA) or by targeted repression of pluripotency factor, POU5F1. A Wnt pathway real-time-PCR array was used to evaluate changes in gene expression as cells differentiated. Highlighted Wnt pathway genes were then specifically repressed using siRNA or stable shRNA and transfected EC cells were assessed for proliferation, differentiation status and levels of core pluripotency genes. Canonical Wnt signalling activity was low basally in undifferentiated EC cells, but substantially increased with induced differentiation. Wnt pathway gene expression levels were compared during induced differentiation and many components were altered including ligands (WNT2B), receptors (FZD5, FZD6, FZD10), secreted inhibitors (SFRP4, SFRP1), and other effectors of Wnt signalling (FRAT2, DAAM1, PITX2, Porcupine). Independent repression of FZD5, FZD7 and WNT5A using transient as well as stable methods of RNA interference (RNAi) inhibited cell growth of pluripotent NT2/D1 human EC cells, but did not appreciably induce differentiation or repress key pluripotency genes. Silencing of FZD7 gave the greatest growth suppression in all human EC cell lines tested including NT2/D1, NT2/D1-R1, Tera-1 and 833

<