WorldWideScience

Sample records for humane purposes chemical

  1. Chemical profiling of chemical warfare agents for forensic purposes

    NARCIS (Netherlands)

    Noort, D.; Reuver, L.P.J. de; Fidder, A.; Tromp, M.; Verschraagen, M.

    2010-01-01

    A program has been initiated towards the chemical profiling of chemical warfare agents, in order to support forensic investigations towards synthesis routes, production sites and suspect chemical suppliers. Within the first stage of the project various chemical warfare agents (VX, sulfur mustard,

  2. Chemical allergy in humans

    DEFF Research Database (Denmark)

    Kimber, Ian; Basketter, David A; Thyssen, Jacob P

    2014-01-01

    Abstract There is considerable interest in the immunobiological processes through which the development of allergic sensitization to chemicals is initiated and orchestrated. One of the most intriguing issues is the basis for the elicitation by chemical sensitizers of different forms of allergic...... reaction; that is, allergic contact dermatitis or sensitization of the respiratory tract associated with occupational asthma. Studies in rodents have revealed that differential forms of allergic sensitization to chemicals are, in large part at least, a function of the selective development of discrete...... functional sub-populations of CD4(+) and CD8(+) T-lymphocytes. Evidence for a similar association of chemical allergy in humans with discrete T-lymphocyte populations is, however, limited. It is of some interest, therefore, that two recent articles from different teams of investigators have shed new light...

  3. DYNSYL: a general-purpose dynamic simulator for chemical processes

    International Nuclear Information System (INIS)

    Patterson, G.K.; Rozsa, R.B.

    1978-01-01

    Lawrence Livermore Laboratory is conducting a safeguards program for the Nuclear Regulatory Commission. The goal of the Material Control Project of this program is to evaluate material control and accounting (MCA) methods in plants that handle special nuclear material (SNM). To this end we designed and implemented the dynamic chemical plant simulation program DYNSYL. This program can be used to generate process data or to provide estimates of process performance; it simulates both steady-state and dynamic behavior. The MCA methods that may have to be evaluated range from sophisticated on-line material trackers such as Kalman filter estimators, to relatively simple material balance procedures. This report describes the overall structure of DYNSYL and includes some example problems. The code is still in the experimental stage and revision is continuing

  4. Physical and chemical assessment of MSF distillate and SWRO product for drinking purpose

    KAUST Repository

    Gacem, Yasmine; Taleb, Safia; Ramdani, Amina; Senadjki, Samia; Ghaffour, NorEddine

    2012-01-01

    The objective of this study was to evaluate the physical and chemical proprieties of desalinated seawater produced by Multi Stage Flash (MSF) and Reverse Osmosis (RO) processes for drinking purpose. The final products, after post

  5. MR chemical shift imaging of human atheroma

    International Nuclear Information System (INIS)

    Mohiaddin, R.H.; Underwood, R.; Firmin, D.; Abdulla, A.K.; Rees, S.; Longmore, D.

    1988-01-01

    The lipid content of atheromatous plaques has been measured with chemical shift MR imaging by taking advantage of the different resonance frequencies of protons in lipid and water. Fifteen postmortem aortic specimens of the human descending aorta and the aortae of seven patients with documented peripheral vascular disease were studied at 0.5 T. Spin-echo images were used to localize the lesions before acquisition of the chemical shift images. The specimens were examined histologically, and the lipid distribution in the plaque showed good correlation with the chemical shift data. Validation in vivo and clinical applications remain to be established

  6. Physical and chemical assessment of MSF distillate and SWRO product for drinking purpose

    KAUST Repository

    Gacem, Yasmine

    2012-03-01

    The objective of this study was to evaluate the physical and chemical proprieties of desalinated seawater produced by Multi Stage Flash (MSF) and Reverse Osmosis (RO) processes for drinking purpose. The final products, after post-treatment and blending, of Kahrama MSF and Bousfer SWRO plants located in different sites were investigated in this study. Different samples were taken from raw water and product before and after post-treatments in both plants. The physical and chemical balance revealed that the desalinated water produced by MSF plant is of better quality than that produced by the SWRO plant. The Langelier Saturation Index (LSI) was used as an indicator of the aggressiveness and corrosiveness of potable water. Indeed, the LSI of the distillate was slightly positive with over 77% of the values ranging from 0 to 0.13 while about 23% of the values were negative. This is due to the increase of MSF product water temperature from 29 °C to 33.82 °C during the investigation period and the calcium levels which decreased to a minimum value of 45.95. mg/l. On the other hand, the SWRO desalinated water had a negative LSI with values ranging from -3.27 to -1.85. These results are not within the recommended LSI values (between 0 and 0.4), which means that the product is highly aggressive and becomes improper for human consumption. These negative values are directly related to the RO product water temperature below 24.6 °C and calcium concentration below 16.03. mg/l as well as the lack of proper post-treatment process. From this investigation, it was recommended to improve the RO product post-treatment to make the remineralization process more effective. Some recommended guidelines suggested by the authors were presented in this paper. © 2012 Elsevier B.V.

  7. Environmental Chemicals and Human Neurotoxicity: Magnitude ...

    African Journals Online (AJOL)

    Olaleye

    altered neurocthemical, electrophysiological or behavioural functions. The adverse effects of neurotoxicity are among the most feared ill health in humans ... chemicals through air, food, or drinking water. The infamous ..... environment can disrupt the neurological control .... that perception and memory gradually fade,.

  8. Atomic scale chemical tomography of human bone

    Science.gov (United States)

    Langelier, Brian; Wang, Xiaoyue; Grandfield, Kathryn

    2017-01-01

    Human bone is a complex hierarchical material. Understanding bone structure and its corresponding composition at the nanometer scale is critical for elucidating mechanisms of biomineralization under healthy and pathological states. However, the three-dimensional structure and chemical nature of bone remains largely unexplored at the nanometer scale due to the challenges associated with characterizing both the structural and chemical integrity of bone simultaneously. Here, we use correlative transmission electron microscopy and atom probe tomography for the first time, to our knowledge, to reveal structures in human bone at the atomic level. This approach provides an overlaying chemical map of the organic and inorganic constituents of bone on its structure. This first use of atom probe tomography on human bone reveals local gradients, trace element detection of Mg, and the co-localization of Na with the inorganic-organic interface of bone mineral and collagen fibrils, suggesting the important role of Na-rich organics in the structural connection between mineral and collagen. Our findings provide the first insights into the hierarchical organization and chemical heterogeneity in human bone in three-dimensions at its smallest length scale - the atomic level. We demonstrate that atom probe tomography shows potential for new insights in biomineralization research on bone.

  9. Chemical Biomarkers of Human Breast Milk Pollution

    Directory of Open Access Journals (Sweden)

    Benedetta Marchi

    2008-01-01

    Full Text Available Human milk is, without question, the best source of nutrition for infants containing the optimal balance of fats, carbohydrates and proteins for developing babies. Breastfeeding provides a range of benefits for growth, immunity and development building a powerful bond between mother and her child. Recognition of the manifold benefits of breast milk has led to the adoption of breast-feeding policies by numerous health and professional organizations such as the World Health Organization and American Academy of Pediatrics.In industrially developed as well as in developing nations, human milk contamination by toxic chemicals such as heavy metals, dioxins and organohalogen compounds, however, is widespread and is the consequence of decades of inadequately controlled pollution. Through breastfeeding, the mother may transfer to the suckling infant potentially toxic chemicals to which the mother has previously been exposed.In the present review, environmental exposure, acquisition and current levels of old and emerging classes of breast milk pollutants are systematically presented. Although scientific evidences indicated that the advantages of breast-feeding outweigh any risks from contaminants, it is important to identify contaminant trends, to locate disproportionately exposed populations, and to take public health measures to improve chemical BM pollution as possible.

  10. General-purpose chemical analyzer for on-line analyses of radioactive solutions

    International Nuclear Information System (INIS)

    Spencer, W.A.; Kronberg, J.W.

    1983-01-01

    An automated analyzer is being developed to perform analytical measurements on radioactive solutions on-line in a hostile environment. This General Purpose Chemical Analyzer (GPCA) samples a process stream, adds reagents, measures solution absorbances or electrode potentials, and automatically calculates the results. The use of modular components, under microprocessor control, permits a single analyzer design to carry out many types of analyses. This paper discusses the more important design criteria for the GPCA, and describes the equipment being tested in a prototype unit

  11. Determination of some variables of human dentin for dosimetric purposes

    International Nuclear Information System (INIS)

    Peres, C.

    1990-01-01

    The initial objective of this work is to determine the atomic composition of human dentin, using various techniques of measurements such as X-Ray fluorescence, atomic absorption, spectrophotometry, volumetric analysis, chemistry, colorimetry and thermogravimetry. With the values of the effective atomic number Z bar dependent of the quality of the ionizing radiation, one can find the kind of material that can be used for a phantom equivalent to dentin. (author)

  12. Chemical ecology of interactions between human skin microbiota and mosquitoes

    NARCIS (Netherlands)

    Verhulst, N.O.; Takken, W.; Dicke, M.; Schraa, G.; Smallegange, R.C.

    2010-01-01

    Microbiota on the human skin plays a major role in body odour production. The human microbial and chemical signature displays a qualitative and quantitative correlation. Genes may influence the chemical signature by shaping the composition of the microbiota. Recent studies on human skin microbiota,

  13. Chemical incidents resulted in hazardous substances releases in the context of human health hazards.

    OpenAIRE

    Palaszewska-Tkacz, Anna; Czerczak, Sławomir; Konieczko, Katarzyna

    2017-01-01

    Objectives: The research purpose was to analyze data concerning chemical incidents in Poland collected in 1999–2009 in terms of health hazards. Material and Methods: The data was obtained, using multimodal information technology (IT) system, from chemical incidents reports prepared by rescuers at the scene. The final analysis covered sudden events associated with uncontrolled release of hazardous chemical substances or mixtures, which may potentially lead to human exposure. Releases of uniden...

  14. Human Metabolism and Interactions of Deployment-Related Chemicals

    National Research Council Canada - National Science Library

    Hodgson, Ernest

    2003-01-01

    This study examines the human-metabolism and metabolic interactions of a subset of deployment-related chemicals, including chlorpyrifos, DEET, permethrin, pyridostigmine bromide, and sulfur mustard metabolites...

  15. Comparison of the chemical behaviour of humanized ACMS VS. Human IGG radiolabeled with 99mTc

    International Nuclear Information System (INIS)

    Rivero Santamaria, Alejandro; Zayas Crespo, Francisco; Mesa Duennas, Niurka; Castillo Vitloch, Adolfo J.

    2003-01-01

    The purpose of this work is to compare the chemical behaviour of humanized AcMs vs. human IgG radiolabeled with 99 mTc. to this end, 3 immunoglobulins were analyzed, the IgG (human), the humanized monoclonal antibody R3 (Acm-R3h) and the humanized monoclonal antibody T1. The results obtained reveal slight differences as regards the behaviour of theses immunoglobulins before the labelling with 99T c, which shows differences in the chemical behaviour of these proteins. Although in theory the modifications that are made to the AcMs in order to humanize them must not affect their chemical behaviour, the obtained data indicate that the conditions for their radiolabelling should not be extrapolated from other proteins; on the contrary, particular procedures should be elaborated for each AcM-h

  16. Investigation of correlations in some chemical impurities and isotope ratios for nuclear forensic purposes

    International Nuclear Information System (INIS)

    Wallenius, M.; Mayer, K.; Nicholl, A.; Horta, J.

    2002-01-01

    geographic location. Furthermore, we performed measurements of impurities and the n( 18 O)/n( 16 O) ratio in a set of uranium dioxide pellet samples (from different production batches) that had been produced in the same facility. This 'horizontal' comparison (same facility and same material type) aims at providing information on the consistency of data obtained and on the variation in the level and the relative abundance of some impurities. A better understanding of the propagation of chemical impurities from the base material to the final product and the correlation between the relative concentrations of individual impurities is important in the definition of characteristic impurities for nuclear forensic purposes. (author)

  17. Concept for Recycling Waste Biomass from the Sugar Industry for Chemical and Biotechnological Purposes.

    Science.gov (United States)

    Modelska, Magdalena; Berlowska, Joanna; Kregiel, Dorota; Cieciura, Weronika; Antolak, Hubert; Tomaszewska, Jolanta; Binczarski, Michał; Szubiakiewicz, Elzbieta; Witonska, Izabela A

    2017-09-13

    The objective of this study was to develop a method for the thermally-assisted acidic hydrolysis of waste biomass from the sugar industry (sugar beet pulp and leaves) for chemical and biotechnological purposes. The distillates, containing furfural, can be catalytically reduced directly into furfurayl alcohol or tetrahydrofurfuryl alcohol. The sugars present in the hydrolysates can be converted by lactic bacteria into lactic acid, which, by catalytic reduction, leads to propylene glycol. The sugars may also be utilized by microorganisms in the process of cell proliferation, and the biomass obtained used as a protein supplement in animal feed. Our study also considered the effects of the mode and length of preservation (fresh, ensilage, and drying) on the yields of furfural and monosaccharides. The yield of furfural in the distillates was measured using gas chromatography with flame ionization detector (GC-FID). The content of monosaccharides in the hydrolysates was measured spectrophotometrically using enzymatic kits. Biomass preserved under all tested conditions produced high yields of furfural, comparable to those for fresh material. Long-term storage of ensiled waste biomass did not result in loss of furfural productivity. However, there were significant reductions in the amounts of monosaccharides in the hydrolysates.

  18. Environmental Chemicals and Human Neurotoxicity: Magnitude ...

    African Journals Online (AJOL)

    Olaleye

    metals such as lead and arsenic in drinking water. This article ..... adequate supply of energy, oxygen and essential nutrients but ... vitamins and minerals such as vitamins C and E balance the ... Chemicals may interact with the DNA molecule ...

  19. 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.

  20. Protection of Human Beings Trafficked for the Purpose of Organ Removal: Recommendations

    OpenAIRE

    Pascalev, Assya; Van Assche, Kristof; S?ndor, Judit; Codreanu, Natalia; Naqvi, Anwar; Gunnarson, Martin; Frunza, Mihaela; Yankov, Jordan

    2016-01-01

    Abstract This report presents a comprehensive set of recommendations for protection of human beings who are trafficked for the purpose of organ removal or are targeted for such trafficking. Developed by an interdisciplinary group of international experts under the auspices of the project Trafficking in Human Beings for the Purpose of Organ Removal (also known as the HOTT project), these recommendations are grounded in the view that an individual who parts with an organ for money within an ill...

  1. Chemical Contaminants in Raw and Pasteurized Human Milk.

    Science.gov (United States)

    Hartle, Jennifer C; Cohen, Ronald S; Sakamoto, Pauline; Barr, Dana Boyd; Carmichael, Suzan L

    2018-05-01

    Environmental contaminants ranging from legacy chemicals like p,p'-dichlorodiphenyltrichloroethane (DDT) to emerging chemicals like phthalates are ubiquitous. Research aims/questions: This research aims to examine the presence and co-occurrence of contaminants in human milk and effects of pasteurization on human milk chemical contaminants. We analyzed human milk donated by 21 women to a milk bank for 23 chemicals, including the persistent organic pollutants (POPs) polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), dichlorodiphenyltrichloroethane (DDT), and dichlorodiphenyldichloroethylene (DDE) isomers that are known to sequester in adipose tissue, along with the current-use and nonpersistent pesticides chlorpyrifos and permethrin, phthalates, and bisphenol A (BPA). Human milk was analyzed raw and pasteurized for these chemicals using gas chromatography-tandem mass spectrometry for the POPs and high-performance liquid chromatography-tandem mass spectrometry for non-POPs. Within the different chemical classes, PBDE47, PCB153, ppDDE, and MEHHP (phthalate metabolite) had the highest median concentrations and were observed in all samples. We also observed chlorpyrifos and BPA in all samples and permethrin in 90% of the samples tested. Only two chemicals, chlorpyrifos and permethrin, were susceptible to substantial degradation from pasteurization, a standard method for processing donated human milk. We detected 19 of 23 chemicals in all of our prepasteurized milk and 18 of 23 chemicals in all of our pasteurized milk. Pasteurization did not affect the presence of most of the chemicals. Future research should continue to explore human milk for potential chemical contamination and as a means to surveil exposures among women and children.

  2. High Throughput Heuristics for Prioritizing Human Exposure to Environmental Chemicals

    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, f...

  3. 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

  4. Fabrication of radiation sources for educational purposes from chemical fertilizers using compressing and forming method

    International Nuclear Information System (INIS)

    Kawano, Takao

    2008-01-01

    Chemical fertilizers contain potassium, which is composed of a small amount of naturally occurring potassium-40. The potassium-40 radionuclide emits beta and gamma radiation. Three brands of chemical fertilizer were used to fabricate disk-shaped radiation sources and the fabricated radiation sources were examined for applicability to an educational radiation course. In the examination, tests to determine dependence of count rate on distance, shielding thickness, and shielding materials were conducted using the radiation sources. Results showed that radiation sources fabricated from the three brands of chemical fertilizer were equivalent for explaining radiation characteristics, particularly those related to the dependence of radiation strength on distance and shielding thickness. The relation between shielding effect and mass density can be explained qualitatively. Thus, chemical fertilizer radiation sources can be a useful teaching aid for educational courses to better promote understanding of radiation characteristics and the principles of radiation protection. (author)

  5. Inactivation of human norovirus using chemical sanitizers.

    Science.gov (United States)

    Kingsley, David H; Vincent, Emily M; Meade, Gloria K; Watson, Clytrice L; Fan, Xuetong

    2014-02-03

    The porcine gastric mucin binding magnetic bead (PGM-MB) assay was used to evaluate the ability of chlorine, chlorine dioxide, peroxyacetic acid, hydrogen peroxide, and trisodium phosphate to inactivate human norovirus within 10% stool filtrate. One-minute free chlorine treatments at concentrations of 33 and 189 ppm reduced virus binding in the PGM-MB assay by 1.48 and 4.14 log₁₀, respectively, suggesting that chlorine is an efficient sanitizer for inactivation of human norovirus (HuNoV). Five minute treatments with 5% trisodium phosphate (pH~12) reduced HuNoV binding by 1.6 log₁₀, suggesting that TSP, or some other high pH buffer, could be used to treat food and food contact surfaces to reduce HuNoV. One minute treatments with 350 ppm chlorine dioxide dissolved in water did not reduce PGM-MB binding, suggesting that the sanitizer may not be suitable for HuNoV inactivation in liquid form. However a 60-min treatment with 350 ppm chlorine dioxide did reduce human norovirus by 2.8 log₁₀, indicating that chlorine dioxide had some, albeit limited, activity against HuNoV. Results also suggest that peroxyacetic acid has limited effectiveness against human norovirus, since 1-min treatments with up to 195 ppm reduced human norovirus binding by chlorine (sodium hypochlorite) as a HuNoV disinfectant wherever possible. Copyright © 2013. Published by Elsevier B.V.

  6. Purposeful synthesis of chemical elements and ecologically pure mobile sources of energy

    International Nuclear Information System (INIS)

    Krivitsky, V. A.; Gareev, F. A.

    2007-01-01

    It is well known [1] that the natural geo-transmutation of chemical elements occurs in the atmosphere and earth in the regions of a strong change in geo-, bio-, acoustic-, and electromagnetic fields. The mineral row materials contain the same accompanying chemical combinations which are independent of mineral deposit [2]. This means that the formation of chemical elements occurs in the same physical and chemical conditions. These conditions were simulated on the fundamental cooperative resonance synchronization principle [1]. The experimental facility was constructed on the basis of our model which provided with the calculated final chemical elements. These experimental results indicate new possibilities for, simulating, inducing and controlling nuclear reactions by low energy external fields. The borrowing from the geo-transmutation mechanisms of chemical elements creates the fundamental directions in low energy nuclear reaction researches for construction of new ecologically pure mobile sources of energy independent of oil, gas and coal, new substances, and technologies. References [1] F.A. Gareev, I.E. Zhidkova, E-print arXiv Nucl-th/0610002 2006. [2] V.A. Krivzskii, Transmutazija ximicheskix elementov v evolyuzii Semli (in Russian), Moscow 2003

  7. Assessing chemical mutagens: the risk to humans

    International Nuclear Information System (INIS)

    Brewen, J.G.

    1978-01-01

    Some topics discussed are as follows: chromosomal aberrations induced by x radiation, tritiated thymidine, maleic hydrazide, and nitrogen mustard; removal of pyrimidine dimers by photoreactivation in amphibian cells following uv radiation; effects of 4-nitroquinoline-oxide on leukocytes from XP and normal patients; DNA as a target for alkylating agents; sensitivity of spermatogonia to chemical mutagens; chromosomal aberrations induced by 8-ethoxycaffeine, methoxycaffeine, cytosine arabinoside, streptonigrin, bleomycin, and phleomycin; effects of MMS and triethylenemelamine on germ cells; and use of chromosomal aberrations for improving risk estimates for ionizing radiation

  8. 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

  9. Chemical, physical and isotopic characterization of U3Si2, for nuclear forensics purposes

    International Nuclear Information System (INIS)

    Rosa, Daniele Scarpim

    2011-01-01

    In the early 1990's, the first illicit trafficking of nuclear and radioactive materials was observed mainly in Europe. A decade marked by numerous cases of seizures of these materials. As a result, these events have become the subject of criminal forensic investigations and develop from there, nuclear forensics. In Brazil there are no illicit trafficking official records of nuclear material, however, is widely known the extraction and illegal transportation of radioactive geological materials, and the materials pieces attachment used as shielding for radioactive sources. One of the main tools used in nuclear forensics is the nuclear materials databases establishment. These documents must contain the most information as possible about the physical, chemical and nuclear material seized, allowing the identification of their origin, manufacturing process or age. Thus, it sets characteristic composition standards of each material, called 'chemical signatures' (chemical finger print). In this work nuclear forensic protocol was adopted as well as the three stages of assessment suggested by International Atomic Energy Agency (IAEA) in identifying the origin of uranium silicide (U 3 Si 2 ). Assays were performed in order to make physical, chemical and isotopic characterization of the studied materials and compared the data with those obtained for other uranium compounds (Uranium tetrafluoride, UF 4 ; uranium oxide, UO 2 and U 3 O 8 ; Yellow cake) by establishing a characteristic signature for each one. Through the assays the uranium compounds were classify by origin groups, as far as they are from different manufactured process and/ or origin. It was also possible to show the importance of a nuclear forensic database during an investigation of a nuclear forensic event. (author)

  10. Enrolment Purposes, Instructional Activities, and Perceptions of Attitudinal Learning in a Human Trafficking MOOC

    Science.gov (United States)

    Watson, Sunnie Lee; Kim, Woori

    2016-01-01

    This study examines learner enrolment purposes, perceptions on instructional activities and their relationship to learning gains in a Massive Open Online Course (MOOC) for attitudinal change regarding human trafficking. Using an author-developed survey, learners reported their perceptions on instructional activities and learning gains within the…

  11. The Role and Purposes of Public Schools and Religious Fundamentalism: An International Human Rights Law Perspective

    Science.gov (United States)

    Hodgson, Douglas Charles

    2012-01-01

    The question of what are today the legitimate and proper role and purposes of public schools can only be answered by a close examination and analysis of the human right to education which has been developed by such international organizations as the United Nations and the United Nations Educational, Scientific and Cultural Organization, and by…

  12. Thriving with Social Purpose: An Integrative Approach to the Development of Optimal Human Functioning

    Science.gov (United States)

    Ford, Martin E.; Smith, Peyton R.

    2007-01-01

    This article responds to the need to synthesize theory and research in educational psychology by introducing the Thriving with Social Purpose (TSP) conceptual framework. TSP results when the four components of human motivation--goals, capability beliefs, context beliefs, and emotions--are amplified in dynamic, mutually reinforcing patterns. The…

  13. A Chemical Probe that Labels Human Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Nao Hirata

    2014-03-01

    Full Text Available A small-molecule fluorescent probe specific for human pluripotent stem cells would serve as a useful tool for basic cell biology research and stem cell therapy. Screening of fluorescent chemical libraries with human induced pluripotent stem cells (iPSCs and subsequent evaluation of hit molecules identified a fluorescent compound (Kyoto probe 1 [KP-1] that selectively labels human pluripotent stem cells. Our analyses indicated that the selectivity results primarily from a distinct expression pattern of ABC transporters in human pluripotent stem cells and from the transporter selectivity of KP-1. Expression of ABCB1 (MDR1 and ABCG2 (BCRP, both of which cause the efflux of KP-1, is repressed in human pluripotent stem cells. Although KP-1, like other pluripotent markers, is not absolutely specific for pluripotent stem cells, the identified chemical probe may be used in conjunction with other reagents.

  14. Physico-chemical characterization of banana varieties resistant to black leaf streak disease for industrial purposes

    Directory of Open Access Journals (Sweden)

    Rossana Catie Bueno de Godoy

    2016-01-01

    Full Text Available ABSTRACT: Cultivated bananas have very low genetic diversity making them vulnerable to diseases such as black-Sigatoka leaf spot. However, the decision to adopt a new banana variety needs to be based on a robust evaluation of agronomical and physical-chemical characteristics. Here, we characterize new banana varieties resistant to black-Sigatoka leaf spot and compare them to the most widely used traditional variety (Grand Naine. Each variety was evaluated for a range of physic-chemical attributes associated with industrial processing and flavor: pH, TTA, TSS/TTA, total sugars, reducing sugars and non-reducing sugars, humidity, total solids and yield. The Thap Maeo variety had the highest potential as a substitute for the Grand Naine variety, having higher levels of total soluble solids, reducing sugars, total sugars and humidity. The Caipira and FHIA 2 varieties also performed well in comparison with the Grand Naine variety. Cluster analysis indicated that the Grand Naine variety was closely associated with varieties from the Gross Michel subgroup (Bucaneiro, Ambrosia and Calipso and the Caipira variety, all of which come from the same AAA genomic group. It was concluded that several of the new resistant varieties could potentially substitute the traditional variety in areas affected by black-Sigatoka leaf spot disease.

  15. Human Genetic Marker for Resistance to Radiation and Chemicals

    International Nuclear Information System (INIS)

    Lieberman, Howard B.

    2001-01-01

    TO characterize the human HRDAD9 gene and evaluate its potential as a biomarker to predict susceptibility to the deleterious health effects potentially caused by exposure to radiations or chemicals present at DOE hazardous waste cleanup sites. HRAD9 is a human gene that is highly conserved throughout evolution. Related genes have been isolated from yeasts and mice, underscoring its biological significance. Most of our previous work involved characterization of the yeast gene cognate, wherein it was determined that the corresponding protein plays a significant role in promoting resistance of cells to radiations and chemicals, and in particular, controlling cell growth in response to DNA damage

  16. USING STATISTICAL METHODS FOR ESTIMATING STUDENTS’ OPINION ON THE PURPOSE OF HUMAN LIFE

    Directory of Open Access Journals (Sweden)

    Aivaz M. KAMER AINUR

    2013-06-01

    Full Text Available Currently, two anthropological models are dominant in Romania. The first is the atheistic-evolutionary model and the second is the Christian model. The purpose of this article is to assess the students’ opinion on the two anthropological models and, in particular, on the purpose of human life. To that effect, there have been used the coefficients of association between the main aspects of the two models. Starting from the two outlined approaches, this paper aims to investigate the opinions of the students from two different specializations within Ovidius University of Constanta – the Faculty of Economics and the Faculty of Theology – on the issues mentioned above

  17. Protection of Human Beings Trafficked for the Purpose of Organ Removal: Recommendations.

    Science.gov (United States)

    Pascalev, Assya; Van Assche, Kristof; Sándor, Judit; Codreanu, Natalia; Naqvi, Anwar; Gunnarson, Martin; Frunza, Mihaela; Yankov, Jordan

    2016-02-01

    This report presents a comprehensive set of recommendations for protection of human beings who are trafficked for the purpose of organ removal or are targeted for such trafficking. Developed by an interdisciplinary group of international experts under the auspices of the project Trafficking in Human Beings for the Purpose of Organ Removal (also known as the HOTT project), these recommendations are grounded in the view that an individual who parts with an organ for money within an illegal scheme is ipso facto a victim and that the crime of trafficking in human beings for the purpose of organ removal (THBOR) intersects with the crime of trafficking in organs. Consequently, the protection of victims should be a priority for all actors involved in antitrafficking activities: those combating organ-related crimes, such as health organizations and survivor support services, and those combating trafficking in human beings, such as the criminal justice sectors. Taking into account the special characteristics of THBOR, the authors identify 5 key stakeholders in the protection of human beings trafficked for organ removal or targeted for such trafficking: states, law enforcement agencies and judiciary, nongovernmental organizations working in the areas of human rights and antitrafficking, transplant centers and health professionals involved in transplant medicine, and oversight bodies. For each stakeholder, the authors identify key areas of concern and concrete measures to identify and protect the victims of THBOR. The aim of the recommendations is to contribute to the development of a nonlegislative response to THBOR, to promote the exchange of knowledge and best practices in the area of victim protection, and to facilitate the development of a policy-driven action plan for the protection of THBOR victims in the European Union and worldwide.

  18. Review of chemical and radiotoxicological properties of polonium for internal contamination purposes.

    Science.gov (United States)

    Ansoborlo, Eric; Berard, Philippe; Den Auwer, Christophe; Leggett, Rich; Menetrier, Florence; Younes, Ali; Montavon, Gilles; Moisy, Philippe

    2012-08-20

    The discovery of polonium (Po) was first published in July, 1898 by P. Curie and M. Curie. It was the first element to be discovered by the radiochemical method. Polonium can be considered as a famous but neglected element: only a few studies of polonium chemistry have been published, mostly between 1950 and 1990. The recent (2006) event in which (210)Po evidently was used as a poison to kill A. Litvinenko has raised new interest in polonium. 2011 being the 100th anniversary of the Marie Curie Nobel Prize in Chemistry, the aim of this review is to look at the several aspects of polonium linked to its chemical properties and its radiotoxicity, including (i) its radiochemistry and interaction with matter; (ii) its main sources and uses; (iii) its physicochemical properties; (iv) its main analytical methods; (v) its background exposure risk in water, food, and other environmental media; (vi) its biokinetics and distribution following inhalation, ingestion, and wound contamination; (vii) its dosimetry; and (viii) treatments available (decorporation) in case of internal contamination.

  19. Disk shaped radiation sources for education purposes made of chemical fertilizer

    International Nuclear Information System (INIS)

    Kawano, Takao

    2008-01-01

    A method for fabricating a disk-shaped radiation source from material containing natural radioisotopes was developed. In this compression and formation method, a certain amount of powdered material is placed in a stainless steel formwork and compressed to form a solid disk. Using this method, educational radiation sources were fabricated using commercially available chemical fertilizers that naturally contain the radionuclide, 40 K, which emits either beta or gamma rays, at each disintegration. The compression and formation method was evaluated by inspecting eleven radiation sources thus fabricated. Then the suitability of the fertilizer radiation source as an education aid was evaluated. The results showed that the method could be used to fabricate radiation sources without the need for learning special skills or techniques. It was also found that the potassium fertilizer radiation source could be used to demonstrate that the inverse-square law can be applied to the distance between the radiation source and detector, and that an exponential relationship can be seen between the shielding effectiveness and the total thickness of the shielding materials. It is concluded that a natural fertilizer radiation source is an appropriate aid for demonstrating the characteristics of radiation. (author)

  20. Direct action of endocrine disrupting chemicals on human sperm

    DEFF Research Database (Denmark)

    Schiffer, Christian; Müller, Astrid; Egeberg, Dorte L

    2014-01-01

    Synthetic endocrine disrupting chemicals (EDCs), omnipresent in food, household, and personal care products, have been implicated in adverse trends in human reproduction, including infertility and increasing demand for assisted reproduction. Here, we study the action of 96 ubiquitous EDCs on huma...

  1. Food safety. [chemical contaminants and human toxic diseases

    Science.gov (United States)

    Pier, S. M.; Valentine, J. L.

    1975-01-01

    Illness induced by unsafe food is a problem of great public health significance. This study relates exclusively to the occurrence of chemical agents which will result in food unsafe for human consumption since the matter of food safety is of paramount importance in the mission and operation of the manned spacecraft program of the National Aeronautics and Space Administration.

  2. 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.

  3. Chemical decontamination for decommissioning purposes. (Vigorous decontamination tests of steel samples in a special test loop)

    International Nuclear Information System (INIS)

    Bregani, F.; Pascali, R.; Rizzi, R.

    1984-01-01

    The aim of the research activities described was to develop vigorous decontamination techniques for decommissioning purposes, taking into account the cost of treatment of the radwaste, to achieve possibly unrestricted release of the treated components, and to obtain know-how for in situ hard decontamination. The decontamination procedures for strong decontamination have been optimized in static and dynamic tests (DECO-loop). The best values have been found for: (i) hydrochloric acid: 4 to 5% vol. at low temperature, 0.7 to 1% vol. at high temperature (80 0 C); (ii) hydrofluoric plus nitric acid: 1.5% vol. HF + 5% vol. HNO 3 at low temperature; 0.3 to 0.5% vol. HF + 2.5 to 5% vol. HNO 3 at high temperature. High flow rates are not necessary, but a good re-circulation of the solution is needed. The final contamination levels, after total oxide removal, are in accordance with limits indicated for unrestricted release of materials in some countries. The arising of the secondary waste is estimated. Decontamination of a 10 m 2 surface would typically produce 0.5 to 3.0 kg of dry waste, corresponding to 1.6 to 10 kg of concrete conditioned waste

  4. Radiation chemical technology for production of polymeric hydrogels for medical purposes

    International Nuclear Information System (INIS)

    Mun, G.A.; Nurkeeva, Z.S.; Akhmetkalieva, G.; Sergaziev, A.D.; Petukhov, V.K.; Lyssukhin, S.N.; Chakrov, P.V.

    2003-01-01

    Full text: Polymeric hydrogels are water-swelling cross-linked hydrophilic polymers with ability to store reversibly great amount of water (more than 1000 g of water per 1 g of dry polymer). At present they found a lot of different applications in highly developed countries in science and industry. The set of unique physicochemical and biomedical properties (regulated sorption ability in respect to water and biological liquids, biocompatibility, soft tissue state, permeability in respect to small and big molecules, non-toxicity, etc.) allows their application in medicine. According to the clinical data there are no materials that can compete with hydrogels in development of endo-prostheses of soft-tissues in surgery, contact lenses for eyesight correction, hemo-compatible materials, novel for treatment of wounds and burns, targeted drug delivery systems. Polymeric hydrogels today practically substitute the traditional hydrophobic bases (Vaseline, lanolin) in technology of drug forms for development of ointments and dressings, containing natural and synthetic physiologically active substances. The advantages of hydrogels in comparison with hydrophobic analogues are obvious due to the drainage effect, homogenous distribution of drugs, better contact with wound, painless removing by water washing. The polymeric hydrogels are not produced in Kazakhstan in spite of the big source of raw materials. The aim of the present work is the development of radiation-chemical technology and development of polymeric biomedical hydrogels production based on raw materials of Kazakhstan. The novel types of polymeric hydrogel materials are developed by the authors of the report based on vinyl ethers of glycols, which produced in 'Alash Ltd.' (Temirtau). The great fundamental information content has been obtained about these monomers and polymers including direct quantitative data of their structure formation mechanism and physicochemical properties. These data served as a basis for

  5. 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.

  6. "Human Nature": Chemical Engineering Students' Ideas about Human Relationships with the Natural World

    Science.gov (United States)

    Goldman, Daphne; Assaraf, Orit Ben-Zvi; Shemesh, Julia

    2014-01-01

    While importance of environmental ethics, as a component of sustainable development, in preparing engineers is widely acknowledged, little research has addressed chemical engineers' environmental concerns. This study aimed to address this void by exploring chemical engineering students' values regarding human-nature relationships. The study was…

  7. Physico-Chemical Alternatives in Lignocellulosic Materials in Relation to the Kind of Component for Fermenting Purposes

    Directory of Open Access Journals (Sweden)

    Alberto Coz

    2016-07-01

    Full Text Available The complete bioconversion of the carbohydrate fraction is of great importance for a lignocellulosic-based biorefinery. However, due to the structure of the lignocellulosic materials, and depending basically on the main parameters within the pretreatment steps, numerous byproducts are generated and they act as inhibitors in the fermentation operations. In this sense, the impact of inhibitory compounds derived from lignocellulosic materials is one of the major challenges for a sustainable biomass-to-biofuel and -bioproduct industry. In order to minimise the negative effects of these compounds, numerous methodologies have been tested including physical, chemical, and biological processes. The main physical and chemical treatments have been studied in this work in relation to the lignocellulosic material and the inhibitor in order to point out the best mechanisms for fermenting purposes. In addition, special attention has been made in the case of lignocellulosic hydrolysates obtained by chemical processes with SO2, due to the complex matrix of these materials and the increase in these methodologies in future biorefinery markets. Recommendations of different detoxification methods have been given.

  8. Microbial DNA fingerprinting of human fingerprints: dynamic colonization of fingertip microflora challenges human host inferences for forensic purposes.

    Science.gov (United States)

    Tims, Sebastian; van Wamel, Willem; Endtz, Hubert P; van Belkum, Alex; Kayser, Manfred

    2010-09-01

    Human fingertip microflora is transferred to touched objects and may provide forensically relevant information on individual hosts, such as on geographic origins, if endogenous microbial skin species/strains would be retrievable from physical fingerprints and would carry geographically restricted DNA diversity. We tested the suitability of physical fingerprints for revealing human host information, with geographic inference as example, via microbial DNA fingerprinting. We showed that the transient exogenous fingertip microflora is frequently different from the resident endogenous bacteria of the same individuals. In only 54% of the experiments, the DNA analysis of the transient fingertip microflora allowed the detection of defined, but often not the major, elements of the resident microflora. Although we found microbial persistency in certain individuals, time-wise variation of transient and resident microflora within individuals was also observed when resampling fingerprints after 3 weeks. While microbial species differed considerably in their frequency spectrum between fingerprint samples from volunteers in Europe and southern Asia, there was no clear geographic distinction between Staphylococcus strains in a cluster analysis, although bacterial genotypes did not overlap between both continental regions. Our results, though limited in quantity, clearly demonstrate that the dynamic fingerprint microflora challenges human host inferences for forensic purposes including geographic ones. Overall, our results suggest that human fingerprint microflora is too dynamic to allow for forensic marker developments for retrieving human information.

  9. Comparison of Machine Learning Methods for the Purpose Of Human Fall Detection

    Directory of Open Access Journals (Sweden)

    Strémy Maximilián

    2014-12-01

    Full Text Available According to several studies, the European population is rapidly aging far over last years. It is therefore important to ensure that aging population is able to live independently without the support of working-age population. In accordance with the studies, fall is the most dangerous and frequent accident in the everyday life of aging population. In our paper, we present a system to track the human fall by a visual detection, i.e. using no wearable equipment. For this purpose, we used a Kinect sensor, which provides the human body position in the Cartesian coordinates. It is possible to directly capture a human body because the Kinect sensor has a depth and also an infrared camera. The first step in our research was to detect postures and classify the fall accident. We experimented and compared the selected machine learning methods including Naive Bayes, decision trees and SVM method to compare the performance in recognizing the human postures (standing, sitting and lying. The highest classification accuracy of over 93.3% was achieved by the decision tree method.

  10. 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...

  11. Dual purpose microalgae-bacteria-based systems that treat wastewater and produce biodiesel and chemical products within a biorefinery.

    Science.gov (United States)

    Olguín, Eugenia J

    2012-01-01

    Excess greenhouse gas emissions and the concomitant effect on global warming have become significant environmental, social and economic threats. In this context, the development of renewable, carbon-neutral and economically feasible biofuels is a driving force for innovation worldwide. A lot of effort has been put into developing biodiesel from microalgae. However, there are still a number of technological, market and policy barriers that are serious obstacles to the economic feasibility and competitiveness of such biofuels. Conversely, there are also a number of business opportunities if the production of such alternative biofuel becomes part of a larger integrated system following the Biorefinery strategy. In this case, other biofuels and chemical products of high added value are produced, contributing to an overall enhancement of the economic viability of the whole integrated system. Additionally, dual purpose microalgae-bacteria-based systems for treating wastewater and production of biofuels and chemical products significantly contribute to a substantial saving in the overall cost of microalgae biomass production. These types of systems could help to improve the competitiveness of biodiesel production from microalgae, according to some recent Life Cycle Analysis studies. Furthermore, they do not compete for fresh water resources for agricultural purposes and add value to treating the wastewater itself. This work reviews the most recent and relevant information about these types of dual purpose systems. Several aspects related to the treatment of municipal and animal wastewater with simultaneous recovery of microalgae with potential for biodiesel production are discussed. The use of pre-treated waste or anaerobic effluents from digested waste as nutrient additives for weak wastewater is reviewed. Isolation and screening of microalgae/cyanobacteria or their consortia from various wastewater streams, and studies related to population dynamics in mixed cultures

  12. 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

  13. Technology and human purpose: the problem of solids transport on the Earth's surface

    Science.gov (United States)

    Haff, P. K.

    2012-11-01

    Displacement of mass of limited deformability ("solids") on the Earth's surface is opposed by friction and (the analog of) form resistance - impediments relaxed by rotational motion, self-powering of mass units, and transport infrastructure. These features of solids transport first evolved in the biosphere prior to the emergence of technology, allowing slope-independent, diffusion-like motion of discrete objects as massive as several tons, as illustrated by animal foraging and movement along game trails. However, high-energy-consumption technology powered by fossil fuels required a mechanism that could support fast advective transport of solids, i.e., long-distance, high-volume, high-speed, unidirectional, slope-independent transport across the land surface of materials like coal, containerized fluids, minerals, and economic goods. Pre-technology nature was able to sustain regional- and global-scale advection only in the limited form of piggybacking on geophysical flows of water (river sediment) and air (dust). The appearance of a mechanism for sustained advection of solids independent of fluid flows and gravity appeared only upon the emergence of human purpose. Purpose enables solids advection by, in effect, simulating a continuous potential gradient, otherwise lacking, between discrete and widely separated fossil-fuel energy sources and sinks. Invoking purpose as a mechanism in solids advection is an example of the need to import anthropic principles and concepts into the language and methodology of modern Earth system dynamics. As part of the emergence of a generalized solids advection mechanism, several additional transport requirements necessary to the function of modern large-scale technological systems were also satisfied. These include spatially accurate delivery of advected payload, targetability to essentially arbitrarily located destinations (such as cities), and independence of structure of advected payload from transport mechanism. The latter property

  14. Chemical Conversion of Human Fibroblasts into Functional Schwann Cells

    Directory of Open Access Journals (Sweden)

    Eva C. Thoma

    2014-10-01

    Full Text Available Direct transdifferentiation of somatic cells is a promising approach to obtain patient-specific cells for numerous applications. However, conversion across germ-layer borders often requires ectopic gene expression with unpredictable side effects. Here, we present a gene-free approach that allows efficient conversion of human fibroblasts via a transient progenitor stage into Schwann cells, the major glial cell type of peripheral nerves. Using a multikinase inhibitor, we transdifferentiated fibroblasts into transient neural precursors that were subsequently further differentiated into Schwann cells. The resulting induced Schwann cells (iSCs expressed numerous Schwann cell-specific proteins and displayed neurosupportive and myelination capacity in vitro. Thus, we established a strategy to obtain mature Schwann cells from human postnatal fibroblasts under chemically defined conditions without the introduction of ectopic genes.

  15. Study and structural and chemical characterization of human dental smalt by electron microscopy

    International Nuclear Information System (INIS)

    Belio R, I.A.; Reyes G, J.

    1998-01-01

    The study of human dental smalt has been subject to investigation for this methods with electron microscopy, electron diffraction, X-ray diffraction and image simulation programs have been used with the purpose to determine its chemical and structural characteristics of the organic and inorganic materials. This work has been held mainly for the characterization of hydroxyapatite (Ca) 10 (PO 4 ) 6 (OH 4 ) 2 , inorganic material which conforms the dental smalt in 97%, so observing its structural unity which is composed by the prisms and these by crystals and atoms. It was subsequently initiated the study of the organic material, with is precursor of itself. (Author)

  16. Understanding human quality judgment in assessing online forum contents for thread retrieval purpose

    Science.gov (United States)

    Ismail, Zuriati; Salim, Naomie; Huspi, Sharin Hazlin

    2017-10-01

    Compared to traditional materials or journals, user-generated contents are not peer-reviewed. Lack of quality control and the explosive growth of web contents make the task of finding quality information on the web especially critical. The existence of new facilities for producing web contents such as forum makes this issue more significant. This study focuses on online forums threads or discussion, where the forums contain valuable human-generated information in a form of discussions. Due to the unique structure of the online forum pages, special techniques are required to organize and search for information in these forums. Quality biased retrieval is a retrieval approach that search for relevant document and prioritized higher quality documents. Despite major concern of quality content and recent development of quality biased retrieval, there is an urgent need to understand how quality content is being judged, for retrieval and performance evaluation purposes. Furthermore, even though there are various studies on the quality of information, there is no standard framework that has been established. The primary aim of this paper is to contribute to the understanding of human quality judgment in assessing online forum contents. The foundation of this study is to compare and evaluate different frameworks (for quality biased retrieval and information quality). This led to the finding that many quality dimensions are redundant and some dimensions are understood differently between different studies. We conducted a survey on crowdsourcing community to measure the importance of each quality dimensions found in various frameworks. Accuracy and ease of understanding are among top important dimensions while threads popularity and contents manipulability are among least important dimensions. This finding is beneficial in evaluating contents of online forum.

  17. Chemical incidents resulted in hazardous substances releases in the context of human health hazards

    Directory of Open Access Journals (Sweden)

    Anna Pałaszewska-Tkacz

    2017-02-01

    Full Text Available Objectives: The research purpose was to analyze data concerning chemical incidents in Poland collected in 1999–2009 in terms of health hazards. Material and Methods: The data was obtained, using multimodal information technology (IT system, from chemical incidents reports prepared by rescuers at the scene. The final analysis covered sudden events associated with uncontrolled release of hazardous chemical substances or mixtures, which may potentially lead to human exposure. Releases of unidentified substances where emergency services took action to protect human health or environment were also included. Results: The number of analyzed chemical incidents in 1999–2009 was 2930 with more than 200 different substances released. The substances were classified into 13 groups of substances and mixtures posing analogous risks. Most common releases were connected with non-flammable corrosive liquids, including: hydrochloric acid (199 cases, sulfuric(VI acid (131 cases, sodium and potassium hydroxides (69 cases, ammonia solution (52 cases and butyric acid (32 cases. The next group were gases hazardous only due to physico-chemical properties, including: extremely flammable propane-butane (249 cases and methane (79 cases. There was no statistically significant trend associated with the total number of incidents. Only with the number of incidents with flammable corrosive, toxic and/or harmful liquids, the regression analysis revealed a statistically significant downward trend. The number of victims reported was 1997, including 1092 children and 18 fatalities. Conclusions: The number of people injured, number of incidents and the high 9th place of Poland in terms of the number of Seveso establishments, and 4 times higher number of hazardous industrial establishments not covered by the Seveso Directive justify the need for systematic analysis of hazards and their proper identification. It is advisable enhance health risk assessment, both qualitative and

  18. Methodological issues in human studies of endocrine disrupting chemicals.

    Science.gov (United States)

    Lee, Duk-Hee; Jacobs, David R

    2015-12-01

    Possible harm from endocrine disrupting chemicals (EDCs) in humans is speculated based on two types of evidence; 1) increasing trends of suspected diseases in ecological studies of populations and 2) findings from traditional epidemiological studies of individuals. However, ecological findings are not regarded as direct human evidence of the relation between EDCs and disease, while the evidence among epidemiological studies of individuals is often inconsistent. Thus, a criticism is that linking EDCs and health in human is naively presumed without solid evidence. However, human studies of EDCs are methodologically complex and understanding methodological issues will help to interpret findings from existing human studies and to properly design optimal human studies. The key issues are low reliability of exposure assessment of EDCs with short half-lives, EDC mixtures, possibility of non-monotonic dose-response relationships, non-existence of an unexposed group, difficulties in measuring exposure during critical periods, and interactions with established risk factors. Furthermore, EDC mixtures may affect human health through other mechanisms than traditional endocrine disruption, for example glutathione depletion or mitochondrial dysfunction. Given this complexity, the most plausible scenario in humans is that exposure to EDC mixtures leads to increasing risk of related diseases at the ecological level, but inconsistent associations would be expected in traditional epidemiological studies. Although epidemiologists have long relied on Bradford Hill's criteria to objectively evaluate whether associations observed in epidemiology can be interpreted as causal, there are challenges to use these criteria for EDCs, particularly concerning consistency across studies and the findings of linear dose-response relationships. At the individual level, compared to EDCs with short half-lives, epidemiological studies of EDCs with long half-lives among populations with a relatively low

  19. Representations as mediation between purposes as junior secondary science students learn about the human body

    Science.gov (United States)

    Olander, Clas; Wickman, Per-Olof; Tytler, Russell; Ingerman, Åke

    2018-01-01

    The aim of this article is to investigate students' meaning-making processes of multiple representations during a teaching sequence about the human body in lower secondary school. Two main influences are brought together to accomplish the analysis: on the one hand, theories on signs and representations as scaffoldings for learning and, on the other hand, pragmatist theories on how continuity between the purposes of different inquiry activities can be sustained. Data consist of 10 videotaped and transcribed lessons with 14-year-old students (N = 26) in Sweden. The analysis focused instances where meaning of representations was negotiated. Findings indicate that continuity is established in multiple ways, for example, as the use of metaphors articulated as an interlanguage expression that enables the students (and the teacher) to maintain the conversation and explain pressing issues in ways that support of the end-in-view of the immediate action. Continuity is also established between every day and scientific registers and between organisation levels as well as between the smaller parts and the whole system.

  20. Use of Validation by Enterprises for Human Resource and Career Development Purposes. Cedefop Reference Series No 96

    Science.gov (United States)

    Cedefop - European Centre for the Development of Vocational Training, 2014

    2014-01-01

    European enterprises give high priority to assessing skills and competences, seeing this as crucial for recruitment and human resource management. Based on a survey of 400 enterprises, 20 in-depth case studies and interviews with human resource experts in 10 countries, this report analyses the main purposes of competence assessment, the standards…

  1. Synthesis of reference compounds related to Chemical Weapons Convention for verification and drug development purposes – a Brazilian endeavour

    Science.gov (United States)

    Cavalcante, S. F. A.; de Paula, R. L.; Kitagawa, D. A. S.; Barcellos, M. C.; Simas, A. B. C.; Granjeiro, J. M.

    2018-03-01

    This paper deals with challenges that Brazilian Army Organic Synthesis Laboratory has been going through to access reference compounds related to the Chemical Weapons Convention in order to support verification analysis and for research of novel antidotes. Some synthetic procedures to produce the chemicals, as well as Quality Assurance issues and a brief introduction of international agreements banning chemical weapons are also presented.

  2. Role of human neurobehavioural tests in regulatory activity on chemicals

    Science.gov (United States)

    Stephens, R.; Barker, P.

    1998-01-01

    Psychological performance tests have been used since the mid-1960s in occupational and environmental health toxicology. The interpretation of significantly different test scores in neurobehavioural studies is not straightforward in the regulation of chemicals. This paper sets out some issues which emerged from discussions at an international workshop, organised by the United Kingdom Health and Safety Executive (HSE), to discuss differences in interpretation of human neurobehavioural test data in regulatory risk assessments. The difficulties encountered by regulators confronted with neurobehavioural studies seem to be twofold; some studies lack scientific rigor; other studies, although scientifically sound, are problematic because it is not clear what interpretation to place on the results. Issues relating to each of these points are discussed. Next, scenarios within which to consider the outcomes of neurobehavioural studies are presented. Finally, conclusions and recommendations for further work are put forward.   PMID:9624273

  3. Concepts in causality: chemically induced human urinary bladder cancer

    International Nuclear Information System (INIS)

    Lower, G.M. Jr.

    1982-01-01

    A significant portion of the incidence of human urinary bladder cancer can be attributed to occupational and cultural (tobacco smoking) situations associated with exposures to various arylamines, many of which represent established human carcinogens. A brief historical overview of research in bladder cancer causality indicates that the identification of causal agents and causal mechanism has been approached and rests upon information gathered at the organismal (geographical/historical), cellular, and molecular levels of biologic organization. This viewpoint speaks of a natural evolution within the biomedical sciences; a natural evolution from descriptive approaches to mechanistic approaches; and a natural evolution from more or less independent discipline-oriented approaches to hierarchically organized multidisciplinary approaches. Available information relevant to bladder cancer causality can be readily integrated into general conceptual frameworks to yield a hierarchial view of the natural history of urinary bladder cancer, a view consistent with contemporary natural systems and information theory and perhaps relevant also to other chemically induced epithelial cancers. Such frameworks are useful in appreciating the spatial and temporal boundaries and interrelationships in causality and the conceptual interrelationships within the biomedical sciences. Recent approaches in molecular epidemiology and the assessment of relative individual susceptibility to bladder cancer indicate that such frameworks are useful in forming hypotheses

  4. Chemical Achievers: The Human Face of the Chemical Sciences (by Mary Ellen Bowden)

    Science.gov (United States)

    Kauffman, George B.

    1999-02-01

    Chemical Heritage Foundation: Philadelphia, PA, 1997. viii + 180 pp. 21.6 x 27.8 cm. ISBN 0-941901-15-1. Paper. 20.00 (10.00 for high school teachers who provide documentation). At a 1991 summer workshop sponsored by the Chemical Heritage Foundation and taught by Derek A. Davenport and William B. Jensen, high school and college teachers of introductory chemistry requested a source of pictorial material about famous chemical scientists suitable as a classroom aid. CHF responded by publishing this attractive, inexpensive paperback volume, which reflects the considerable research effort needed to locate appropriate images and to write the biographical essays. Printed on heavy, glossy paper and spiral bound to facilitate conversion to overhead transparencies, it contains 157 images from pictorial collections at CHF and many other institutions on two types of achievers: the historical "greats" most often referred to in introductory courses, and scientists who made contributions in areas of the chemical sciences that are of special relevance to modern life and the career choices students will make. The pictures are intended to provide the "human face" of the book's subtitle- "to point to the human beings who had the insights and made the major advances that [teachers] ask students to master." Thus, for example, Boyle's law becomes less cold and abstract if the student can connect it with the two portraits of the Irish scientist even if his face is topped with a wig. Marie Curie can be seen in the role of wife and mother as well as genius scientist in the photographs of her with her two daughters, one of whom also became a Nobel laureate. And students are reminded of the ubiquity of the contribution of the chemical scientists to all aspects of our everyday life by the stories and pictures of Wallace Hume Carothers' path to nylon, Percy Lavon Julian's work on hormones, and Charles F. Chandler and Rachel Carson's efforts to preserve the environment. In addition to portraits

  5. Exploring the Possibility of Peak Individualism, Humanity's Existential Crisis, and an Emerging Age of Purpose.

    Science.gov (United States)

    Grant, Gabriel B

    2017-01-01

    There is an emerging cultural narrative in the United States that we are entering an age of purpose-that millennials, more than any other generation, are searching for purpose and purposeful work (Sheahan, 2005) and that we are entering an era or economy of purpose (Hurst, 2014). For profit, non-profit, and educational institutions are perceiving and adapting to serve millennials' demand for purpose in life, specifically within the workplace (Klein et al., 2015). Yet, longitudinal studies of purpose do not exist, and millennials are also referred to as GenMe. Existing quantitative research suggests they (we) are increasingly individualistic, materialistic, and narcissistic (Greenfield, 2013). Google's digitization of millions of books and the Ngram Viewer allow for quantified analysis of culture over the past two centuries. This tool was used to quantitatively test the popular notion that there is a rise in demand for purpose. Analysis reveals a growing interest in purpose-in-life and a shift toward collectivistic values emerging over the lifespan of the millennial generation.

  6. Exploring the Possibility of Peak Individualism, Humanity's Existential Crisis, and an Emerging Age of Purpose

    Science.gov (United States)

    Grant, Gabriel B.

    2017-01-01

    There is an emerging cultural narrative in the United States that we are entering an age of purpose—that millennials, more than any other generation, are searching for purpose and purposeful work (Sheahan, 2005) and that we are entering an era or economy of purpose (Hurst, 2014). For profit, non-profit, and educational institutions are perceiving and adapting to serve millennials' demand for purpose in life, specifically within the workplace (Klein et al., 2015). Yet, longitudinal studies of purpose do not exist, and millennials are also referred to as GenMe. Existing quantitative research suggests they (we) are increasingly individualistic, materialistic, and narcissistic (Greenfield, 2013). Google's digitization of millions of books and the Ngram Viewer allow for quantified analysis of culture over the past two centuries. This tool was used to quantitatively test the popular notion that there is a rise in demand for purpose. Analysis reveals a growing interest in purpose-in-life and a shift toward collectivistic values emerging over the lifespan of the millennial generation. PMID:28928689

  7. Exploring the Possibility of Peak Individualism, Humanity's Existential Crisis, and an Emerging Age of Purpose

    Directory of Open Access Journals (Sweden)

    Gabriel B. Grant

    2017-09-01

    Full Text Available There is an emerging cultural narrative in the United States that we are entering an age of purpose—that millennials, more than any other generation, are searching for purpose and purposeful work (Sheahan, 2005 and that we are entering an era or economy of purpose (Hurst, 2014. For profit, non-profit, and educational institutions are perceiving and adapting to serve millennials' demand for purpose in life, specifically within the workplace (Klein et al., 2015. Yet, longitudinal studies of purpose do not exist, and millennials are also referred to as GenMe. Existing quantitative research suggests they (we are increasingly individualistic, materialistic, and narcissistic (Greenfield, 2013. Google's digitization of millions of books and the Ngram Viewer allow for quantified analysis of culture over the past two centuries. This tool was used to quantitatively test the popular notion that there is a rise in demand for purpose. Analysis reveals a growing interest in purpose-in-life and a shift toward collectivistic values emerging over the lifespan of the millennial generation.

  8. The influence of human factor on security of software intended for educational purposes

    Directory of Open Access Journals (Sweden)

    Valeriy Valentinovich Gurov

    2016-06-01

    Full Text Available The report considers the construction and analysis of attack tree on the software tools intended for educational purposes. This takes into account different groups of attackers. The criterion of security for such tools is introduced.

  9. An optimized chemical synthesis of human relaxin-2.

    Science.gov (United States)

    Barlos, Kostas K; Gatos, Dimitrios; Vasileiou, Zoe; Barlos, Kleomenis

    2010-04-01

    Human gene 2 relaxin (RLX) is a member of the insulin superfamily and is a multi-functional factor playing a vital role in pregnancy, aging, fibrosis, cardioprotection, vasodilation, inflammation, and angiogenesis. RLX is currently applied in clinical trials to cure among others acute heart failure, fibrosis, and preeclampsia. The synthesis of RLX by chemical methods is difficult because of the insolubility of its B-chain and the required laborious and low yielding site-directed combination of its A (RLXA) and B (RLXB) chains. We report here that oxidation of the Met(25) residue of RLXB improves its solubility, allowing its effective solid-phase synthesis and application in random interchain combination reactions with RLXA. Linear Met(O)(25)-RLX B-chain (RLXBO) reacts with a mixture of isomers of bicyclic A-chain (bcRLXA) giving exclusively the native interchain combination. Applying this method Met(O)(25)-RLX (RLXO) was obtained in 62% yield and was easily converted to RLX in 78% yield, by reduction with ammonium iodide. Copyright (c) 2010 European Peptide Society and John Wiley & Sons, Ltd.

  10. Problem formulation for risk assessment of combined exposures to chemicals and other stressors in humans.

    Science.gov (United States)

    Solomon, Keith R; Wilks, Martin F; Bachman, Ammie; Boobis, Alan; Moretto, Angelo; Pastoor, Timothy P; Phillips, Richard; Embry, Michelle R

    2016-11-01

    When the human health risk assessment/risk management paradigm was developed, it did not explicitly include a "problem formulation" phase. The concept of problem formulation was first introduced in the context of ecological risk assessment (ERA) for the pragmatic reason to constrain and focus ERAs on the key questions. However, this need also exists for human health risk assessment, particularly for cumulative risk assessment (CRA), because of its complexity. CRA encompasses the combined threats to health from exposure via all relevant routes to multiple stressors, including biological, chemical, physical and psychosocial stressors. As part of the HESI Risk Assessment in the 21st Century (RISK21) Project, a framework for CRA was developed in which problem formulation plays a critical role. The focus of this effort is primarily on a chemical CRA (i.e., two or more chemicals) with subsequent consideration of non-chemical stressors, defined as "modulating factors" (ModFs). Problem formulation is a systematic approach that identifies all factors critical to a specific risk assessment and considers the purpose of the assessment, scope and depth of the necessary analysis, analytical approach, available resources and outcomes, and overall risk management goal. There are numerous considerations that are specific to multiple stressors, and proper problem formulation can help to focus a CRA to the key factors in order to optimize resources. As part of the problem formulation, conceptual models for exposures and responses can be developed that address these factors, such as temporal relationships between stressors and consideration of the appropriate ModFs.

  11. `Human nature': Chemical engineering students' ideas about human relationships with the natural world

    Science.gov (United States)

    Goldman, Daphne; Ben-Zvi Assaraf, Orit; Shemesh, Julia

    2014-05-01

    While importance of environmental ethics, as a component of sustainable development, in preparing engineers is widely acknowledged, little research has addressed chemical engineers' environmental concerns. This study aimed to address this void by exploring chemical engineering students' values regarding human-nature relationships. The study was conducted with 247 3rd-4th year chemical engineering students in Israeli Universities. It employed the New Ecological Paradigm (NEP)-questionnaire to which students added written explanations. Quantitative analysis of NEP-scale results shows that the students demonstrated moderately ecocentric orientation. Explanations to the NEP-items reveal diverse, ambivalent ideas regarding the notions embodied in the NEP, strong scientific orientation and reliance on technology for addressing environmental challenges. Endorsing sustainability implies that today's engineers be equipped with an ecological perspective. The capacity of Higher Education to enable engineers to develop dispositions about human-nature interrelationships requires adaptation of curricula towards multidisciplinary, integrative learning addressing social-political-economic-ethical perspectives, and implementing critical-thinking within the socio-scientific issues pedagogical approach.

  12. Transgenerational effects of radiation and chemicals in mice and humans

    International Nuclear Information System (INIS)

    Nomura, Taisei

    2006-01-01

    Parental exposure of mice to radiation and chemicals causes a variety of adverse effects (e.g., tumors, congenital malformations and embryonic deaths) in the progeny and the tumor-susceptibility phenotype is transmissible beyond the first post-radiation generation. The induced rates of tumors were 100-fold higher than those known for mouse specific locus mutations. There were clear strain differences in the types of naturally-occurring and induced tumors and most of the latter were malignant. Another important finding was that germ-line exposure elicited very weak tumorigenic responses, but caused persistent hypersensitivity in the offspring for the subsequent development of cancer by the postnatal environment. Activations of oncogenes, ras, mos, abl, etc. and mutations in tumor suppressor genes such as p53 were also detected in specific tumors in cancer-prone descendants. However, the majority of tumors observed in the progeny were those commonly observed in the strains that were used and oncogene activations were rarely observed in these tumors. It can be hypothesized that genetic instability modifies tumor occurrence in a transgenerational manner, but so far no links could be established between chromosomal and molecular changes and transmissible tumor risks. Our data are consistent with the hypothesis that cumulative changes in many normal but cancer-related genes affecting immunological, biochemical and physiological functions may slightly elevate the incidence of tumors or fasten the tumor development. This hypothesis is supported by our GeneChip analyses which showed suppression and/or over-expression of many such genes in the offspring of mice exposed to radiation. In humans, a higher risk of leukemia and birth defects has been reported in the children of fathers who had been exposed to radionuclides in the nuclear reprocessing plants and to diagnostic radiation. These findings have not been supported in the children of atomic bomb survivors in Hiroshima

  13. The University Council for Workforce and Human Resource Education: Its History, Purpose, and Activities

    Science.gov (United States)

    Johnson, Scott D.; Martinez, Reynaldo L., Jr.

    2009-01-01

    This article features the University Council for Workforce and Human Resource Education, a nonprofit organization representing leading United States universities that offer graduate programs in career and technical education (CTE) and human resource development (HRD). The mission of the Council is to be a recognized force in shaping the future of…

  14. Establishing trafficking in human beings for the purpose of organ removal and improving cross-border collaboration in criminal cases

    NARCIS (Netherlands)

    Rijken, Conny

    2016-01-01

    In this short summary report on the legal definition of trafficking in human beings for the purpose of organ removal and improving cross-border collaboration in criminal cases, challenges, and recommendations in the areas of defining the crime, criminal investigation and prosecution, and

  15. Approach to modeling of human performance for purposes of probabilistic risk assessment

    International Nuclear Information System (INIS)

    Swain, A.D.

    1983-01-01

    This paper describes the general approach taken in NUREG/CR-1278 to model human performance in sufficienct detail to permit probabilistic risk assessments of nuclear power plant operations. To show the basis for the more specific models in the above NUREG, a simplified model of the human component in man-machine systems is presented, the role of performance shaping factors is discussed, and special problems in modeling the cognitive aspect of behavior are described

  16. Consensus models to predict endocrine disruption for all human-exposure chemicals (AAAS Annual Meeting)

    Science.gov (United States)

    Humans are potentially exposed to tens of thousands of man-made chemicals in the environment. It is well known that some environmental chemicals mimic natural hormones and thus have the potential to be endocrine disruptors. Most of these environmental chemicals have never been te...

  17. Human Metabolism and Interactions of Deployment-Related Chemicals

    National Research Council Canada - National Science Library

    Hodgson, Ernest; Brimfield, Alan A; Goldstein, Joyce E; Rose, Randy L; Wallace, Andrew D

    2008-01-01

    .... The metabolism of chlorpyrifos, DEET, permethrin, pyridostigmine bromide, sulfur mustard, naphthalene and nonane as well as a number of their metabolites and related chemicals was investigated...

  18. A predictive model of chemical flooding for enhanced oil recovery purposes: Application of least square support vector machine

    Directory of Open Access Journals (Sweden)

    Mohammad Ali Ahmadi

    2016-06-01

    Full Text Available Applying chemical flooding in petroleum reservoirs turns into interesting subject of the recent researches. Developing strategies of the aforementioned method are more robust and precise when they consider both economical point of views (net present value (NPV and technical point of views (recovery factor (RF. In the present study huge attempts are made to propose predictive model for specifying efficiency of chemical flooding in oil reservoirs. To gain this goal, the new type of support vector machine method which evolved by Suykens and Vandewalle was employed. Also, high precise chemical flooding data banks reported in previous works were employed to test and validate the proposed vector machine model. According to the mean square error (MSE, correlation coefficient and average absolute relative deviation, the suggested LSSVM model has acceptable reliability; integrity and robustness. Thus, the proposed intelligent based model can be considered as an alternative model to monitor the efficiency of chemical flooding in oil reservoir when the required experimental data are not available or accessible.

  19. Scoring and ranking of metabolic trees to computationally prioritize chemicals for testing using fit-for-purpose in vitro estrogen receptor assay

    Science.gov (United States)

    Increasing awareness about endocrine disrupting chemicals (EDCs) in the environment has driven concern about their potential impact on human health and wildlife. Tens of thousands of natural and synthetic xenobiotics are presently in commerce with little to no toxicity data and t...

  20. Representations as Mediation between Purposes as Junior Secondary Science Students Learn about the Human Body

    Science.gov (United States)

    Olander, Clas; Wickman, Per-Olof; Tytler, Russell; Ingerman, Åke

    2018-01-01

    The aim of this article is to investigate students' meaning-making processes of multiple representations during a teaching sequence about the human body in lower secondary school. Two main influences are brought together to accomplish the analysis: on the one hand, theories on signs and representations as scaffoldings for learning and, on the…

  1. Should the scope of human mixture risk assessment span legislative/regulatory silos for chemicals?

    Science.gov (United States)

    Evans, Richard M; Martin, Olwenn V; Faust, Michael; Kortenkamp, Andreas

    2016-02-01

    Current chemicals regulation operates almost exclusively on a chemical-by-chemical basis, however there is concern that this approach may not be sufficiently protective if two or more chemicals have the same toxic effect. Humans are indisputably exposed to more than one chemical at a time, for example to the multiple chemicals found in food, air and drinking water, and in household and consumer products, and in cosmetics. Assessment of cumulative risk to human health and/or the environment from multiple chemicals and routes can be done in a mixture risk assessment (MRA). Whilst there is a broad consensus on the basic science of mixture toxicology, the path to regulatory implementation of MRA within chemical risk assessment is less clear. In this discussion piece we pose an open question: should the scope of human MRA cross legislative remits or 'silos'? We define silos as, for instance, legislation that defines risk assessment practice for a subset of chemicals, usually on the basis of substance/product, media or process orientation. Currently any form of legal mandate for human MRA in the EU is limited to only a few pieces of legislation. We describe two lines of evidence, illustrated with selected examples, that are particularly pertinent to this question: 1) evidence that mixture effects have been shown for chemicals regulated in different silos and 2) evidence that humans are co-exposed to chemicals from different silos. We substantiate the position that, because there is no reason why chemicals allocated to specific regulatory silos would have non-overlapping risk profiles, then there is also no reason to expect that MRA limited only to chemicals within one silo can fully capture the risk that may be present to human consumers. Finally, we discuss possible options for implementation of MRA and we hope to prompt wider discussion of this issue. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  2. A general-purpose framework to simulate musculoskeletal system of human body: using a motion tracking approach.

    Science.gov (United States)

    Ehsani, Hossein; Rostami, Mostafa; Gudarzi, Mohammad

    2016-02-01

    Computation of muscle force patterns that produce specified movements of muscle-actuated dynamic models is an important and challenging problem. This problem is an undetermined one, and then a proper optimization is required to calculate muscle forces. The purpose of this paper is to develop a general model for calculating all muscle activation and force patterns in an arbitrary human body movement. For this aim, the equations of a multibody system forward dynamics, which is considered for skeletal system of the human body model, is derived using Lagrange-Euler formulation. Next, muscle contraction dynamics is added to this model and forward dynamics of an arbitrary musculoskeletal system is obtained. For optimization purpose, the obtained model is used in computed muscle control algorithm, and a closed-loop system for tracking desired motions is derived. Finally, a popular sport exercise, biceps curl, is simulated by using this algorithm and the validity of the obtained results is evaluated via EMG signals.

  3. Microbial DNA fingerprinting of human fingerprints: dynamic colonization of fingertip microflora challenges human host inferences for forensic purposes

    NARCIS (Netherlands)

    S. Tims (Sebastian); W.J.B. van Wamel (Willem); H.P. Endtz (Hubert); A.F. van Belkum (Alex); M.H. Kayser (Manfred)

    2009-01-01

    textabstractHuman fingertip microflora is transferred to touched objects and may provide forensically relevant information on individual hosts, such as on geographic origins, if endogenous microbial skin species/strains would be retrievable from physical fingerprints and would carry geographically

  4. 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.

  5. The Hague Recommendations: Improving Nonlegislative Responses to Trafficking in Human Beings for the Purpose of Organ Removal

    Science.gov (United States)

    Ambagtsheer, Frederike; Weimar, Willem

    2016-01-01

    Abstract Over the years, the trade in human organs has become an object of international concern. Since the 1980s, antiorgan trade initiatives have mainly involved the strengthening of legislative responses. Little attention however is given to nonlegislative responses by law enforcement authorities. The HOTT project is a European Union-funded research project titled “trafficking in human beings for the purpose of organ removal.” Its objectives are to increase knowledge, raise awareness, and improve the nonlegislative response to the crime. Its consortium organized a “Writers' Conference” in The Hague, The Netherlands at Europol's Headquarters where a group of 40 experts, consisting of transplant professionals, law enforcement officials, and policy makers, formulated recommendations to improve nonlegislative responses. These recommendations, presented hereafter, address the ethical and legal obligations of health care providers, the protection of persons trafficked for the purpose of organ removal, strengthening cross-border collaboration in criminal cases, and stimulating partnerships between transplant professionals and law enforcement. These recommendations offer ways in which transplant professionals can contribute to improving the nonlegislative response to trafficking in human beings for the purpose of organ removal. PMID:27500254

  6. The Hague Recommendations: Improving Nonlegislative Responses to Trafficking in Human Beings for the Purpose of Organ Removal.

    Science.gov (United States)

    Ambagtsheer, Frederike; Weimar, Willem

    2016-02-01

    Over the years, the trade in human organs has become an object of international concern. Since the 1980s, antiorgan trade initiatives have mainly involved the strengthening of legislative responses. Little attention however is given to nonlegislative responses by law enforcement authorities. The HOTT project is a European Union-funded research project titled "trafficking in human beings for the purpose of organ removal." Its objectives are to increase knowledge, raise awareness, and improve the nonlegislative response to the crime. Its consortium organized a "Writers' Conference" in The Hague, The Netherlands at Europol's Headquarters where a group of 40 experts, consisting of transplant professionals, law enforcement officials, and policy makers, formulated recommendations to improve nonlegislative responses. These recommendations, presented hereafter, address the ethical and legal obligations of health care providers, the protection of persons trafficked for the purpose of organ removal, strengthening cross-border collaboration in criminal cases, and stimulating partnerships between transplant professionals and law enforcement. These recommendations offer ways in which transplant professionals can contribute to improving the nonlegislative response to trafficking in human beings for the purpose of organ removal.

  7. Development and Fit-for-Purpose Validation of a Soluble Human Programmed Death-1 Protein Assay.

    Science.gov (United States)

    Ni, Yan G; Yuan, Xiling; Newitt, John A; Peterson, Jon E; Gleason, Carol R; Haulenbeek, Jonathan; Santockyte, Rasa; Lafont, Virginie; Marsilio, Frank; Neely, Robert J; DeSilva, Binodh; Piccoli, Steven P

    2015-07-01

    Programmed death-1 (PD-1) protein is a co-inhibitory receptor which negatively regulates immune cell activation and permits tumors to evade normal immune defense. Anti-PD-1 antibodies have been shown to restore immune cell activation and effector function-an exciting breakthrough in cancer immunotherapy. Recent reports have documented a soluble form of PD-1 (sPD-1) in the circulation of normal and disease state individuals. A clinical assay to quantify sPD-1 would contribute to the understanding of sPD-1-function and facilitate the development of anti-PD-1 drugs. Here, we report the development and validation of a sPD-1 protein assay. The assay validation followed the framework for full validation of a biotherapeutic pharmacokinetic assay. A purified recombinant human PD-1 protein was characterized extensively and was identified as the assay reference material which mimics the endogenous analyte in structure and function. The lower limit of quantitation (LLOQ) was determined to be 100 pg/mL, with a dynamic range spanning three logs to 10,000 pg/mL. The intra- and inter-assay imprecision were ≤15%, and the assay bias (percent deviation) was ≤10%. Potential matrix effects were investigated in sera from both normal healthy volunteers and selected cancer patients. Bulk-prepared frozen standards and pre-coated Streptavidin plates were used in the assay to ensure consistency in assay performance over time. This assay appears to specifically measure total sPD-1 protein since the human anti-PD-1 antibody, nivolumab, and the endogenous ligands of PD-1 protein, PDL-1 and PDL-2, do not interfere with the assay.

  8. 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

  9. Neutron activation analysis of single human hairs and possible applications for forensic purposes

    International Nuclear Information System (INIS)

    Dybczynski, R.; Boboli, K.

    1975-01-01

    A new analytical procedure that enables to determine more than 10 trace elements in single, 3 cm human hair segments by neutron activation analysis (NAA) was elaborated. Application of a special washing procedure of hair (before irradiation) made possible to lower sodium content by two orders of magnitude without affecting trace element content. After irradiation in the thermal neutron flux of about 10 14 n.cm -2 .sec -1 the activity of hair was measured with 70 cm 3 Ge(Li) detector coupled to 4000 channel pulse height analyser. As an alternative method, a destructive version of NAA with ion exchange group separation of radionuclides was applied. It was found that sometimes high gradients of element concentration along the hair length exist and that there is without any doubt a distinct influence of environmental factor on the content of some trace elements in hair. The criminalistic aspects of hair analysis were also studied using new statistical criterion for elimination (identification). Both possibilities and limitations of the method are discussed. (author)

  10. Technical, organizational and human-centered requirements for the purpose of accident management

    International Nuclear Information System (INIS)

    Berning, A.; Fassmann, W.; Preischl, W.

    1998-01-01

    A catalog of ergonomic recommendations for organizational measures and design of paper documented work aids for accident management situations in nuclear power plants was developed. Attention was given to provide recommendations meeting practical needs and being sufficiently flexible to allow plant specific [aptation. A weight was assigned to each recommendation indicating its importance. The development of the recommendations was based on the state of the art concerning research and practical experience. Results from walk-/talk-through experiments, training and exercises, discussions with on-site experts, and investigations of emergency manuals from German and foreign nuclear power plants were taken into account. The catalog is founded on a bro[ knowledge base covering important aspects. The catalog is intended for qualitative evaluation and design of organizational measures and procedures. The catalog shall assure high quality. The project further provides an important contribution to the standardization of organizational and human centered demands concerning accident management procedures. Thus it can contribute to develop general regulations regarding ergonomic design of accident management measures. (orig.) [de

  11. Forensic DNA Phenotyping: Predicting human appearance from crime scene material for investigative purposes.

    Science.gov (United States)

    Kayser, Manfred

    2015-09-01

    Forensic DNA Phenotyping refers to the prediction of appearance traits of unknown sample donors, or unknown deceased (missing) persons, directly from biological materials found at the scene. "Biological witness" outcomes of Forensic DNA Phenotyping can provide investigative leads to trace unknown persons, who are unidentifiable with current comparative DNA profiling. This intelligence application of DNA marks a substantially different forensic use of genetic material rather than that of current DNA profiling presented in the courtroom. Currently, group-specific pigmentation traits are already predictable from DNA with reasonably high accuracies, while several other externally visible characteristics are under genetic investigation. Until individual-specific appearance becomes accurately predictable from DNA, conventional DNA profiling needs to be performed subsequent to appearance DNA prediction. Notably, and where Forensic DNA Phenotyping shows great promise, this is on a (much) smaller group of potential suspects, who match the appearance characteristics DNA-predicted from the crime scene stain or from the deceased person's remains. Provided sufficient funding being made available, future research to better understand the genetic basis of human appearance will expectedly lead to a substantially more detailed description of an unknown person's appearance from DNA, delivering increased value for police investigations in criminal and missing person cases involving unknowns. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. A nucleic acid dependent chemical photocatalysis in live human cells

    DEFF Research Database (Denmark)

    Arian, Dumitru; Cló, Emiliano; Gothelf, Kurt V

    2010-01-01

    Only two nucleic acid directed chemical reactions that are compatible with live cells have been reported to date. Neither of these processes generate toxic species from nontoxic starting materials. Reactions of the latter type could be applied as gene-specific drugs, for example, in the treatment...

  13. [Endoscopic diagnosis of local chemical burn of mucous membranes of the stomach, induced with the purpose of simulation of gastric ulcer].

    Science.gov (United States)

    Byzov, N V; Plekhanov, V N

    2013-01-01

    With the purpose of improvement of diagnosis of induced gastric ulcer were examined 11 patients who took aggressive agents for simulation of gastric ulcer and 33 patients who took pseudo-aggressive agents. Observables, conduced diagnosis of local chemical burn of mucous coat of stomach during initial 6 days after taking aggressive agents. Stages of ulcerous process, resulting from local chemical burn of mucous coat of stomach, coressponds to real gactric ulcer. Gelatin capsule using as a container for delivery of aggressive agents, melts in stomach in 5-6 minutes after taking. Independent from body position, mucous coat of greater curvature of the stomach is damaged. It is impossible to simulate duodenal bulb ulcer using the gelatine capsule or ball made of breadcrumb. The last method of delivery of aggressive agent can damage the small intestine because of uncontrollability of the place of breaking the ball.

  14. Endocrine distrupting chemicals and human health: The plausibility ...

    African Journals Online (AJOL)

    The plausibility of research results on DDT and reproductive health ... cals in the environment and that human health is inextri- cably linked to the health of .... periods of folliculo-genesis or embryo-genesis that increases risk for adverse effects.

  15. Decree No 73-138 of 12 February 1973 in implementation of the Act of 1 August 1905 on repression of fraud concerning chemical products in human foodstuffs and articles in contact with food and beverages for human and animal consumption, as well as processes and products used for cleaning such articles

    International Nuclear Information System (INIS)

    1973-01-01

    For purposes of health protection, this Decree prescribes detailed conditions governing trade in foods and beverages containing chemical products for human and animal consumption, including irradiated food. (NEA) [fr

  16. Melatonin: a chemical photoperiodic signal with clinical significance in humans.

    Science.gov (United States)

    Pang, S F; Pang, C S; Poon, A M; Lee, P P; Liu, Z M; Shiu, S Y

    1998-03-01

    Secretion of pineal melatonin exhibits a diumal rhythm and a seasonal rhythm in humans. Night-time melatonin is high at 3-5 year-old and decreases with age. Many drugs and pathological conditions also change melatonin levels in the circulation. Melatonin has a mild sedative effect and has been used effectively in synchronizing the sleep-wake cycle of patients with sleep disorders. Immunoenhancing, anti-cancer, anti-aging and anti-oxidant effects of melatonin have been proposed. Recent studies suggest that melatonin receptors are present in central and peripheral tissues. The importance of melatonin receptors on the nervous, reproductive, immune and renal functions is implicated. Studies on the molecular biology, physiology and pathology of melatonin receptors in different tissues are progressing rapidly. The physiological and pathological changes in melatonin secretion, multifarious melatonin actions, and diverse melatonin receptors reported suggest that melatonin is a photoperiodic signal with clinical significance in humans.

  17. In vitro cytotoxicity of chemical preservatives on human fibroblast cells

    Directory of Open Access Journals (Sweden)

    Daniel Gonsales Spindola

    2018-05-01

    Full Text Available ABSTRACT Preservatives are widely used substances that are commonly added to various cosmetic and pharmaceutical products to prevent or inhibit microbial growth. In this study, we compared the in vitro cytotoxicity of different types of currently used preservatives, including methylparaben, imidazolidinyl urea (IMU, and sodium benzoate, using the human newborn fibroblast cell line CCD1072Sk. Of the tested preservatives, only IMU induced a reduction in cell viability, as shown using the MTT assay and propidium iodide staining (IMU>methylparaben>sodium benzoate. IMU was shown to promote homeostatic alterations potentially related to the initiation of programed cell death, such as decreased mitochondrial membrane potential and caspase-3 activation, in the treated cells. Methylparaben and sodium benzoate were shown to have a very low cytotoxic activity. Taken together, our results suggest that IMU induces programed cell death in human fibroblasts by a canonical intrinsic pathway via mitochondrial perturbation and subsequent release of proapoptotic factors.

  18. 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.

  19. 42 CFR 68c.1 - What is the scope and purpose of the National Institute of Child Health and Human Development...

    Science.gov (United States)

    2010-10-01

    ... Institute of Child Health and Human Development (NICHD) Contraception and Infertility Research Loan... purpose of the National Institute of Child Health and Human Development (NICHD) Contraception and... payments under the National Institute of Child Health and Human Development (NICHD) Contraception and...

  20. Simplified fate modelling in respect to ecotoxicological and human toxicological characterisation of emissions of chemical compounds

    DEFF Research Database (Denmark)

    Birkved, Morten; Heijungs, Reinout

    2011-01-01

    The impact assessment of chemical compounds in Life Cycle Impact Assessment (LCIA) and Environmental Risk Assessment (ERA) requires a vast amount of data on the properties of the chemical compounds being assessed. The purpose of the present study is to explore statistical options for reduction...... of the data demand associated with characterisation of chemical emissions in LCIA and ERA.Based on a USEtox™ characterisation factor set consisting of 3,073 data records, multi-dimensional bilinear models for emission compartment specific fate characterisation of chemical emissions were derived by application...... the independent chemical input parameters from the minimum data set, needed for characterisation in USEtox™, according to general availability, importance and relevance for fate factor prediction.Each approach (63% and 75% of the minimum data set needed for characterisation in USEtox™) yielded 66 meta...

  1. Human factors in equipment development for the Space Shuttle - A study of the general purpose work station

    Science.gov (United States)

    Junge, M. K.; Giacomi, M. J.

    1981-01-01

    The results of a human factors test to assay the suitability of a prototype general purpose work station (GPWS) for biosciences experiments on the fourth Spacelab mission are reported. The evaluation was performed to verify that users of the GPWS would optimally interact with the GPWS configuration and instrumentation. Six male subjects sat on stools positioned to allow assimilation of the zero-g body posture. Trials were run concerning the operator viewing angles facing the console, the console color, procedures for injecting rates with dye, a rat blood cell count, mouse dissection, squirrel monkey transfer, and plant fixation. The trials were run for several days in order to gage improvement or poor performance conditions. Better access to the work surface was found necessary, together with more distinct and better located LEDs, better access window latches, clearer sequences on control buttons, color-coded sequential buttons, and provisions made for an intercom system when operators of the GPWS work in tandem.

  2. Molecular restrictions for human eye irritation by chemical vapors

    International Nuclear Information System (INIS)

    Cometto-Muniz, J. Enrique; Cain, William S.; Abraham, Michael H.

    2005-01-01

    Previous research showed a cut-off along homologous volatile organic compounds (VOCs) in their ability to produce acute human mucosal irritation. The present study sought to specify the particular cut-off homolog for sensory eye irritation in an acetate and n-alcohol series. A 1900-ml glass vessel system and a three-alternative forced-choice procedure served to test nonyl, decyl, and dodecyl acetate, and 1-nonanol, 1-decanol, and 1-undecanol. Flowrate to the eye ranged from 2 to 8 L/min and time of exposure from 3 to 24 s. Decyl acetate and 1-undecanol were the shortest homologs that failed to produce eye irritation under all conditions, producing a cut-off effect. Increasing the vapor concentration of decyl acetate and 1-undecanol by 3 and 8 times, respectively, via heating them to 37 deg C made either or both VOCs detectable to only half of the 12 subjects tested, even though the higher vapor concentration was well above a predicted eye irritation threshold. When eye irritation thresholds for homologous acetates and n-alcohols were plotted as a function of the longest unfolded length of the molecule, the values for decyl acetate and 1-undecanol fell within a restricted range of 18 to 19 A. The outcome suggests that the basis for the cut-off is biological, that is, the molecule lacks a key size or structure to trigger transduction, rather than physical, that is, the vapor concentration is too low to precipitate detection

  3. Chemical warfare agent simulants for human volunteer trials of emergency decontamination: A systematic review

    OpenAIRE

    James, Thomas; Wyke, Stacey; Marczylo, Tim; Collins, Samuel; Gaulton, Tom; Foxall, Kerry; Amlôt, Richard; Duarte‐Davidson, Raquel

    2017-01-01

    Abstract Incidents involving the release of chemical agents can pose significant risks to public health. In such an event, emergency decontamination of affected casualties may need to be undertaken to reduce injury and possible loss of life. To ensure these methods are effective, human volunteer trials (HVTs) of decontamination protocols, using simulant contaminants, have been conducted. Simulants must be used to mimic the physicochemical properties of more harmful chemicals, while remaining ...

  4. Environmental chemicals in human milk: a review of levels, infant exposures and health, and guidance for future research

    International Nuclear Information System (INIS)

    LaKind, Judy S.; Amina Wilkins, A.; Berlin, Cheston M.

    2004-01-01

    The aim of this review is to introduce the reader to various science and policy aspects of the topic of environmental chemicals in human milk. Although information on environmental chemicals in human milk has been available since the 1950s, it is only relatively recently that public awareness of the issue has grown. This review on environmental chemicals in human milk provides a resource summarizing what is currently known about levels and trends of environmental chemicals in human milk, potential infant exposures, and benefits of breast-feeding relative to the risks of exposures to environmental chemicals. The term 'environmental chemicals', as it pertains to human milk, refers to many classes of exogenous chemicals that may be detected in human milk. For example, pharmaceutical agents and alcohol are environmental chemicals that have been found in human milk. Other chemicals, such as heavy metals and volatile organic compounds, have also been detected in human milk. Most research on environmental chemicals in human milk has concentrated on persistent, bioaccumulative, and toxic (PBT) chemicals. In this review, a description of human milk is provided, including a brief review of endogenous substances in human milk. Determinants of levels of PBTs are discussed, as are models that have been developed to predict levels of PBTs in human milk and associated body burdens in breast-feeding infants. Methodologies for human milk sampling and analysis, and concepts for consideration in interpretation and communication of study results, as developed by the Technical Workshop on Human Milk Surveillance and Research for Environmental Chemicals in the United States are described. Studies which have compared the health risks and benefits associated with breast-feeding and formula-feeding are discussed

  5. An Extended Chemical Plant Environmental Protection Game on Addressing Uncertainties of Human Adversaries.

    Science.gov (United States)

    Zhu, Zhengqiu; Chen, Bin; Qiu, Sihang; Wang, Rongxiao; Chen, Feiran; Wang, Yiping; Qiu, Xiaogang

    2018-03-27

    Chemical production activities in industrial districts pose great threats to the surrounding atmospheric environment and human health. Therefore, developing appropriate and intelligent pollution controlling strategies for the management team to monitor chemical production processes is significantly essential in a chemical industrial district. The literature shows that playing a chemical plant environmental protection (CPEP) game can force the chemical plants to be more compliant with environmental protection authorities and reduce the potential risks of hazardous gas dispersion accidents. However, results of the current literature strictly rely on several perfect assumptions which rarely hold in real-world domains, especially when dealing with human adversaries. To address bounded rationality and limited observability in human cognition, the CPEP game is extended to generate robust schedules of inspection resources for inspection agencies. The present paper is innovative on the following contributions: (i) The CPEP model is extended by taking observation frequency and observation cost of adversaries into account, and thus better reflects the industrial reality; (ii) Uncertainties such as attackers with bounded rationality, attackers with limited observation and incomplete information (i.e., the attacker's parameters) are integrated into the extended CPEP model; (iii) Learning curve theory is employed to determine the attacker's observability in the game solver. Results in the case study imply that this work improves the decision-making process for environmental protection authorities in practical fields by bringing more rewards to the inspection agencies and by acquiring more compliance from chemical plants.

  6. An Extended Chemical Plant Environmental Protection Game on Addressing Uncertainties of Human Adversaries

    Science.gov (United States)

    Wang, Rongxiao; Chen, Feiran; Wang, Yiping; Qiu, Xiaogang

    2018-01-01

    Chemical production activities in industrial districts pose great threats to the surrounding atmospheric environment and human health. Therefore, developing appropriate and intelligent pollution controlling strategies for the management team to monitor chemical production processes is significantly essential in a chemical industrial district. The literature shows that playing a chemical plant environmental protection (CPEP) game can force the chemical plants to be more compliant with environmental protection authorities and reduce the potential risks of hazardous gas dispersion accidents. However, results of the current literature strictly rely on several perfect assumptions which rarely hold in real-world domains, especially when dealing with human adversaries. To address bounded rationality and limited observability in human cognition, the CPEP game is extended to generate robust schedules of inspection resources for inspection agencies. The present paper is innovative on the following contributions: (i) The CPEP model is extended by taking observation frequency and observation cost of adversaries into account, and thus better reflects the industrial reality; (ii) Uncertainties such as attackers with bounded rationality, attackers with limited observation and incomplete information (i.e., the attacker’s parameters) are integrated into the extended CPEP model; (iii) Learning curve theory is employed to determine the attacker’s observability in the game solver. Results in the case study imply that this work improves the decision-making process for environmental protection authorities in practical fields by bringing more rewards to the inspection agencies and by acquiring more compliance from chemical plants. PMID:29584679

  7. An Extended Chemical Plant Environmental Protection Game on Addressing Uncertainties of Human Adversaries

    Directory of Open Access Journals (Sweden)

    Zhengqiu Zhu

    2018-03-01

    Full Text Available Chemical production activities in industrial districts pose great threats to the surrounding atmospheric environment and human health. Therefore, developing appropriate and intelligent pollution controlling strategies for the management team to monitor chemical production processes is significantly essential in a chemical industrial district. The literature shows that playing a chemical plant environmental protection (CPEP game can force the chemical plants to be more compliant with environmental protection authorities and reduce the potential risks of hazardous gas dispersion accidents. However, results of the current literature strictly rely on several perfect assumptions which rarely hold in real-world domains, especially when dealing with human adversaries. To address bounded rationality and limited observability in human cognition, the CPEP game is extended to generate robust schedules of inspection resources for inspection agencies. The present paper is innovative on the following contributions: (i The CPEP model is extended by taking observation frequency and observation cost of adversaries into account, and thus better reflects the industrial reality; (ii Uncertainties such as attackers with bounded rationality, attackers with limited observation and incomplete information (i.e., the attacker’s parameters are integrated into the extended CPEP model; (iii Learning curve theory is employed to determine the attacker’s observability in the game solver. Results in the case study imply that this work improves the decision-making process for environmental protection authorities in practical fields by bringing more rewards to the inspection agencies and by acquiring more compliance from chemical plants.

  8. Decontamination and management of human remains following incidents of hazardous chemical release.

    Science.gov (United States)

    Hauschild, Veronique D; Watson, Annetta; Bock, Robert

    2012-01-01

    To provide specific guidance and resources for systematic and orderly decontamination of human remains resulting from a chemical terrorist attack or accidental chemical release. A detailed review and health-based decision criteria protocol is summarized. Protocol basis and logic are derived from analyses of compound-specific toxicological data and chemical/physical characteristics. Guidance is suitable for civilian or military settings where human remains potentially contaminated with hazardous chemicals may be present, such as sites of transportation accidents, terrorist operations, or medical examiner processing points. Guidance is developed from data-characterizing controlled experiments with laboratory animals, fabrics, and materiel. Logic and specific procedures for decontamination and management of remains, protection of mortuary affairs personnel, and decision criteria to determine when remains are sufficiently decontaminated are presented. Established procedures as well as existing materiel and available equipment for decontamination and verification provide reasonable means to mitigate chemical hazards from chemically exposed remains. Unique scenarios such as those involving supralethal concentrations of certain liquid chemical warfare agents may prove difficult to decontaminate but can be resolved in a timely manner by application of the characterized systematic approaches. Decision criteria and protocols to "clear" decontaminated remains for transport and processing are also provided. Once appropriate decontamination and verification have been accomplished, normal procedures for management of remains and release can be followed.

  9. Endocrine-disrupting chemicals and obesity development in humans: A review

    DEFF Research Database (Denmark)

    Tang-Péronard, Jeanett; Andersen, Helle Raun; Jensen, Tina Kold

    2011-01-01

    This study reviewed the literature on the relations between exposure to chemicals with endocrine-disrupting abilities and obesity in humans. The studies generally indicated that exposure to some of the endocrine-disrupting chemicals was associated with an increase in body size in humans...... dibenzofurans found either associations with weight gain or an increase in waist circumference, or no association. The one study investigating relations with bisphenol A found no association. Studies investigating prenatal exposure indicated that exposure in utero may cause permanent physiological changes...

  10. Framework for integrating human and animal data in chemical risk assessment.

    Science.gov (United States)

    Lavelle, Karlene S; Robert Schnatter, A; Travis, Kim Z; Swaen, Gerard M H; Pallapies, Dirk; Money, Chris; Priem, Peter; Vrijhof, Henk

    2012-03-01

    Although regulatory agencies formally encourage the integration of all available data in chemical risk assessment, consistent implementation of this practice has been constrained by the lack of a clear, systematic method for doing so. In this paper, we describe a methodology for evaluating, classifying and integrating human and animal data into the risk assessment process that incorporates: (1) a balanced appraisal of human and animal data, (2) relevance to different stages of the risk assessment process, and (3) accommodation for different data quality requirements. The proposed framework offers a flexible, step-wise approach for determining which set of available data best support the chemical risk assessment that involves the rating and relative ranking of human and animal data quality. The evaluation of human data incorporates seven data quality elements, nature and specificity of the lead effect; evaluation of animal data incorporates data quality and relevance to humans. Results of simulations with selected chemicals previously evaluated in a formal risk assessment generally agreed with existing regulatory guidance. Application of the proposed framework across a wider range of chemical agents will improve transparency of the risk assessment process and validity of results, while informing continuous refinements to this evolving methodology. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Repair of human DNA: radiation and chemical damage in normal and xeroderma pigmentosum cells

    International Nuclear Information System (INIS)

    Regan, J.D.; Setlow, R.B.

    1976-01-01

    We present the experimental evidence we have gathered, using a particular assay for DNA repair in human cells, the photolysis of bromodeoxyuridine (BrdUrd) incorporated during repair. This assay characterizes the sequence of repair events that occur in human cells after radiation, both ultraviolet and ionizing, and permits an estimation of the size of the average repaired region after these physical insults to DNA. We will discuss chemical insults to DNA and attempt to liken the repair processes after chemical damages of various kinds to those repair processes that occur in human DNA after damage from physical agents. We will also show results indicating that, under certain conditions, repair events resembling those seen after uv-irradiation can be observed in normal human cells after ionizing radiation. Furthermore the XP cells, defective in the repair of uv-induced DNA damage, show defective repair of these uv-like DNA lesions induced by ionizing radiation

  12. CHEMICALS

    CERN Multimedia

    Medical Service

    2002-01-01

    It is reminded that all persons who use chemicals must inform CERN's Chemistry Service (TIS-GS-GC) and the CERN Medical Service (TIS-ME). Information concerning their toxicity or other hazards as well as the necessary individual and collective protection measures will be provided by these two services. Users must be in possession of a material safety data sheet (MSDS) for each chemical used. These can be obtained by one of several means : the manufacturer of the chemical (legally obliged to supply an MSDS for each chemical delivered) ; CERN's Chemistry Service of the General Safety Group of TIS ; for chemicals and gases available in the CERN Stores the MSDS has been made available via EDH either in pdf format or else via a link to the supplier's web site. Training courses in chemical safety are available for registration via HR-TD. CERN Medical Service : TIS-ME :73186 or service.medical@cern.ch Chemistry Service : TIS-GS-GC : 78546

  13. Comparative sensitivity of human and rat neural cultures to chemical-induced inhibition of neurite outgrowth

    Energy Technology Data Exchange (ETDEWEB)

    Harrill, Joshua A.; Freudenrich, Theresa M.; Robinette, Brian L.; Mundy, William R., E-mail: mundy.william@epa.gov

    2011-11-15

    There is a need for rapid, efficient and cost-effective alternatives to traditional in vivo developmental neurotoxicity testing. In vitro cell culture models can recapitulate many of the key cellular processes of nervous system development, including neurite outgrowth, and may be used as screening tools to identify potential developmental neurotoxicants. The present study compared primary rat cortical cultures and human embryonic stem cell-derived neural cultures in terms of: 1) reproducibility of high content image analysis based neurite outgrowth measurements, 2) dynamic range of neurite outgrowth measurements and 3) sensitivity to chemicals which have been shown to inhibit neurite outgrowth. There was a large increase in neurite outgrowth between 2 and 24 h in both rat and human cultures. Image analysis data collected across multiple cultures demonstrated that neurite outgrowth measurements in rat cortical cultures were more reproducible and had higher dynamic range as compared to human neural cultures. Human neural cultures were more sensitive than rat cortical cultures to chemicals previously shown to inhibit neurite outgrowth. Parallel analysis of morphological (neurite count, neurite length) and cytotoxicity (neurons per field) measurements were used to detect selective effects on neurite outgrowth. All chemicals which inhibited neurite outgrowth in rat cortical cultures did so at concentrations which did not concurrently affect the number of neurons per field, indicating selective effects on neurite outgrowth. In contrast, more than half the chemicals which inhibited neurite outgrowth in human neural cultures did so at concentrations which concurrently decreased the number of neurons per field, indicating that effects on neurite outgrowth were secondary to cytotoxicity. Overall, these data demonstrate that the culture models performed differently in terms of reproducibility, dynamic range and sensitivity to neurite outgrowth inhibitors. While human neural

  14. Comparative sensitivity of human and rat neural cultures to chemical-induced inhibition of neurite outgrowth

    International Nuclear Information System (INIS)

    Harrill, Joshua A.; Freudenrich, Theresa M.; Robinette, Brian L.; Mundy, William R.

    2011-01-01

    There is a need for rapid, efficient and cost-effective alternatives to traditional in vivo developmental neurotoxicity testing. In vitro cell culture models can recapitulate many of the key cellular processes of nervous system development, including neurite outgrowth, and may be used as screening tools to identify potential developmental neurotoxicants. The present study compared primary rat cortical cultures and human embryonic stem cell-derived neural cultures in terms of: 1) reproducibility of high content image analysis based neurite outgrowth measurements, 2) dynamic range of neurite outgrowth measurements and 3) sensitivity to chemicals which have been shown to inhibit neurite outgrowth. There was a large increase in neurite outgrowth between 2 and 24 h in both rat and human cultures. Image analysis data collected across multiple cultures demonstrated that neurite outgrowth measurements in rat cortical cultures were more reproducible and had higher dynamic range as compared to human neural cultures. Human neural cultures were more sensitive than rat cortical cultures to chemicals previously shown to inhibit neurite outgrowth. Parallel analysis of morphological (neurite count, neurite length) and cytotoxicity (neurons per field) measurements were used to detect selective effects on neurite outgrowth. All chemicals which inhibited neurite outgrowth in rat cortical cultures did so at concentrations which did not concurrently affect the number of neurons per field, indicating selective effects on neurite outgrowth. In contrast, more than half the chemicals which inhibited neurite outgrowth in human neural cultures did so at concentrations which concurrently decreased the number of neurons per field, indicating that effects on neurite outgrowth were secondary to cytotoxicity. Overall, these data demonstrate that the culture models performed differently in terms of reproducibility, dynamic range and sensitivity to neurite outgrowth inhibitors. While human neural

  15. Comparison between cytogenetic damage induced in human lymphocytes by environmental chemicals or radiation

    Energy Technology Data Exchange (ETDEWEB)

    Cebulska-Wasilewska, A. [Institute of Nuclear Physics, Cracow (Poland)

    1997-12-31

    Author compared cytogenetic effects of chemicals (benzene and the member at benzene related compounds) and ionizing radiation on the human lymphocytes. Levels of various types of cytogenetic damage observed among people from petroleum plants workers groups are similar to the levels of damages detected in the blood of people suspected of the accidental exposure to a radiation source

  16. Comparison between cytogenetic damage induced in human lymphocytes by environmental chemicals or radiation

    International Nuclear Information System (INIS)

    Cebulska-Wasilewska, A.

    1997-01-01

    Author compared cytogenetic effects of chemicals (benzene and the member at benzene related compounds) and ionizing radiation on the human lymphocytes. Levels of various types of cytogenetic damage observed among people from petroleum plants workers groups are similar to the levels of damages detected in the blood of people suspected of the accidental exposure to a radiation source

  17. Mining Human Biomonitoring Data to Identify Prevalent Chemical Mixtures (SOT abstract)

    Science.gov (United States)

    Through food, water, air, and consumer products, humans are exposed to tens of thousands of environmental chemicals, and most of these have not been evaluated to determine their potential toxicities. In recent years, high-throughput screening (HTS) methods have been developed tha...

  18. COMPARISON OF CHEMICAL-INDUCED CHANGES IN PROLIFERATION AND APOPTOSIS IN HUMAN AND MOUSE NEUROPROGENITOR CELLS.

    Science.gov (United States)

    There is a need to develop rapid and efficient models for screening chemicals for their potential to cause developmental neurotoxicity. Use of in vitro neuronal models, including human cells, is one approach that allows for timely, cost-effective toxicity screening. The present s...

  19. Comparison of Chemical-induced Changes in Proliferation and Apoptosis in Human and Mouse Neuroprogenitor Cells.***

    Science.gov (United States)

    There is a need to develop rapid and efficient models to screen chemicals for their potential to cause developmental neurotoxicity. Use of in vitro neuronal models, including human cells, is one approach that allows for timely, cost-effective toxicity screening. The present study...

  20. A Cell Model to Evaluate Chemical Effects on Adult Human Cardiac Progenitor Cell Differentiation and Function

    Science.gov (United States)

    Adult cardiac stem cells (CSC) and progenitor cells (CPC) represent a population of cells in the heart critical for its regeneration and function over a lifetime. The impact of chemicals on adult human CSC/CPC differentiation and function is unknown. Research was conducted to dev...

  1. Continuous, real-time bioimaging of chemical bioavailability and toxicology using autonomously bioluminescent human cell lines

    Science.gov (United States)

    Xu, Tingting; Close, Dan M.; Webb, James D.; Price, Sarah L.; Ripp, Steven A.; Sayler, Gary S.

    2013-05-01

    Bioluminescent imaging is an emerging biomedical surveillance strategy that uses external cameras to detect in vivo light generated in small animal models of human physiology or in vitro light generated in tissue culture or tissue scaffold mimics of human anatomy. The most widely utilized of reporters is the firefly luciferase (luc) gene; however, it generates light only upon addition of a chemical substrate, thus only generating intermittent single time point data snapshots. To overcome this disadvantage, we have demonstrated substrate-independent bioluminescent imaging using an optimized bacterial bioluminescence (lux) system. The lux reporter produces bioluminescence autonomously using components found naturally within the cell, thereby allowing imaging to occur continuously and in real-time over the lifetime of the host. We have validated this technology in human cells with demonstrated chemical toxicological profiling against exotoxin exposures at signal strengths comparable to existing luc systems (~1.33 × 107 photons/second). As a proof-in-principle demonstration, we have engineered breast carcinoma cells to express bioluminescence for real-time screening of endocrine disrupting chemicals and validated detection of 17β-estradiol (EC50 = ~ 10 pM). These and other applications of this new reporter technology will be discussed as potential new pathways towards improved models of target chemical bioavailability, toxicology, efficacy, and human safety.

  2. Chemical UV Filters Mimic the Effect of Progesterone on Ca(2+) Signaling in Human Sperm Cells

    DEFF Research Database (Denmark)

    Rehfeld, A; Dissing, S; Skakkebæk, N E

    2016-01-01

    Progesterone released by cumulus cells surrounding the egg induces a Ca(2+) influx into human sperm cells via the cationic channel of sperm (CatSper) Ca(2+) channel and controls multiple Ca(2+)-dependent responses essential for fertilization. We hypothesized that chemical UV filters may mimic...

  3. H-1 chemical shift imaging characterization of human brain tumor and edema

    NARCIS (Netherlands)

    Sijens, PE; Oudkerk, M

    Longitudinal (T1) and transverse (T2) relaxation times of metabolites in human brain tumor, peritumoral edema, and unaffected brain tissue were assessed from point resolved spectroscopy (PRESS) H-1 chemical shift imaging results at different repetition times (TR = 1500 and 5000 ms; T1: n = 19) and

  4. 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

  5. Concentrations and chemical species of arsenic in human urine and hair

    Energy Technology Data Exchange (ETDEWEB)

    Yamato, Naohisa (St. Marianna Univ. School of Medicine, Kawasaki (Japan))

    1988-05-01

    Because marine products are rich in arsenic, the concentration of arsenic in the human urine varies greatly with the state of ingestion of marine products. It has been revealed that inorganic arsenic is methylated in the human body to form MAA (methylarsonic acid) and DMAA (dimethylarsinic acid). It appears therefore that the arsenic present in the human urine is a mixture of the arsenic originating from marine products and the arsenic metabolized in vivo. Recent studies have shown that inorganic arsenic and methylarsenic compounds are quite different in toxicity and effect on the living body due to their difference in chemical species. Finding the chemical species of arsenic in the urine and hair of normal subjects will therefore provide valuable basal data for the biological monitoring of arsenic exposure and for toxicological studies of arsenic.

  6. Chemical reaction vector embeddings: towards predicting drug metabolism in the human gut microbiome.

    Science.gov (United States)

    Mallory, Emily K; Acharya, Ambika; Rensi, Stefano E; Turnbaugh, Peter J; Bright, Roselie A; Altman, Russ B

    2018-01-01

    Bacteria in the human gut have the ability to activate, inactivate, and reactivate drugs with both intended and unintended effects. For example, the drug digoxin is reduced to the inactive metabolite dihydrodigoxin by the gut Actinobacterium E. lenta, and patients colonized with high levels of drug metabolizing strains may have limited response to the drug. Understanding the complete space of drugs that are metabolized by the human gut microbiome is critical for predicting bacteria-drug relationships and their effects on individual patient response. Discovery and validation of drug metabolism via bacterial enzymes has yielded >50 drugs after nearly a century of experimental research. However, there are limited computational tools for screening drugs for potential metabolism by the gut microbiome. We developed a pipeline for comparing and characterizing chemical transformations using continuous vector representations of molecular structure learned using unsupervised representation learning. We applied this pipeline to chemical reaction data from MetaCyc to characterize the utility of vector representations for chemical reaction transformations. After clustering molecular and reaction vectors, we performed enrichment analyses and queries to characterize the space. We detected enriched enzyme names, Gene Ontology terms, and Enzyme Consortium (EC) classes within reaction clusters. In addition, we queried reactions against drug-metabolite transformations known to be metabolized by the human gut microbiome. The top results for these known drug transformations contained similar substructure modifications to the original drug pair. This work enables high throughput screening of drugs and their resulting metabolites against chemical reactions common to gut bacteria.

  7. Coupling of physical erosion and chemical weathering after phases of intense human activity

    Science.gov (United States)

    Schoonejans, Jerome; Vanacker, Veerle; Opfergelt, Sophie; Ameijeiras-Mariño, Yolanda; Kubik, Peter W.

    2014-05-01

    Anthropogenic disturbance of natural vegetation profoundly alters the lateral and vertical fluxes of soil nutrients and particles at the land surface. Human-induced acceleration of soil erosion can thereby result in an imbalance between physical erosion, soil production and chemical weathering. The (de-)coupling between physical erosion and chemical weathering in ecosystems with strong anthropogenic disturbances is not yet fully understood, as earlier studies mostly focused on natural ecosystems. In this study, we explore the chemical weathering intensity for four study sites located in the Internal Zone of the Spanish Betic Cordillera. Most of the sites belong to the Nevado-Filabres complex, but are characterized by different rates of long-term exhumation, 10Be catchment-wide denudation and hill slope morphology. Denudation rates are generally low, but show large variation between the three sites (from 23 to 246 mm kyr-1). The magnitude of denudation rates is consistent with longer-term uplift rates derived from marine deposits, fission-track measurements and vertical fault slip rates. Two to three soil profiles were sampled per study site at exposed ridge tops. All soils overly fractured mica schist, and are very thin (< 60cm). In each soil profile, we sampled 5 depth slices, rock fragments and the (weathered) bedrock. In total, 38 soil and 20 rock samples were analyzed for their chemical composition. The chemical weathering intensity is constrained by the Chemical Depletion Fraction that is based on a chemical mass balance approach using Zr as an immobile element. Chemical weathering accounts for 5 to 35% of the total mass lost due to denudation. We observe systematically higher chemical weathering intensities (CDFs) in sites with lower denudation rates (and vice versa), suggesting that weathering is supply-limited. Our measurements of soil elemental losses from 10 soil profiles suggest that the observed variation in chemical weathering is strongly associated

  8. Identifying developmental toxicity pathways for a subset of ToxCast chemicals using human embryonic stem cells and metabolomics

    Science.gov (United States)

    Metabolomics analysis was performed on the supernatant of human embryonic stem (hES) cell cultures exposed to a blinded subset of 11 chemicals selected from the chemical library of EPA's ToxCast™ chemical screening and prioritization research project. Metabolites from hES cultur...

  9. Additive mixture effects of estrogenic chemicals in human cell-based assays can be influenced by inclusion of chemicals with differing effect profiles.

    Directory of Open Access Journals (Sweden)

    Richard Mark Evans

    Full Text Available A growing body of experimental evidence indicates that the in vitro effects of mixtures of estrogenic chemicals can be well predicted from the estrogenicity of their components by the concentration addition (CA concept. However, some studies have observed small deviations from CA. Factors affecting the presence or observation of deviations could include: the type of chemical tested; number of mixture components; mixture design; and assay choice. We designed mixture experiments that address these factors, using mixtures with high numbers of components, chemicals from diverse chemical groups, assays with different in vitro endpoints and different mixture designs and ratios. Firstly, the effects of mixtures composed of up to 17 estrogenic chemicals were examined using estrogenicity assays with reporter-gene (ERLUX and cell proliferation (ESCREEN endpoints. Two mixture designs were used: 1 a 'balanced' design with components present in proportion to a common effect concentration (e.g. an EC(10 and 2 a 'non-balanced' design with components in proportion to potential human tissue concentrations. Secondly, the individual and simultaneous ability of 16 potential modulator chemicals (each with minimal estrogenicity to influence the assay outcome produced by a reference mixture of estrogenic chemicals was examined. Test chemicals included plasticizers, phthalates, metals, PCBs, phytoestrogens, PAHs, heterocyclic amines, antioxidants, UV filters, musks, PBDEs and parabens. In all the scenarios tested, the CA concept provided a good prediction of mixture effects. Modulation studies revealed that chemicals possessing minimal estrogenicity themselves could reduce (negatively modulate the effect of a mixture of estrogenic chemicals. Whether the type of modulation we observed occurs in practice most likely depends on the chemical concentrations involved, and better information is required on likely human tissue concentrations of estrogens and of potential

  10. Additive mixture effects of estrogenic chemicals in human cell-based assays can be influenced by inclusion of chemicals with differing effect profiles.

    Science.gov (United States)

    Evans, Richard Mark; Scholze, Martin; Kortenkamp, Andreas

    2012-01-01

    A growing body of experimental evidence indicates that the in vitro effects of mixtures of estrogenic chemicals can be well predicted from the estrogenicity of their components by the concentration addition (CA) concept. However, some studies have observed small deviations from CA. Factors affecting the presence or observation of deviations could include: the type of chemical tested; number of mixture components; mixture design; and assay choice. We designed mixture experiments that address these factors, using mixtures with high numbers of components, chemicals from diverse chemical groups, assays with different in vitro endpoints and different mixture designs and ratios. Firstly, the effects of mixtures composed of up to 17 estrogenic chemicals were examined using estrogenicity assays with reporter-gene (ERLUX) and cell proliferation (ESCREEN) endpoints. Two mixture designs were used: 1) a 'balanced' design with components present in proportion to a common effect concentration (e.g. an EC(10)) and 2) a 'non-balanced' design with components in proportion to potential human tissue concentrations. Secondly, the individual and simultaneous ability of 16 potential modulator chemicals (each with minimal estrogenicity) to influence the assay outcome produced by a reference mixture of estrogenic chemicals was examined. Test chemicals included plasticizers, phthalates, metals, PCBs, phytoestrogens, PAHs, heterocyclic amines, antioxidants, UV filters, musks, PBDEs and parabens. In all the scenarios tested, the CA concept provided a good prediction of mixture effects. Modulation studies revealed that chemicals possessing minimal estrogenicity themselves could reduce (negatively modulate) the effect of a mixture of estrogenic chemicals. Whether the type of modulation we observed occurs in practice most likely depends on the chemical concentrations involved, and better information is required on likely human tissue concentrations of estrogens and of potential modulators

  11. Screening organic chemicals in commerce for emissions in the context of environmental and human exposure.

    Science.gov (United States)

    Breivik, Knut; Arnot, Jon A; Brown, Trevor N; McLachlan, Michael S; Wania, Frank

    2012-08-01

    Quantitative knowledge of organic chemical release into the environment is essential to understand and predict human exposure as well as to develop rational control strategies for any substances of concern. While significant efforts have been invested to characterize and screen organic chemicals for hazardous properties, relatively less effort has been directed toward estimating emissions and hence also risks. Here, a rapid throughput method to estimate emissions of discrete organic chemicals in commerce has been developed, applied and evaluated to support screening studies aimed at ranking and identifying chemicals of potential concern. The method builds upon information in the European Union Technical Guidance Document and utilizes information on quantities in commerce (production and/or import rates), chemical function (use patterns) and physical-chemical properties to estimate emissions to air, soil and water within the OECD for five stages of the chemical life-cycle. The method is applied to 16,029 discrete substances (identified by CAS numbers) from five national and international high production volume lists. As access to consistent input data remains fragmented or even impossible, particular attention is given to estimating, evaluating and discussing uncertainties in the resulting emission scenarios. The uncertainty for individual substances typically spans 3 to 4 orders of magnitude for this initial tier screening method. Information on uncertainties in emissions is useful as any screening or categorization methods which solely rely on threshold values are at risk of leading to a significant number of either false positives or false negatives. A limited evaluation of the screening method's estimates for a sub-set of about 100 substances, compared against independent and more detailed emission scenarios presented in various European Risk Assessment Reports, highlights that up-to-date and accurate information on quantities in commerce as well as a detailed

  12. Partitioning of polar and non-polar neutral organic chemicals into human and cow milk.

    Science.gov (United States)

    Geisler, Anett; Endo, Satoshi; Goss, Kai-Uwe

    2011-10-01

    The aim of this work was to develop a predictive model for milk/water partition coefficients of neutral organic compounds. Batch experiments were performed for 119 diverse organic chemicals in human milk and raw and processed cow milk at 37°C. No differences (milk were observed. The polyparameter linear free energy relationship model fit the calibration data well (SD=0.22 log units). An experimental validation data set including hormones and hormone active compounds was predicted satisfactorily by the model. An alternative modelling approach based on log K(ow) revealed a poorer performance. The model presented here provides a significant improvement in predicting enrichment of potentially hazardous chemicals in milk. In combination with physiologically based pharmacokinetic modelling this improvement in the estimation of milk/water partitioning coefficients may allow a better risk assessment for a wide range of neutral organic chemicals. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. 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.

  14. Establishing Trafficking in Human Beings for the Purpose of Organ Removal and Improving Cross-Border Collaboration in Criminal Cases: Recommendations.

    Science.gov (United States)

    Holmes, Paul; Rijken, Conny; D'Orsi, Sergio; Esser, Luuk; Hol, Floor; Gallagher, Anne; Greenberg, Galit; Helberg, Louis; Horvatits, Lisa; McCarthy, Sean; Ratel, Jonathan; Scheper-Hughes, Nancy; Forsythe, John

    2016-02-01

    In this short summary report on the legal definition of trafficking in human beings for the purpose of organ removal and improving cross-border collaboration in criminal cases, challenges, and recommendations in the areas of defining the crime, criminal investigation and prosecution, and cross-border cooperation are made. These are the outcomes of a working group discussion during the writers' conference of the HOTT project, a European Union-funded project against trafficking in human beings for the purpose of organ removal.

  15. Human genetic marker for resistance to radiations and chemicals. 1998 annual progress report

    International Nuclear Information System (INIS)

    Lieberman, H.B.

    1998-01-01

    'The broad objective of the project is to understand the molecular basis for the response of cells to radiations and chemicals, with the pragmatic goal of being able to identify human subpopulations that are exceptionally sensitive to DNA damaging agents. The project focuses on HRAD9, a human orthologue of the fission yeast Schizosaccharomyces pombe gene rad9. S. pombe rad9::ura4+ mutant cells are highly sensitive to ionizing radiation, UV and many chemicals, such as the DNA synthesis inhibitor hydroxyurea. They also lack the ability to delay cycling transiently in S phase or in G2 following a block in DNA replication or after incurring DNA damage, respectively -i.e., they lack checkpoint controls. The attempt by mutant cells to progress through mitosis in the absence of fully intact DNA accounts at least in part for their sensitivity to DNA damaging agents. Cells bearing rad9::ura4+ also aberrantly regulate UVDE, an enzyme that participates in a secondary DNA excision repair pathway. The key role played by S. pombe rad9 in promoting resistance to chemicals and radiations suggests that the evolutionarily conserved human cognate also has important functions in mammals. The first set of aims in this proposal centers on characterizing the structure and expression of HRAD9, to assess structure/function relationships and potentially link protein activity to a specific tissue. The next set of aims focuses on determining the role of HRAD9 in radio/chemoresponsiveness and cancer.'

  16. Chemical warfare agent simulants for human volunteer trials of emergency decontamination: A systematic review.

    Science.gov (United States)

    James, Thomas; Wyke, Stacey; Marczylo, Tim; Collins, Samuel; Gaulton, Tom; Foxall, Kerry; Amlôt, Richard; Duarte-Davidson, Raquel

    2018-01-01

    Incidents involving the release of chemical agents can pose significant risks to public health. In such an event, emergency decontamination of affected casualties may need to be undertaken to reduce injury and possible loss of life. To ensure these methods are effective, human volunteer trials (HVTs) of decontamination protocols, using simulant contaminants, have been conducted. Simulants must be used to mimic the physicochemical properties of more harmful chemicals, while remaining non-toxic at the dose applied. This review focuses on studies that employed chemical warfare agent simulants in decontamination contexts, to identify those simulants most suitable for use in HVTs of emergency decontamination. Twenty-two simulants were identified, of which 17 were determined unsuitable for use in HVTs. The remaining simulants (n = 5) were further scrutinized for potential suitability according to toxicity, physicochemical properties and similarities to their equivalent toxic counterparts. Three suitable simulants, for use in HVTs were identified; methyl salicylate (simulant for sulphur mustard), diethyl malonate (simulant for soman) and malathion (simulant for VX or toxic industrial chemicals). All have been safely used in previous HVTs, and have a range of physicochemical properties that would allow useful inference to more toxic chemicals when employed in future studies of emergency decontamination systems. © 2017 Crown Copyright. Journal of Applied Toxicology published by John Wiley & Sons, Ltd.

  17. Impact of chemical peeling combined with negative pressure on human skin.

    Science.gov (United States)

    Kim, S J; Kang, I J; Shin, M K; Jeong, K H; Baek, J H; Koh, J S; Lee, S J

    2016-10-01

    In vivo changes in skin barrier function after chemical peeling with alpha hydroxyacids (AHAs) have been previously reported. However, the additional effects of physical treatment with chemical agents on skin barrier function have not been adequately studied. This study measured the degree of acute skin damage and the time required for skin barrier repair using non-invasive bioengineering methods in vivo with human skin to investigate the additional effect of a 4% AHA chemical jet accelerated at supersonic velocities. Thirteen female subjects (average age: 29.54 ± 4.86 years) participated in this study. The faces of the subjects were divided into half according to the block randomization design and were then assigned to receive AHA peeling alone or AHA peeling combined with pneumatic pressure on each side of the face. Transepidermal water loss (TEWL), skin colour and skin blood flow were evaluated at baseline and at 30 min, 2, 5 and 7 days after treatment. The TEWL and skin blood flow were significantly increased after 30 min in chemodermabrasion compared with chemical peeling alone (P peeling alone (P < 0.05). Chemodermabrasion can temporarily impair skin barriers, but it is estimated that it can enhance the skin barrier function after 7 days compared to the use of a chemical agent alone. In addition, chemodermabrasion has a more effective impact in the dermis and relatively preserves the skin barrier. © 2016 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  18. EDC IMPACT: Chemical UV filters can affect human sperm function in a progesterone-like manner

    Directory of Open Access Journals (Sweden)

    A Rehfeld

    2017-12-01

    Full Text Available Human sperm cell function must be precisely regulated to achieve natural fertilization. Progesterone released by the cumulus cells surrounding the egg induces a Ca2+ influx into human sperm cells via the CatSper Ca2+-channel and thereby controls sperm function. Multiple chemical UV filters have been shown to induce a Ca2+ influx through CatSper, thus mimicking the effect of progesterone on Ca2+ signaling. We hypothesized that these UV filters could also mimic the effect of progesterone on sperm function. We examined 29 UV filters allowed in sunscreens in the US and/or EU for their ability to affect acrosome reaction, penetration, hyperactivation and viability in human sperm cells. We found that, similar to progesterone, the UV filters 4-MBC, 3-BC, Meradimate, Octisalate, BCSA, HMS and OD-PABA induced acrosome reaction and 3-BC increased sperm penetration into a viscous medium. The capacity of the UV filters to induce acrosome reaction and increase sperm penetration was positively associated with the ability of the UV filters to induce a Ca2+ influx. None of the UV filters induced significant changes in the proportion of hyperactivated cells. In conclusion, chemical UV filters that mimic the effect of progesterone on Ca2+ signaling in human sperm cells can similarly mimic the effect of progesterone on acrosome reaction and sperm penetration. Human exposure to these chemical UV filters may impair fertility by interfering with sperm function, e.g. through induction of premature acrosome reaction. Further studies are needed to confirm the results in vivo.

  19. EDC IMPACT: Chemical UV filters can affect human sperm function in a progesterone-like manner.

    Science.gov (United States)

    Rehfeld, A; Egeberg, D L; Almstrup, K; Petersen, J H; Dissing, S; Skakkebæk, N E

    2018-01-01

    Human sperm cell function must be precisely regulated to achieve natural fertilization. Progesterone released by the cumulus cells surrounding the egg induces a Ca 2+ influx into human sperm cells via the CatSper Ca 2+ -channel and thereby controls sperm function. Multiple chemical UV filters have been shown to induce a Ca 2+ influx through CatSper, thus mimicking the effect of progesterone on Ca 2+ signaling. We hypothesized that these UV filters could also mimic the effect of progesterone on sperm function. We examined 29 UV filters allowed in sunscreens in the US and/or EU for their ability to affect acrosome reaction, penetration, hyperactivation and viability in human sperm cells. We found that, similar to progesterone, the UV filters 4-MBC, 3-BC, Meradimate, Octisalate, BCSA, HMS and OD-PABA induced acrosome reaction and 3-BC increased sperm penetration into a viscous medium. The capacity of the UV filters to induce acrosome reaction and increase sperm penetration was positively associated with the ability of the UV filters to induce a Ca 2+ influx. None of the UV filters induced significant changes in the proportion of hyperactivated cells. In conclusion, chemical UV filters that mimic the effect of progesterone on Ca 2+ signaling in human sperm cells can similarly mimic the effect of progesterone on acrosome reaction and sperm penetration. Human exposure to these chemical UV filters may impair fertility by interfering with sperm function, e.g. through induction of premature acrosome reaction. Further studies are needed to confirm the results in vivo . © 2018 The authors.

  20. 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.

  1. In Silico Prediction for Intestinal Absorption and Brain Penetration of Chemical Pesticides in Humans.

    Science.gov (United States)

    Chedik, Lisa; Mias-Lucquin, Dominique; Bruyere, Arnaud; Fardel, Olivier

    2017-06-30

    Intestinal absorption and brain permeation constitute key parameters of toxicokinetics for pesticides, conditioning their toxicity, including neurotoxicity. However, they remain poorly characterized in humans. The present study was therefore designed to evaluate human intestine and brain permeation for a large set of pesticides ( n = 338) belonging to various chemical classes, using an in silico graphical BOILED-Egg/SwissADME online method based on lipophilicity and polarity that was initially developed for drugs. A high percentage of the pesticides (81.4%) was predicted to exhibit high intestinal absorption, with a high accuracy (96%), whereas a lower, but substantial, percentage (38.5%) displayed brain permeation. Among the pesticide classes, organochlorines ( n = 30) constitute the class with the lowest percentage of intestine-permeant members (40%), whereas that of the organophosphorus compounds ( n = 99) has the lowest percentage of brain-permeant chemicals (9%). The predictions of the permeations for the pesticides were additionally shown to be significantly associated with various molecular descriptors well-known to discriminate between permeant and non-permeant drugs. Overall, our in silico data suggest that human exposure to pesticides through the oral way is likely to result in an intake of these dietary contaminants for most of them and brain permeation for some of them, thus supporting the idea that they have toxic effects on human health, including neurotoxic effects.

  2. Assessment of immunotoxicity induced by chemicals in human precision-cut lung slices (PCLS).

    Science.gov (United States)

    Lauenstein, L; Switalla, S; Prenzler, F; Seehase, S; Pfennig, O; Förster, C; Fieguth, H; Braun, A; Sewald, K

    2014-06-01

    Occupational asthma can be induced by a number of chemicals at the workplace. Risk assessment of potential sensitizers is mostly performed in animal experiments. With increasing public demand for alternative methods, human precision-cut lung slices (PCLS) have been developed as an ex vivo model. Human PCLS were exposed to increasing concentrations of 20 industrial chemicals including 4 respiratory allergens, 11 contact allergens, and 5 non-sensitizing irritants. Local respiratory irritation was characterized and expressed as 75% (EC25) and 50% (EC50) cell viability with respect to controls. Dose-response curves of all chemicals except for phenol were generated. Local respiratory inflammation was quantified by measuring the production of cytokines and chemokines. TNF-α and IL-1α were increased significantly in human PCLS after exposure to the respiratory sensitizers trimellitic anhydride (TMA) and ammonium hexachloroplatinate (HClPt) at subtoxic concentrations, while contact sensitizers and non-sensitizing irritants failed to induce the release of these cytokines to the same extent. Interestingly, significant increases in T(H)1/T(H)2 cytokines could be detected only after exposure to HClPt at a subtoxic concentration. In conclusion, allergen-induced cytokines were observed but not considered as biomarkers for the differentiation between respiratory and contact sensitizers. Our preliminary results show an ex vivo model which might be used for prediction of chemical-induced toxicity, but is due to its complex three-dimensional structure not applicable for a simple screening of functional and behavior changes of certain cell populations such as dendritic cells and T-cells in response to allergens. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Chemical composition and binary mixture of human urinary stones using FT-Raman spectroscopy method.

    Science.gov (United States)

    Selvaraju, R; Raja, A; Thiruppathi, G

    2013-10-01

    In the present study the human urinary stones were observed in their different chemical compositions of calcium oxalate monohydrate, calcium oxalate dihydrate, calcium phosphate, struvite (magnesium ammonium phosphate), uric acid, cystine, oxammite (ammonium oxalate monohydrate), natroxalate (sodium oxalate), glushinkite (magnesium oxalate dihydrate) and moolooite (copper oxalate) were analyzed using Fourier Transform-Raman (FT-Raman) spectroscopy. For the quantitative analysis, various human urinary stone samples are used for ratios calculation of binary mixtures compositions such as COM/COD, HAP/COD, HAP/COD, Uric acid/COM, uric acid/COD and uric acid/HAP. The calibration curve is used for further analysis of binary mixture of human urinary stones. For the binary mixture calculation the various intensities bands at 1462 cm(-1) (I(COM)), 1473 cm(-1) (I(COD)), 961 cm(-1) (I(HAP)) and 1282 cm(-1) (I(UA)) were used. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Chemical allergens stimulate human epidermal keratinocytes to produce lymphangiogenic vascular endothelial growth factor.

    Science.gov (United States)

    Bae, Ok-Nam; Ahn, Seyeon; Jin, Sun Hee; Hong, Soo Hyun; Lee, Jinyoung; Kim, Eun-Sun; Jeong, Tae Cheon; Chun, Young-Jin; Lee, Ai-Young; Noh, Minsoo

    2015-03-01

    Allergic contact dermatitis (ACD) is a cell-mediated immune response that involves skin sensitization in response to contact with various allergens. Angiogenesis and lymphangiogenesis both play roles in the allergic sensitization process. Epidermal keratinocytes can produce vascular endothelial growth factor (VEGF) in response to UV irradiation and during wound healing. However, the effect of haptenic chemical allergens on the VEGF production of human keratinocytes, which is the primary contact site of toxic allergens, has not been thoroughly researched. We systematically investigated whether immune-regulatory cytokines and chemical allergens would lead to the production of VEGF in normal human keratinocytes (NHKs) in culture. VEGF production significantly increased when NHKs were treated with IFNγ, IL-1α, IL-4, IL-6, IL-17A, IL-22 or TNFα. Among the human sensitizers listed in the OECD Test Guideline (TG) 429, we found that CMI/MI, DNCB, 4-phenylenediamine, cobalt chloride, 2-mercaptobenzothiazole, citral, HCA, cinnamic alcohol, imidazolidinyl urea and nickel chloride all significantly upregulated VEGF production in NHKs. In addition, common human haptenic allergens such as avobenzone, formaldehyde and urushiol, also induced the keratinocyte-derived VEGF production. VEGF upregulation by pro-inflammatory stimuli, IFNγ, DNCB or formaldehyde is preceded by the production of IL-8, an acute inflammatory phase cytokine. Lymphangiogenic VEGF-C gene transcription was significantly increased when NHKs were treated with formaldehyde, DNCB or urushiol, while transcription of VEGF-A and VEGF-B did not change. Therefore, the chemical allergen-induced VEGF upregulation is mainly due to the increase in lymphangiogenic VEGF-C transcription in NHKs. These results suggest that keratinocyte-derived VEGF may regulate the lymphangiogenic process during the skin sensitization process of ACD. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Bombom para dietas especiais: avaliação química e sensorial Chocolate confectionery for special purposes: chemical and sensorial evaluation

    Directory of Open Access Journals (Sweden)

    Marissol Richter

    2007-03-01

    Full Text Available Bombom é o produto constituído por massa de chocolate ou por um núcleo formado de recheios diversos, recobertos por uma camada de chocolate. Alimentos para fins especiais (diet são aqueles nos quais ocorrem modificações no conteúdo de nutrientes, adequados à utilização em dietas diferenciadas. O termo light pode ser utilizado quando for cumprido o atributo de redução mínima de 25% no valor energético total ou no conteúdo de nutrientes de alimentos comparados. Foram desenvolvidos um bombom controle e formulações de bombons diet/light, sendo apenas uma formulação selecionada para estudo. Um bombom comercial foi utilizado como referência. Foram elaboradas análises químicas (obtenção do valor calórico e análise sensorial (teste de aceitação com escala hedônica híbrida para avaliação dos produtos. A substituição dos açúcares por edulcorantes e agentes de corpo foi satisfatória, assim como o uso do substituto de gordura Benefat®. Na análise sensorial, o bombom especial obteve altos níveis de intenção de compra, podendo nesta análise ser considerado como um produto de grande potencial de mercado.Chocolate confectionery is a product consisting of either chocolate mass or a nucleus containing several fillings covered with a chocolate layer. Foods for special purposes are those in which modifications are made in what is related to the nutrients content, adapted to the utilization in differentiated diets. The term light is applied to a product providing it fulfils the attribute of a 25% minimum reduction in the total energetic value or nutrients content if compared to a similar, standard product. Two series of chocolate confectionery samples were prepared: a control sample and ten diet and light formulations, and one of these formulations was selected. A commercial chocolate confectionery was used as reference. The chocolate confectionery samples (control and special were compared using chemical and sensorial

  6. Surface chemical functionalities affect the behavior of human adipose-derived stem cells in vitro

    International Nuclear Information System (INIS)

    Liu, Xujie; Feng, Qingling; Bachhuka, Akash; Vasilev, Krasimir

    2013-01-01

    This study examines the effect of surface chemical functionalities on the behavior of human adipose-derived stem cells (hASCs) in vitro. Plasma polymerized films rich in amine (-NH 2 ), carboxyl (-COOH) and methyl (-CH 3 ), were generated on hydroxyapatite (HAp) substrates. The surface chemical functionalities were characterized by X-ray photoelectron spectroscopy (XPS). The ability of different substrates to absorb proteins was evaluated. The results showed that substrates modified with hydrophilic functional group (-COOH and -NH 2 ) can absorb more proteins than these modified with more hydrophobic functional group (-CH 3 ). The behavior of human adipose-derived stem cells (hASCs) cultured on different substrates was investigated in vitro: cell counting kit-8 (CCK-8) analysis was used to characterize cell proliferation, scanning electronic microscopy (SEM) analysis was used to characterize cell morphology and alkaline phosphatase (ALP) activity analysis was used to account for differentiation. The results of this study demonstrated that the -NH 2 modified surfaces encourage osteogenic differentiation; the -COOH modified surfaces promote cell adhesion and spreading and the -CH 3 modified surfaces have the lowest ability to induce osteogenic differentiation. These findings confirmed that the surface chemical states of biomaterials can affect the behavior of hASCs in vitro.

  7. Surface chemical functionalities affect the behavior of human adipose-derived stem cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xujie [State key laboratory of new ceramics and fine processing, School of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Feng, Qingling, E-mail: biomater@mail.tsinghua.edu.cn [State key laboratory of new ceramics and fine processing, School of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Bachhuka, Akash [Mawson Institute, University of South Australia, Mawson Lakes 5095 (Australia); Vasilev, Krasimir [Mawson Institute, University of South Australia, Mawson Lakes 5095 (Australia); School of Advanced Manufacturing, University of South Australia, Mawson Lakes 5095 (Australia)

    2013-04-01

    This study examines the effect of surface chemical functionalities on the behavior of human adipose-derived stem cells (hASCs) in vitro. Plasma polymerized films rich in amine (-NH{sub 2}), carboxyl (-COOH) and methyl (-CH{sub 3}), were generated on hydroxyapatite (HAp) substrates. The surface chemical functionalities were characterized by X-ray photoelectron spectroscopy (XPS). The ability of different substrates to absorb proteins was evaluated. The results showed that substrates modified with hydrophilic functional group (-COOH and -NH{sub 2}) can absorb more proteins than these modified with more hydrophobic functional group (-CH{sub 3}). The behavior of human adipose-derived stem cells (hASCs) cultured on different substrates was investigated in vitro: cell counting kit-8 (CCK-8) analysis was used to characterize cell proliferation, scanning electronic microscopy (SEM) analysis was used to characterize cell morphology and alkaline phosphatase (ALP) activity analysis was used to account for differentiation. The results of this study demonstrated that the -NH{sub 2} modified surfaces encourage osteogenic differentiation; the -COOH modified surfaces promote cell adhesion and spreading and the -CH{sub 3} modified surfaces have the lowest ability to induce osteogenic differentiation. These findings confirmed that the surface chemical states of biomaterials can affect the behavior of hASCs in vitro.

  8. Body composition of two human cadavers by neutron activation and chemical analysis

    International Nuclear Information System (INIS)

    Knight, G.S.; Beddoe, A.H.; Streat, S.J.; Hill, G.L.

    1986-01-01

    In vivo neutron activation analysis (NAA) is currently used to measure body composition in metabolic and nutritional studies in many clinical situations, but has not previously been validated by comparison with chemical analysis of human cadavers. Total body nitrogen (TBN) and chlorine (TBCl) were measured in two human cadavers by NAA before homogenization and chemical analysis (CHEM) after (cadaver 1: TBN, 1.47 NAA, 1.51 CHEM; TBCl, 0.144 NAA, 0.147 CHEM; cadaver 2: TBN, 0.576 NAA, 0.572 CHEM; TBCl, 0.0227 NAA, 0.0250 CHEM). The homogenates were also analyzed by NAA, and no significant differences were found, indicating that the effects of elemental inhomogeneity on the measurement of TBN and TBCl are insignificant. Total body water, fat, protein, minerals, and carbohydrates were measured chemically for each cadaver and compared with estimates for these compartments obtained from a body composition model, which when used in vivo involves NAA and tritium dilution. The agreement found justifies the use of the model for the measurement of changes in total body protein, water, and fat in sequential studies in groups of patients

  9. Endocrine effects of chemicals: aspects of hazard identification and human health risk assessment.

    Science.gov (United States)

    Dekant, Wolfgang; Colnot, Thomas

    2013-12-16

    Hazard and risk assessment of chemicals with endocrine activity is hotly debated due to claimed non-monotonous dose-response curves in the low-dose region. In hazard identification a clear definition of "endocrine disruptors" (EDs) is required; this should be based on the WHO/IPCS definition of EDs and on adverse effects demonstrated in intact animals or humans. Therefore, endocrine effects are a mode of action potentially resulting in adverse effects; any classification should not be based on a mode of action, but on adverse effects. In addition, when relying on adverse effects, most effects reported in the low-dose region will not qualify for hazard identification since most have little relation to an adverse effect. Non-monotonous dose-response curves that had been postulated from limited, exploratory studies could also not be reproduced in targeted studies with elaborate quality assurance. Therefore, regulatory agencies or advisory bodies continue to apply the safety-factor method or the concept of "margin-of-exposure" based on no observed adverse effect levels (NOAELs) in the risk assessment of chemicals with weak hormonal activity. Consistent with this approach, tolerable levels regarding human exposure have been defined for such chemicals. To conclusively support non-monotonous dose-response curves, targeted experiments with a sufficient number of animals, determination of adverse endpoints, adequate statistics and quality control would be required. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  10. Chemical allergens stimulate human epidermal keratinocytes to produce lymphangiogenic vascular endothelial growth factor

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Ok-Nam [College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan 426-791 (Korea, Republic of); Ahn, Seyeon; Jin, Sun Hee; Hong, Soo Hyun; Lee, Jinyoung [College of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul 151-742 (Korea, Republic of); Kim, Eun-Sun [College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan 426-791 (Korea, Republic of); Jeong, Tae Cheon [College of Pharmacy, Yeungnam University, Gyeongsan 712-749 (Korea, Republic of); Chun, Young-Jin [College of Pharmacy, Chung-Ang University, Seoul 156-756 (Korea, Republic of); Lee, Ai-Young, E-mail: leeay@duih.org [Department of Dermatology, Dongguk University Ilsan Hospital, Goyang 410-773 (Korea, Republic of); Noh, Minsoo, E-mail: minsoo@alum.mit.edu [College of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul 151-742 (Korea, Republic of)

    2015-03-01

    Allergic contact dermatitis (ACD) is a cell-mediated immune response that involves skin sensitization in response to contact with various allergens. Angiogenesis and lymphangiogenesis both play roles in the allergic sensitization process. Epidermal keratinocytes can produce vascular endothelial growth factor (VEGF) in response to UV irradiation and during wound healing. However, the effect of haptenic chemical allergens on the VEGF production of human keratinocytes, which is the primary contact site of toxic allergens, has not been thoroughly researched. We systematically investigated whether immune-regulatory cytokines and chemical allergens would lead to the production of VEGF in normal human keratinocytes (NHKs) in culture. VEGF production significantly increased when NHKs were treated with IFNγ, IL-1α, IL-4, IL-6, IL-17A, IL-22 or TNFα. Among the human sensitizers listed in the OECD Test Guideline (TG) 429, we found that CMI/MI, DNCB, 4-phenylenediamine, cobalt chloride, 2-mercaptobenzothiazole, citral, HCA, cinnamic alcohol, imidazolidinyl urea and nickel chloride all significantly upregulated VEGF production in NHKs. In addition, common human haptenic allergens such as avobenzone, formaldehyde and urushiol, also induced the keratinocyte-derived VEGF production. VEGF upregulation by pro-inflammatory stimuli, IFNγ, DNCB or formaldehyde is preceded by the production of IL-8, an acute inflammatory phase cytokine. Lymphangiogenic VEGF-C gene transcription was significantly increased when NHKs were treated with formaldehyde, DNCB or urushiol, while transcription of VEGF-A and VEGF-B did not change. Therefore, the chemical allergen-induced VEGF upregulation is mainly due to the increase in lymphangiogenic VEGF-C transcription in NHKs. These results suggest that keratinocyte-derived VEGF may regulate the lymphangiogenic process during the skin sensitization process of ACD. - Highlights: • Pro-inflammatory cytokines induced VEGF production in normal human

  11. Chemical allergens stimulate human epidermal keratinocytes to produce lymphangiogenic vascular endothelial growth factor

    International Nuclear Information System (INIS)

    Bae, Ok-Nam; Ahn, Seyeon; Jin, Sun Hee; Hong, Soo Hyun; Lee, Jinyoung; Kim, Eun-Sun; Jeong, Tae Cheon; Chun, Young-Jin; Lee, Ai-Young; Noh, Minsoo

    2015-01-01

    Allergic contact dermatitis (ACD) is a cell-mediated immune response that involves skin sensitization in response to contact with various allergens. Angiogenesis and lymphangiogenesis both play roles in the allergic sensitization process. Epidermal keratinocytes can produce vascular endothelial growth factor (VEGF) in response to UV irradiation and during wound healing. However, the effect of haptenic chemical allergens on the VEGF production of human keratinocytes, which is the primary contact site of toxic allergens, has not been thoroughly researched. We systematically investigated whether immune-regulatory cytokines and chemical allergens would lead to the production of VEGF in normal human keratinocytes (NHKs) in culture. VEGF production significantly increased when NHKs were treated with IFNγ, IL-1α, IL-4, IL-6, IL-17A, IL-22 or TNFα. Among the human sensitizers listed in the OECD Test Guideline (TG) 429, we found that CMI/MI, DNCB, 4-phenylenediamine, cobalt chloride, 2-mercaptobenzothiazole, citral, HCA, cinnamic alcohol, imidazolidinyl urea and nickel chloride all significantly upregulated VEGF production in NHKs. In addition, common human haptenic allergens such as avobenzone, formaldehyde and urushiol, also induced the keratinocyte-derived VEGF production. VEGF upregulation by pro-inflammatory stimuli, IFNγ, DNCB or formaldehyde is preceded by the production of IL-8, an acute inflammatory phase cytokine. Lymphangiogenic VEGF-C gene transcription was significantly increased when NHKs were treated with formaldehyde, DNCB or urushiol, while transcription of VEGF-A and VEGF-B did not change. Therefore, the chemical allergen-induced VEGF upregulation is mainly due to the increase in lymphangiogenic VEGF-C transcription in NHKs. These results suggest that keratinocyte-derived VEGF may regulate the lymphangiogenic process during the skin sensitization process of ACD. - Highlights: • Pro-inflammatory cytokines induced VEGF production in normal human

  12. Development of a systematic method to assess similarity between nanomaterials for human hazard evaluation purposes - lessons learnt.

    NARCIS (Netherlands)

    Vdz Park, Margriet; Catalán, Julia; Ferraz, Natalia; Cabellos, Joan; Vanhauten, Ralph; Vázquez-Campos, Socorro; Janer, Gemma

    2018-01-01

    Within the EU FP-7 GUIDEnano project, a methodology was developed to systematically quantify the similarity between a nanomaterial (NM) that has been tested in toxicity studies and the NM for which risk needs to be evaluated, for the purpose of extrapolating toxicity data between the two materials.

  13. Particle size: a missing factor in risk assessment of human exposure to toxic chemicals in settled indoor dust.

    Science.gov (United States)

    Cao, Zhi-Guo; Yu, Gang; Chen, Yong-Shan; Cao, Qi-Ming; Fiedler, Heidelore; Deng, Shu-Bo; Huang, Jun; Wang, Bin

    2012-11-15

    For researches on toxic chemicals in settled indoor dust, selection of dust fraction is a critical influencing factor to the accuracy of human exposure risk assessment results. However, analysis of the selection of dust fraction in recent studies revealed that there is no consensus. This study classified and presented researches on distribution of toxic chemicals according to dust particle size and on relationship between dust particle size and human exposure possibility. According to the literature, beyond the fact that there were no consistent conclusions on particle size distribution of adherent fraction, dust with particle size less than 100 μm should be paid more attention and that larger than 250 μm is neither adherent nor proper for human exposure risk assessment. Calculation results based on literature data show that with different selections of dust fractions, analytical results of toxic chemicals would vary up to 10-fold, which means that selecting dust fractions arbitrarily will lead to large errors in risk assessment of human exposure to toxic chemicals in settled dust. Taking into account the influence of dust particle size on risk assessment of human exposure to toxic chemicals, a new methodology for risk assessment of human exposure to toxic chemicals in settled indoor dust is proposed and human exposure parameter systems to settled indoor dust are advised to be established at national and regional scales all over the world. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Physico chemical study of the uptake of some radionuclides by the human bone powder

    International Nuclear Information System (INIS)

    Mohamed, S.A.

    1989-01-01

    Human bone femurs were freed from flesh and marrow, crushed and ground to a grain size below 50 in diameter. Fat was extracted from one third of the powder (FFB). protein was extracted from the second third (PFB) and the third portion was without any treatment as raw bone powder (RB). Physical and chemical properties of bone powder such as density, chemical composition, calcium content, and nitrogen content were investigated. Experimental procedures followed two techniques: - Schweitzer and Nehls technique (164) where a large reaction vessel was used. - Harrison et al technique (90) where the batch system was used. Counting systems applied were : beta counting for 89 Sr and gamma counting for 60 Co and 6 5 Zn

  15. A chemically defined substrate for the expansion and neuronal differentiation of human pluripotent stem cell-derived neural progenitor cells

    Directory of Open Access Journals (Sweden)

    Yihuan Tsai

    2015-07-01

    Full Text Available Due to the limitation of current pharmacological therapeutic strategies, stem cell therapies have emerged as a viable option for treating many incurable neurological disorders. Specifically, human pluripotent stem cell (hPSC-derived neural progenitor cells (hNPCs, a multipotent cell population that is capable of near indefinite expansion and subsequent differentiation into the various cell types that comprise the central nervous system (CNS, could provide an unlimited source of cells for such cell-based therapies. However the clinical application of these cells will require (i defined, xeno-free conditions for their expansion and neuronal differentiation and (ii scalable culture systems that enable their expansion and neuronal differentiation in numbers sufficient for regenerative medicine and drug screening purposes. Current extracellular matrix protein (ECMP-based substrates for the culture of hNPCs are expensive, difficult to isolate, subject to batch-to-batch variations, and, therefore, unsuitable for clinical application of hNPCs. Using a high-throughput array-based screening approach, we identified a synthetic polymer, poly(4-vinyl phenol (P4VP, that supported the long-term proliferation and self-renewal of hNPCs. The hNPCs cultured on P4VP maintained their characteristic morphology, expressed high levels of markers of multipotency, and retained their ability to differentiate into neurons. Such chemically defined substrates will eliminate critical roadblocks for the utilization of hNPCs for human neural regenerative repair, disease modeling, and drug discovery.

  16. Purification and functional characterization of nine human Aquaporins produced in Saccharomyces cerevisiae for the purpose of biophysical characterization

    DEFF Research Database (Denmark)

    Pedersen, Per Amstrup; Gourdon, Pontus Emanuel; Gotfryd, Kamil

    2017-01-01

    investigated the capacity of S. cerevisiae to deliver high yields of prime quality human AQPs, focusing on poorly characterized members including some previously shown to be difficult to isolate. Exploiting GFP labeled forms we comprehensively optimized production and purification procedures resulting...... in satisfactory yields of all nine AQP targets. We applied the obtained knowledge to successfully upscale purification of histidine tagged human AQP10 produced in large bioreactors. Glycosylation analysis revealed that AQP7 and 12 were O-glycosylated, AQP10 was N-glycosylated while the other AQPs were...... not glycosylated. We furthermore performed functional characterization and found that AQP 2, 6 and 8 allowed flux of water whereas AQP3, 7, 9, 10, 11 and 12 also facilitated a glycerol flux. In conclusion, our S. cerevisiae platform emerges as a powerful tool for isolation of functional, difficult-to-express human...

  17. 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...

  18. Integrating mechanistic and polymorphism data to characterize human genetic susceptibility for environmental chemical risk assessment in the 21st century

    International Nuclear Information System (INIS)

    Mortensen, Holly M.; Euling, Susan Y.

    2013-01-01

    Response to environmental chemicals can vary widely among individuals and between population groups. In human health risk assessment, data on susceptibility can be utilized by deriving risk levels based on a study of a susceptible population and/or an uncertainty factor may be applied to account for the lack of information about susceptibility. Defining genetic susceptibility in response to environmental chemicals across human populations is an area of interest in the NAS' new paradigm of toxicity pathway-based risk assessment. Data from high-throughput/high content (HT/HC), including -omics (e.g., genomics, transcriptomics, proteomics, metabolomics) technologies, have been integral to the identification and characterization of drug target and disease loci, and have been successfully utilized to inform the mechanism of action for numerous environmental chemicals. Large-scale population genotyping studies may help to characterize levels of variability across human populations at identified target loci implicated in response to environmental chemicals. By combining mechanistic data for a given environmental chemical with next generation sequencing data that provides human population variation information, one can begin to characterize differential susceptibility due to genetic variability to environmental chemicals within and across genetically heterogeneous human populations. The integration of such data sources will be informative to human health risk assessment

  19. The Life Mission Theory VI. A Theory for the Human Character: Healing with Holistic Medicine Through Recovery of Character and Purpose of Life

    Directory of Open Access Journals (Sweden)

    Søren Ventegodt

    2004-01-01

    Full Text Available The human character can be understood as an extension of the life mission or purpose of life, and explained as the primary tool of a person to impact others and express the purpose of life. Repression of the human character makes it impossible for a person to realize his personal mission in life and, therefore, is one of the primary causes of self-repression resulting in poor quality of life, health, and ability. From Hippocrates to Hahnemann, repression of physical, mental, and spiritual character can be seen as the prime cause of disease, while recovery of character has been the primary intention of the treatment. In this paper, human character is explained as an intersubjective aspect of consciousness with the ability to influence the consciousness of another person directly. To understand consciousness, we reintroduce the seven-ray theory of consciousness explaining consciousness in accordance with a fractal ontology with a bifurcation number of seven (the numbers four to ten work almost as well. A case report on a female, aged 35 years, with severe hormonal disturbances, diagnosed with extremely early menopause, is presented and treated according to the theory of holistic existential healing (the holistic process theory of healing. After recovery of her character and purpose of life, her quality of life dramatically improved and hormonal status normalized. We believe that the recovery of human character and purpose of life was the central intention of Hippocrates and thus the original essence of western medicine. Interestingly, there are strong parallels to the peyote medicine of the Native Americans, the African Sangomas, the Australian Aboriginal healers, and the old Nordic medicine. The recovery of human character was also the intention of Hahnemann's homeopathy. We believe that we are at the core of consciousness-based medicine, as recovery of purpose of life and human character has been practiced as medicine in most human cultures

  20. Assessment of skin exposure to N,N-dimethylformamide and methyl ethylketone through chemical protective gloves and decontamination of gloves for reuse purposes.

    Science.gov (United States)

    Chao, Keh-Ping; Wang, Ping; Chen, Chen-Peng; Tang, Ping-Yu

    2011-02-15

    N,N-dimethylformamide (DMF) and methyl ethylketone (MEK) are the hazardous chemicals commonly used in the synthetic leather industries. Although chemical protective gloves provide adequate skin exposure protection to workers in these industries, there is currently no clear guideline or understanding with regard to the use duration of these gloves. In this study, the permeation of DMF/MEK mixture through neoprene gloves and the desorption of chemicals from contaminated gloves were conducted using the ASTM F739 cell. The acceptable use duration time of the gloves against DMF/MEK permeation was estimated by assuming a critical body burden of chemical exposure as a result of dermal absorption. In a re-exposure cycle of 5 days, decontamination of the gloves by aeration at 25°C was found to be inadequate in a reduction of breakthrough time as compared to a new unexposed glove. However, decontamination of the gloves by heating at 70 or 100°C showed that the protective coefficient of the exposed gloves had similar levels of resistance to DMF/MEK as that of new gloves. Implications of this study include an understanding of the use duration of neoprene gloves and proper decontamination of chemical protective gloves for reuse. Copyright © 2010 Elsevier B.V. All rights reserved.

  1. In silico prediction of potential chemical reactions mediated by human enzymes.

    Science.gov (United States)

    Yu, Myeong-Sang; Lee, Hyang-Mi; Park, Aaron; Park, Chungoo; Ceong, Hyithaek; Rhee, Ki-Hyeong; Na, Dokyun

    2018-06-13

    Administered drugs are often converted into an ineffective or activated form by enzymes in our body. Conventional in silico prediction approaches focused on therapeutically important enzymes such as CYP450. However, there are more than thousands of different cellular enzymes that potentially convert administered drug into other forms. We developed an in silico model to predict which of human enzymes including metabolic enzymes as well as CYP450 family can catalyze a given chemical compound. The prediction is based on the chemical and physical similarity between known enzyme substrates and a query chemical compound. Our in silico model was developed using multiple linear regression and the model showed high performance (AUC = 0.896) despite of the large number of enzymes. When evaluated on a test dataset, it also showed significantly high performance (AUC = 0.746). Interestingly, evaluation with literature data showed that our model can be used to predict not only enzymatic reactions but also drug conversion and enzyme inhibition. Our model was able to predict enzymatic reactions of a query molecule with a high accuracy. This may foster to discover new metabolic routes and to accelerate the computational development of drug candidates by enabling the prediction of the potential conversion of administered drugs into active or inactive forms.

  2. Hyperspectral and differential CARS microscopy for quantitative chemical imaging in human adipocytes

    Science.gov (United States)

    Di Napoli, Claudia; Pope, Iestyn; Masia, Francesco; Watson, Peter; Langbein, Wolfgang; Borri, Paola

    2014-01-01

    In this work, we demonstrate the applicability of coherent anti-Stokes Raman scattering (CARS) micro-spectroscopy for quantitative chemical imaging of saturated and unsaturated lipids in human stem-cell derived adipocytes. We compare dual-frequency/differential CARS (D-CARS), which enables rapid imaging and simple data analysis, with broadband hyperspectral CARS microscopy analyzed using an unsupervised phase-retrieval and factorization method recently developed by us for quantitative chemical image analysis. Measurements were taken in the vibrational fingerprint region (1200–2000/cm) and in the CH stretch region (2600–3300/cm) using a home-built CARS set-up which enables hyperspectral imaging with 10/cm resolution via spectral focussing from a single broadband 5 fs Ti:Sa laser source. Through a ratiometric analysis, both D-CARS and phase-retrieved hyperspectral CARS determine the concentration of unsaturated lipids with comparable accuracy in the fingerprint region, while in the CH stretch region D-CARS provides only a qualitative contrast owing to its non-linear behavior. When analyzing hyperspectral CARS images using the blind factorization into susceptibilities and concentrations of chemical components recently demonstrated by us, we are able to determine vol:vol concentrations of different lipid components and spatially resolve inhomogeneities in lipid composition with superior accuracy compared to state-of-the art ratiometric methods. PMID:24877002

  3. Modulation of cytokine expression in human macrophages by endocrine-disrupting chemical Bisphenol-A

    International Nuclear Information System (INIS)

    Liu, Yanzhen; Mei, Chenfang; Liu, Hao; Wang, Hongsheng; Zeng, Guoqu; Lin, Jianhui; Xu, Meiying

    2014-01-01

    Highlights: • Effects of BPA on the cytokines expression of human macrophages were investigated. • BPA increased pro-inflammation cytokines TNF-α and IL-6 production. • BPA decreased anti-inflammation IL-10 and TGF-β production. • ERα/β/ERK/NF-κB signaling involved in BPA-mediated cytokines expression. - Abstract: Exposure to environmental endocrine-disrupting chemical Bisphenol-A (BPA) is often associated with dysregulated immune homeostasis, but the mechanisms remain unclear. In the present study, the effects of BPA on the cytokines responses of human macrophages were investigated. Treatment with BPA increased pro-inflammation cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production, but decreased anti-inflammation cytokines interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) production in THP1 macrophages, as well as in primary human macrophages. BPA effected cytokines expression through estrogen receptor α/β (ERα/β)-dependent mechanism with the evidence of ERα/β antagonist reversed the expression of cytokines. We also identified that activation of extracellular regulated protein kinases (ERK)/nuclear factor κB (NF-κB) signal cascade marked the effects of BPA on cytokines expression. Our results indicated that BPA effected inflammatory responses of macrophages via modulating of cytokines expression, and provided a new insight into the link between exposure to BPA and human health

  4. Modulation of cytokine expression in human macrophages by endocrine-disrupting chemical Bisphenol-A

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yanzhen; Mei, Chenfang [State Key Laboratory of Applied Microbiology Southern China, Guangzhou 510070 (China); Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Institute of Microbiology, Guangzhou 510070 (China); Liu, Hao [Affiliated Cancer Hospital and Cancer Research Institute, Guangzhou Medical University, Guangzhou 510095 (China); Wang, Hongsheng [Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006 (China); Zeng, Guoqu; Lin, Jianhui [State Key Laboratory of Applied Microbiology Southern China, Guangzhou 510070 (China); Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Institute of Microbiology, Guangzhou 510070 (China); Xu, Meiying, E-mail: xumy@gdim.cn [State Key Laboratory of Applied Microbiology Southern China, Guangzhou 510070 (China); Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Institute of Microbiology, Guangzhou 510070 (China)

    2014-09-05

    Highlights: • Effects of BPA on the cytokines expression of human macrophages were investigated. • BPA increased pro-inflammation cytokines TNF-α and IL-6 production. • BPA decreased anti-inflammation IL-10 and TGF-β production. • ERα/β/ERK/NF-κB signaling involved in BPA-mediated cytokines expression. - Abstract: Exposure to environmental endocrine-disrupting chemical Bisphenol-A (BPA) is often associated with dysregulated immune homeostasis, but the mechanisms remain unclear. In the present study, the effects of BPA on the cytokines responses of human macrophages were investigated. Treatment with BPA increased pro-inflammation cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production, but decreased anti-inflammation cytokines interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) production in THP1 macrophages, as well as in primary human macrophages. BPA effected cytokines expression through estrogen receptor α/β (ERα/β)-dependent mechanism with the evidence of ERα/β antagonist reversed the expression of cytokines. We also identified that activation of extracellular regulated protein kinases (ERK)/nuclear factor κB (NF-κB) signal cascade marked the effects of BPA on cytokines expression. Our results indicated that BPA effected inflammatory responses of macrophages via modulating of cytokines expression, and provided a new insight into the link between exposure to BPA and human health.

  5. Retinyl β-glucoronide: its occurrence in human serum, chemical synthesis and biological activity

    International Nuclear Information System (INIS)

    Barua, A.B.; Batres, R.O.; Olson, J.A.

    1986-01-01

    When retinol is administered to rats, retinyl and retinoyl β-glucuronides appear in the bile. Retinyl or retinoyl β-glucuronide is also synthesized in vitro when rat liver microsomes are incubated with uridinediphosphoglucuronic acid and either retinol or retinoic acid. Retinoyl β-glucuronide, a major metabolite of retinoic acid in a number of tissues, is highly active biologically, has been chemically synthesized, and is found in human blood. The physiological significance of the glucuronides of vitamin A are not known yet. To investigate further its metabolism and possible physiological role, retinyl β-glucuronide was chemically synthesized from retinol and characterized by study of its ultra-violet spectrum (γ/sub max/ 325 nm in methanol, 329 nm in water), 1 H-NMR and mass spectra. Retinyl β-glucuronide was extensively hydrolyzed by bacterial β-glucuronidase to retinol. Retinyl β-glucuronide is soluble in water and was detected in significant amounts in the serum of healthy human adults. The biological activity of synthetic retinyl β-glucuronide was determined in rats by the rat growth bioassay method

  6. Researching chemicals in human milk can be conducted without discouraging breastfeeding

    Directory of Open Access Journals (Sweden)

    José G. Dórea

    2012-05-01

    Full Text Available Continued monitoring of environmental chemicals is important for understanding human exposure and potentially related health risk(s. Cinar et al. [1] contribute to our knowledge on infant exposures to environmental chemicals in breast milk. However, the messages implicit both in the title and in the paper itself are unnecessarily alarming and are likely to be interpreted by mothers and health professionals as indicating that breast feeding is generally unsafe in certain regions of Turkey. For example, the conclusion that “Rural area also may not be safe for breastfeed babies” is based on an evaluation of 90 women, without regard to differences in their potential exposure patterns; lifestyle, smoking status, occupation, body mass index, or residential history. It is unclear whether these women are in any way representative of rural areas in Turkey, or rural areas in general. Further, the authors do not provide reference values with which to compare the levels of metals that they report, and the values that they report for several metals are 10-1000 times higher than the levels reported in other studies (although it is unclear whether they have reported the levels with correct units; the authors note that the mothers’ levels were lower than recommended levels of 10 microg/L (Hg and 30 microg/L (Pb while describing the mothers’ reported levels as being in the low parts per million range [Table 4]. Only under exceptional circumstances including clinical treatment with certain pharmaceuticals or in cases of accidental poisonings have the occurrence of chemicals in breast milk resulted in a recommendation to avoid breastfeeding. Otherwise, studies have shown that breastfeeding can counter subtle adverse effects associated with in utero maternal exposure to hazardous substances [2]. Numerous studies demonstrate the superiority of breastfeeding in lowering risk of adverse health outcomes when compared to formula-fed infants. Thus, the World

  7. Establishing Trafficking in Human Beings for the Purpose of Organ Removal and Improving Cross-Border Collaboration in Criminal Cases: Recommendations

    OpenAIRE

    Holmes, Paul; Rijken, Conny; D'Orsi, Sergio; Esser, Luuk; Hol, Floor; Gallagher, Anne; Greenberg, Galit; Helberg, Louis; Horvatits, Lisa; McCarthy, Sean; Ratel, Jonathan; Scheper-Hughes, Nancy; Forsythe, John

    2016-01-01

    Abstract In this short summary report on the legal definition of trafficking in human beings for the purpose of organ removal and improving cross-border collaboration in criminal cases, challenges, and recommendations in the areas of defining the crime, criminal investigation and prosecution, and cross-border cooperation are made. These are the outcomes of a working group discussion during the writers' conference of the HOTT project, a European Union-funded project against trafficking in huma...

  8. Human volunteer studies with non-pharmaceutical chemicals: metabolism and pharmacokinetic studies.

    Science.gov (United States)

    Wilks, M F; Woollen, B H

    1994-06-01

    1. Human volunteer studies are an essential part of drug development but their use in the area of non-pharmaceutical chemicals has so far been very limited. Such studies can have considerable value in the assessment and improvement of the safe use of chemicals. 2. Once metabolic pathways and target metabolites have been identified in volunteers this information can be used in studies in the workplace or in the general population. Studies should be performed selectively only if there is both a toxic hazard and a significant exposure potential. In addition, they should only be carried out if the required information cannot be obtained in any other way. 3. Volunteer studies with non-pharmaceuticals have become increasingly acceptable in the light of established international guidelines, no-fault compensation, improvements in study design and technical developments which allow the use of very low dose levels. The final decision on whether to carry out a study must always rest with an independent ethical committee. 4. The practical aspects of the study should be specified in a detailed protocol conforming with the principles of good clinical practice. The safety of volunteers must be of paramount concern throughout. Depending on the nature of the chemical and the study, it may be advisable to carry out studies in a clinical facility where equipment is available for the treatment of any emergencies that might occur. 5. Numerous investigators have now shown that human volunteer studies are ethically acceptable, practicable and yield important information. The risk to volunteers is minimal and this approach can lead to an improved foundation for occupational hygiene standards, more accurate risk assessment and thus better protection of the workforce and the general population.

  9. The development of a nuclear chemical plant human reliability management approach: HRMS and JHEDI

    International Nuclear Information System (INIS)

    Kirwan, Barry

    1997-01-01

    -be-assessed, task or scenario. The extrapolation process therefore required a set of PSF profiles for a number of real and representative data-based scenarios, and empirically-derived rules to extrapolate to new but similar scenarios. Using existing nuclear chemical plant human error and other data, a PSF profiling and extrapolation system was developed, which could assess most HEPs required for nuclear chemical risk assessments. The two techniques were then employed in a major risk assessment, with HRMS being utilised for approximately twenty high risk scenarios, and JHEDI being used to calculate well over five hundred HEPs for a large range of tasks and scenarios, by a number of assessors

  10. Chemical Rescue of Enzymes: Proton Transfer in Mutants of Human Carbonic Anhydrase II

    Science.gov (United States)

    Maupin, C. Mark; Castillo, Norberto; Taraphder, Srabani; Tu, Chingkuang; McKenna, Robert; Silverman, David N.; Voth, Gregory A.

    2011-01-01

    In human carbonic anhydrase II (HCA II) the mutation of position 64 from histidine to alanine (H64A) disrupts the rate limiting proton transfer (PT) event, resulting in a reduction of the catalytic activity of the enzyme as compared to the wild-type. Potential of mean force (PMF) calculations utilizing the multistate empirical valence bond (MS-EVB) methodology for H64A HCA II give a PT free energy barrier significantly higher than that found in the wild-type enzyme. This high barrier, determined in the absence of exogenous buffer and assuming no additional ionizable residues in the PT pathway, indicates the likelihood of alternate enzyme pathways that utilize either ionizable enzyme residues (self-rescue) and/or exogenous buffers (chemical rescue). It has been shown experimentally that the catalytic activity of H64A HCA II can be chemically rescued to near wild type levels by the addition of the exogenous buffer 4-methylimidazole (4MI). Crystallographic studies have identified two 4MI binding sites, yet site specific mutations intended to disrupt 4MI binding have demonstrated these sites to be non-productive. In the present work MS-EVB simulations show that binding of 4MI near Thr199 in the H64A HCA II mutant, a binding site determined by NMR spectroscopy, results in a viable chemical rescue pathway. Additional viable rescue pathways are also identified where 4MI acts as a proton transport intermediary from the active site to ionizable residues on the rim of the active site, revealing a probable mode of action for the chemical rescue pathway PMID:21452838

  11. Clinically Detectable Dental Identifiers Observed in Intra-oral Photographs and Extra-oral Radiographs, Validated for Human Identification Purposes.

    Science.gov (United States)

    Angelakopoulos, Nikolaos; Franco, Ademir; Willems, Guy; Fieuws, Steffen; Thevissen, Patrick

    2017-07-01

    Screening the prevalence and pattern of dental identifiers contributes toward the process of human identification. This research investigated the uniqueness of clinical dental identifiers in photographs and radiographs. Panoramic and lateral cephalometric radiographs and five intra-oral photographs of 1727 subjects were used. In a target set, two observers examined different subjects. In a subset, both observers examined the same subjects (source set). The distance between source and target subjects was quantified for each identifier. The percentage of subjects in the target set being at least as close as the correct subject was assessed. The number of molars (34.6%), missing teeth (42%), and displaced teeth (59.9%) were the most unique identifiers in photographs and panoramic and lateral cephalometric radiographs, respectively. The pattern of rotated teeth (14.9%) was the most unique in photographs, while displaced teeth was in panoramic (37.6%) and lateral cephalometric (54.8%) radiographs. Morphological identifiers were the most unique, highlighting their importance for human identifications. © 2016 American Academy of Forensic Sciences.

  12. [Collections of human biological resources for research purposes: from regulations to the need of a guide of good collection practices].

    Science.gov (United States)

    Le Roux, N; de Montgolfier, S; di Donato, J-H; Boccon-Gibod, L; Teillac, P; Hervé, C; Berthon, P

    2003-12-01

    In France, collections of human biological resources are regulated by the "Bioethics Law", currently in revision. Hence, we analyse the regulatory and ethical issues of these practices in the context of scientific research. The ultimate aim of such collections is to improve biological and medical knowledge. We think that the French regulatory system is quite complicated and non-explicit for "collection holders". The multiplicity of legal texts concerning this activity has made their application difficult, especially in the absence of application decrees. The project amending the actual law has clarified the legal status of collections but it did not shed light on the status of human body detached parts. Furthermore, the text is still very far from the international bioethical recommendations, and does not reflect the actual collection's implementation. The establishment of a guideline of Good Collection Practices, based on clear principles, should help to simplify the situation, especially when it is imbedded in the regulation and linked to control procedures. It would allow a balance between collective interests and the protection of individuals, taking into account of the international highly competitive scientific and economical constraints. The major issue is to preserve and to perpetuate the existing and future collections because of their precious value as an important tool for biomedical knowledge. The efficiency of a regulation depends on its legibility and accessibility, two requirements that seem to determine the acceptance of the regulatory tool and its application allowing subsequently to reach fairness in proceedings.

  13. Relationship between chemical composition and biological function of Pseudomonas aeruginosa lipopolysaccharide: effect on human neutrophil chemotaxis and oxidative burst

    DEFF Research Database (Denmark)

    Kharazmi, A; Fomsgaard, A; Conrad, R S

    1991-01-01

    There are conflicting data on the effect of bacterial lipopolysaccharides (LPS) on the function of human neutrophils. The present study was designed to examine the relationship between chemical composition and the modulatory effect of LPS on human neutrophil function. LPS was extracted from five...

  14. Implications of global climate change for the assessment and management of human health risks of chemicals in the natural environment.

    Science.gov (United States)

    Balbus, John M; Boxall, Alistair B A; Fenske, Richard A; McKone, Thomas E; Zeise, Lauren

    2013-01-01

    Global climate change (GCC) is likely to alter the degree of human exposure to pollutants and the response of human populations to these exposures, meaning that risks of pollutants could change in the future. The present study, therefore, explores how GCC might affect the different steps in the pathway from a chemical source in the environment through to impacts on human health and evaluates the implications for existing risk-assessment and management practices. In certain parts of the world, GCC is predicted to increase the level of exposure of many environmental pollutants due to direct and indirect effects on the use patterns and transport and fate of chemicals. Changes in human behavior will also affect how humans come into contact with contaminated air, water, and food. Dietary changes, psychosocial stress, and coexposure to stressors such as high temperatures are likely to increase the vulnerability of humans to chemicals. These changes are likely to have significant implications for current practices for chemical assessment. Assumptions used in current exposure-assessment models may no longer apply, and existing monitoring methods may not be robust enough to detect adverse episodic changes in exposures. Organizations responsible for the assessment and management of health risks of chemicals therefore need to be more proactive and consider the implications of GCC for their procedures and processes. Copyright © 2012 SETAC.

  15. Human and animal health risk assessments of chemicals in the food chain: comparative aspects and future perspectives.

    Science.gov (United States)

    Dorne, J L C M; Fink-Gremmels, J

    2013-08-01

    Chemicals from anthropogenic and natural origins enter animal feed, human food and water either as undesirable contaminants or as part of the components of a diet. Over the last five decades, considerable efforts and progress to develop methodologies to protect humans and animals against potential risks associated with exposure to such potentially toxic chemicals have been made. This special issue presents relevant methodological developments and examples of risk assessments of undesirable substances in the food chain integrating the animal health and the human health perspective and refers to recent Opinions of the Scientific Panel on Contaminants in the Food Chain (CONTAM) of the European Food Safety Authority (EFSA). This introductory review aims to give a comparative account of the risk assessment steps used in human health and animal health risk assessments for chemicals in the food chain and provides a critical view of the data gaps and future perspectives for this cross-disciplinary field. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Joint purpose?

    DEFF Research Database (Denmark)

    Pristed Nielsen, Helene

    2013-01-01

    Starting from Crenshaw´s point that antiracism often fails to interrogate patriarchy and that feminism often reproduces racist practices (1991: 1252), this paper asks: What are the theoretical reasons for believing that feminism and anti-racism can be regarded as fighting for the joint purpose...

  17. A review of human biomonitoring data used in regulatory risk assessment under Canada's Chemicals Management Program.

    Science.gov (United States)

    Zidek, Angelika; Macey, Kristin; MacKinnon, Leona; Patel, Mikin; Poddalgoda, Devika; Zhang, Yi

    2017-03-01

    As a part of the Chemicals Management Plan launched in 2006, the Government of Canada is assessing and managing, where appropriate, the potential health and ecological risks associated with approximately 4300 substances under the Canadian Environmental Protection Act (1999). Since that time, nearly 3000 substances have been assessed, with human biomonitoring (HBM) data playing an increasingly important role for some substances. Case studies are presented, including both inorganic and organic substances (i.e., selenium, triclosan, phthalates), which highlight the impact and overall role HBM has had in regulatory decision making in Canada for these three substances as well as criteria used in the application of HBM data in human health risk assessment. An overview of its limitations in terms of how and when HBM data can be applied, when assessing human health in a regulatory setting, is discussed as well as the role HBM data can play in priority setting. Crown Copyright © 2016. Published by Elsevier GmbH. All rights reserved.

  18. Determining 'age at death' for forensic purposes using human bone by a laboratory-based biomechanical analytical method.

    Science.gov (United States)

    Zioupos, P; Williams, A; Christodoulou, G; Giles, R

    2014-05-01

    be applied worldwide following stringent laboratory protocols. As such, this technique contributes significantly to improving age estimation and therefore identification methods for forensic and other purposes. © 2013 Elsevier Ltd. All rights reserved.

  19. Chemical Pesticides and Human Health: The Urgent Need for a New Concept in Agriculture.

    Science.gov (United States)

    Nicolopoulou-Stamati, Polyxeni; Maipas, Sotirios; Kotampasi, Chrysanthi; Stamatis, Panagiotis; Hens, Luc

    2016-01-01

    The industrialization of the agricultural sector has increased the chemical burden on natural ecosystems. Pesticides are agrochemicals used in agricultural lands, public health programs, and urban green areas in order to protect plants and humans from various diseases. However, due to their known ability to cause a large number of negative health and environmental effects, their side effects can be an important environmental health risk factor. The urgent need for a more sustainable and ecological approach has produced many innovative ideas, among them agriculture reforms and food production implementing sustainable practice evolving to food sovereignty. It is more obvious than ever that the society needs the implementation of a new agricultural concept regarding food production, which is safer for man and the environment, and to this end, steps such as the declaration of Nyéléni have been taken.

  20. Chemical pesticides and human health: The urgent need for a new concept in agriculture

    Directory of Open Access Journals (Sweden)

    Polyxeni Nicolopoulou-Stamati

    2016-07-01

    Full Text Available The industrialization of the agricultural sector has increased the chemical burden on natural ecosystems. Pesticides are agrochemicals used in agricultural lands, public health programs and urban green areas in order to protect plants and humans from various diseases. However, due to their known ability to cause a large number of negative health and environmental effects, their side effects can be an important environmental health risk factor. The urgent need for a more sustainable and ecological approach has produced many innovative ideas, among them agriculture reforms and food production implementing sustainable practice evolving to food sovereignty. It is more obvious than ever that the society needs the implementation of a new agricultural concept regarding food production which is safer for man and the environment, and to this end, steps such as the declaration of Nyéléni have been taken.

  1. Effect of chemical mutagens and carcinogens on gene expression profiles in human TK6 cells.

    Directory of Open Access Journals (Sweden)

    Lode Godderis

    Full Text Available Characterization of toxicogenomic signatures of carcinogen exposure holds significant promise for mechanistic and predictive toxicology. In vitro transcriptomic studies allow the comparison of the response to chemicals with diverse mode of actions under controlled experimental conditions. We conducted an in vitro study in TK6 cells to characterize gene expression signatures of exposure to 15 genotoxic carcinogens frequently used in European industries. We also examined the dose-responsive changes in gene expression, and perturbation of biochemical pathways in response to these carcinogens. TK6 cells were exposed at 3 dose levels for 24 h with and without S9 human metabolic mix. Since S9 had an impact on gene expression (885 genes, we analyzed the gene expression data from cells cultures incubated with S9 and without S9 independently. The ribosome pathway was affected by all chemical-dose combinations. However in general, no similar gene expression was observed among carcinogens. Further, pathways, i.e. cell cycle, DNA repair mechanisms, RNA degradation, that were common within sets of chemical-dose combination were suggested by clustergram. Linear trends in dose-response of gene expression were observed for Trichloroethylene, Benz[a]anthracene, Epichlorohydrin, Benzene, and Hydroquinone. The significantly altered genes were involved in the regulation of (anti- apoptosis, maintenance of cell survival, tumor necrosis factor-related pathways and immune response, in agreement with several other studies. Similarly in S9+ cultures, Benz[a]pyrene, Styrene and Trichloroethylene each modified over 1000 genes at high concentrations. Our findings expand our understanding of the transcriptomic response to genotoxic carcinogens, revealing the alteration of diverse sets of genes and pathways involved in cellular homeostasis and cell cycle control.

  2. [Physical and chemical characterization of industrial nixtamalized corn flour for human consumption in Central America].

    Science.gov (United States)

    Bressani, R; Turcios, J C; Reyes, L; Mérida, R

    2001-09-01

    The objective of this study was the characterization of industrial nixtamalized maize flour for human consumption and which are marketed in Central America for some selected physical and chemical properties which may contribute to food composition information and help nutrition and micronutrient fortification programs. A total of 12 brands purchased in triplicate were obtained from supermarkets in Guatemala, El Salvador and Honduras. These samples were kept under refrigeration until analyzed. The physical parameters measured and results were the following: particle size with most samples having a high percentage of particles greater than 60 mesh, pH (5.4-7.5), water absorption index (WAI) (3.4-4.0 g gel/g sample), water soluble index (WSI) (4.8-7.8 g/100 g) and flour density (0.410-0.547 g/ml). The differences were statistically significant for all parameters measured, except for WAI. The chemical characteristics included, moisture, protein, fat, ash and dietetic fiber. Differences between flour samples were statistically significant except for fat content. Protein content was low, ranging between 6.7-8.1 g/100 g and total dietary fiber varied between 7.7-12.0 g/100 g. The samples were analyzed for phytic acid with a variation from 632 to 903 mg/100 g, with statistical significant differences. The samples were also analyzed for total and soluble (pH 7.5) iron, phosphorus, calcium, potassium, zinc, copper, manganese, and magnesium. The difference in the iron and calcium content between flour samples were statistically significant. The physical and chemical variability found between flour samples of nixtamalized maize was relatively high and it is recommended to establish quality standards through raw material and process standardization for greater effectiveness of nutrition programs and activities on micronutrient fortification which may be pursued in the future.

  3. Chemical disinfection of non-porous inanimate surfaces experimentally contaminated with four human pathogenic viruses.

    Science.gov (United States)

    Sattar, S A; Springthorpe, V S; Karim, Y; Loro, P

    1989-06-01

    The chemical disinfection of virus-contaminated non-porous inanimate surfaces was investigated using coxsackievirus B3, adenovirus type 5, parainfluenza virus type 3 and coronavirus 229E as representatives of important nosocomial viral pathogens. A 10 microliter amount of the test virus, suspended in either faeces or mucin, was placed onto each stainless steel disk (about 1 cm in diameter) and the inoculum allowed to dry for 1 h under ambient conditions. Sixteen disinfectant formulations were selected for this study based on the findings of an earlier investigation with a human rotavirus. After 1 min exposure to 20 microliters of the disinfectant, the virus from the disks was immediately eluted into tryptose phosphate broth and plaque assayed. Using an efficacy criterion of a 3 log10 or greater reduction in virus infectivity titre and irrespective of the virus suspending medium, only the following five disinfectants proved to be effective against all the four viruses tested: (1) 2% glutaraldehyde normally used as an instrument soak, (2) a strongly alkaline mixture of 0.5% sodium o-benzyl-p-chlorophenate and 0.6% sodium lauryl sulphate, generally used as a domestic disinfectant cleaner for hard surfaces, (3) a 0.04% solution of a quaternary ammonium compound containing 7% hydrochloric acid, which is the basis of many toilet bowl cleaners, (4) chloramine T at a minimum free chlorine level of 3000 p.p.m. and (5) sodium hypochlorite at a minimum free chlorine concentration of 5000 p.p.m. Of those chemicals suitable for use as topical antiseptics, 70% ethanol alone or products containing at least 70% ethanol were ineffective only against coxsackievirus B3. These results emphasize the care needed in selecting chemical disinfectants for routine use in infection control.

  4. A chemically defined substrate for the expansion and neuronal differentiation of human pluripotent stem cell-derived neural progenitor cells.

    Science.gov (United States)

    Tsai, Yihuan; Cutts, Josh; Kimura, Azuma; Varun, Divya; Brafman, David A

    2015-07-01

    Due to the limitation of current pharmacological therapeutic strategies, stem cell therapies have emerged as a viable option for treating many incurable neurological disorders. Specifically, human pluripotent stem cell (hPSC)-derived neural progenitor cells (hNPCs), a multipotent cell population that is capable of near indefinite expansion and subsequent differentiation into the various cell types that comprise the central nervous system (CNS), could provide an unlimited source of cells for such cell-based therapies. However the clinical application of these cells will require (i) defined, xeno-free conditions for their expansion and neuronal differentiation and (ii) scalable culture systems that enable their expansion and neuronal differentiation in numbers sufficient for regenerative medicine and drug screening purposes. Current extracellular matrix protein (ECMP)-based substrates for the culture of hNPCs are expensive, difficult to isolate, subject to batch-to-batch variations, and, therefore, unsuitable for clinical application of hNPCs. Using a high-throughput array-based screening approach, we identified a synthetic polymer, poly(4-vinyl phenol) (P4VP), that supported the long-term proliferation and self-renewal of hNPCs. The hNPCs cultured on P4VP maintained their characteristic morphology, expressed high levels of markers of multipotency, and retained their ability to differentiate into neurons. Such chemically defined substrates will eliminate critical roadblocks for the utilization of hNPCs for human neural regenerative repair, disease modeling, and drug discovery. Copyright © 2015. Published by Elsevier B.V.

  5. Learnings from LCA-based methods: should chemicals in food packaging be a priority focus to protect human health?

    DEFF Research Database (Denmark)

    Ernstoff, Alexi; Stylianou, Katerina S.; Fantke, Peter

    2017-01-01

    Given the scale and variety of human health damage (HHD) caused by food systems, prioritization methods are urgently needed. In this study HHD is estimated for case studies on red meat and sugary sweetened beverages (SSB) packaged in high-impact polystyrene (HIPS) due to various relevant health...... impacts. Specifically, we aim to asses if chemicals in food packaging are important to HHD in a life cycle context. The functional unit is "daily consumption of a packaged food per person in the United States." Method developments focus on human toxicity characterization of chemicals migrating from...... packaging into food. Chemicals and their concentrations in HIPS were identified from regulatory lists. A new high-throughput model estimated migration into food, depending on properties of chemicals, packaging, food, and scenario, and HHD was extrapolated following LCA characterization methods. An LCA...

  6. Human and animal health risk assessments of chemicals in the food chain: Comparative aspects and future perspectives

    International Nuclear Information System (INIS)

    Dorne, J.L.C.M.; Fink-Gremmels, J.

    2013-01-01

    Chemicals from anthropogenic and natural origins enter animal feed, human food and water either as undesirable contaminants or as part of the components of a diet. Over the last five decades, considerable efforts and progress to develop methodologies to protect humans and animals against potential risks associated with exposure to such potentially toxic chemicals have been made. This special issue presents relevant methodological developments and examples of risk assessments of undesirable substances in the food chain integrating the animal health and the human health perspective and refers to recent Opinions of the Scientific Panel on Contaminants in the Food Chain (CONTAM) of the European Food Safety Authority (EFSA). This introductory review aims to give a comparative account of the risk assessment steps used in human health and animal health risk assessments for chemicals in the food chain and provides a critical view of the data gaps and future perspectives for this cross-disciplinary field. - Highlights: ► Principles of human and animal health risk assessment. ► Data gaps for each step of animal health risk assessment. ► Implications of animal risk assessment on human risk assessment. ► Future perspectives on chemical risk assessment

  7. Human and animal health risk assessments of chemicals in the food chain: Comparative aspects and future perspectives

    Energy Technology Data Exchange (ETDEWEB)

    Dorne, J.L.C.M., E-mail: jean-lou.dorne@efsa.europa.eu [Emerging Risk Unit, Via Carlo Magno 1A, 43126 Parma (Italy); Fink-Gremmels, J. [Utrecht University, Faculty of Veterinary Medicine, Institute for Risk Assessment Sciences, Yalelaan 104, 3584 CM Utrecht (Netherlands)

    2013-08-01

    Chemicals from anthropogenic and natural origins enter animal feed, human food and water either as undesirable contaminants or as part of the components of a diet. Over the last five decades, considerable efforts and progress to develop methodologies to protect humans and animals against potential risks associated with exposure to such potentially toxic chemicals have been made. This special issue presents relevant methodological developments and examples of risk assessments of undesirable substances in the food chain integrating the animal health and the human health perspective and refers to recent Opinions of the Scientific Panel on Contaminants in the Food Chain (CONTAM) of the European Food Safety Authority (EFSA). This introductory review aims to give a comparative account of the risk assessment steps used in human health and animal health risk assessments for chemicals in the food chain and provides a critical view of the data gaps and future perspectives for this cross-disciplinary field. - Highlights: ► Principles of human and animal health risk assessment. ► Data gaps for each step of animal health risk assessment. ► Implications of animal risk assessment on human risk assessment. ► Future perspectives on chemical risk assessment.

  8. Chemical composition of tempeh from soybean cultivars specially developed for human consumption

    Directory of Open Access Journals (Sweden)

    Ana Carla Furlan Bavia

    2012-09-01

    Full Text Available Tempeh is a food obtained by fermentation of soybean grains by the fungus Rizophus oligosporus. It is a traditional Indonesian food that presents benefits for human health protecting against diarrhea and chronic diseases. Tempeh processing includes dehulling, cooking, inoculation, and fermentation. In this study, chemical characteristics of tempeh prepared with soybean cultivars specially developed for human consumption (BRS 216, BRS 232, BRS 257, and BRS 267 were investigated. Soybean grains and tempeh obtained from these cultivars were analyzed for oil, protein, antinutrional factors, and isoflavone content. Cultivar BRS 216 presented the highest protein content in the grains (36.81% and in tempeh (51.99%. On average, the protein content in tempeh increased 16% in relation to that of soybean grains. Isoflavone content was higher in the grains than in tempeh with significant differences among the cultivars. However, the aglycones content increased about 50% in tempeh (49.00 mg.100 g-1 on average compared to that of raw material (soybean grains - 21.49 mg.100 g-1, on average. The content of Kunitz trypsin inhibitor (KSTI reduced 83% in tempeh, on average, as compared to the value found in the grains. Phytic acid content was similar in both tempeh and the grains.

  9. Human biomonitoring after chemical incidents and during short-term maintenance work as a tool for exposure analysis and assessment.

    Science.gov (United States)

    Bader, M; Van Weyenbergh, T; Verwerft, E; Van Pul, J; Lang, S; Oberlinner, C

    2014-12-15

    Human biomonitoring (HBM) is frequently used for the analysis and assessment of exposure to chemicals under routine working conditions. In recent years, HBM has also been applied to monitor the exposure of the general population, and of emergency responders in the aftermath of chemical incidents. Two examples of targeted HBM programs in the chemical industry are described and discussed in this paper: (1) analysis and assessment of the exposure of firefighters and chemical workers after the spill of p-chloroaniline from a burning chemical barrel, and (2) biomonitoring of maintenance workers potentially exposed to benzene during regular turnarounds. The results of these investigations underline that human biomonitoring contributes substantially to comprehensive exposure analyses, human health risk assessments and communication. In addition, regular HBM surveillance and feedback can assist in the continuous improvement of workplace safety measures and exposure control. In conclusion, data on accidental or short-term exposure to hazardous chemicals are an important source of information for the further development of limit and assessment values, the validation of biomarkers and of targeted HBM programs for both routine monitoring and disaster management. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. Cytogenetic damages induced in vivo in human lymphocytes by environmental chemicals or radiation

    International Nuclear Information System (INIS)

    Cebulska-Wasilewska, A.

    1999-01-01

    The importance of various environmental exposures has been evident in variation in cancer incidence and mortality. Benzene is considered to be a human carcinogen, is clastogenic to rodents and humans, and it affects the immune response. Workers in various industrial plants, are exposed to benzene and benzene related compounds as a result of various activities in which benzene is processed, generated or used. Major sources of environmental exposure to benzene related compounds, continue to be active and passive smoking, auto exhaust, and driving or riding in automobiles. Benzene is of a particular interest, not only because of its known toxicity, but also because this was to be the parent compound and a model for extensive programs of metabolism of a variety of aromatic chemicals. Ionizing radiation is an unavoidable physical agent that is presented in environment, and public opinion is well aware against radiation risk and strongly against it. The aim of the presentation was comparison between cytogenetic damages induced in vivo by environmental chemicals with those of radiation. Results from biomonitoring survey on genotoxicity in human blood cells of benzene and benzene related compounds were compared to damages detected in lymphocytes of persons who had been accidentally exposed to gamma radiation. In the groups, that had been occupationally or environmentally exposed to benzene related compound, total aberration frequencies, or percent of aberrant cells ranged between 0 - 0.16 aberrations/cell or 16% of aberrant cells respectively. A multivariate regression analysis confirmed: (i) a significant association between cytogenetic damage and exposure to benzene related compound, (ii) a possible association between cytogenetic damage and cancer, (iii) a significant influence of smoking habit. In 1996 few persons were suspected of accidental exposure to gamma radiation. To estimate the absorbed doses, lymphocytes from their blood have been analyzed for the presence of

  11. Establishment of IL-7 Expression Reporter Human Cell Lines, and Their Feasibility for High-Throughput Screening of IL-7-Upregulating Chemicals.

    Directory of Open Access Journals (Sweden)

    Yeon Sook Cho

    Full Text Available Interleukin-7 (IL-7 is a cytokine essential for T cell homeostasis, and is clinically important. However, the regulatory mechanism of IL-7 gene expression is not well known, and a systematic approach to screen chemicals that regulate IL-7 expression has not yet been developed. In this study, we attempted to develop human reporter cell lines using CRISPR/Cas9-mediated genome editing technology. For this purpose, we designed donor DNA that contains an enhanced green fluorescent protein (eGFP gene, drug selection cassette, and modified homologous arms which are considered to enhance the translation of the eGFP reporter transcript, and also a highly efficient single-guide RNA with a minimal off-target effect to target the IL-7 start codon region. By applying this system, we established IL-7 eGFP reporter cell lines that could report IL-7 gene transcription based on the eGFP protein signal. Furthermore, we utilized the cells to run a pilot screen campaign for IL-7-upregulating chemicals in a high-throughput format, and identified a chemical that can up-regulate IL-7 gene transcription. Collectively, these results suggest that our IL-7 reporter system can be utilized in large-scale chemical library screening to reveal novel IL-7 regulatory pathways and to identify potential drugs for development of new treatments in immunodeficiency disease.

  12. Full-thickness human skin explants for testing the toxicity of topically applied chemicals

    International Nuclear Information System (INIS)

    Nakamura, M.; Rikimaru, T.; Yano, T.; Moore, K.G.; Pula, P.J.; Schofield, B.H.; Dannenberg, A.M. Jr.

    1990-01-01

    This report describes a model organ-culture system for testing the toxicity of chemical substances that are topically applied to human skin. In this system, the viable keratinocytes in the full-thickness skin explants are protected by the same keratinized layer as skin remaining on the donor, and toxicity can be assessed microscopically and/or biochemically. The human skin specimens were discards from a variety of surgical procedures. They were cut into full-thickness 1.0-cm2 explants, and briefly exposed to the military vesicant sulfur mustard (SM), which was used as a model toxicant. The explants were then organ cultured in small Petri dishes for 24 h at 36 degrees C. In the 0.03-1.0% dosage range, a straight-line dose-response relationship occurred between the concentration of SM applied and the number of paranuclear vacuoles seen histologically in the epidermis. Within the same SM dosage range, there was also a proportional decrease in 14C-leucine incorporation by the explants. Thus, the number of paranuclear vacuoles reflected decreases in protein synthesis by the injured epidermal cells. The epidermis of full-thickness untreated (control) human skin explants usually remained viable for 7 d when stored at 4 degrees C in culture medium. During storage, a relatively small number of paranuclear vacuoles developed within the epidermis, but the explants were still quite satisfactory for testing SM toxicity. Incubation (for 4 or 24 h at 36 degrees C) of such control skin explants reduced (often by 50%) the small number of paranuclear vacuoles produced during 4-7 d of storage. This reduction was probably caused by autolysis of many of the vacuolated cells. Two types of paranuclear vacuoles could be identified by both light and electron microscopy: a storage type and a toxicant type. The storage type seemed to be caused by autolysis of cell components

  13. Full-thickness human skin explants for testing the toxicity of topically applied chemicals

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, M.; Rikimaru, T.; Yano, T.; Moore, K.G.; Pula, P.J.; Schofield, B.H.; Dannenberg, A.M. Jr. (Johns Hopkins Univ., Baltimore, MD (USA))

    1990-09-01

    This report describes a model organ-culture system for testing the toxicity of chemical substances that are topically applied to human skin. In this system, the viable keratinocytes in the full-thickness skin explants are protected by the same keratinized layer as skin remaining on the donor, and toxicity can be assessed microscopically and/or biochemically. The human skin specimens were discards from a variety of surgical procedures. They were cut into full-thickness 1.0-cm2 explants, and briefly exposed to the military vesicant sulfur mustard (SM), which was used as a model toxicant. The explants were then organ cultured in small Petri dishes for 24 h at 36 degrees C. In the 0.03-1.0% dosage range, a straight-line dose-response relationship occurred between the concentration of SM applied and the number of paranuclear vacuoles seen histologically in the epidermis. Within the same SM dosage range, there was also a proportional decrease in 14C-leucine incorporation by the explants. Thus, the number of paranuclear vacuoles reflected decreases in protein synthesis by the injured epidermal cells. The epidermis of full-thickness untreated (control) human skin explants usually remained viable for 7 d when stored at 4 degrees C in culture medium. During storage, a relatively small number of paranuclear vacuoles developed within the epidermis, but the explants were still quite satisfactory for testing SM toxicity. Incubation (for 4 or 24 h at 36{degrees}C) of such control skin explants reduced (often by 50%) the small number of paranuclear vacuoles produced during 4-7 d of storage. This reduction was probably caused by autolysis of many of the vacuolated cells. Two types of paranuclear vacuoles could be identified by both light and electron microscopy: a storage type and a toxicant type. The storage type seemed to be caused by autolysis of cell components.

  14. Exposure to widespread environmental endocrine disrupting chemicals and human sperm sex ratio

    International Nuclear Information System (INIS)

    Jurewicz, Joanna; Radwan, Michał; Sobala, Wojciech; Radwan, Paweł; Jakubowski, Lucjusz; Wielgomas, Bartosz; Ligocka, Danuta; Brzeźnicki, Sławomir; Hanke, Wojciech

    2016-01-01

    In recent years, a trend toward a declining proportion of male births has been noted in several, but not all, industrialized countries. The underlying reason for the drop in the sex ratio is unclear, but one theory states that widespread environmental endocrine disrupting chemicals affecting the male reproductive system in a negative manner could be part of the explanation. The present study was designed to investigate whether the urinary phthalate, pyrethroids and polycyclic aromatic hydrocarbons metabolites concentrations were associated with sperm Y:X ratio. The study population consisted of 194 men aged under 45 years of age who attended infertility clinic in Lodz, Poland for diagnostic purposes with normal semen concentration of 20–300 mln/ml or with slight oligozoospermia (semen concentration of 15–20 mln/ml) (WHO, 1999). The Y:X ratio was assessed by fluorescent in situ hybridization. Urinary concentrations of 1-hydroxypyrene were measured by high performance liquid chromatography, phthalate metabolites were analyzed using a procedure based on the LC-MS/MS methods and metabolites of synthetic pyrethroids were assessed by gas chromatography ion-tap mass spectrometry method. After adjustment for potential confounders (past diseases, age, abstinence, smoking, alcohol consumption, sperm concentration, motility, morphology) 5OH MEHP, CDCCA to TDCCA and 1-OHP was negatively related to Y:X sperm chromosome ratio (p = 0.033, p < 0.001, p = 0.047 respectively). As this is the first study to elucidate the association between the level of metabolites of widespread environmental endocrine disrupting chemicals (phthalates, synthetic pyrethroids, polycyclic aromatic hydrocarbons) on sex chromosome ratio in sperm therefore, these findings require further replication in other populations. - Highlights: • Urinary phthalate metabolites levels were significantly associated with a decrease in Y/X chromosome bearing sperm. • The levels of 1-hydroxypyrene in urine

  15. Epigenetic alterations induced by genotoxic occupational and environmental human chemical carcinogens: A systematic literature review

    Science.gov (United States)

    Chappell, Grace; Pogribny, Igor P.; Guyton, Kathryn Z.; Rusyn, Ivan

    2016-01-01

    Accumulating evidence suggests that epigenetic alterations play an important role in chemically-induced carcinogenesis. Although the epigenome and genome may be equally important in carcinogenicity, the genotoxicity of chemical agents and exposure-related transcriptomic responses have been more thoroughly studied and characterized. To better understand the evidence for epigenetic alterations of human carcinogens, and the potential association with genotoxic endpoints, we conducted a systematic review of published studies of genotoxic carcinogens that reported epigenetic endpoints. Specifically, we searched for publications reporting epigenetic effects for the 28 agents and occupations included in Monograph Volume 100F of the International Agency for the Research on Cancer (IARC) that were classified as “carcinogenic to humans” (Group 1) with strong evidence of genotoxic mechanisms of carcinogenesis. We identified a total of 158 studies that evaluated epigenetic alterations for 12 of these 28 carcinogenic agents and occupations (1,3-butadiene, 4-aminobiphenyl, aflatoxins, benzene, benzidine, benzo[a]pyrene, coke production, formaldehyde, occupational exposure as a painter, sulfur mustard, and vinyl chloride). Aberrant DNA methylation was most commonly studied, followed by altered expression of non-coding RNAs and histone changes (totaling 85, 59 and 25 studies, respectively). For 3 carcinogens (aflatoxins, benzene and benzo[a]pyrene), 10 or more studies reported epigenetic effects. However, epigenetic studies were sparse for the remaining 9 carcinogens; for 4 agents, only 1 or 2 published reports were identified. While further research is needed to better identify carcinogenesis-associated epigenetic perturbations for many potential carcinogens, published reports on specific epigenetic endpoints can be systematically identified and increasingly incorporated in cancer hazard assessments. PMID:27234561

  16. Modulation of Xenobiotic Metabolizing Enzyme and Transporter Gene Expression in Primary Cultures of Human Hepatocytes by ToxCast Chemicals

    Science.gov (United States)

    ToxCast chemicals were assessed for induction or suppression of xenobiotic metabolizing enzyme and transporter gene expression using primary human hepatocytes. The mRNA levels of 14 target and 2 control genes were measured: ABCB1, ABCB11, ABCG2, SLCO1B1, CYP1A1, CYP1A2, CYP2B6, C...

  17. RODENT AND HUMAN NEUROPROGENITOR CELLS FOR HIGH-CONTENT SCREENS OF CHEMICAL EFFECTS ON PROLIFERATION AND APOPTOSIS

    Science.gov (United States)

    The objective of these experiments is to develop high-throughput screens for proliferation and apoptosis in order to compare rodent and human neuroprogenitor cell responses to potential developmental neurotoxicants. Effects of 4 chemicals on proliferation and apoptosis in mouse c...

  18. Human Pluripotent Stem Cell-Based Assay Predicts Developmental Toxicity Potential of ToxCast Chemicals (ACT meeting)

    Science.gov (United States)

    Worldwide initiatives to screen for toxicity potential among the thousands of chemicals currently in use require inexpensive and high-throughput in vitro models to meet their goals. The devTOX quickPredict platform is an in vitro human pluripotent stem cell-based assay used to as...

  19. A quantitative assay of cortisol in human plasma by high performance liquid chromatography using a selective chemically bonded stationary phase

    NARCIS (Netherlands)

    van den Berg, J.H.M.; Mol, C.R.; Deelder, R.S.; Thijssen, J.H.H.

    1977-01-01

    The extraction and subsequent liquid chromatographic analysis of human plasma samples for cortisol is described. Extraction and chromatography are optimized, resulting in a recovery for cortisol of 96% and a detection limit of 1 microgram cortisol in 100 ml plasma. The application of two chemically

  20. [Chemical, chemosensory and human-sensory experiments on taste and flavor of carrots].

    Science.gov (United States)

    Schaller, R G; Broda, S; Schnitzler, W H

    1998-12-01

    The relationship between sensory quality of carrots and their contents and composition of essential oils and total sugars as influenced by nitrogen fertilization was investigated. Carrots (Daucus carota L.) of the variety 'Nanthya' F1 (S&G Sandoz Seeds) were grown in Weihenstephan 1996 with three levels of inorganic nitrogen fertilization (3 levels in 4 replications). Medium- and higher-boiling flavour-components were extracted as essential oils and separated gas-chromatographically (GC-FID). Lower-boiling flavour-components were taken from the headspace and analysed chemosensorially. The human sensory assessments were performed by an untrained panel of 300 people (students and employees of the TU München)--these results were compared with those of the chemical analyses. Carrots with lower nitrogen application were found to taste more intensive, more fruity, sweeter and better and at the same time less bitter and less earthy. They had higher contents of total sugar and a higher percentage of dry matter. Fertilization with nitrogen does not only affect the quantity but also the composition of the essential oils. The taste intensive was positively correlated with the quantity of essential oils, the taste sweet was positively correlated with the content of total sugars. It was possible to differentiate the carrots from each other by chemo-sensorial headspace analyses according to their N-fertilization levels.

  1. Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming.

    Science.gov (United States)

    Moreau, Thomas; Evans, Amanda L; Vasquez, Louella; Tijssen, Marloes R; Yan, Ying; Trotter, Matthew W; Howard, Daniel; Colzani, Maria; Arumugam, Meera; Wu, Wing Han; Dalby, Amanda; Lampela, Riina; Bouet, Guenaelle; Hobbs, Catherine M; Pask, Dean C; Payne, Holly; Ponomaryov, Tatyana; Brill, Alexander; Soranzo, Nicole; Ouwehand, Willem H; Pedersen, Roger A; Ghevaert, Cedric

    2016-04-07

    The production of megakaryocytes (MKs)--the precursors of blood platelets--from human pluripotent stem cells (hPSCs) offers exciting clinical opportunities for transfusion medicine. Here we describe an original approach for the large-scale generation of MKs in chemically defined conditions using a forward programming strategy relying on the concurrent exogenous expression of three transcription factors: GATA1, FLI1 and TAL1. The forward programmed MKs proliferate and differentiate in culture for several months with MK purity over 90% reaching up to 2 × 10(5) mature MKs per input hPSC. Functional platelets are generated throughout the culture allowing the prospective collection of several transfusion units from as few as 1 million starting hPSCs. The high cell purity and yield achieved by MK forward programming, combined with efficient cryopreservation and good manufacturing practice (GMP)-compatible culture, make this approach eminently suitable to both in vitro production of platelets for transfusion and basic research in MK and platelet biology.

  2. Attachment, Growth, and Detachment of Human Mesenchymal Stem Cells in a Chemically Defined Medium

    Directory of Open Access Journals (Sweden)

    Denise Salzig

    2016-01-01

    Full Text Available The manufacture of human mesenchymal stem cells (hMSCs for clinical applications requires an appropriate growth surface and an optimized, preferably chemically defined medium (CDM for expansion. We investigated a new protein/peptide-free CDM that supports the adhesion, growth, and detachment of an immortalized hMSC line (hMSC-TERT as well as primary cells derived from bone marrow (bm-hMSCs and adipose tissue (ad-hMSCs. We observed the rapid attachment and spreading of hMSC-TERT cells and ad-hMSCs in CDM concomitant with the expression of integrin and actin fibers. Cell spreading was promoted by coating the growth surface with collagen type IV and fibronectin. The growth of hMSC-TERT cells was similar in CDM and serum-containing medium whereas the lag phase of bm-hMSCs was prolonged in CDM. FGF-2 or surface coating with collagen type IV promoted the growth of bm-hMSCs, but laminin had no effect. All three cell types retained their trilineage differentiation capability in CDM and were detached by several enzymes (but not collagenase in the case of hMSC-TERT cells. The medium and coating did not affect detachment efficiency but influenced cell survival after detachment. CDM combined with cell-specific surface coatings and/or FGF-2 supplements is therefore as effective as serum-containing medium for the manufacture of different hMSC types.

  3. Surface chemical composition of human maxillary first premolar as assessed by X-ray photoelectron spectroscopy (XPS)

    Science.gov (United States)

    Lou, Leo; Nelson, Alan E.; Heo, Giseon; Major, Paul W.

    2008-08-01

    The surface chemical composition of dental enamel has been postulated as a contributing factor in the variation of bond strength of brackets bonded to teeth, and hence, the probability of bracket failure during orthodontic treatment. This study systematically investigated the chemical composition of 98 bonding surfaces of human maxillary premolars using X-ray photoelectron spectroscopy (XPS) to ascertain compositional differences between right and left first premolars. The major elements detected in all samples were calcium, phosphorus, oxygen, nitrogen and carbon. Surface compositions were highly variable between samples and several elements were found to be highly correlated. No statistical significant difference in the chemical composition of the maxillary right and left first premolars was found ( p > 0.05). Knowledge of the chemical composition of enamel surfaces will facilitate future studies that relate this information to the variations in dental enamel bond strength.

  4. Surface chemical composition of human maxillary first premolar as assessed by X-ray photoelectron spectroscopy (XPS)

    Energy Technology Data Exchange (ETDEWEB)

    Lou, Leo [Orthodontic Graduate Program, Faculty of Medicine and Dentistry, University of Alberta (Canada); Nelson, Alan E. [Department of Chemical and Materials Engineering, University of Alberta (Canada)], E-mail: aenelson@dow.com; Heo, Giseon [Department of Statistics, Department of Dentistry, University of Alberta (Canada); Major, Paul W. [Orthodontic Graduate Program, Faculty of Medicine and Dentistry, University of Alberta (Canada)

    2008-08-30

    The surface chemical composition of dental enamel has been postulated as a contributing factor in the variation of bond strength of brackets bonded to teeth, and hence, the probability of bracket failure during orthodontic treatment. This study systematically investigated the chemical composition of 98 bonding surfaces of human maxillary premolars using X-ray photoelectron spectroscopy (XPS) to ascertain compositional differences between right and left first premolars. The major elements detected in all samples were calcium, phosphorus, oxygen, nitrogen and carbon. Surface compositions were highly variable between samples and several elements were found to be highly correlated. No statistical significant difference in the chemical composition of the maxillary right and left first premolars was found (p > 0.05). Knowledge of the chemical composition of enamel surfaces will facilitate future studies that relate this information to the variations in dental enamel bond strength.

  5. Human toxicology of chemical mixtures toxic consequences beyond the impact of one-component product and environmental exposures

    CERN Document Server

    Zeliger, Harold I

    2011-01-01

    In this important reference work, Zeliger catalogs the known effects of chemical mixtures on the human body and also proposes a framework for understanding and predicting their actions in terms of lipophile (fat soluble)/hydrophile (water soluble) interactions. The author's focus is on illnesses that ensue following exposures to mixtures of chemicals that cannot be attributed to any one component of the mixture. In the first part the mechanisms of chemical absorption at a molecular and macromolecular level are explained, as well as the body's methods of defending itself against xenobiotic intrusion. Part II examines the sources of the chemicals discussed, looking at air and water pollution, food additives, pharmaceuticals, etc. Part III, which includes numerous case studies, examines specific effects of particular mixtures on particular body systems and organs and presents a theoretical framework for predicting what the effects of uncharacterized mixtures might be. Part IV covers regulatory requirements and t...

  6. Surface chemical composition of human maxillary first premolar as assessed by X-ray photoelectron spectroscopy (XPS)

    International Nuclear Information System (INIS)

    Lou, Leo; Nelson, Alan E.; Heo, Giseon; Major, Paul W.

    2008-01-01

    The surface chemical composition of dental enamel has been postulated as a contributing factor in the variation of bond strength of brackets bonded to teeth, and hence, the probability of bracket failure during orthodontic treatment. This study systematically investigated the chemical composition of 98 bonding surfaces of human maxillary premolars using X-ray photoelectron spectroscopy (XPS) to ascertain compositional differences between right and left first premolars. The major elements detected in all samples were calcium, phosphorus, oxygen, nitrogen and carbon. Surface compositions were highly variable between samples and several elements were found to be highly correlated. No statistical significant difference in the chemical composition of the maxillary right and left first premolars was found (p > 0.05). Knowledge of the chemical composition of enamel surfaces will facilitate future studies that relate this information to the variations in dental enamel bond strength

  7. High-Throughput Screening of Chemical Effects on Steroidogenesis Using H295R Human Adrenocortical Carcinoma Cells.

    Science.gov (United States)

    Karmaus, Agnes L; Toole, Colleen M; Filer, Dayne L; Lewis, Kenneth C; Martin, Matthew T

    2016-04-01

    Disruption of steroidogenesis by environmental chemicals can result in altered hormone levels causing adverse reproductive and developmental effects. A high-throughput assay using H295R human adrenocortical carcinoma cells was used to evaluate the effect of 2060 chemical samples on steroidogenesis via high-performance liquid chromatography followed by tandem mass spectrometry quantification of 10 steroid hormones, including progestagens, glucocorticoids, androgens, and estrogens. The study employed a 3 stage screening strategy. The first stage established the maximum tolerated concentration (MTC; ≥ 70% viability) per sample. The second stage quantified changes in hormone levels at the MTC whereas the third stage performed concentration-response (CR) on a subset of samples. At all stages, cells were prestimulated with 10 µM forskolin for 48 h to induce steroidogenesis followed by chemical treatment for 48 h. Of the 2060 chemical samples evaluated, 524 samples were selected for 6-point CR screening, based in part on significantly altering at least 4 hormones at the MTC. CR screening identified 232 chemical samples with concentration-dependent effects on 17β-estradiol and/or testosterone, with 411 chemical samples showing an effect on at least one hormone across the steroidogenesis pathway. Clustering of the concentration-dependent chemical-mediated steroid hormone effects grouped chemical samples into 5 distinct profiles generally representing putative mechanisms of action, including CYP17A1 and HSD3B inhibition. A distinct pattern was observed between imidazole and triazole fungicides suggesting potentially distinct mechanisms of action. From a chemical testing and prioritization perspective, this assay platform provides a robust model for high-throughput screening of chemicals for effects on steroidogenesis. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology.

  8. Scalable cultivation of human pluripotent stem cells on chemically-defined surfaces

    Science.gov (United States)

    Hsiung, Michael Chi-Wei

    Human stem cells (SCs) are classified as self-renewing cells possessing great ability in therapeutic applications due of their ability to differentiate along any major cell lineage in the human body. Despite their restorative potential, widespread use of SCs is hampered by strenuous control issues. Along with the need for strict xeno-free environments to sustain growth in culture, current methods for growing human pluripotent stem cells (hPSCs) rely on platforms which impede large-scale cultivation and therapeutic delivery. Hence, any progress towards development of large-scale culture systems is severely hindered. In a concentrated effort to develop a scheme that can serve as a model precursor for large scale SC propagation in clinical use, we have explored methods for cultivating hPSCs on completely defined surfaces. We discuss novel approaches with the potential to go beyond the limitations presented by current methods. In particular, we studied the cultivation of human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) on surface which underwent synthetic or chemical modification. Current methods for hPSCs rely on animal-based extracellular matrices (ECMs) such as mouse embryonic fibroblasts (MEFs) or feeders and murine sacoma cell-derived substrates to facilitate their growth. While these layers or coatings can be used to maximize the output of hPSC production, they cannot be considered for clinical use because they risk introducing foreign pathogens into culture. We have identified and developed conditions for a completely defined xeno-free substrate used for culturing hPSCs. By utilizing coupling chemistry, we can functionalize ester groups on a given surface and conjugate synthetic peptides containing the arginine-glycine-aspartic acid (RGD) motif, known for their role in cell adhesion. This method offers advantages over traditional hPSC culture by keeping the modified substrata free of xenogenic response and can be scaled up in

  9. Chemicals agents and human male fertility: Review of the past thirty years literature; Sostanze chimiche e infertilita` maschile: Rassegna degli studi condotti negli ultimi trenta anni

    Energy Technology Data Exchange (ETDEWEB)

    Traina, Maria Elsa; Urbani, Elisabetta [Istituto Superiore di Sanita`, Rome (Italy). Lab. di Igiene Ambientale; Petrelli, Grazia; Pasquali, Massimo; Pace, Francesca [Istituto Superiore di Sanita`, Rome (Italy). Lab. di Epidemiologia e Biostatistica

    1997-03-01

    The effects of several industrial and environmental pollutants on the male reproductive system are known from animal studies, but to date the impact on human fertility is still scarcely documented by epidemiological studies. The literature of the past thirty years on the adverse effects of occupational chemical factors on human male fertility is reviewed. Eighty-nine studies have been analysed with the purpose to identify the substances and/or the working categories investigated and to evaluate the methods used. Since 1977 the interest has been focused on the human exposures to 1,2-dibromochloropropane, a powerful spermatotoxic agent, but a consistent number of studies was also related to other active ingredients of pesticides (lindane, carbaryl, 2,4-dichlorofenoxiacetic acid), solvents (glycol ethers, carbon disulfide) and heavy metals (lead, cadmium). Among the indicators used in these studies to evaluate the effects on male fertility, the seminal parameters are analysed in 67 % of the reports; blood hormonal tests are done in 54 % of the cases. The literature suggests that further epidemiological studies need to be conducted in other working categories; more attention should be paid to the sensitivity and biological significance of the male reproductive parameters used in human studies.

  10. Assessment of therapeutic effect of human choriogonadotropin in a chemical cystitis model

    Directory of Open Access Journals (Sweden)

    Serhat Tanik

    2017-05-01

    Full Text Available In this study, female rats induced with chemical cystitis were administered the hormone human choriogonadotropin (HCG, and it was aimed to reveal the usefulness of HCG in the treatment of interstitial cystitis/bladder pain syndrome. The materials for this study were 32 Wistar albino female rats. The study groups were formed as follows: the cystitis group (Group 1, the cystitis + HCG protection group (Group 2, the cystitis + HCG treatment group (Group 3, and the control group (Group 4, with eight rats in each group. In this study, blood and urine samples were taken from the rats, they were euthanized, and their bladders were removed for glutathione, malondialdehyde, tumor necrosis factor alpha, and interferon gamma measurements. It was observed that tissue damage in Group 2 was lower than that in the other two groups. Glutathione levels in Groups 2 and 4 were significantly higher than in Groups 1 and 3 (p = 0.01. Malondialdehyde levels of Groups 2 and 4 were significantly lower than the values in Groups 1 and 3 (p < 0.001. When the cystitis groups were compared in terms of their interferon gamma and tumor necrosis factor alpha levels, the lowest interferon gamma and tumor necrosis factor alpha levels were detected in Group 3. It was found that HCG has positive effects on experimental cystitis in rats. This study revealed that HCG should be researched as a therapeutic agent and formed a step for studies to be carried out on this subject.

  11. Bioactive Ti metal analogous to human cancellous bone: Fabrication by selective laser melting and chemical treatments.

    Science.gov (United States)

    Pattanayak, Deepak K; Fukuda, A; Matsushita, T; Takemoto, M; Fujibayashi, S; Sasaki, K; Nishida, N; Nakamura, T; Kokubo, T

    2011-03-01

    Selective laser melting (SLM) is a useful technique for preparing three-dimensional porous bodies with complicated internal structures directly from titanium (Ti) powders without any intermediate processing steps, with the products being expected to be useful as a bone substitute. In this study the necessary SLM processing conditions to obtain a dense product, such as the laser power, scanning speed, and hatching pattern, were investigated using a Ti powder of less than 45 μm particle size. The results show that a fully dense plate thinner than 1.8 mm was obtained when the laser power to scanning speed ratio was greater than 0.5 and the hatch spacing was less than the laser diameter, with a 30 μm thick powder layer. Porous Ti metals with structures analogous to human cancellous bone were fabricated and the compressive strength measured. The compressive strength was in the range 35-120 MPa when the porosity was in the range 75-55%. Porous Ti metals fabricated by SLM were heat-treated at 1300 °C for 1h in an argon gas atmosphere to smooth the surface. Such prepared specimens were subjected to NaOH, HCl, and heat treatment to provide bioactivity. Field emission scanning electron micrographs showed that fine networks of titanium oxide were formed over the whole surface of the porous body. These treated porous bodies formed bone-like apatite on their surfaces in a simulated body fluid within 3 days. In vivo studies showed that new bone penetrated into the pores and directly bonded to the walls within 12 weeks after implantation into the femur of Japanese white rabbits. The percentage bone affinity indices of the chemical- and heat-treated porous bodies were significantly higher than that of untreated implants. Copyright © 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  12. A fit-for-purpose LC-MS/MS method for the simultaneous quantitation of ATP and 2,3-DPG in human K2EDTA whole blood.

    Science.gov (United States)

    Kim, Hyeryun; Kosinski, Penelope; Kung, Charles; Dang, Lenny; Chen, Yue; Yang, Hua; Chen, Yuan-Shek; Kramer, Jordyn; Liu, Guowen

    2017-09-01

    Many hemolytic anemias results in major metabolic abnormalities: two common metabolite abnormalities include increased levels of 2,3-diphosphoglycerate (2,3-DPG) and decreased levels of adenosine triphosphate (ATP). To better monitor the concentration changes of these metabolites, the development of a reliable LC-MS/MS method to quantitatively profile the concentrations of 2, 3-DPG and ATP in whole blood is essential to understand the effects of investigational therapeutics. Accurate quantification of both compounds imposes great challenges to bioanalytical scientists due to their polar, ionic and endogenous nature. Here we present an LC-MS/MS method for the reliable quantification of 2,3-DPG and ATP from K 2 EDTA human whole blood (WB) simultaneously. Whole blood samples were spiked with stable isotope labeled internal standards, processed by protein precipitation extraction, and analyzed using zwitterionic ion chromatography-hydrophilic interaction chromatography (ZIC-HILIC) coupled with tandem mass spectrometry. The linear analytical range of the assay was 50-3000μg/mL. The fit-for-purpose method demonstrated excellent accuracy and precision. The overall accuracy was within ±10.5% (%RE) for both analytes and the intra- and inter-assay precision (%CV) were less than 6.7% and 6.2% for both analytes, respectively. ATP and 2,3-DPG were found to be stable in human K 2 EDTA blood for at least 8h at 4°C, 96days when stored at -70°C and after three freeze/thaw cycles. The assay has been successfully applied to K 2 EDTA human whole blood samples to support clinical studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. In vitro cardiotoxicity assessment of environmental chemicals using an organotypic human induced pluripotent stem cell-derived model

    Energy Technology Data Exchange (ETDEWEB)

    Sirenko, Oksana, E-mail: oksana.sirenko@moldev.com [Molecular Devices, LLC, Sunnyvale, CA (United States); Grimm, Fabian A. [Department of Veterinary Integrative Biosciences, Texas A& M University, College Station, TX (United States); Ryan, Kristen R. [Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States); Iwata, Yasuhiro; Chiu, Weihsueh A. [Department of Veterinary Integrative Biosciences, Texas A& M University, College Station, TX (United States); Parham, Frederick [Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States); Wignall, Jessica A. [ICF, Fairfax, VA (United States); Anson, Blake [Cellular Dynamics International, Madison, WI (United States); Cromwell, Evan F. [Protein Fluidics, Inc., Burlingame, CA (United States); Behl, Mamta [Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States); Rusyn, Ivan [Department of Veterinary Integrative Biosciences, Texas A& M University, College Station, TX (United States); Tice, Raymond R. [Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States)

    2017-05-01

    An important target area for addressing data gaps through in vitro screening is the detection of potential cardiotoxicants. Despite the fact that current conservative estimates relate at least 23% of all cardiovascular disease cases to environmental exposures, the identities of the causative agents remain largely uncharacterized. Here, we evaluate the feasibility of a combinatorial in vitro/in silico screening approach for functional and mechanistic cardiotoxicity profiling of environmental hazards using a library of 69 representative environmental chemicals and drugs. Human induced pluripotent stem cell-derived cardiomyocytes were exposed in concentration-response for 30 min or 24 h and effects on cardiomyocyte beating and cellular and mitochondrial toxicity were assessed by kinetic measurements of intracellular Ca{sup 2+} flux and high-content imaging using the nuclear dye Hoechst 33342, the cell viability marker Calcein AM, and the mitochondrial depolarization probe JC-10. More than half of the tested chemicals exhibited effects on cardiomyocyte beating after 30 min of exposure. In contrast, after 24 h, effects on cell beating without concomitant cytotoxicity were observed in about one third of the compounds. Concentration-response data for in vitro bioactivity phenotypes visualized using the Toxicological Prioritization Index (ToxPi) showed chemical class-specific clustering of environmental chemicals, including pesticides, flame retardants, and polycyclic aromatic hydrocarbons. For environmental chemicals with human exposure predictions, the activity-to-exposure ratios between modeled blood concentrations and in vitro bioactivity were between one and five orders of magnitude. These findings not only demonstrate that some ubiquitous environmental pollutants might have the potential at high exposure levels to alter cardiomyocyte function, but also indicate similarities in the mechanism of these effects both within and among chemicals and classes. - Highlights:

  14. In vitro cardiotoxicity assessment of environmental chemicals using an organotypic human induced pluripotent stem cell-derived model

    International Nuclear Information System (INIS)

    Sirenko, Oksana; Grimm, Fabian A.; Ryan, Kristen R.; Iwata, Yasuhiro; Chiu, Weihsueh A.; Parham, Frederick; Wignall, Jessica A.; Anson, Blake; Cromwell, Evan F.; Behl, Mamta; Rusyn, Ivan; Tice, Raymond R.

    2017-01-01

    An important target area for addressing data gaps through in vitro screening is the detection of potential cardiotoxicants. Despite the fact that current conservative estimates relate at least 23% of all cardiovascular disease cases to environmental exposures, the identities of the causative agents remain largely uncharacterized. Here, we evaluate the feasibility of a combinatorial in vitro/in silico screening approach for functional and mechanistic cardiotoxicity profiling of environmental hazards using a library of 69 representative environmental chemicals and drugs. Human induced pluripotent stem cell-derived cardiomyocytes were exposed in concentration-response for 30 min or 24 h and effects on cardiomyocyte beating and cellular and mitochondrial toxicity were assessed by kinetic measurements of intracellular Ca 2+ flux and high-content imaging using the nuclear dye Hoechst 33342, the cell viability marker Calcein AM, and the mitochondrial depolarization probe JC-10. More than half of the tested chemicals exhibited effects on cardiomyocyte beating after 30 min of exposure. In contrast, after 24 h, effects on cell beating without concomitant cytotoxicity were observed in about one third of the compounds. Concentration-response data for in vitro bioactivity phenotypes visualized using the Toxicological Prioritization Index (ToxPi) showed chemical class-specific clustering of environmental chemicals, including pesticides, flame retardants, and polycyclic aromatic hydrocarbons. For environmental chemicals with human exposure predictions, the activity-to-exposure ratios between modeled blood concentrations and in vitro bioactivity were between one and five orders of magnitude. These findings not only demonstrate that some ubiquitous environmental pollutants might have the potential at high exposure levels to alter cardiomyocyte function, but also indicate similarities in the mechanism of these effects both within and among chemicals and classes. - Highlights:

  15. Study and structural and chemical characterization of human dental smalt by electron microscopy; Estudio y caracterizacion estructural y quimico del esmalte dental humano por microscopia electronica

    Energy Technology Data Exchange (ETDEWEB)

    Belio R, I A; Reyes G, J [Instituto de Fisica, UNAM, A.P. 20-364, 01000 Mexico D.F. (Mexico)

    1998-07-01

    The study of human dental smalt has been subject to investigation for this methods with electron microscopy, electron diffraction, X-ray diffraction and image simulation programs have been used with the purpose to determine its chemical and structural characteristics of the organic and inorganic materials. This work has been held mainly for the characterization of hydroxyapatite (Ca){sub 10} (PO{sub 4}){sub 6} (OH{sub 4}){sub 2}, inorganic material which conforms the dental smalt in 97%, so observing its structural unity which is composed by the prisms and these by crystals and atoms. It was subsequently initiated the study of the organic material, with is precursor of itself. (Author)

  16. Constance Gunderson, Human Trafficking: The Trafficking of Women in Northern Germany for the Purpose of Sexual Exploitation. Systematic Overview of Community Based Responses and Challenges (Bremen: Lit Verlag, 2012

    Directory of Open Access Journals (Sweden)

    Markus Meckl

    2013-03-01

    Full Text Available A review of the following book: Constance Gunderson, Human Trafficking: The Trafficking of Women in Northern Germany for the Purpose of Sexual Exploitation. Systematic Overview of Community based responses and challenges (Bremen: Lit Verlag, Bremen 2012

  17. 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

  18. Violence: A non-chemical stressor and how it impacts human ...

    Science.gov (United States)

    Objectives of this presentation Define non-chemical stressors and provide overview of non-chemical stressors in a child’s social environment Summarize existing research on exposure to violence as a non-chemical stressor for children under 18 years of age Show that exposure to violence (a non-chemical stressor) may modify the biological response to chemical exposures To be presented at the Seventh Annual Session on Empowering Sustainability on Earth. Empowering Sustainability is an initiative at the University of California, Irvine, dedicated to connecting sustainability leaders across generations, countries, and disciplines and fostering engagement and research. Launched in 2011, the UCI Summer Seminar Series "Empowering Sustainability on Earth" is co-hosted each July by the UCI Newkirk Center for Science and Society, presenting a series of seminars for the next generation of leaders of global sustainability from over 70 countries around the world. The seminar talks are open to the public.

  19. Exposure to different toxic chemicals: a threat to environment and human health in mining sites in Tanzania

    International Nuclear Information System (INIS)

    Magduala, J.J.

    2009-01-01

    The mining activities in Tanzania have been existed since time immemorial whereby traditional mining was practiced. However until now the country is still endowed with abundant mineral resources including gold, tanzanite diamonds, iron ore, salt, gypsum, gemstones, natural gas, phosphate, coal, cobalt and nickel. The country's major gold fields are located in Geita, Musoma, Tarime, Chunya and Mpanda. During the last decade, local and foreign investors intensified their mining activities in Tanzania. This resulted in increased use of hazardous chemicals like mercury and cyanide which are harmful and toxic. In this report, the extent and impact to long term exposure of such chemicals to both natural environment and animals including human beings will be discussed. Recommendations to local and international investors and policy markers regarding the safe and sustainable use of harmful chemicals will also be discussed.(author)

  20. Identifying developmental toxicity pathways for a subset of ToxCast chemicals using human embryonic stem cells and metabolomics

    International Nuclear Information System (INIS)

    Kleinstreuer, N.C.; Smith, A.M.; West, P.R.; Conard, K.R.; Fontaine, B.R.; Weir-Hauptman, A.M.; Palmer, J.A.; Knudsen, T.B.; Dix, D.J.; Donley, E.L.R.; Cezar, G.G.

    2011-01-01

    Metabolomics analysis was performed on the supernatant of human embryonic stem (hES) cell cultures exposed to a blinded subset of 11 chemicals selected from the chemical library of EPA's ToxCast™ chemical screening and prioritization research project. Metabolites from hES cultures were evaluated for known and novel signatures that may be indicative of developmental toxicity. Significant fold changes in endogenous metabolites were detected for 83 putatively annotated mass features in response to the subset of ToxCast chemicals. The annotations were mapped to specific human metabolic pathways. This revealed strong effects on pathways for nicotinate and nicotinamide metabolism, pantothenate and CoA biosynthesis, glutathione metabolism, and arginine and proline metabolism pathways. Predictivity for adverse outcomes in mammalian prenatal developmental toxicity studies used ToxRefDB and other sources of information, including Stemina Biomarker Discovery's predictive DevTox® model trained on 23 pharmaceutical agents of known developmental toxicity and differing potency. The model initially predicted developmental toxicity from the blinded ToxCast compounds in concordance with animal data with 73% accuracy. Retraining the model with data from the unblinded test compounds at one concentration level increased the predictive accuracy for the remaining concentrations to 83%. These preliminary results on a 11-chemical subset of the ToxCast chemical library indicate that metabolomics analysis of the hES secretome provides information valuable for predictive modeling and mechanistic understanding of mammalian developmental toxicity. -- Highlights: ► We tested 11 environmental compounds in a hESC metabolomics platform. ► Significant changes in secreted small molecule metabolites were observed. ► Perturbed mass features map to pathways critical for normal development and pregnancy. ► Arginine, proline, nicotinate, nicotinamide and glutathione pathways were affected.

  1. Identifying developmental toxicity pathways for a subset of ToxCast chemicals using human embryonic stem cells and metabolomics

    Energy Technology Data Exchange (ETDEWEB)

    Kleinstreuer, N.C., E-mail: kleinstreuer.nicole@epa.gov [NCCT, US EPA, RTP, NC 27711 (United States); Smith, A.M.; West, P.R.; Conard, K.R.; Fontaine, B.R. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); Weir-Hauptman, A.M. [Covance, Inc., Madison, WI 53704 (United States); Palmer, J.A. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); Knudsen, T.B.; Dix, D.J. [NCCT, US EPA, RTP, NC 27711 (United States); Donley, E.L.R. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); Cezar, G.G. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); University of Wisconsin-Madison, Madison, WI 53706 (United States)

    2011-11-15

    Metabolomics analysis was performed on the supernatant of human embryonic stem (hES) cell cultures exposed to a blinded subset of 11 chemicals selected from the chemical library of EPA's ToxCast Trade-Mark-Sign chemical screening and prioritization research project. Metabolites from hES cultures were evaluated for known and novel signatures that may be indicative of developmental toxicity. Significant fold changes in endogenous metabolites were detected for 83 putatively annotated mass features in response to the subset of ToxCast chemicals. The annotations were mapped to specific human metabolic pathways. This revealed strong effects on pathways for nicotinate and nicotinamide metabolism, pantothenate and CoA biosynthesis, glutathione metabolism, and arginine and proline metabolism pathways. Predictivity for adverse outcomes in mammalian prenatal developmental toxicity studies used ToxRefDB and other sources of information, including Stemina Biomarker Discovery's predictive DevTox Registered-Sign model trained on 23 pharmaceutical agents of known developmental toxicity and differing potency. The model initially predicted developmental toxicity from the blinded ToxCast compounds in concordance with animal data with 73% accuracy. Retraining the model with data from the unblinded test compounds at one concentration level increased the predictive accuracy for the remaining concentrations to 83%. These preliminary results on a 11-chemical subset of the ToxCast chemical library indicate that metabolomics analysis of the hES secretome provides information valuable for predictive modeling and mechanistic understanding of mammalian developmental toxicity. -- Highlights: Black-Right-Pointing-Pointer We tested 11 environmental compounds in a hESC metabolomics platform. Black-Right-Pointing-Pointer Significant changes in secreted small molecule metabolites were observed. Black-Right-Pointing-Pointer Perturbed mass features map to pathways critical for normal

  2. Primary cilia: the chemical antenna regulating human adipose-derived stem cell osteogenesis.

    Directory of Open Access Journals (Sweden)

    Josephine C Bodle

    Full Text Available Adipose-derived stem cells (ASC are multipotent stem cells that show great potential as a cell source for osteogenic tissue replacements and it is critical to understand the underlying mechanisms of lineage specification. Here we explore the role of primary cilia in human ASC (hASC differentiation. This study focuses on the chemosensitivity of the primary cilium and the action of its associated proteins: polycystin-1 (PC1, polycystin-2 (PC2 and intraflagellar transport protein-88 (IFT88, in hASC osteogenesis. To elucidate cilia-mediated mechanisms of hASC differentiation, siRNA knockdown of PC1, PC2 and IFT88 was performed to disrupt cilia-associated protein function. Immunostaining of the primary cilium structure indicated phenotypic-dependent changes in cilia morphology. hASC cultured in osteogenic differentiation media yielded cilia of a more elongated conformation than those cultured in expansion media, indicating cilia-sensitivity to the chemical environment and a relationship between the cilium structure and phenotypic determination. Abrogation of PC1, PC2 and IFT88 effected changes in both hASC proliferation and differentiation activity, as measured through proliferative activity, expression of osteogenic gene markers, calcium accretion and endogenous alkaline phosphatase activity. Results indicated that IFT88 may be an early mediator of the hASC differentiation process with its knockdown increasing hASC proliferation and decreasing Runx2, alkaline phosphatase and BMP-2 mRNA expression. PC1 and PC2 knockdown affected later osteogenic gene and end-product expression. PC1 knockdown resulted in downregulation of alkaline phosphatase and osteocalcin gene expression, diminished calcium accretion and reduced alkaline phosphatase enzymatic activity. Taken together our results indicate that the structure of the primary cilium is intimately associated with the process of hASC osteogenic differentiation and that its associated proteins are critical

  3. Chemical composition and antibacterial activity of essential oils against human pathogenic bacteria

    NARCIS (Netherlands)

    Sokovic, M.; Marin, P.D.; Brkic, D.; Griensven, van L.J.L.D.

    2008-01-01

    The chemical composition and antibacterial activity of essential oils from 10 aromatic plants Matricaria chamommilla, Mentha piperita, M. spicata, Lavandula angustifolia, Ocimum basilicum, Thymus vulgaris, Origanum vulgare, Salvia officinalis, Citrus limon and C. aurantium have been determined.

  4. Association between chemical pattern in breast milk and congenital cryptorchidism: modelling of complex human exposures

    DEFF Research Database (Denmark)

    Krysiak-Baltyn, Konrad; Toppari, J.; Skakkebaek, N. E.

    2012-01-01

    , polybrominated biphenyls and organochlorine pesticides. Computational analysis of the data was performed using logistic regression and three multivariate machine learning classifiers. Furthermore, we performed systems biology analysis to explore the chemical influence on a molecular level. After correction...... and cryptorchidism than Finnish samples. Moreover, PCBs were indicated as having a protective effect within the Danish cohort, which was supported by molecular data recovered through systems biology. Our results lend further support to the hypothesis that the mixture of environmental chemicals may contribute...

  5. Mandatory Submission to The Identification of Genetic Profile for Criminal Purpose: A Broach Pursuant to the Right to Privacy and Dignity of the Human Person

    Directory of Open Access Journals (Sweden)

    George Maia Santos

    2015-12-01

    Full Text Available This article aims to demonstrate that the mandatory submission convicted of a crime committed, intentionally, with serious violence against person or heinous crime, to identify the genetic profile by DNA extraction - deoxyribonucleic acid, although by proper and painless technique is offensive to fundamental rights. For this purpose, it is part of the overall concept of the right to privacy, which is configured as a negative right or protection against unlawful state mismanagement, in order to protect a need or a basic right to the free individual self-determination. Then genetic intimacy is defined as an asset able to reveal the physical, psychological, behavioral and disease features, which, if disclosed or accessed without the consent of the accused, may generate stigmatization and discrimination of the subject involved, violating in this way, therefore, the right to privacy. In conclusion, we move towards emphasizing besides the right to privacy, compulsory provision of biological material to identify the genetic profile is offensive to fundamental rights to physical liberty or outpatient; physical integrity; to the freedom of religion or conscience; non-discrimination; the silence and non-production of evidences against himself, and in last instance, the biggest vector of all fundamental rights: the dignity of the human person.

  6. Potential hazards to embryo implantation: A human endometrial in vitro model to identify unwanted antigestagenic actions of chemicals

    International Nuclear Information System (INIS)

    Fischer, L.; Deppert, W.R.; Pfeifer, D.; Stanzel, S.; Weimer, M.; Hanjalic-Beck, A.; Stein, A.; Straßer, M.; Zahradnik, H.P.; Schaefer, W.R.

    2012-01-01

    Embryo implantation is a crucial step in human reproduction and depends on the timely development of a receptive endometrium. The human endometrium is unique among adult tissues due to its dynamic alterations during each menstrual cycle. It hosts the implantation process which is governed by progesterone, whereas 17β-estradiol regulates the preceding proliferation of the endometrium. The receptors for both steroids are targets for drugs and endocrine disrupting chemicals. Chemicals with unwanted antigestagenic actions are potentially hazardous to embryo implantation since many pharmaceutical antiprogestins adversely affect endometrial receptivity. This risk can be addressed by human tissue-specific in vitro assays. As working basis we compiled data on chemicals interacting with the PR. In our experimental work, we developed a flexible in vitro model based on human endometrial Ishikawa cells. Effects of antiprogestin compounds on pre-selected target genes were characterized by sigmoidal concentration–response curves obtained by RT-qPCR. The estrogen sulfotransferase (SULT1E1) was identified as the most responsive target gene by microarray analysis. The agonistic effect of progesterone on SULT1E1 mRNA was concentration-dependently antagonized by RU486 (mifepristone) and ZK137316 and, with lower potency, by 4-nonylphenol, bisphenol A and apigenin. The negative control methyl acetoacetate showed no effect. The effects of progesterone and RU486 were confirmed on the protein level by Western blotting. We demonstrated proof of principle that our Ishikawa model is suitable to study quantitatively effects of antiprogestin-like chemicals on endometrial target genes in comparison to pharmaceutical reference compounds. This test is useful for hazard identification and may contribute to reduce animal studies. -- Highlights: ► We compare progesterone receptor-mediated endometrial effects of chemicals and drugs. ► 4-Nonylphenol, bisphenol A and apigenin exert weak

  7. Potential hazards to embryo implantation: A human endometrial in vitro model to identify unwanted antigestagenic actions of chemicals

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, L.; Deppert, W.R. [Department of Obstetrics and Gynecology, University Hospital Freiburg (Germany); Pfeifer, D. [Department of Hematology and Oncology, University Hospital Freiburg (Germany); Stanzel, S.; Weimer, M. [Department of Biostatistics, German Cancer Research Center, Heidelberg (Germany); Hanjalic-Beck, A.; Stein, A.; Straßer, M.; Zahradnik, H.P. [Department of Obstetrics and Gynecology, University Hospital Freiburg (Germany); Schaefer, W.R., E-mail: wolfgang.schaefer@uniklinik-freiburg.de [Department of Obstetrics and Gynecology, University Hospital Freiburg (Germany)

    2012-05-01

    Embryo implantation is a crucial step in human reproduction and depends on the timely development of a receptive endometrium. The human endometrium is unique among adult tissues due to its dynamic alterations during each menstrual cycle. It hosts the implantation process which is governed by progesterone, whereas 17β-estradiol regulates the preceding proliferation of the endometrium. The receptors for both steroids are targets for drugs and endocrine disrupting chemicals. Chemicals with unwanted antigestagenic actions are potentially hazardous to embryo implantation since many pharmaceutical antiprogestins adversely affect endometrial receptivity. This risk can be addressed by human tissue-specific in vitro assays. As working basis we compiled data on chemicals interacting with the PR. In our experimental work, we developed a flexible in vitro model based on human endometrial Ishikawa cells. Effects of antiprogestin compounds on pre-selected target genes were characterized by sigmoidal concentration–response curves obtained by RT-qPCR. The estrogen sulfotransferase (SULT1E1) was identified as the most responsive target gene by microarray analysis. The agonistic effect of progesterone on SULT1E1 mRNA was concentration-dependently antagonized by RU486 (mifepristone) and ZK137316 and, with lower potency, by 4-nonylphenol, bisphenol A and apigenin. The negative control methyl acetoacetate showed no effect. The effects of progesterone and RU486 were confirmed on the protein level by Western blotting. We demonstrated proof of principle that our Ishikawa model is suitable to study quantitatively effects of antiprogestin-like chemicals on endometrial target genes in comparison to pharmaceutical reference compounds. This test is useful for hazard identification and may contribute to reduce animal studies. -- Highlights: ► We compare progesterone receptor-mediated endometrial effects of chemicals and drugs. ► 4-Nonylphenol, bisphenol A and apigenin exert weak

  8. Military chemical warfare agent human subjects testing: part 1--history of six-decades of military experiments with chemical warfare agents.

    Science.gov (United States)

    Brown, Mark

    2009-10-01

    Military chemical warfare agent testing from World War I to 1975 produced thousands of veterans with concerns of possible long-term health consequences. Clinical and research evaluation of potential long-term health effects has been difficult because the exposures occurred decades ago, the identity of troops exposed and exposure magnitudes are uncertain, and acute effects during experiments poorly documented. In contrast, a companion article describes the large amount of information available about the specific agents tested and their long-term health effects. This short history describes U.S. military chemical-agent experiments with human subjects and identifies tested agents. Finally, the demonstrated need to anticipate future health concerns from military personnel involved in such military testing suggests current and future military researchers should be required, by law and regulation, to fully record the identity of those exposed, relevant exposure magnitude, and complete medical information for all subjects. New study protocols and institutional review board approvals for research involving military personnel should reflect this need.

  9. Xenobiotic metabolism capacities of human skin in comparison with a 3D-epidermis model and keratinocyte-based cell culture as in vitro alternatives for chemical testing: phase II enzymes.

    Science.gov (United States)

    Götz, Christine; Pfeiffer, Roland; Tigges, Julia; Ruwiedel, Karsten; Hübenthal, Ulrike; Merk, Hans F; Krutmann, Jean; Edwards, Robert J; Abel, Josef; Pease, Camilla; Goebel, Carsten; Hewitt, Nicola; Fritsche, Ellen

    2012-05-01

    The 7th Amendment to the EU Cosmetics Directive prohibits the use of animals in cosmetic testing for certain endpoints, such as genotoxicity. Therefore, skin in vitro models have to replace chemical testing in vivo. However, the metabolic competence neither of human skin nor of alternative in vitro models has so far been fully characterized, although skin is the first-pass organ for accidentally or purposely (cosmetics and pharmaceuticals) applied chemicals. Thus, there is an urgent need to understand the xenobiotic-metabolizing capacities of human skin and to compare these activities to models developed to replace animal testing. We have measured the activity of the phase II enzymes glutathione S-transferase, UDP-glucuronosyltransferase and N-acetyltransferase in ex vivo human skin, the 3D epidermal model EpiDerm 200 (EPI-200), immortalized keratinocyte-based cell lines (HaCaT and NCTC 2544) and primary normal human epidermal keratinocytes. We show that all three phase II enzymes are present and highly active in skin as compared to phase I. Human skin, therefore, represents a more detoxifying than activating organ. This work systematically compares the activities of three important phase II enzymes in four different in vitro models directly to human skin. We conclude from our studies that 3D epidermal models, like the EPI-200 employed here, are superior over monolayer cultures in mimicking human skin xenobiotic metabolism and thus better suited for dermatotoxicity testing. © 2012 John Wiley & Sons A/S.

  10. Clinical Holistic Medicine: Induction of Spontaneous Remission of Cancer by Recovery of the Human Character and the Purpose of Life (the Life Mission

    Directory of Open Access Journals (Sweden)

    Søren Ventegodt

    2004-01-01

    Full Text Available The recovery of the human character and purpose of life with consciousness-based medicine seems to be able to induce spontaneous remissions in several diseases. On two different occasions, we observed breast tumors reduced to less than half their original diameters (clinically judged during a holistic session, when working with the patients in accordance with the holistic process theory of healing, the life mission theory, and the theory of human character. One tumor was histologically diagnosed as malign breast cancer prior to the session, while the other was under examination. As both patients had the affected regions of the breast surgically removed immediately after the session, we are unable to determine if they were actually healed by the holistic treatment. We find it extremely interesting that the size of a tumor can be reduced dramatically within a few hours of holistic treatment, when the patient is highly motivated for personal development. The reduction of tumor size is in accordance with the holistic view that many types of cancer are caused by emotional and existential disturbances. From a holistic perspective, cancer can be understood as a simple disturbance of the cells, arising from the tissue holding on to a trauma with strong emotional content. This is called “a blockage”, where the function of the cells is changed from their original function in the tissue to a function of holding emotions. The reduction of the tumor in the two cases happened when old painful emotions were identified in the tissues, in and around the tumor, and processed into understanding; when the patients finally did let go of negative beliefs and attitudes that had kept the feeling(s repressed to that part of the body, the tumor first softened and then disappeared, presumably by apoptosis. We believe that the consciousness-based/holistic medical toolbox has a serious additional offer to cancer patients, and we will therefore strongly encourage the

  11. Human exposure to chemical mixtures: Challenges for the integration of toxicology with epidemiology data in risk assessment.

    Science.gov (United States)

    Hernández, Antonio F; Tsatsakis, Aristidis M

    2017-05-01

    Little is known about the potential adverse effects from longterm exposure to complex mixtures at low doses, close to health-based reference values. Traditional chemical-specific risk assessment based on animal testing may be insufficient and the lack of toxicological studies on chemical mixtures remains a major regulatory challenge. Hence, new methodologies on cumulative risk assessment are being developed but still present major limitations. Evaluation of chemical mixture effects requires an integrated and systematic approach and close collaboration across different scientific fields, particularly toxicology, epidemiology, exposure science, risk assessment and statistics for a proper integration of data from all these disciplines. Well designed and conducted epidemiological studies can take advantage of this new paradigm and can provide insight to support the correlation between humans low-dose exposures and diseases, thus avoiding the uncertainty associated with extrapolation across species. In this regard, human epidemiology studies may play a significant role in the new vision of toxicity testing. However, this type of information has not been fully considered in risk assessment, mainly due to the inherent limitations of epidemiologic studies. An integrated approach of in vivo, in vitro and in silico data, together with systematic reviews or meta-analysis of high quality epidemiological studies will improve the robustness of risk assessment of chemical mixtures and will provide a stronger basis for regulatory decisions. The ultimate goal is that experimental and mechanistic data can lend support and biological plausibility to the human epidemiological observations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. A High Power Solar Electric Propulsion - Chemical Mission for Human Exploration of Mars

    Science.gov (United States)

    Burke, Laura M.; Martini, Michael C.; Oleson, Steven R.

    2014-01-01

    Recently Solar Electric Propulsion (SEP) as a main propulsion system has been investigated as an option to support manned space missions to near-Earth destinations for the NASA Gateway spacecraft. High efficiency SEP systems are able to reduce the amount of propellant long duration chemical missions require, ultimately reducing the required mass delivered to Low Earth Orbit (LEO) by a launch vehicle. However, for long duration interplanetary Mars missions, using SEP as the sole propulsion source alone may not be feasible due to the long trip times to reach and insert into the destination orbit. By combining an SEP propulsion system with a chemical propulsion system the mission is able to utilize the high-efficiency SEP for sustained vehicle acceleration and deceleration in heliocentric space and the chemical system for orbit insertion maneuvers and trans-earth injection, eliminating the need for long duration spirals. By capturing chemically instead of with low-thrust SEP, Mars stay time increases by nearly 200 days. Additionally, the size the of chemical propulsion system can be significantly reduced from that of a standard Mars mission because the SEP system greatly decreases the Mars arrival and departure hyperbolic excess velocities (V(sub infinity)).

  13. Evaluation of a Silicone Membrane as an Alternative to Human Skin for Determining Skin Permeation Parameters of Chemical Compounds.

    Science.gov (United States)

    Uchida, Takashi; Yakumaru, Masafumi; Nishioka, Keisuke; Higashi, Yoshihiro; Sano, Tomohiko; Todo, Hiroaki; Sugibayashi, Kenji

    2016-01-01

    We evaluated the effectiveness of a silicone membrane as an alternative to human skin using the skin permeation parameters of chemical compounds. An in vitro permeation study using 15 model compounds was conducted, and permeation parameters comprising permeability coefficient (P), diffusion parameter (DL(-2)), and partition parameter (KL) were calculated from each permeation profile. Significant correlations were obtained in log P, log DL(-2), and log KL values between the silicone membrane and human skin. DL(-2) values of model compounds, except flurbiprofen, in the silicone membrane were independent of the lipophilicity of the model compounds and were 100-fold higher than those in human skin. For antipyrine and caffeine, which are hydrophilic, KL values in the silicone membrane were 100-fold lower than those in human skin, and P values, calculated as the product of a DL(-2) and KL, were similar. For lipophilic compounds, such as n-butyl paraben and flurbiprofen, KL values for silicone were similar to or 10-fold higher than those in human skin, and P values for silicone were 100-fold higher than those in human skin. Furthermore, for amphiphilic compounds with log Ko/w values from 0.5 to 3.5, KL values in the silicone membrane were 10-fold lower than those in human skin, and P values for silicone were 10-fold higher than those in human skin. The silicone membrane was useful as a human skin alternative in an in vitro skin permeation study. However, depending on the lipophilicity of the model compounds, some parameters may be over- or underestimated.

  14. Prediction of rodent carcinogenic potential of naturally occurring chemicals in the human diet using high-throughput QSAR predictive modeling

    International Nuclear Information System (INIS)

    Valerio, Luis G.; Arvidson, Kirk B.; Chanderbhan, Ronald F.; Contrera, Joseph F.

    2007-01-01

    Consistent with the U.S. Food and Drug Administration (FDA) Critical Path Initiative, predictive toxicology software programs employing quantitative structure-activity relationship (QSAR) models are currently under evaluation for regulatory risk assessment and scientific decision support for highly sensitive endpoints such as carcinogenicity, mutagenicity and reproductive toxicity. At the FDA's Center for Food Safety and Applied Nutrition's Office of Food Additive Safety and the Center for Drug Evaluation and Research's Informatics and Computational Safety Analysis Staff (ICSAS), the use of computational SAR tools for both qualitative and quantitative risk assessment applications are being developed and evaluated. One tool of current interest is MDL-QSAR predictive discriminant analysis modeling of rodent carcinogenicity, which has been previously evaluated for pharmaceutical applications by the FDA ICSAS. The study described in this paper aims to evaluate the utility of this software to estimate the carcinogenic potential of small, organic, naturally occurring chemicals found in the human diet. In addition, a group of 19 known synthetic dietary constituents that were positive in rodent carcinogenicity studies served as a control group. In the test group of naturally occurring chemicals, 101 were found to be suitable for predictive modeling using this software's discriminant analysis modeling approach. Predictions performed on these compounds were compared to published experimental evidence of each compound's carcinogenic potential. Experimental evidence included relevant toxicological studies such as rodent cancer bioassays, rodent anti-carcinogenicity studies, genotoxic studies, and the presence of chemical structural alerts. Statistical indices of predictive performance were calculated to assess the utility of the predictive modeling method. Results revealed good predictive performance using this software's rodent carcinogenicity module of over 1200 chemicals

  15. Chemicals identified in human biological media: a data base. Third annual report, October 1981

    Energy Technology Data Exchange (ETDEWEB)

    Cone, M.V.; Baldauf, M.F.; Martin, F.M. (comps.)

    1981-12-01

    Data from almost 1600 of the 3800 body-burden documents collected to date have been entered in the data base as of October 1981. The emphasis on including recent literature and significant research documents has resulted in a chronological mix of articles from 1974 to the present. When body-burden articles are identified, data are extracted and entered in the data base by chemical and tissue/body fluid. Each data entry comprises a single record (or line entry) and is assigned a record number. If a particular document deals with more than one chemical and/or tissue, there will be multiple records for that document. For example, a study of 5 chemicals in each of 3 tissues has 15 different records (or 15 line entries) in the data base with 15 record numbers. Record numbers are assigned consecutively throughout the entire data base and appear in the upper left corner of the first column for each record.

  16. Predictive performance of the human Cell Line Activation Test (h-CLAT) for lipophilic chemicals with high octanol-water partition coefficients.

    Science.gov (United States)

    Takenouchi, Osamu; Miyazawa, Masaaki; Saito, Kazutoshi; Ashikaga, Takao; Sakaguchi, Hitoshi

    2013-01-01

    To meet the urgent need for a reliable alternative test for predicting skin sensitizing potential of many chemicals, we have developed a cell-based in vitro test, human Cell Line Activation Test (h-CLAT). However, the predictive performance for lipophilic chemicals in the h-CLAT still remains relatively unknown. Moreover, it's suggested that low water solubility of chemicals might induce false negative outcomes. Thus, in this study, we tested relatively low water soluble 37 chemicals with log Kow values above and below 3.5 in the h-CLAT. The small-scale assessment resulted in nine false negative outcomes for chemicals with log Kow values greater than 3.5. We then created a dataset of 143 chemicals by combining the existing dataset of 106 chemicals and examined the predictive performance of the h-CLAT for chemicals with a log Kow of less than 3.5; a total of 112 chemicals from the 143 chemicals in the dataset. The sensitivity and overall accuracy for the 143 chemicals were 83% and 80%, respectively. In contrast, sensitivity and overall accuracy for the 112 chemicals with log Kow values below 3.5 improved to 94% and 88%, respectively. These data suggested that the h-CLAT could successfully detect sensitizers with log Kow values up to 3.5. When chemicals with log Kow values greater than 3.5 that were deemed positive by h-CLAT were included with the 112 chemicals, the sensitivity and accuracy in terms of the resulting applicable 128 chemicals out of the 143 chemicals became 95% and 88%, respectively. The use of log Kow values gave the h-CLAT a higher predictive performance. Our results demonstrated that the h-CLAT could predict sensitizing potential of various chemicals, which contain lipophilic chemicals using a large-scale chemical dataset.

  17. Review of the state of the art of human biomonitoring for chemical substances and its application to human exposure assessment for food safety

    DEFF Research Database (Denmark)

    Choi, Judy; Mørck, Thit Aarøe; Polcher, Alexandra

    2015-01-01

    Human biomonitoring (HBM) measures the levels of substances in body fluids and tissues. Many countries have conducted HBM studies, yet little is known about its application towards chemical risk assessment, particularly in relation to food safety. Therefore a literature search was performed...... in several databases and conference proceedings for 2002 – 2014. Definitions of HBM and biomarkers, HBM techniques and requirements, and the possible application to the different steps of risk assessment were described. The usefulness of HBM for exposure assessment of chemical substances from food source...... safety areas (namely exposure assessment), and for the implementation of a systematic PMM approach. But further work needs to be done to improve usability. Major deficits are the lack of HBM guidance values on a considerable number of substance groups, for which health based guidance values (HBGVs) have...

  18. A predictive toxicogenomics signature to classify genotoxic versus non-genotoxic chemicals in human TK6 cells

    Directory of Open Access Journals (Sweden)

    Andrew Williams

    2015-12-01

    Full Text Available Genotoxicity testing is a critical component of chemical assessment. The use of integrated approaches in genetic toxicology, including the incorporation of gene expression data to determine the DNA damage response pathways involved in response, is becoming more common. In companion papers previously published in Environmental and Molecular Mutagenesis, Li et al. (2015 [6] developed a dose optimization protocol that was based on evaluating expression changes in several well-characterized stress-response genes using quantitative real-time PCR in human lymphoblastoid TK6 cells in culture. This optimization approach was applied to the analysis of TK6 cells exposed to one of 14 genotoxic or 14 non-genotoxic agents, with sampling 4 h post-exposure. Microarray-based transcriptomic analyses were then used to develop a classifier for genotoxicity using the nearest shrunken centroids method. A panel of 65 genes was identified that could accurately classify toxicants as genotoxic or non-genotoxic. In Buick et al. (2015 [1], the utility of the biomarker for chemicals that require metabolic activation was evaluated. In this study, TK6 cells were exposed to increasing doses of four chemicals (two genotoxic that require metabolic activation and two non-genotoxic chemicals in the presence of rat liver S9 to demonstrate that S9 does not impair the ability to classify genotoxicity using this genomic biomarker in TK6cells.

  19. CHEMICAL MARKERS OF HUMAN WASTE CONTAMINATION IN SOURCE WATERS: A SIMPLIFIED ANALYTICAL APPROACH

    Science.gov (United States)

    Giving public water authorities a tool to monitor and measure levels of human waste contamination of waters simply and rapidly would enhance public protection. This methodology, using both urobilin and azithromycin (or any other human-use pharmaceutical) could be used to give pub...

  20. Aggregating human exposure to chemicals: An overview of tools and methodologies

    NARCIS (Netherlands)

    Delmaar JE; Engelen JGM van; AFSSET; SIR

    2007-01-01

    Available computer models for estimating the exposure to substances from multiple consumer products are not suited for this task. Consumers are daily exposed to chemical substances from consumer products. The level of this exposure has to be assessed to evaluate the consequences of exposure to a

  1. 24 CFR 51.200 - Purpose.

    Science.gov (United States)

    2010-04-01

    ... Conventional Fuels or Chemicals of an Explosive or Flammable Nature § 51.200 Purpose. The purpose of this... store, handle, or process hazardous substances; (b) Alert those responsible for the siting of HUD...

  2. Accelerated generation of human induced pluripotent stem cells with retroviral transduction and chemical inhibitors under physiological hypoxia

    Energy Technology Data Exchange (ETDEWEB)

    Shimada, Hidenori [Department of Bioartificial Organs, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawaharacho, Shogoin, Sakyoku, Kyoto 606-8507 (Japan); Hashimoto, Yoshiya [Department of Biomaterials, Osaka Dental University, 8-1, Hanazonocho, Kuzuha, Hirakatashi, Osaka 573-1121 (Japan); Nakada, Akira; Shigeno, Keiji [Department of Bioartificial Organs, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawaharacho, Shogoin, Sakyoku, Kyoto 606-8507 (Japan); Nakamura, Tatsuo, E-mail: nakamura@frontier.kyoto-u.ac.jp [Department of Bioartificial Organs, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawaharacho, Shogoin, Sakyoku, Kyoto 606-8507 (Japan)

    2012-01-13

    Highlights: Black-Right-Pointing-Pointer Very rapid generation of human iPS cells under optimized conditions. Black-Right-Pointing-Pointer Five chemical inhibitors under hypoxia boosted reprogramming. Black-Right-Pointing-Pointer We performed genome-wide DNA methylation analysis. -- Abstract: Induced pluripotent stem (iPS) cells are generated from somatic cells by the forced expression of a defined set of pluripotency-associated transcription factors. Human iPS cells can be propagated indefinitely, while maintaining the capacity to differentiate into all cell types in the body except for extra-embryonic tissues. This technology not only represents a new way to use individual-specific stem cells for regenerative medicine but also constitutes a novel method to obtain large amounts of disease-specific cells for biomedical research. Despite their great potential, the long reprogramming process (up to 1 month) remains one of the most significant challenges facing standard virus-mediated methodology. In this study, we report the accelerated generation of human iPS cells from adipose-derived stem (ADS) cells, using a new combination of chemical inhibitors under a setting of physiological hypoxia in conjunction with retroviral transduction of Oct4, Sox2, Klf4, and L-Myc. Under optimized conditions, we observed human embryonic stem (ES)-like cells as early as 6 days after the initial retroviral transduction. This was followed by the emergence of fully reprogrammed cells bearing Tra-1-81-positive and DsRed transgene-silencing properties on day 10. The resulting cell lines resembled human ES cells in many respects including proliferation rate, morphology, pluripotency-associated markers, global gene expression patterns, genome-wide DNA methylation states, and the ability to differentiate into all three of the germ layers, both in vitro and in vivo. Our method, when combined with chemical inhibitors under conditions of physiological hypoxia, offers a powerful tool for rapidly

  3. Accelerated generation of human induced pluripotent stem cells with retroviral transduction and chemical inhibitors under physiological hypoxia

    International Nuclear Information System (INIS)

    Shimada, Hidenori; Hashimoto, Yoshiya; Nakada, Akira; Shigeno, Keiji; Nakamura, Tatsuo

    2012-01-01

    Highlights: ► Very rapid generation of human iPS cells under optimized conditions. ► Five chemical inhibitors under hypoxia boosted reprogramming. ► We performed genome-wide DNA methylation analysis. -- Abstract: Induced pluripotent stem (iPS) cells are generated from somatic cells by the forced expression of a defined set of pluripotency-associated transcription factors. Human iPS cells can be propagated indefinitely, while maintaining the capacity to differentiate into all cell types in the body except for extra-embryonic tissues. This technology not only represents a new way to use individual-specific stem cells for regenerative medicine but also constitutes a novel method to obtain large amounts of disease-specific cells for biomedical research. Despite their great potential, the long reprogramming process (up to 1 month) remains one of the most significant challenges facing standard virus-mediated methodology. In this study, we report the accelerated generation of human iPS cells from adipose-derived stem (ADS) cells, using a new combination of chemical inhibitors under a setting of physiological hypoxia in conjunction with retroviral transduction of Oct4, Sox2, Klf4, and L-Myc. Under optimized conditions, we observed human embryonic stem (ES)-like cells as early as 6 days after the initial retroviral transduction. This was followed by the emergence of fully reprogrammed cells bearing Tra-1-81-positive and DsRed transgene-silencing properties on day 10. The resulting cell lines resembled human ES cells in many respects including proliferation rate, morphology, pluripotency-associated markers, global gene expression patterns, genome-wide DNA methylation states, and the ability to differentiate into all three of the germ layers, both in vitro and in vivo. Our method, when combined with chemical inhibitors under conditions of physiological hypoxia, offers a powerful tool for rapidly generating bona fide human iPS cells and facilitates the application of i

  4. Human Stem Cell Derived Cardiomyocytes: An Alternative Model to Evaluate Environmental Chemical Cardiac Safety and Development of Predictive Adverse Outcome Pathways

    Science.gov (United States)

    Chemical spills and associated deaths in the US has increased 2.6-fold and 16-fold from 1983 to 2012, respectfully. In addition, the number of chemicals to which humans are exposed to in the environment has increased almost 10-fold from 2001 to 2013 within the US. Internationally...

  5. Chemical disinfection of non-porous inanimate surfaces experimentally contaminated with four human pathogenic viruses.

    OpenAIRE

    Sattar, S. A.; Springthorpe, V. S.; Karim, Y.; Loro, P.

    1989-01-01

    The chemical disinfection of virus-contaminated non-porous inanimate surfaces was investigated using coxsackievirus B3, adenovirus type 5, parainfluenza virus type 3 and coronavirus 229E as representatives of important nosocomial viral pathogens. A 10 microliter amount of the test virus, suspended in either faeces or mucin, was placed onto each stainless steel disk (about 1 cm in diameter) and the inoculum allowed to dry for 1 h under ambient conditions. Sixteen disinfectant formulations were...

  6. Chemical composition and antibacterial activity of essential oils against human pathogenic bacteria

    OpenAIRE

    Sokovic, M.; Marin, P.D.; Brkic, D.; Griensven, van, L.J.L.D.

    2008-01-01

    The chemical composition and antibacterial activity of essential oils from 10 aromatic plants Matricaria chamommilla, Mentha piperita, M. spicata, Lavandula angustifolia, Ocimum basilicum, Thymus vulgaris, Origanum vulgare, Salvia officinalis, Citrus limon and C. aurantium have been determined. Antibacterial activity of these oils and their components; i.e. linalyl acetate, linalool, limonene, pinene, ß-pinene, 1,8-cineole, camphor, carvacrol, thymol and menthol were assayed against a variety...

  7. Nature's chemical signatures in human olfaction: a foodborne perspective for future biotechnology.

    Science.gov (United States)

    Dunkel, Andreas; Steinhaus, Martin; Kotthoff, Matthias; Nowak, Bettina; Krautwurst, Dietmar; Schieberle, Peter; Hofmann, Thomas

    2014-07-07

    The biocatalytic production of flavor naturals that determine chemosensory percepts of foods and beverages is an ever challenging target for academic and industrial research. Advances in chemical trace analysis and post-genomic progress at the chemistry-biology interface revealed odor qualities of nature's chemosensory entities to be defined by odorant-induced olfactory receptor activity patterns. Beyond traditional views, this review and meta-analysis now shows characteristic ratios of only about 3 to 40 genuine key odorants for each food, from a group of about 230 out of circa 10 000 food volatiles. This suggests the foodborn stimulus space has co-evolved with, and roughly match our circa 400 olfactory receptors as best natural agonists. This perspective gives insight into nature's chemical signatures of smell, provides the chemical odor codes of more than 220 food samples, and beyond addresses industrial implications for producing recombinants that fully reconstruct the natural odor signatures for use in flavors and fragrances, fully immersive interactive virtual environments, or humanoid bioelectronic noses. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Approaches to advancing quantitative human health risk assessment of environmental chemicals in the post-genomic era.

    Science.gov (United States)

    Chiu, Weihsueh A; Euling, Susan Y; Scott, Cheryl Siegel; Subramaniam, Ravi P

    2013-09-15

    The contribution of genomics and associated technologies to human health risk assessment for environmental chemicals has focused largely on elucidating mechanisms of toxicity, as discussed in other articles in this issue. However, there is interest in moving beyond hazard characterization to making more direct impacts on quantitative risk assessment (QRA)--i.e., the determination of toxicity values for setting exposure standards and cleanup values. We propose that the evolution of QRA of environmental chemicals in the post-genomic era will involve three, somewhat overlapping phases in which different types of approaches begin to mature. The initial focus (in Phase I) has been and continues to be on "augmentation" of weight of evidence--using genomic and related technologies qualitatively to increase the confidence in and scientific basis of the results of QRA. Efforts aimed towards "integration" of these data with traditional animal-based approaches, in particular quantitative predictors, or surrogates, for the in vivo toxicity data to which they have been anchored are just beginning to be explored now (in Phase II). In parallel, there is a recognized need for "expansion" of the use of established biomarkers of susceptibility or risk of human diseases and disorders for QRA, particularly for addressing the issues of cumulative assessment and population risk. Ultimately (in Phase III), substantial further advances could be realized by the development of novel molecular and pathway-based biomarkers and statistical and in silico models that build on anticipated progress in understanding the pathways of human diseases and disorders. Such efforts would facilitate a gradual "reorientation" of QRA towards approaches that more directly link environmental exposures to human outcomes. Published by Elsevier Inc.

  9. Approaches to advancing quantitative human health risk assessment of environmental chemicals in the post-genomic era

    Energy Technology Data Exchange (ETDEWEB)

    Chiu, Weihsueh A., E-mail: chiu.weihsueh@epa.gov [National Center for Environmental Assessment, U.S. Environmental Protection Agency, Washington DC, 20460 (United States); Euling, Susan Y.; Scott, Cheryl Siegel; Subramaniam, Ravi P. [National Center for Environmental Assessment, U.S. Environmental Protection Agency, Washington DC, 20460 (United States)

    2013-09-15

    The contribution of genomics and associated technologies to human health risk assessment for environmental chemicals has focused largely on elucidating mechanisms of toxicity, as discussed in other articles in this issue. However, there is interest in moving beyond hazard characterization to making more direct impacts on quantitative risk assessment (QRA) — i.e., the determination of toxicity values for setting exposure standards and cleanup values. We propose that the evolution of QRA of environmental chemicals in the post-genomic era will involve three, somewhat overlapping phases in which different types of approaches begin to mature. The initial focus (in Phase I) has been and continues to be on “augmentation” of weight of evidence — using genomic and related technologies qualitatively to increase the confidence in and scientific basis of the results of QRA. Efforts aimed towards “integration” of these data with traditional animal-based approaches, in particular quantitative predictors, or surrogates, for the in vivo toxicity data to which they have been anchored are just beginning to be explored now (in Phase II). In parallel, there is a recognized need for “expansion” of the use of established biomarkers of susceptibility or risk of human diseases and disorders for QRA, particularly for addressing the issues of cumulative assessment and population risk. Ultimately (in Phase III), substantial further advances could be realized by the development of novel molecular and pathway-based biomarkers and statistical and in silico models that build on anticipated progress in understanding the pathways of human diseases and disorders. Such efforts would facilitate a gradual “reorientation” of QRA towards approaches that more directly link environmental exposures to human outcomes.

  10. Approaches to advancing quantitative human health risk assessment of environmental chemicals in the post-genomic era

    International Nuclear Information System (INIS)

    Chiu, Weihsueh A.; Euling, Susan Y.; Scott, Cheryl Siegel; Subramaniam, Ravi P.

    2013-01-01

    The contribution of genomics and associated technologies to human health risk assessment for environmental chemicals has focused largely on elucidating mechanisms of toxicity, as discussed in other articles in this issue. However, there is interest in moving beyond hazard characterization to making more direct impacts on quantitative risk assessment (QRA) — i.e., the determination of toxicity values for setting exposure standards and cleanup values. We propose that the evolution of QRA of environmental chemicals in the post-genomic era will involve three, somewhat overlapping phases in which different types of approaches begin to mature. The initial focus (in Phase I) has been and continues to be on “augmentation” of weight of evidence — using genomic and related technologies qualitatively to increase the confidence in and scientific basis of the results of QRA. Efforts aimed towards “integration” of these data with traditional animal-based approaches, in particular quantitative predictors, or surrogates, for the in vivo toxicity data to which they have been anchored are just beginning to be explored now (in Phase II). In parallel, there is a recognized need for “expansion” of the use of established biomarkers of susceptibility or risk of human diseases and disorders for QRA, particularly for addressing the issues of cumulative assessment and population risk. Ultimately (in Phase III), substantial further advances could be realized by the development of novel molecular and pathway-based biomarkers and statistical and in silico models that build on anticipated progress in understanding the pathways of human diseases and disorders. Such efforts would facilitate a gradual “reorientation” of QRA towards approaches that more directly link environmental exposures to human outcomes

  11. Life cycle risks for human health: a comparison of petroleum versus bio-based production of five bulk organic chemicals.

    Science.gov (United States)

    Roes, Alexander L; Patel, Martin K

    2007-10-01

    This article describes the development and application of a generic approach to the comparative assessment of risks related to the production of organic chemicals by petrochemical processes versus white biotechnology. White biotechnology, also referred to as industrial biotechnology, typically uses bio-based feedstocks instead of the fossil raw materials used in the petrochemical sector. The purpose of this study was to investigate whether the production of chemicals by means of white biotechnology has lower conventional risks than their production by petrochemical processes. Conventional risks are the risks of well-established processes, and not those related to genetically modified microorganisms and plants. Our approach combines classical risk assessment methods (largely based on toxicology), as developed by the life cycle assessment (LCA) community, with statistics on technological disasters, accidents, and work-related illnesses. Moreover, it covers the total process chain for both petrochemical and bio-based products from cradle to grave. The approach was applied to five products: the plastics polytrimethylene terephthalate (PTT), polyhydroxyalkanoates (PHA), polyethylene terephthalate (PET), polyethylene (PE), and ethanol. Our results show that the conventional risks related to the white biotechnology products studied are lower than those of the petrochemical products. However, considering the uncertainties with respect to the ranges of input data, the (incomplete) coverage of emissions by the environmental priority strategies (EPS) 2000 method, and the uncertainties of the assumptions made in this study (i.e., large to very large), the differences in results between bio-based and petrochemical products fall into the uncertainty range. Because of this, future research is necessary to decrease the uncertainties before we can conclude that the conventional risks of biotechnologically produced chemicals are lower than those of fossil-fuel-derived chemicals.

  12. Resveratrol ameliorates the chemical and microbial induction of inflammation and insulin resistance in human placenta, adipose tissue and skeletal muscle.

    Science.gov (United States)

    Tran, Ha T; Liong, Stella; Lim, Ratana; Barker, Gillian; Lappas, Martha

    2017-01-01

    Gestational diabetes mellitus (GDM), which complicates up to 20% of all pregnancies, is associated with low-grade maternal inflammation and peripheral insulin resistance. Sterile inflammation and infection are key mediators of this inflammation and peripheral insulin resistance. Resveratrol, a stilbene-type phytophenol, has been implicated to exert beneficial properties including potent anti-inflammatory and antidiabetic effects in non-pregnant humans and experimental animal models of GDM. However, studies showing the effects of resveratrol on inflammation and insulin resistance associated with GDM in human tissues have been limited. In this study, human placenta, adipose (omental and subcutaneous) tissue and skeletal muscle were stimulated with pro-inflammatory cytokines TNF-α and IL-1β, the bacterial product lipopolysaccharide (LPS) and the synthetic viral dsRNA analogue polyinosinic:polycytidylic acid (poly(I:C)) to induce a GDM-like model. Treatment with resveratrol significantly reduced the expression and secretion of pro-inflammatory cytokines IL-6, IL-1α, IL-1β and pro-inflammatory chemokines IL-8 and MCP-1 in human placenta and omental and subcutaneous adipose tissue. Resveratrol also significantly restored the defects in the insulin signalling pathway and glucose uptake induced by TNF-α, LPS and poly(I:C). Collectively, these findings suggest that resveratrol reduces inflammation and insulin resistance induced by chemical and microbial products. Resveratrol may be a useful preventative therapeutic for pregnancies complicated by inflammation and insulin resistance, like GDM.

  13. The surface chemical reactivity of particles and its impact on human health

    Science.gov (United States)

    Setyan, A.; Sauvain, J. J.; Riediker, M.; Guillemin, M.; Rossi, M. J.

    2017-12-01

    The chemical composition of the particle-air interface is the gateway to chemical reactions of gases with condensed phase particles. It is of prime importance to understand the reactivity of particles and their interaction with surrounding gases, biological membranes, and solid supports. We used a Knudsen flow reactor to quantify functional groups on the surface of a few selected particle types. This technique is based on a heterogeneous titration reaction between a probe gas and a specific functional group on the particle surface. Six probe gases have been selected for the identification and quantification of important functional groups: N(CH3)3 for the titration of acidic sites, NH2OH for the detection of carbonyl functions (aldehydes and ketones) and/or oxidized sites owing to its strong reducing properties, CF3COOH and HCl for basic sites of different strength, O3 and NO2 for oxidizable groups. We also studied the kinetics of the reactions between particles and probe gases (uptake coefficient γ0). We tested the surface chemical composition and oxidation states of laboratory-generated aerosols (3 amorphous carbons, 2 flame soots, 2 Diesel particles, 2 secondary organic aerosols [SOA], 4 multiwall carbon nanotubes [MWCNT], 3 TiO2, and 2 metal salts) and of aerosols sampled in several bus depots. The sampling of particles in the bus depots was accompanied by the collection of urine samples of mechanics working full-time in these bus depots, and the quantification of 8-hydroxy-2'-deoxyguanosine, a biomarker of oxidative stress. The increase in oxidative stress biomarker levels over a working day was correlated (pcellular antioxidants.

  14. Modelling the acid/base 1H NMR chemical shift limits of metabolites in human urine.

    Science.gov (United States)

    Tredwell, Gregory D; Bundy, Jacob G; De Iorio, Maria; Ebbels, Timothy M D

    2016-01-01

    Despite the use of buffering agents the 1 H NMR spectra of biofluid samples in metabolic profiling investigations typically suffer from extensive peak frequency shifting between spectra. These chemical shift changes are mainly due to differences in pH and divalent metal ion concentrations between the samples. This frequency shifting results in a correspondence problem: it can be hard to register the same peak as belonging to the same molecule across multiple samples. The problem is especially acute for urine, which can have a wide range of ionic concentrations between different samples. To investigate the acid, base and metal ion dependent 1 H NMR chemical shift variations and limits of the main metabolites in a complex biological mixture. Urine samples from five different individuals were collected and pooled, and pre-treated with Chelex-100 ion exchange resin. Urine samples were either treated with either HCl or NaOH, or were supplemented with various concentrations of CaCl 2 , MgCl 2 , NaCl or KCl, and their 1 H NMR spectra were acquired. Nonlinear fitting was used to derive acid dissociation constants and acid and base chemical shift limits for peaks from 33 identified metabolites. Peak pH titration curves for a further 65 unidentified peaks were also obtained for future reference. Furthermore, the peak variations induced by the main metal ions present in urine, Na + , K + , Ca 2+ and Mg 2+ , were also measured. These data will be a valuable resource for 1 H NMR metabolite profiling experiments and for the development of automated metabolite alignment and identification algorithms for 1 H NMR spectra.

  15. Chemical Carcinogen (Hydrazine et al.) Induced Carcinogenesis of Human Diploid Cells in Vitro

    Science.gov (United States)

    1982-09-07

    untreated cell popula- pared from the stock solutions in complete growth tions were seeded onto CES in vitro. The CES medium (CIM). Thee solutions were added...time from induction pared to metastases IFig. IBl. We want to imply to neoplasia of 6 to 10 wk instead of 1 to 1.5 yr. that these chemical carcinogen...This definition was used because the pathologist was ds:b celular invasion Into CE,, an organ culture, In vitro. Thw two Interpretations am not

  16. Chemical form of selenium affects its uptake, transport, and glutathione peroxidase activity in the human intestinal Caco-2 cell model.

    Science.gov (United States)

    Zeng, Huawei; Jackson, Matthew I; Cheng, Wen-Hsing; Combs, Gerald F

    2011-11-01

    Determining the effect of selenium (Se) chemical form on uptake, transport, and glutathione peroxidase activity in human intestinal cells is critical to assess Se bioavailability at nutritional doses. In this study, we found that two sources of L-selenomethionine (SeMet) and Se-enriched yeast each increased intracellular Se content more effectively than selenite or methylselenocysteine (SeMSC) in the human intestinal Caco-2 cell model. Interestingly, SeMSC, SeMet, and digested Se-enriched yeast were transported at comparable efficacy from the apical to basolateral sides, each being about 3-fold that of selenite. In addition, these forms of Se, whether before or after traversing from apical side to basolateral side, did not change the potential to support glutathione peroxidase (GPx) activity. Although selenoprotein P has been postulated to be a key Se transport protein, its intracellular expression did not differ when selenite, SeMSC, SeMet, or digested Se-enriched yeast was added to serum-contained media. Taken together, our data show, for the first time, that the chemical form of Se at nutritional doses can affect the absorptive (apical to basolateral side) efficacy and retention of Se by intestinal cells; but that, these effects are not directly correlated to the potential to support GPx activity.

  17. Human Error Analysis in a Permit to Work System: A Case Study in a Chemical Plant

    Directory of Open Access Journals (Sweden)

    Mehdi Jahangiri

    2016-03-01

    Conclusion: The SPAR-H method applied in this study could analyze and quantify the potential human errors and extract the required measures for reducing the error probabilities in PTW system. Some suggestions to reduce the likelihood of errors, especially in the field of modifying the performance shaping factors and dependencies among tasks are provided.

  18. CHEMICAL MARKERS OF HUMAN WASTE CONTAMINATION: ANALYSIS OF UROBILIN AND PHARMACEUTICALS IN SOURCE WATERS

    Science.gov (United States)

    Giving public water authorities another tool to monitor and measure levels of human waste contamination of waters simply and rapidly would enhance public protection. Most of the methods used today detect such contamination by quantifying microbes occurring in feces in high enough...

  19. The physico-chemical, antigenic, and functional heterogeneity of human serum amyloid A

    International Nuclear Information System (INIS)

    Martin, M.E.; HUq, A.; Rosenthal, C.J.

    1986-01-01

    In the present study we attempted to develop a rapid method to isolate serum amyloid A isomers (SAA is.) and to determine whether this physicochemical heterogeneity corresponds to an antigenic and functional one. Pure human low molecular SAA (SAAL) was prepared from the serum of 6 patients (pts.) using standard techniques. Preparative isoelectric focusing in agarose/sephadex gels was used to separate SAAL is. Monoclonal antibodies (m. abs.) to SAAL and to AA were prepared by hybridization of P3XU-1 nonsecretory murine myeloma cells with murine spleen cells from Balb/c mice immunized with pooled SAAL and AA respectively. Four distinctly migrating SAAL isomers with PI's of 4.9, 5.8, 6.6, and 7.2 were isolated from 6 pts. while only three isomers were separated from the pt. with myasthenia gravis. Four m. abs. to SAAL, one to AA, six m. abs. to SAAL-2 is. and one to SAAL-1 is. were generated in murine ascitic fluid. Dishes coated with the four human SAA is., human AA, various mammalian and human proteins as well as with serum from 31 pts. with metastatic Ca. and 23 pts. with inflammatory diseases (ID) were reacted with the m. abs. The amount of binding was determined using 125 I labelled goat antimouse serum. The m. abs. to SAA were found specific for human SAA recognizing two different patterns in relationship to the intensity of binding to SAA is. One of them (7A2-43) had a greater affinity for SAA from pts with ID, while the other (5A6-5) reacted stronger with SAA from pts with metastatic Ca

  20. Recombinant human albumin supports single cell cloning of CHO cells in chemically defined media.

    Science.gov (United States)

    Zhu, Jiang; Wooh, Jong Wei; Hou, Jeff Jia Cheng; Hughes, Benjamin S; Gray, Peter P; Munro, Trent P

    2012-01-01

    Biologic drugs, such as monoclonal antibodies, are commonly made using mammalian cells in culture. The cell lines used for manufacturing should ideally be clonal, meaning derived from a single cell, which represents a technically challenging process. Fetal bovine serum is often used to support low cell density cultures, however, from a regulatory perspective, it is preferable to avoid animal-derived components to increase process consistency and reduce the risk of contamination from adventitious agents. Chinese hamster ovary (CHO) cells are the most widely used cell line in industry and a large number of serum-free, protein-free, and fully chemically defined growth media are commercially available, although these media alone do not readily support efficient single cell cloning. In this work, we have developed a simple, fully defined, single-cell cloning media, specifically for CHO cells, using commercially available reagents. Our results show that a 1:1 mixture of CD-CHO™ and DMEM/F12 supplemented with 1.5 g/L of recombinant albumin (Albucult®) supports single cell cloning. This formulation can support recovery of single cells in 43% of cultures compared to 62% in the presence of serum. Copyright © 2012 American Institute of Chemical Engineers (AIChE).

  1. The Role of Molecular Biology in the Biomonitoring of Human Exposure to Chemicals

    Directory of Open Access Journals (Sweden)

    Balam Muñoz

    2010-11-01

    Full Text Available Exposure to different substances in an occupational environment is of utmost concern to global agencies such as the World Health Organization and the International Labour Organization. Interest in improving work health conditions, particularly of those employees exposed to noxious chemicals, has increased considerably and has stimulated the search for new, more specific and selective tests. Recently, the field of molecular biology has been indicated as an alternative technique for monitoring personnel while evaluating work-related pathologies. Originally, occupational exposure to environmental toxicants was assessed using biochemical techniques to determine the presence of higher concentrations of toxic compounds in blood, urine, or other fluids or tissues; results were used to evaluate potential health risk. However, this approach only estimates the presence of a noxious chemical and its effects, but does not prevent or diminish the risk. Molecular biology methods have become very useful in occupational medicine to provide more accurate and opportune diagnostics. In this review, we discuss the role of the following common techniques: (1 Use of cell cultures; (2 evaluation of gene expression; (3 the “omic” sciences (genomics, transcriptomics, proteomics and metabolomics and (4 bioinformatics. We suggest that molecular biology has many applications in occupational health where the data can be applied to general environmental conditions.

  2. Modified clay minerals efficiency against chemical and biological warfare agents for civil human protection.

    Science.gov (United States)

    Plachá, Daniela; Rosenbergová, Kateřina; Slabotínský, Jiří; Kutláková, Kateřina Mamulová; Studentová, Soňa; Martynková, Gražyna Simha

    2014-04-30

    Sorption efficiencies of modified montmorillonite and vermiculite of their mono ionic Na and organic HDTMA and HDP forms were studied against chemical and biological warfare agents such as yperite and selected bacterial strains. Yperite interactions with modified clay minerals were observed through its capture in low-density polyethylene foil-modified clay composites by measuring yperite gas permeation with using chemical indication and gas chromatography methods. The antibacterial activities of synthetized organoclays were tested against selected Gram-positive and Gram-negative bacterial species in minimum inhibitory concentration tests. The obtained results showed a positive influence of modified clay minerals on the significant yperite breakthrough-time increase. The most effective material was the polyethylene-Na form montmorillonite, while the polyethylene-Na form vermiculite showed the lowest efficiency. With increasing organic cations loading in the interlayer space the montmorillonite efficiency decreased, and in the case of vermiculite an opposite effect was observed. Generally the modified montmorillonites were more effective than modified vermiculites. The HDP cations seem to be more effective compare to the HDTMA. The antibacterial activity tests confirmed efficiency of all organically modified clay minerals against Gram-positive bacteria. The confirmation of antibacterial activity against Y. pestis, plague bacteria, is the most interesting result of this part of the study. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Applying quantitative metabolomics based on chemical isotope labeling LC-MS for detecting potential milk adulterant in human milk.

    Science.gov (United States)

    Mung, Dorothea; Li, Liang

    2018-02-25

    There is an increasing demand for donor human milk to feed infants for various reasons including that a mother may be unable to provide sufficient amounts of milk for their child or the milk is considered unsafe for the baby. Selling and buying human milk via the Internet has gained popularity. However, there is a risk of human milk sold containing other adulterants such as animal or plant milk. Analytical tools for rapid detection of adulterants in human milk are needed. We report a quantitative metabolomics method for detecting potential milk adulterants (soy, almond, cow, goat and infant formula milk) in human milk. It is based on the use of a high-performance chemical isotope labeling (CIL) LC-MS platform to profile the metabolome of an unknown milk sample, followed by multivariate or univariate comparison of the resultant metabolomic profile with that of human milk to determine the differences. Using dansylation LC-MS to profile the amine/phenol submetabolome, we could detect an average of 4129 ± 297 (n = 9) soy metabolites, 3080 ± 470 (n = 9) almond metabolites, 4256 ± 136 (n = 18) cow metabolites, 4318 ± 198 (n = 9) goat metabolites, 4444 ± 563 (n = 9) infant formula metabolites, and 4020 ± 375 (n = 30) human metabolites. This high level of coverage allowed us to readily differentiate the six different types of samples. From the analysis of binary mixtures of human milk containing 5, 10, 25, 50 and 75% other type of milk, we demonstrated that this method could be used to detect the presence of as low as 5% adulterant in human milk. We envisage that this method could be applied to detect contaminant or adulterant in other types of food or drinks. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Perfluorinated chemicals: Differential toxicity, inhibition of aromatase activity and alteration of cellular lipids in human placental cells

    Energy Technology Data Exchange (ETDEWEB)

    Gorrochategui, Eva; Pérez-Albaladejo, Elisabet [Department of Environmental Chemistry, IDAEA–CSIC, 08034 Barcelona, Catalonia (Spain); Casas, Josefina [Department of Biomedicinal Chemistry, IQAC–CSIC, 08034 Barcelona, Catalonia (Spain); Lacorte, Sílvia, E-mail: slbqam@cid.csic.es [Department of Environmental Chemistry, IDAEA–CSIC, 08034 Barcelona, Catalonia (Spain); Porte, Cinta, E-mail: cinta.porte@cid.csic.es [Department of Environmental Chemistry, IDAEA–CSIC, 08034 Barcelona, Catalonia (Spain)

    2014-06-01

    The cytotoxicity of eight perfluorinated chemicals (PFCs), namely, perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorododecanoic acid (PFDoA), perfluorobutanesulfonate (PFBS), perfluorohexanesulfonate (PFHxS) and perfluorooctanesulfonate (PFOS) was assessed in the human placental choriocarcinoma cell line JEG-3. Only the long chain PFCs – PFOS, PFDoA, PFNA, PFOA – showed significant cytotoxicity in JEG-3 cells with EC50 values in the range of 107 to 647 μM. The observed cytotoxicity was to some extent related to a higher uptake of the longer chain PFCs by cells (PFDoA > PFOS ≫ PFNA > PFOA > PFHxA). Moreover, this work evidences a high potential of PFOS, PFOA and PFBS to act as aromatase inhibitors in placental cells with IC50s in the range of 57–80 μM, the inhibitory effect of PFBS being particularly important despite the rather low uptake of the compound by cells. Finally, exposure of JEG-3 cells to a mixture of the eight PFCs (0.6 μM each) led to a relative increase (up to 3.4-fold) of several lipid classes, including phosphatidylcholines (PCs), plasmalogen PC and lyso plasmalogen PC, which suggests an interference of PFCs with membrane lipids. Overall, this work highlights the ability of the PFC mixture to alter cellular lipid pattern at concentrations well below those that generate toxicity, and the potential of the short chain PFBS, often considered a safe substitute of PFOS, to significantly inhibit aromatase activity in placental cells. - Highlights: • Eight perfluorinated chemicals of different chain lengths have been selected. • Long chain ones – PFOS, PFDoA, PFNA, PFOA – were cytotoxic in placenta cells. • The uptake of long chain perfluorinated chemicals by cells was comparatively higher. • PFOS, PFOA and the short chain PFBS significantly inhibited aromatase activity. • A mixture of perfluorinated chemicals significantly altered placenta cell

  5. An overview of human biomonitoring of environmental chemicals in the Canadian Health Measures Survey: 2007-2019.

    Science.gov (United States)

    Haines, Douglas A; Saravanabhavan, Gurusankar; Werry, Kate; Khoury, Cheryl

    2017-03-01

    Human biomonitoring (HBM) is used to indicate and quantify exposure by measuring environmental chemicals, their metabolites or reaction products in biological specimens. The biomonitoring component of the Canadian Health Measures Survey (CHMS) is the most comprehensive initiative providing general population HBM data in Canada. The CHMS is an ongoing cross-sectional direct measures survey implemented in 2-year cycles. It provides nationally-representative data on health, nutritional status, environmental exposures, and related risks and protective characteristics. The survey follows a robust planning, design and sampling protocol as well as a comprehensive quality assurance and quality control regime implemented for all aspect of the survey to ensure the validity of the HBM results. HBM blood and urine data are available for CHMS cycles 1 (2007-2009), 2 (2009-2011) and 3 (2012-2013). Field collection has been completed for cycle 4 (2014-2015), with cycle 5 (2016-2017) in progress and cycle 6 planning (2018-2019) being finalized. Biomonitoring results for 279 chemicals are expected over the six cycles of the CHMS (220 in individual blood, urine or hair samples, and 59 in pooled serum samples). The chemicals include metals and trace elements, polychlorinated biphenyls (PCBs), organochlorines, flame retardants, perfluoroalkyl substances, volatile organic compounds (VOCs) and metabolites, environmental phenols, triclocarban, acrylamide, pesticides (e.g., triazines, carbamates, organophosphates, phenoxy, pyrethroids) and/or their metabolites, chlorophenols, polycyclic aromatic hydrocarbon (PAH) metabolites, phthalates and alternate plasticizer metabolites, and tobacco biomarkers. Approximately one half of the chemicals measured in individual blood and urine samples over the first three cycles were detected in more than 60% of samples. CHMS biomonitoring data have been used to establish baseline HBM concentrations in Canadians; inform public health, regulatory risk

  6. Perfluorinated chemicals: Differential toxicity, inhibition of aromatase activity and alteration of cellular lipids in human placental cells

    International Nuclear Information System (INIS)

    Gorrochategui, Eva; Pérez-Albaladejo, Elisabet; Casas, Josefina; Lacorte, Sílvia; Porte, Cinta

    2014-01-01

    The cytotoxicity of eight perfluorinated chemicals (PFCs), namely, perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorododecanoic acid (PFDoA), perfluorobutanesulfonate (PFBS), perfluorohexanesulfonate (PFHxS) and perfluorooctanesulfonate (PFOS) was assessed in the human placental choriocarcinoma cell line JEG-3. Only the long chain PFCs – PFOS, PFDoA, PFNA, PFOA – showed significant cytotoxicity in JEG-3 cells with EC50 values in the range of 107 to 647 μM. The observed cytotoxicity was to some extent related to a higher uptake of the longer chain PFCs by cells (PFDoA > PFOS ≫ PFNA > PFOA > PFHxA). Moreover, this work evidences a high potential of PFOS, PFOA and PFBS to act as aromatase inhibitors in placental cells with IC50s in the range of 57–80 μM, the inhibitory effect of PFBS being particularly important despite the rather low uptake of the compound by cells. Finally, exposure of JEG-3 cells to a mixture of the eight PFCs (0.6 μM each) led to a relative increase (up to 3.4-fold) of several lipid classes, including phosphatidylcholines (PCs), plasmalogen PC and lyso plasmalogen PC, which suggests an interference of PFCs with membrane lipids. Overall, this work highlights the ability of the PFC mixture to alter cellular lipid pattern at concentrations well below those that generate toxicity, and the potential of the short chain PFBS, often considered a safe substitute of PFOS, to significantly inhibit aromatase activity in placental cells. - Highlights: • Eight perfluorinated chemicals of different chain lengths have been selected. • Long chain ones – PFOS, PFDoA, PFNA, PFOA – were cytotoxic in placenta cells. • The uptake of long chain perfluorinated chemicals by cells was comparatively higher. • PFOS, PFOA and the short chain PFBS significantly inhibited aromatase activity. • A mixture of perfluorinated chemicals significantly altered placenta cell

  7. Cellular uptake and cytotoxic potential of respirable bentonite particles with different quartz contents and chemical modifications in human lung fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Geh, Stefan; Rettenmeier, Albert W.; Dopp, Elke [University Hospital, Institute of Hygiene and Occupational Medicine, Essen (Germany); Yuecel, Raif [University Hospital, Institute of Cell Biology (Cancer Research), Essen (Germany); Duffin, Rodger [Institute of Environmental Health Research (IUF), Duesseldorf (Germany); University of Edinburgh, ELEGI COLT Lab, Scotland (United Kingdom); Albrecht, Catrin; Borm, Paul J.A. [Institute of Environmental Health Research (IUF), Duesseldorf (Germany); Armbruster, Lorenz [Verein fuer Technische Sicherheit und Umweltschutz e.V., Gotha (Germany); Raulf-Heimsoth, Monika; Bruening, Thomas [Research Institute for Occupational Medicine of the Institutions for Statutory Accident Insurance and Prevention (BGFA), Bochum (Germany); Hoffmann, Eik [University of Rostock, Institute of Biology, Department of Cell Biology and Biosystems Technology, Rostock (Germany)

    2006-02-01

    Considering the biological reactivity of pure quartz in lung cells, there is a strong interest to clarify the cellular effects of respirable siliceous dusts, like bentonites. In the present study, we investigated the cellular uptake and the cytotoxic potential of bentonite particles (Oe< 10 {mu}m) with an {alpha}-quartz content of up to 6% and different chemical modifications (activation: alkaline, acidic, organic) in human lung fibroblasts (IMR90). Additionally, the ability of the particles to induce apoptosis in IMR90-cells and the hemolytic activity was tested. All bentonite samples were tested for endotoxins with the in vitro-Pyrogen test and were found to be negative. Cellular uptake of particles by IMR90-cells was studied by transmission electron microscopy (TEM). Cytotoxicity was analyzed in IMR90-cells by determination of viable cells using flow cytometry and by measuring of the cell respiratory activity. Induced apoptotic cells were detected by AnnexinV/Propidiumiodide-staining and gel electrophoresis. Our results demonstrate that activated bentonite particles are better taken up by IMR90-cells than untreated (native) bentonite particles. Also, activated bentonite particles with a quartz content of 5-6% were more cytotoxic than untreated bentonites or bentonites with a quartz content lower than 4%. The bentonite samples induced necrotic as well as apoptotic cell death. In general, bentonites showed a high membrane-damaging potential shown as hemolytic activity in human erythrocytes. We conclude that cellular effects of bentonite particles in human lung cells are enhanced after chemical treatment of the particles. The cytotoxic potential of the different bentonites is primarily characterized by a strong lysis of the cell membrane. (orig.)

  8. Site-specific chemical conjugation of human Fas ligand extracellular domain using trans-cyclooctene - methyltetrazine reactions.

    Science.gov (United States)

    Muraki, Michiro; Hirota, Kiyonori

    2017-07-03

    Fas ligand plays a key role in the human immune system as a major cell death inducing protein. The extracellular domain of human Fas ligand (hFasLECD) triggers apoptosis of malignant cells, and therefore is expected to have substantial potentials in medical biotechnology. However, the current application of this protein to clinical medicine is hampered by a shortage of the benefits relative to the drawbacks including the side-effects in systemic administration. Effective procedures for the engineering of the protein by attaching useful additional functions are required to overcome the problem. A procedure for the site-specific chemical conjugation of hFasLECD with a fluorochrome and functional proteins was devised using an inverse-electron-demand Diels-Alder reaction between trans-cyclooctene group and methyltetrazine group. The conjugations in the present study were attained by using much less molar excess amounts of the compounds to be attached as compared with the conventional chemical modification reactions using maleimide derivatives in the previous study. The isolated conjugates of hFasLECD with sulfo-Cy3, avidin and rabbit IgG Fab' domain presented the functional and the structural integrities of the attached molecules without impairing the specific binding activity toward human Fas receptor extracellular domain. The present study provided a new fundamental strategy for the production of the engineered hFasLECDs with additional beneficial functions, which will lead to the developments of the improved diagnostic systems and the effective treatment methods of serious diseases by using this protein as a component of novel molecular tools.

  9. Chemical Carcinogen-Induced Changes in tRNA Metabolism in Human Cells.

    Science.gov (United States)

    1981-11-01

    the resolution and quantitation of modified ucleosides in the urine of cancer patients would not be particularly useful for the cell culture studies...Comparison of nucleic acid catabolism by normal human fibroblasts and fibroblasts transformed with methylazoxymethyl alcohol ( MAMA ),an activated...catabolite in long-term, pulse-chase experiments. However, the kinetics of catabolism differed, in that only the MAMA -transformed cells had generated

  10. The study of chemical forms of mercury in human hair and other bio-environmental samples

    International Nuclear Information System (INIS)

    Kratzer, K.; Benes, P.

    1995-01-01

    The results of the continued studies on methods of analysis for forms of mercury in hair, and of the distribution of mercury among inorganic and organic forms in human hair are described. A new method for determining methylmercury has been developed, based on the selective leaching of methylmercury from hair using 2M hydrochioric acid. This method was used, in combination with the determination of mercury by atomic absorption spectrometry, for the analysis of mercury forms in three samples of human hair and two samples of fish homogenate. Good reproducibility of parallel determinations was obtained. The results were compared with literature data for the samples, or with the results of the analysis of the same samples by extraction method described earlier. Good agreement was also found between these methods. Further experiments were concerned with the study of the effect of radiation sterilization on the forms of mercury in hair, of the speciation of 203 Hg formed by irradiation of hair in nuclear reactor and with the labelling of a large batch of human hair with methylmercury. (author)

  11. Chemicals identified in human biological media: a data base. Third annual report, October 1981

    Energy Technology Data Exchange (ETDEWEB)

    Cone, M.V.; Baldauf, M.F.; Martin, F.M. (comps.)

    1981-12-01

    Part 2 contains the data base in tabular format. There are two sections, the first with records on nondrug substances, and the second with records on drugs. Chemicals in each section are arranged alphabetically by CAS preferred name, CAS registry number, formula, atomic weight, melting point, boiling point, and vapor pressure. Tissues are listed alphabetically with exposure route, analytical method, number of cases, range, and mean - when available in the source document. A variety of information may also be included that is pertinent to the range and mean as well as experimental design, demography, health effects, pathology, morphology, and toxicity. Review articles are included in the data base; however, no data have been extracted from such documents because the original research articles are included.

  12. The effects of chemical and radioactive properties of Tl-201 on human erythrocyte glucose 6-phosphate dehydrogenase activity

    International Nuclear Information System (INIS)

    Sahin, Ali; Senturk, Murat; Ciftci, Mehmet; Varoglu, Erhan; Kufrevioglu, Omer Irfan

    2010-01-01

    Aim: The inhibitory effects of thallium-201 ( 201 Tl) solution on human erythrocyte glucose 6-phosphate dehydrogenase (G6PD) activity were investigated. Methods: For this purpose, erythrocyte G6PD was initially purified 835-fold at a yield of 41.7% using 2',5'-Adenosine diphosphate sepharose 4B affinity gel chromatography. The purification was monitored by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, which showed a single band for the final enzyme preparation. The in vitro and in vivo effects of the 201 Tl solution including Tl + , Fe +3 and Cu +2 metals and the in vitro effects of the radiation effect of the 201 Tl solution and non-radioactive Tl + , Fe +3 and Cu +2 metals on human erythrocyte G6PD enzyme were studied. Enzyme activity was determined with the Beutler method at 340 nm using a spectrophotometer. All purification procedures were carried out at +4 deg. C. Results: 201 Tl solution and radiation exposure had inhibitory effects on the enzyme activity. IC 50 value of 201 Tl solution was 36.86 μl ([Tl + ]: 0.0036 μM, [Cu +2 ]: 0.0116 μM, [Fe +3 ]: 0.0132 μM), of human erythrocytes G6PD. Seven human patients were also used for in vivo studies of 201 Tl solution. Furthermore, non-radioactive Tl + , Fe +3 and Cu +2 were found not to have influenced the enzyme in vitro. Conclusion: Human erythrocyte G6PD activity was inhibited by exposure for up to 10 minutes to 0.057 mCi/kg 201 Tl solution. It was detected in in vitro and in vivo studies that the human erythrocyte G6PD enzyme is inhibited due to the radiation effect of 201 Tl solution.

  13. A comparison of pet and purpose-bred research dog (Canis familiaris) performance on human-guided object-choice tasks.

    Science.gov (United States)

    Lazarowski, Lucia; Dorman, David C

    2015-01-01

    Several studies have shown that domestic dogs respond to human social cues such as pointing. Some experiments have shown that pet dogs outperformed wolves in following a momentary distal point. These findings have lent support to the hypothesis that domestication is responsible for domestic dogs' ability to utilize human gestures. Other studies demonstrating comparable performance in human-socialized wolves suggest this skill depends on experience with relevant human stimuli. However, domestic dogs lacking thorough exposure to humans are underrepresented in the comparative literature. The goal of this study was to evaluate pet and kennel-reared research domestic dogs on their ability to follow two types of point in an object-choice task. This study used young adult, intact male research dogs (n=11) and a comparison group of pet dogs living in human homes (n=9). We found that while pet dogs followed the momentary distal point above chance levels, research dogs did not. Both groups followed the simpler dynamic proximal point; however, pet dogs outperformed research dogs on this task. Our results indicate that ontogenetic experiences may influence a domestic dog's ability to use human gestures, highlighting the importance of testing different sub-populations of domestic dogs. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Development of high-performance chemical isotope labeling LC-MS for profiling the human fecal metabolome.

    Science.gov (United States)

    Xu, Wei; Chen, Deying; Wang, Nan; Zhang, Ting; Zhou, Ruokun; Huan, Tao; Lu, Yingfeng; Su, Xiaoling; Xie, Qing; Li, Liang; Li, Lanjuan

    2015-01-20

    Human fecal samples contain endogenous human metabolites, gut microbiota metabolites, and other compounds. Profiling the fecal metabolome can produce metabolic information that may be used not only for disease biomarker discovery, but also for providing an insight about the relationship of the gut microbiome and human health. In this work, we report a chemical isotope labeling liquid chromatography-mass spectrometry (LC-MS) method for comprehensive and quantitative analysis of the amine- and phenol-containing metabolites in fecal samples. Differential (13)C2/(12)C2-dansyl labeling of the amines and phenols was used to improve LC separation efficiency and MS detection sensitivity. Water, methanol, and acetonitrile were examined as an extraction solvent, and a sequential water-acetonitrile extraction method was found to be optimal. A step-gradient LC-UV setup and a fast LC-MS method were evaluated for measuring the total concentration of dansyl labeled metabolites that could be used for normalizing the sample amounts of individual samples for quantitative metabolomics. Knowing the total concentration was also useful for optimizing the sample injection amount into LC-MS to maximize the number of metabolites detectable while avoiding sample overloading. For the first time, dansylation isotope labeling LC-MS was performed in a simple time-of-flight mass spectrometer, instead of high-end equipment, demonstrating the feasibility of using a low-cost instrument for chemical isotope labeling metabolomics. The developed method was applied for profiling the amine/phenol submetabolome of fecal samples collected from three families. An average of 1785 peak pairs or putative metabolites were found from a 30 min LC-MS run. From 243 LC-MS runs of all the fecal samples, a total of 6200 peak pairs were detected. Among them, 67 could be positively identified based on the mass and retention time match to a dansyl standard library, while 581 and 3197 peak pairs could be putatively

  15. Effects of the Endocrine-Disrupting Chemical DDT on Self-Renewal and Differentiation of Human Mesenchymal Stem Cells

    Science.gov (United States)

    Strong, Amy L.; Shi, Zhenzhen; Strong, Michael J.; Miller, David F.B.; Rusch, Douglas B.; Buechlein, Aaron M.; Flemington, Erik K.; McLachlan, John A.; Nephew, Kenneth P.

    2014-01-01

    Background: Although the global use of the endocrine-disrupting chemical DDT has decreased, its persistence in the environment has resulted in continued human exposure. Accumulating evidence suggests that DDT exposure has long-term adverse effects on development, yet the impact on growth and differentiation of adult stem cells remains unclear. Objectives: Human mesenchymal stem cells (MSCs) exposed to DDT were used to evaluate the impact on stem cell biology. Methods: We assessed DDT-treated MSCs for self-renewal, proliferation, and differentiation potential. Whole genome RNA sequencing was performed to assess gene expression in DDT-treated MSCs. Results: MSCs exposed to DDT formed fewer colonies, suggesting a reduction in self-renewal potential. DDT enhanced both adipogenic and osteogenic differentiation, which was confirmed by increased mRNA expression of glucose transporter type 4 (GLUT4), lipoprotein lipase (LpL), peroxisome proliferator-activated receptor gamma (PPARγ), leptin, osteonectin, core binding factor 1 (CBFA1), and FBJ murine osteosarcoma viral oncogene homolog (c-Fos). Expression of factors in DDT-treated cells was similar to that in estrogen-treated MSCs, suggesting that DDT may function via the estrogen receptor (ER)-mediated pathway. The coadministration of ICI 182,780 blocked the effects of DDT. RNA sequencing revealed 121 genes and noncoding RNAs to be differentially expressed in DDT-treated MSCs compared with controls cells. Conclusion: Human MSCs provide a powerful biological system to investigate and identify the molecular mechanisms underlying the effects of environmental agents on stem cells and human health. MSCs exposed to DDT demonstrated profound alterations in self-renewal, proliferation, differentiation, and gene expression, which may partially explain the homeostatic imbalance and increased cancer incidence among those exposed to long-term EDCs. Citation: Strong AL, Shi Z, Strong MJ, Miller DF, Rusch DB, Buechlein AM, Flemington EK

  16. Chemical Constituents of Mangifera indica and Their Antiausterity Activity against the PANC-1 Human Pancreatic Cancer Cell Line.

    Science.gov (United States)

    Nguyen, Hai Xuan; Do, Truong Nhat Van; Le, Tho Huu; Nguyen, Mai Thanh Thi; Nguyen, Nhan Trung; Esumi, Hiroyasu; Awale, Suresh

    2016-08-26

    Human pancreatic cancer cell lines such as PANC-1 have an altered metabolism, enabiling them to tolerate and survive under extreme conditions of nutrient starvation. The search for candidates that inhibit their viability during nutrition starvation represents a novel antiausterity strategy in anticancer drug discovery. A methanol extract of the bark of Mangifera indica was found to inhibit the survival of PANC-1 human pancreatic cancer cells preferentially under nutrient-deprived conditions with a PC50 value of 15.5 μg/mL, without apparent toxicity, in normal nutrient-rich conditions. Chemical investigation on this bioactive extract led to the isolation of 19 compounds (1-19), including two new cycloartane-type triterpenes, mangiferolate A (1) and mangiferolate B (2). The structures of 1 and 2 were determined by NMR spectroscopic analysis. Among the isolated compounds, mangiferolate B (2) and isoambolic acid (12) exhibited potent preferential cytotoxicity against PANC-1 human pancreatic cancer cells under the nutrition-deprived condition with PC50 values of 11.0 and 4.8 μM, respectively.

  17. Monte Carlo simulation of expert judgments on human errors in chemical analysis--a case study of ICP-MS.

    Science.gov (United States)

    Kuselman, Ilya; Pennecchi, Francesca; Epstein, Malka; Fajgelj, Ales; Ellison, Stephen L R

    2014-12-01

    Monte Carlo simulation of expert judgments on human errors in a chemical analysis was used for determination of distributions of the error quantification scores (scores of likelihood and severity, and scores of effectiveness of a laboratory quality system in prevention of the errors). The simulation was based on modeling of an expert behavior: confident, reasonably doubting and irresolute expert judgments were taken into account by means of different probability mass functions (pmfs). As a case study, 36 scenarios of human errors which may occur in elemental analysis of geological samples by ICP-MS were examined. Characteristics of the score distributions for three pmfs of an expert behavior were compared. Variability of the scores, as standard deviation of the simulated score values from the distribution mean, was used for assessment of the score robustness. A range of the score values, calculated directly from elicited data and simulated by a Monte Carlo method for different pmfs, was also discussed from the robustness point of view. It was shown that robustness of the scores, obtained in the case study, can be assessed as satisfactory for the quality risk management and improvement of a laboratory quality system against human errors. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Activation and amplification of c-Ki-ras in a chemically induced transplantable human pancreas carcinoma

    International Nuclear Information System (INIS)

    Parsa, I.; Maheshwari, K.K.

    1986-01-01

    Increasing evidence suggests that carcinogenesis is associated with the stepwise activation of oncogenes. The c-Ki-ras oncogene has been demonstrated in several human solid tumors and is shown to be amplified in tumor cell lines. The authors have probed endonuclease cleaved human pancreas (HP) DNAs and DNAs from an in vitro induced transplantable human pancreas carcinoma (HP-T1) for the presence and/or amplification of c-Ki-ras oncogene. The DNAs were cleaved with BamHI, BgIII, EcoRI, HhaI, HinfI, KpnI, PSTI, PvuII, SaII, SstI, TaqI or XbaI and were subjected to Southern blot analysis using 32 P-labelled EcoRI fragments from HiHi3 clone. The hybridization profiles were similar in both DNAs when digested with BamHI, BgIII, HinfI, KpnI, SaII, SstI, or TaqI. The EcoRI cleaved DNAs from HP and HP-T1 revealed two hybridizing fragments of 6.8 and 3.0 kbp. The 3.0 kbp fragments in DNA from HP-T1 showed more than a 100 folds enhancement as compared to that of HP. The 6.8 hybridizing fragments also appeared 10 fold greater in HP-T1 DNA. Similar enhancements were also present in HP-T1 DNA cleaved with PstI and PvuII. Preliminary results from comparison of poly(A) + RNAs, prepared from total HP and HP-T1 RNAs, by Northern blot analysis using the same probe reflect similar enhancement in RNA from transplantable pancreas carcinoma

  19. An Atmospheric Pressure Chemical Ionization MS/MS Assay Using Online Extraction for the Analysis of 11 Cannabinoids and Metabolites in Human Plasma and Urine.

    Science.gov (United States)

    Klawitter, Jelena; Sempio, Cristina; Mörlein, Sophie; De Bloois, Erik; Klepacki, Jacek; Henthorn, Thomas; Leehey, Maureen A; Hoffenberg, Edward J; Knupp, Kelly; Wang, George S; Hopfer, Christian; Kinney, Greg; Bowler, Russell; Foreman, Nicholas; Galinkin, Jeffrey; Christians, Uwe; Klawitter, Jost

    2017-10-01

    Although, especially in the United States, there has been a recent surge of legalized cannabis for either recreational or medicinal purposes, surprisingly little is known about clinical dose-response relationships, pharmacodynamic and toxicodynamic effects of cannabinoids such as Δ9-tetrahydrocannabinol (THC). Even less is known about other active cannabinoids. To address this knowledge gap, an online extraction, high-performance liquid chromatography coupled with tandem mass spectrometry method for simultaneous quantification of 11 cannabinoids and metabolites including THC, 11-hydroxy-Δ9-tetrahydrocannabinol, 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid, 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid glucuronide (THC-C-gluc), cannabinol, cannabidiol, cannabigerol, cannabidivarin, Δ9-tetrahydrocannabivarin (THCV), and 11-nor-9-carboxy-Δ9-tetrahydrocannabivarin (THCV-COOH) was developed and validated in human urine and plasma. In contrast to atmospheric pressure chemical ionization, electrospray ionization was associated with extensive ion suppression in plasma and urine samples. Thus, the atmospheric pressure chemical ionization assay was validated showing a lower limit of quantification ranging from 0.39 to 3.91 ng/mL depending on study compound and matrix. The upper limit of quantification was 400 ng/mL except for THC-C-gluc with an upper limit of quantification of 2000 ng/mL. The linearity was r > 0.99 for all analyzed calibration curves. Acceptance criteria for intrabatch and interbatch accuracy (85%-115%) and imprecision (<15%) were met for all compounds. In plasma, the only exceptions were THCV (75.3%-121.2% interbatch accuracy) and cannabidivarin (interbatch imprecision, 15.7%-17.2%). In urine, THCV did not meet predefined acceptance criteria for intrabatch accuracy. This assay allows for monitoring not only THC and its major metabolites but also major cannabinoids that are of interest for marijuana research and clinical practice.

  20. Non-integrating episomal plasmid-based reprogramming of human amniotic fluid stem cells into induced pluripotent stem cells in chemically defined conditions.

    Science.gov (United States)

    Slamecka, Jaroslav; Salimova, Lilia; McClellan, Steven; van Kelle, Mathieu; Kehl, Debora; Laurini, Javier; Cinelli, Paolo; Owen, Laurie; Hoerstrup, Simon P; Weber, Benedikt

    2016-01-01

    Amniotic fluid stem cells (AFSC) represent an attractive potential cell source for fetal and pediatric cell-based therapies. However, upgrading them to pluripotency confers refractoriness toward senescence, higher proliferation rate and unlimited differentiation potential. AFSC were observed to rapidly and efficiently reacquire pluripotency which together with their easy recovery makes them an attractive cell source for reprogramming. The reprogramming process as well as the resulting iPSC epigenome could potentially benefit from the unspecialized nature of AFSC. iPSC derived from AFSC also have potential in disease modeling, such as Down syndrome or β-thalassemia. Previous experiments involving AFSC reprogramming have largely relied on integrative vector transgene delivery and undefined serum-containing, feeder-dependent culture. Here, we describe non-integrative oriP/EBNA-1 episomal plasmid-based reprogramming of AFSC into iPSC and culture in fully chemically defined xeno-free conditions represented by vitronectin coating and E8 medium, a system that we found uniquely suited for this purpose. The derived AF-iPSC lines uniformly expressed a set of pluripotency markers Oct3/4, Nanog, Sox2, SSEA-1, SSEA-4, TRA-1-60, TRA-1-81 in a pattern typical for human primed PSC. Additionally, the cells formed teratomas, and were deemed pluripotent by PluriTest, a global expression microarray-based in-silico pluripotency assay. However, we found that the PluriTest scores were borderline, indicating a unique pluripotent signature in the defined condition. In the light of potential future clinical translation of iPSC technology, non-integrating reprogramming and chemically defined culture are more acceptable.

  1. Surface variations affecting human dental enamel studied using nanomechanical and chemical analysis

    Science.gov (United States)

    Dickinson, Michelle Emma

    The enamel surface is the interface between the tooth and its ever changing oral environment. Cavity (caries) formation and extrinsic tooth staining are due, respectively, to degradation of the enamel structure under low pH conditions and interactions between salivary pellicle and dietary elements. Both of these occur at the enamel surface and are caused by the local environment changing the chemistry of the surface. The results can be detrimental to the enamel's mechanical integrity and aesthetics. Incipient carious lesions are the precursor to caries and form due to demineralisation of enamel. These carious lesions are a reversible structure where ions (e.g. Ca2+, F -) can diffuse in (remineralisation) to preserve the tooth's structural integrity. This investigation used controlled in vitro demineralisation and remineralisation to study artificial carious lesion formation and repair. The carious lesions were cross-sectioned and characterised using nanoindentation, electron probe micro-analysis and time of flight secondary ion mass spectrometry. Mechanical and chemical maps showed the carious lesion had a significantly reduced hardness and elastic modulus, and the calcium and phosphate content was lower than in sound enamel. Fluoride based remineralisation treatments gave a new phase (possibly fluorohydroxyapatite) within the lesion with mechanical properties higher than sound enamel. The acquired salivary pellicle is a protein-rich film formed by the physisorption of organic molecules in saliva onto the enamel surface. Its functions include lubrication during mastication and chemical protection. However, pellicle proteins react with dietary elements such as polyphenols (tannins in tea) causing a brown stain. This study has used in vitro dynamic nanoindentation and atomic force microscopy to examine normal and stained pellicles formed in vivo. The effects of polyphenols on the pellicle's mechanical properties and morphology have been studied. It was found that the

  2. Pooled biological specimens for human biomonitoring of environmental chemicals: opportunities and limitations.

    Science.gov (United States)

    Heffernan, Amy L; Aylward, Lesa L; Toms, Leisa-Maree L; Sly, Peter D; Macleod, Matthew; Mueller, Jochen F

    2014-01-01

    Biomonitoring has become the "gold standard" in assessing chemical exposures, and has an important role in risk assessment. The pooling of biological specimens-combining multiple individual specimens into a single sample-can be used in biomonitoring studies to monitor levels of exposure and identify exposure trends or to identify susceptible populations in a cost-effective manner. Pooled samples provide an estimate of central tendency and may also reveal information about variation within the population. The development of a pooling strategy requires careful consideration of the type and number of samples collected, the number of pools required and the number of specimens to combine per pool in order to maximise the type and robustness of the data. Creative pooling strategies can be used to explore exposure-outcome associations, and extrapolation from other larger studies can be useful in identifying elevated exposures in specific individuals. The use of pooled specimens is advantageous as it saves significantly on analytical costs, may reduce the time and resources required for recruitment and, in certain circumstances, allows quantification of samples approaching the limit of detection. In addition, the use of pooled samples can provide population estimates while avoiding ethical difficulties that may be associated with reporting individual results.

  3. Index analysis and human health risk model application for evaluating ambient air-heavy metal contamination in Chemical Valley Sarnia.

    Science.gov (United States)

    Olawoyin, Richard; Schweitzer, Linda; Zhang, Kuangyuan; Okareh, Oladapo; Slates, Kevin

    2018-02-01

    The impacts of air emissions as a consequence of industrial activities around communities of human habitation have been extensively reported. This study is the first to assess potential adverse human health effects in the Chemical Valley Sarnia (CVS) area, around the St. Clair River, using health risk models, ecological and pollution indices. Large quantities of particulate matters (PM) are generated from anthropogenic activities, which contain several heavy metals in trace quantities with potentially adverse effects to humans and environmental health. The distribution, and human health impact assessment of trace element concentrations in PM fractions were examined. Elemental concentrations of As, Cd, Cr (VI), Cu, Fe, Mn, Pb, Ni, Zn were determined in the PM size-segregated samples collected from the CVS area between 2014 and 2017. The results showed relatively high concentration of PM air quality guidelines. Pb concentration (143.03 ± 46.87ηg/m 3 ) was 3.6 times higher than the air quality standards of NAAQS. Cr (VI) showed moderate to considerable contamination ( C f =4) in the CVS while Cr (VI), Pb, and Ni had enrichment factor E f < 3 (minimal), signifying contributions from anthropogenic activities. Pollution load index (P Li ) value observed was 1.4 indicating human health risk from the PM, especially for the children in the area. The deposition fluxes (DΦ) showed that PM-bound metals could potentially bypass the head airways and cause damages to the tracheobronchial tree, increasing the human health risks of nephroblastomasis development. The main route of entry for the heavy metal bound PM in humans were observed as through ingestion and inhalation. The highest total excess cancer risks observed for children (6.7×10 -4 ) and adult (1.0×10 -4 ) indicating potential cancer effects. The Incremental Lifetime Cancer Risk (ILCR) increased from Pb < Ni < Cd < Cr (VI) < As. Overall, children are more likely to develop carcinogenic and non-carcinogenic health

  4. Inhibition of the human liver microsomal and human cytochrome P450 1A2 and 3A4 metabolism of estradiol by deployment-related and other chemicals.

    Science.gov (United States)

    Usmani, Khawja A; Cho, Taehyeon M; Rose, Randy L; Hodgson, Ernest

    2006-09-01

    Cytochromes P450 (P450s) are major catalysts in the metabolism of xenobiotics and endogenous substrates such as estradiol (E2). It has previously been shown that E2 is predominantly metabolized in humans by CYP1A2 and CYP3A4 with 2-hydroxyestradiol (2-OHE2) the major metabolite. This study examines effects of deployment-related and other chemicals on E2 metabolism by human liver microsomes (HLM) and individual P450 isoforms. Kinetic studies using HLM, CYP3A4, and CYP1A2 showed similar affinities (Km) for E2 with respect to 2-OHE2 production. Vmax and CLint values for HLM are 0.32 nmol/min/mg protein and 7.5 microl/min/mg protein; those for CYP3A4 are 6.9 nmol/min/nmol P450 and 291 microl/min/nmol P450; and those for CYP1A2 are 17.4 nmol/min/nmol P450 and 633 microl/min/nmol P450. Phenotyped HLM use showed that individuals with high levels of CYP1A2 and CYP3A4 have the greatest potential to metabolize E2. Preincubation of HLM with a variety of chemicals, including those used in military deployments, resulted in varying levels of inhibition of E2 metabolism. The greatest inhibition was observed with organophosphorus compounds, including chlorpyrifos and fonofos, with up to 80% inhibition for 2-OHE2 production. Carbaryl, a carbamate pesticide, and naphthalene, a jet fuel component, inhibited ca. 40% of E2 metabolism. Preincubation of CYP1A2 with chlorpyrifos, fonofos, carbaryl, or naphthalene resulted in 96, 59, 84, and 87% inhibition of E2 metabolism, respectively. Preincubation of CYP3A4 with chlorpyrifos, fonofos, deltamethrin, or permethrin resulted in 94, 87, 58, and 37% inhibition of E2 metabolism. Chlorpyrifos inhibition of E2 metabolism is shown to be irreversible.

  5. Computer modelling of the chemical speciation of Americium (III) in human body fluids

    International Nuclear Information System (INIS)

    Jiang, Shu-bin; Lei, Jia-rong; Wang, He-yi; Zhong, Zhi-jing; Yang, Yong; Du, Yang

    2008-01-01

    A multi-phase equilibrium model consisted of multi-metal ion and low molecular mass ligands in human body fluid has been constructed to discuss the speciation of Am 3+ in gastric juice, sweat, interstitial fluid, intracellular fluid and urine of human body, respectively. Computer simulations indicated that the major Am(III)P Species were Am 3+ , [Am Cl] 2+ and [AmH 2 PO 4 ] 2+ at pH 4 became dominant with higher pH value when [Am] = 1 x 10 -7 mol/L in gastric juice model and percentage of AmPO 4 increased with [Am]. in sweat system, Am(III) existed with soluble species at pH 4.2∼pH 7.5 when [Am] = 1 x 10 -7 mol/L and Am(III) existed with Am 3+ and [Am OH] 2+ at pH 6.5 when [Am] -10 mol/L or [Am] > 5 x 10 -8 mol/L . With addition of EDTA, the Am(III) existed with soluble [Am EDTA] - whereas the Am(III) existed with insoluble AmPO 4 when [Am] > 1 x 10 -12 mol/L at interstitial fluid. The major Am(III) species was AmPO 4 at pH 7.0 and [Am]=4 x 10 -12 mol/L in intracellular fluid, which implied Am(III) represented strong cell toxicity. The percentage of Am(III) soluble species increased at lower pH hinted that the Am(III), in the form of aerosol, ingested by macrophage, could released into interstitial fluid and bring strong toxicity to skeleton system. The soluble Am(III) species was dominant when pH 4 when pH > 4.5 when [Am] = 1 x 10 -10 Pmol/L in human urine, so it was favorable to excrete Am(III) from kidney by taking acid materials. (author)

  6. [Chemical weapons and chemical terrorism].

    Science.gov (United States)

    Nakamura, Katsumi

    2005-10-01

    Chemical Weapons are kind of Weapons of Mass Destruction (WMD). They were used large quantities in WWI. Historically, large quantities usage like WWI was not recorded, but small usage has appeared now and then. Chemical weapons are so called "Nuclear weapon for poor countrys" because it's very easy to produce/possession being possible. They are categorized (1) Nerve Agents, (2) Blister Agents, (3) Cyanide (blood) Agents, (4) Pulmonary Agents, (5) Incapacitating Agents (6) Tear Agents from the viewpoint of human body interaction. In 1997 the Chemical Weapons Convention has taken effect. It prohibits chemical weapons development/production, and Organization for the Prohibition of Chemical Weapons (OPCW) verification regime contributes to the chemical weapons disposal. But possibility of possession/use of weapons of mass destruction by terrorist group represented in one by Matsumoto and Tokyo Subway Sarin Attack, So new chemical terrorism countermeasures are necessary.

  7. Ultraviolet and chemical induced DNA repair in human cells assayed by bromodeoxyuridine photolysis or cytosine arabinoside arrest

    International Nuclear Information System (INIS)

    Regan, J.D.; Dunn, W.C.

    1979-01-01

    The bromodeoxyuridine photolysis assay of DNA damage in human cells permits an estimate of both the number of repaired regions in the DNA and the size of the average repaired region - the patch size. The antineoplastic agent arabinofuranosyl cytosine (ara-C) can also be employed to assay the magnitude of repair since this agent appears to block rejoining of single-strand incisions made in the DNA during the initial step of repair. Thus, the number of incisions can be accumulated. The ara-C effect is dependent on the presence of hydroxyurea. Both assays can be employed for the study of physical or chemical DNA damages. Results comparing these assays are presented

  8. Human serum albumin (HSA) adsorption onto a-SiC:H thin films deposited by hot wire chemical vapor deposition

    International Nuclear Information System (INIS)

    Swain, Bibhu P.

    2006-01-01

    In the present paper, we report the study of the adsorption behavior of human serum albumin (HSA) onto surfaces of a-SiC:H thin films deposited by using the hot wire chemical vapor deposition (HWCVD) technique. The surface composition and surface energy of the various substrates as well as the evaluation of the adsorbed amount of protein has been carried out by means of X-ray photoelectron spectroscopy (XPS), Fourier transform infra-red (FTIR) spectroscopy, AFM and contact angle measurements. At the immediate effect of HSA interaction with a-SiC:H films N is adsorbed on the surface and stabilized after 3 days. Preliminary observation found that Si and O atom are desorbed from the surface while C and N set adsorbed to the surface of the a-SiC:H film

  9. Human serum albumin (HSA) adsorption onto a-SiC:H thin films deposited by hot wire chemical vapor deposition

    Energy Technology Data Exchange (ETDEWEB)

    Swain, Bibhu P. [Department of Metallurgical Engineering and Materials Science, Indian Institute of Technology, Bombay (India) and Samtel Centre for Display Technologies, Indian Institute of Technology Kanpur, India, Kanpur 208016 (India)]. E-mail: bibhup@iitb.ac.in

    2006-12-15

    In the present paper, we report the study of the adsorption behavior of human serum albumin (HSA) onto surfaces of a-SiC:H thin films deposited by using the hot wire chemical vapor deposition (HWCVD) technique. The surface composition and surface energy of the various substrates as well as the evaluation of the adsorbed amount of protein has been carried out by means of X-ray photoelectron spectroscopy (XPS), Fourier transform infra-red (FTIR) spectroscopy, AFM and contact angle measurements. At the immediate effect of HSA interaction with a-SiC:H films N is adsorbed on the surface and stabilized after 3 days. Preliminary observation found that Si and O atom are desorbed from the surface while C and N set adsorbed to the surface of the a-SiC:H film.

  10. The chemical interactome space between the human host and the genetically defined gut metabotypes

    DEFF Research Database (Denmark)

    Jacobsen, Ulrik Plesner; Nielsen, Henrik Bjørn; Hildebrand, Falk

    2013-01-01

    symbiosis in the gut of mammals, mechanistic understanding of the contributions of the gut microbiome and how variations in the metabotypes are linked to the host health are obscure. Here, we mapped the entire metabolic potential of the gut microiome based solely on metagenomics sequencing data derived from...... pharmacy in our guts. Furthermore, we established connections between the systemic effects of non-antibiotic drugs and the gut microbiome of relevance to drug side effects and health-care solutions.......The bacteria that colonize the gastrointestinal tracts of mammals represent a highly selected microbiome that has a profound influence on human physiology by shaping the host’s metabolic and immune system activity. Despite the recent advances on the biological principles that underlie microbial...

  11. Influence of the chemical composition of human tissues on dose distributions in hadron-therapy

    International Nuclear Information System (INIS)

    Batin, E.

    2008-06-01

    To compute the dose distribution, treatment planning systems require the exact anatomical location of tissues provided by computed tomography (CT) and the exact range of hadron beams in tissues based on the water equivalent ratio (WER). Since CT numbers are determined with x-rays and with an energy different from that used in hadron-therapy, a relation between CT numbers and the WER must to be established. We propose a determination of the WER with a Monte-Carlo simulation (GEANT4). We have determined the WER for 76 human tissues for a 135 MeV proton beam and for a 290 MeV/A carbon beam. The difference between the stoichiometric calibration and the simulated WER is lower than 1%. An additional 2% uncertainty that arises from the uncertainty in the CT numbers measurement should also be considered. The calculated WER were used to convert the deposited energy curve into the human tissue deposited energy curve for a 135 MeV proton beam and for a 290 MeV/A carbon beam. For both beams, the difference between the rescaled Bragg peak location and the one from the simulated curve is lower than 0.5 mm over the whole range of CT numbers. The differences between the maximum deposited energy can reach 3% for the proton beam in bones and vary between 1.5% and 3.5% for all tissues for the carbon beam. The scaling in two dimensions can be improved by using an additional factor that takes the scattering into account. (author)

  12. Chemical modification of human muscle aldose reductase by pyridoxal 5'-phosphate

    International Nuclear Information System (INIS)

    Morjana, N.A.; Lyons, C.; Flynn, T.G.

    1987-01-01

    Aldose reductase (ALR2) is a monomeric oxidoreductase (Mr, 37,000). This enzyme catalyzes the reduction of a wide variety of aliphatic and aromatic aldehydes to their corresponding alcohols. The ability to reduce D-glucose and utilize NADH distinguishes ALR2 from aldehyde reductase (ALR1) which is exclusively NADPH-dependent. As part of a study to determine active site residues critical for binding and catalysis they have investigated the behavior of ALR2 with pyridoxal phosphate (PLP). In contrast to ALR1, which is inactivated by PLP, the reaction of ALR2 with PLP results in a 2-3 fold activation with the incorporation of 1 mol of PLP/mol enzyme. However, despite a 3-fold increase in k/sub cat/, there is also a 13-14 fold increase in the Km for both coenzyme and substrate and catalytic efficiency (k/sub cat//Km) is actually decreased. Reaction of ALR2 with 3 [H] PLP followed by digestion with endoproteinase Lys-C enabled the separation and purification by HPLC of a peptide containing a single pyridoxyllysine residue. The sequence of this 32 residue peptide is highly homologous with a peptide similarly obtained from pig and human ALR1 and is identical with one from pig ALR2. In all four enzymes, pig ALR1, ALR2; human ALR1, ALR2, a tetrapeptide containing the pyridoxylated lysine (I-P-K-S) shows absolute identity. Thus, despite differences in substrate and coenzyme specificity, the active site in both ALR1 and ALR2 is relatively conserved

  13. Bridging the gap between sample collection and laboratory analysis: using dried blood spots to identify human exposure to chemical agents

    Science.gov (United States)

    Hamelin, Elizabeth I.; Blake, Thomas A.; Perez, Jonas W.; Crow, Brian S.; Shaner, Rebecca L.; Coleman, Rebecca M.; Johnson, Rudolph C.

    2016-05-01

    Public health response to large scale chemical emergencies presents logistical challenges for sample collection, transport, and analysis. Diagnostic methods used to identify and determine exposure to chemical warfare agents, toxins, and poisons traditionally involve blood collection by phlebotomists, cold transport of biomedical samples, and costly sample preparation techniques. Use of dried blood spots, which consist of dried blood on an FDA-approved substrate, can increase analyte stability, decrease infection hazard for those handling samples, greatly reduce the cost of shipping/storing samples by removing the need for refrigeration and cold chain transportation, and be self-prepared by potentially exposed individuals using a simple finger prick and blood spot compatible paper. Our laboratory has developed clinical assays to detect human exposures to nerve agents through the analysis of specific protein adducts and metabolites, for which a simple extraction from a dried blood spot is sufficient for removing matrix interferents and attaining sensitivities on par with traditional sampling methods. The use of dried blood spots can bridge the gap between the laboratory and the field allowing for large scale sample collection with minimal impact on hospital resources while maintaining sensitivity, specificity, traceability, and quality requirements for both clinical and forensic applications.

  14. Amelioration of Glucolipotoxicity-Induced Endoplasmic Reticulum Stress by a “Chemical Chaperone” in Human THP-1 Monocytes

    Directory of Open Access Journals (Sweden)

    Raji Lenin

    2012-01-01

    Full Text Available Chronic ER stress is emerging as a trigger that imbalances a number of systemic and arterial-wall factors and promote atherosclerosis. Macrophage apoptosis within advanced atherosclerotic lesions is also known to increase the risk of atherothrombotic disease. We hypothesize that glucolipotoxicity might mediate monocyte activation and apoptosis through ER stress. Therefore, the aims of this study are (a to investigate whether glucolipotoxicity could impose ER stress and apoptosis in THP-1 human monocytes and (b to investigate whether 4-Phenyl butyric acid (PBA, a chemical chaperone could resist the glucolipotoxicity-induced ER stress and apoptosis. Cells subjected to either glucolipotoxicity or tunicamycin exhibited increased ROS generation, gene and protein (PERK, GRP-78, IRE1α, and CHOP expression of ER stress markers. In addition, these cells showed increased TRPC-6 channel expression and apoptosis as revealed by DNA damage and increased caspase-3 activity. While glucolipotoxicity/tunicamycin increased oxidative stress, ER stress, mRNA expression of TRPC-6, and programmed the THP-1 monocytes towards apoptosis, all these molecular perturbations were resisted by PBA. Since ER stress is one of the underlying causes of monocyte dysfunction in diabetes and atherosclerosis, our study emphasize that chemical chaperones such as PBA could alleviate ER stress and have potential to become novel therapeutics.

  15. Evaluation of hazardous chemicals in edible insects and insect-based food intended for human consumption.

    Science.gov (United States)

    Poma, Giulia; Cuykx, Matthias; Amato, Elvio; Calaprice, Chiara; Focant, Jean Francois; Covaci, Adrian

    2017-02-01

    Due to the rapid increase in world population, the waste of food and resources, and non-sustainable food production practices, the use of alternative food sources is currently strongly promoted. In this perspective, insects may represent a valuable alternative to main animal food sources due to their nutritional value and sustainable production. However, edible insects may be perceived as an unappealing food source and are indeed rarely consumed in developed countries. The food safety of edible insects can thus contribute to the process of acceptance of insects as an alternative food source, changing the perception of developed countries regarding entomophagy. In the present study, the levels of organic contaminants (i.e. flame retardants, PCBs, DDT, dioxin compounds, pesticides) and metals (As, Cd, Co, Cr, Cu, Ni, Pb, Sn, Zn) were investigated in composite samples of several species of edible insects (greater wax moth, migratory locust, mealworm beetle, buffalo worm) and four insect-based food items currently commercialized in Belgium. The organic chemical mass fractions were relatively low (PCBs: 27-2065 pg/g ww; OCPs: 46-368 pg/g ww; BFRs: up to 36 pg/g ww; PFRs 783-23800 pg/g ww; dioxin compounds: up to 0.25 pg WHO-TEQ/g ww) and were generally lower than those measured in common animal products. The untargeted screening analysis revealed the presence of vinyltoluene, tributylphosphate (present in 75% of the samples), and pirimiphos-methyl (identified in 50% of the samples). The levels of Cu and Zn in insects were similar to those measured in meat and fish in other studies, whereas As, Co, Cr, Pb, Sn levels were relatively low in all samples (consume these insect species with no additional hazards in comparison to the more commonly consumed animal products. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Constructing the Indicators of Assessing Human Vulnerability to Industrial Chemical Accidents: A Consensus-based Fuzzy Delphi and Fuzzy AHP Approach.

    Science.gov (United States)

    Fatemi, Farin; Ardalan, Ali; Aguirre, Benigno; Mansouri, Nabiollah; Mohammadfam, Iraj

    2017-04-10

    Industrial chemical accidents have been increased in developing countries. Assessing the human vulnerability in the residents of industrial areas is necessary for reducing the injuries and causalities of chemical hazards. The aim of this study was to explore the key indicators for the assessment of human vulnerability in the residents living near chemical installations. The indicators were established in the present study based on the Fuzzy Delphi method (FDM) and Fuzzy Analytic Hierarchy Process (FAHP). The reliability of FDM and FAHP was calculated. The indicators of human vulnerability were explored in two sets of social and physical domains. Thirty-five relevant experts participated in this study during March-July 2015. According to experts, the top three indicators of human vulnerability according to the FDM and FAHP were vulnerable groups, population density, and awareness. Detailed sub-vulnerable groups and awareness were developed based on age, chronic or severe diseases, disability, first responders, and residents, respectively. Each indicator and sub-indicator was weighted and ranked and had an acceptable consistency ratio. The importance of social vulnerability indicators are about 7 times more than physical vulnerability indicators. Among the extracted indicators, vulnerable groups had the highest weight and the greatest impact on human vulnerability. however, further research is needed to investigate the applicability of established indicators and generalizability of the results to other studies. Fuzzy Delphi; Fuzzy AHP; Human vulnerability; Chemical hazards.

  17. The implications of non-linear biological oscillations on human electrophysiology for electrohypersensitivity (EHS) and multiple chemical sensitivity (MCS).

    Science.gov (United States)

    Sage, Cindy

    2015-01-01

    The 'informational content' of Earth's electromagnetic signaling is like a set of operating instructions for human life. These environmental cues are dynamic and involve exquisitely low inputs (intensities) of critical frequencies with which all life on Earth evolved. Circadian and other temporal biological rhythms depend on these fluctuating electromagnetic inputs to direct gene expression, cell communication and metabolism, neural development, brainwave activity, neural synchrony, a diversity of immune functions, sleep and wake cycles, behavior and cognition. Oscillation is also a universal phenomenon, and biological systems of the heart, brain and gut are dependent on the cooperative actions of cells that function according to principles of non-linear, coupled biological oscillations for their synchrony. They are dependent on exquisitely timed cues from the environment at vanishingly small levels. Altered 'informational content' of environmental cues can swamp natural electromagnetic cues and result in dysregulation of normal biological rhythms that direct growth, development, metabolism and repair mechanisms. Pulsed electromagnetic fields (PEMF) and radiofrequency radiation (RFR) can have the devastating biological effects of disrupting homeostasis and desynchronizing normal biological rhythms that maintain health. Non-linear, weak field biological oscillations govern body electrophysiology, organize cell and tissue functions and maintain organ systems. Artificial bioelectrical interference can give false information (disruptive signaling) sufficient to affect critical pacemaker cells (of the heart, gut and brain) and desynchronize functions of these important cells that orchestrate function and maintain health. Chronic physiological stress undermines homeostasis whether it is chemically induced or electromagnetically induced (or both exposures are simultaneous contributors). This can eventually break down adaptive biological responses critical to health

  18. Evidence of the Possible Harm of Endocrine-Disrupting Chemicals in Humans: Ongoing Debates and Key Issues

    Directory of Open Access Journals (Sweden)

    Duk-Hee Lee

    2018-03-01

    Full Text Available Evidence has emerged that endocrine-disrupting chemicals (EDCs can produce adverse effects, even at low doses that are assumed safe. However, systemic reviews and meta-analyses focusing on human studies, especially of EDCs with short half-lives, have demonstrated inconsistent results. Epidemiological studies have insuperable methodological limitations, including the unpredictable net effects of mixtures, non-monotonic dose-response relationships, the non-existence of unexposed groups, and the low reliability of exposure assessment. Thus, despite increases in EDC-linked diseases, traditional epidemiological studies based on individual measurements of EDCs in bio-specimens may fail to provide consistent results. The exposome has been suggested as a promising approach to address the uncertainties surrounding human studies, but it is never free from these methodological issues. Although exposure to EDCs during critical developmental periods is a major concern, continuous exposure to EDCs during non-critical periods is also harmful. Indeed, the evolutionary aspects of epigenetic programming triggered by EDCs during development should be considered because it is a key mechanism for developmental plasticity. Presently, living without EDCs is impossible due to their omnipresence. Importantly, there are lifestyles which can increase the excretion of EDCs or mitigate their harmful effects through the activation of mitohormesis or xenohormesis. Effectiveness of lifestyle interventions should be evaluated as practical ways against EDCs in the real world.

  19. Chemical variability of water and sediment over time and along a mountain river subjected to natural and human impact

    Directory of Open Access Journals (Sweden)

    Szarek-Gwiazda Ewa

    2018-01-01

    Full Text Available We studied the variability of physico-chemical parameters in water, and heavy metal contents in water and sediment over time and along the Carpathian Biała Tarnowska River (southern Poland and related them to catchment geology, human impact and the effect of barriers as a side aspect. The river water was well oxygenated, had pH 7.7–9.5 and was characterised by low and average flow. Temperature, pH and dissolved oxygen did not change significantly, while the contents of major ions, NO3−, NH4+, Mn and Fe increased gradually along the river. The major ion contents were negatively, and nitrate, Mn, and Fe positively, correlated with the flow. We recognise correlations between nitrate, Fe and Mn to be good indicators of soil erosion processes in the catchment. River sediment was unpolluted by most of the studied metals (slightly polluted by Ni and Cd. The differences in the values of some parameters (pH and NH4+, PO43−, HCO3−, Mn, Cd and Pb concentrations in the water, and heavy metals in the sediment upstream and downstream of some of the barriers were determined. Spatiotemporal changes in the values of studied parameters and the results of statistical calculation indicate the impact of human activity in the catchment basin (land use, wastewater on the water chemistry.

  20. Chemical constituents of Hericium erinaceum associated with the inhibitory activity against cellular senescence in human umbilical vascular endothelial cells.

    Science.gov (United States)

    Noh, Hyung Jun; Yang, Hyo Hyun; Kim, Geum Soog; Lee, Seung Eun; Lee, Dae Young; Choi, Je Hun; Kim, Seung Yu; Lee, Eun Suk; Ji, Seung Heon; Kang, Ki Sung; Park, Hye-Jin; Kim, Jae-Ryong; Kim, Ki Hyun

    2015-12-01

    Hericium erinaceum is an edible and medicinal mushroom widely used in Korea, Japan, and China. On the search for biologically active compounds supporting the medicinal usage, the MeOH extract of the fruiting bodies of H. erinaceum was investigated for its chemical constituents. Six compounds were isolated and identified as hericenone D (1), (22E,24R)-5α,8α-epidioxyergosta-6,22-dien-3β-ol (2), erinacerin B (3), hericenone E (4), hericenone F (5) and isohericerin (6) by comparing their spectroscopic data with previously reported values. The inhibitory effects on adriamycin-induced cellular senescence in human dermal fibroblasts (HDFs) and human umbilical vein endothelial cells (HUVECs) of the isolates (1-6) were studied. Among the isolated compounds, ergosterol peroxide (2) reduced senescence associated β-galactosidase (SA-β-gal) activity increased in HUVECs treated with adriamycin. According to experimental data obtained, the active compound may inspire the development of a new pharmacologically useful substance to be used in the treatment and prevention of age-related diseases.

  1. Physical and Chemical Processes and the Morphofunctional Characteristics of Human Erythrocytes in Hyperglycaemia

    Directory of Open Access Journals (Sweden)

    Victor V. Revin

    2017-08-01

    Full Text Available Background: This study examines the effect of graduated hyperglycaemia on the state and oxygen-binding ability of hemoglobin, the correlation of phospholipid fractions and their metabolites in the membrane, the activity of proteolytic enzymes and the morphofunctional state of erythrocytes.Methods: Conformational changes in the molecule of hemoglobin were determined by Raman spectroscopy. The structure of the erythrocytes was analyzed using laser interference microscopy (LIM. To determine the activity of NADN-methemoglobinreductase, we used the P.G. Board method. The degree of glycosylation of the erythrocyte membranes was determined using a method previously described by Felkoren et al. Lipid extraction was performed using the Bligh and Dyer method. Detection of the phospholipids was performed using V. E. Vaskovsky method.Results: Conditions of hyperglycaemia are characterized by a low affinity of hemoglobin to oxygen, which is manifested as a parallel decrease in the content of hemoglobin oxyform and the growth of deoxyform, methemoglobin and membrane-bound hemoglobin. The degree of glycosylation of membrane proteins and hemoglobin is high. For example, in the case of hyperglycaemia, erythrocytic membranes reduce the content of all phospholipid fractions with a simultaneous increase in lysoforms, free fatty acids and the diacylglycerol (DAG. Step wise hyperglycaemia in incubation medium and human erythrocytes results in an increased content of peptide components and general trypsin-like activity in the cytosol, with a simultaneous decreased activity of μ-calpain and caspase 3.Conclusions: Metabolic disorders and damage of cell membranes during hyperglycaemia cause an increase in the population of echinocytes and spherocytes. The resulting disorders are accompanied with a high probability of intravascular haemolysis.

  2. Physical-chemical basis of the protection of slowly frozen human erythrocytes by glycerol

    Energy Technology Data Exchange (ETDEWEB)

    Rall, W.F.; Mazur, P.; Souzu, H.

    1978-07-01

    One theory of freezing damage suggests that slowly cooled cells are killed by being exposed to increasing concentrations of electrolytes as the suspending medium freezes. A corollary to this view is that protective additives such as glycerol protect cells by acting colligatively to reduce the electrolyte concentration at any subzero temperature. Recently published phase-diagram data for the ternary system glycerol-NaCl-water by M.L. Shepard et al. (Cryobiology, 13: 9-23, 1976), in combination with the data on human red cell survival vs. subzero temperature presented here and in the companion study of Souzu and Mazur (Biophys. J., 23: 89-100), permit a precise test of this theory. Appropriate liquidus phase-diagram information for the solutions used in the red cell freezing experiments was obtained by interpolation of liquidus data of Shepard and his co-workers. The results of phase-diagram analysis of red cell survival indicate that the correlation between the temperature that yields 50% hemolysis (LT/sub 50/) and the electrolyte concentration attained at that temperature in various concentrations of glycerol is poor. With increasing concentrations of glycerol, the cells were killed at progressively lower concentrations of NaCl. For example, the LT/sub 50/ for cells frozen in the absence of glycerol corresponds to a NaCl concentration of 12 weight percent (2.4 molal), while for cells frozen in 1.75 M glycerol in buffered saline the LT/sub 50/ corresponds to 3.0 weight percent NaCl (1.3 molal). The data, in combination with other findings, lead to two conclusions: (a) The protection from glycerol is due to its colligative ability to reduce the concentration of sodium chloride in the external medium, but (b) the protection is less than that expected from colligative effects; apparently glycerol itself can also be a source of damage, probably because it renders the red cells susceptible to osmotic shock during thawing.

  3. Reconstituted human corneal epithelium: a new alternative to the Draize eye test for the assessment of the eye irritation potential of chemicals and cosmetic products.

    Science.gov (United States)

    Doucet, O; Lanvin, M; Thillou, C; Linossier, C; Pupat, C; Merlin, B; Zastrow, L

    2006-06-01

    The aim of this study was to evaluate the interest of a new three-dimensional epithelial model cultivated from human corneal cells to replace animal testing in the assessment of eye tolerance. To this end, 65 formulated cosmetic products and 36 chemicals were tested by means of this in vitro model using a simplified toxicokinetic approach. The chemicals were selected from the ECETOC data bank and the EC/HO International validation study list. Very satisfactory results were obtained in terms of concordance with the Draize test data for the formulated cosmetic products. Moreover, the response of the corneal model appeared predictive of human ocular response clinically observed by ophthalmologists. The in vitro scores for the chemicals tested strongly correlated with their respective scores in vivo. For all the compounds tested, the response of the corneal model to irritants was similar regardless of their chemical structure, suggesting a good robustness of the prediction model proposed. We concluded that this new three-dimensional epithelial model, developed from human corneal cells, could be promising for the prediction of eye irritation induced by chemicals and complex formulated products, and that these two types of materials should be tested using a similar protocol. A simple shortening of the exposure period was required for the chemicals assumed to be more aggressively irritant to the epithelial tissues than the cosmetic formulae.

  4. A study on chemical element determinations in human nails by neutron activation analysis

    International Nuclear Information System (INIS)

    Sanches, Thalita Pinheiro; Saiki, Mitiko

    2013-01-01

    Nail analyses have been the object of study in order to assess the levels of elements accumulated in the human organism and to use this tissue to monitor environmental and occupational exposure, to evaluate the nutritional status, to verify intoxication by toxic metals and to diagnose or to prevent diseases. Nail analyses present advantages due to easy sample collection, storage, transportation and this tissue provides element level accumulation over time. However, there is controversy regarding the application of nail analysis data due to difficulties to establish reliable reference values or element concentration ranges as control values. The objective of this study was to evaluate the factors that can affect nail element concentrations for further sample analyses of a group of individuals by applying neutron activation analysis (NAA). Fingernails and toenails collected from adult individuals of both genders, aged 18 to 71 years, living in the Sao Paulo Metropolitan Region were cut in small fragments, cleaned and dried for analyses. Samples and element standards were irradiated for 16 h under a thermal neutron flux of about 4.5 x 10 12 n cm -2 s -1 at the IEA-R1 nuclear research reactor followed by gamma ray spectrometry. Element concentrations for As, Br, Ca, Co, Cr, Cs, Fe, K, La, Na, Rb, Sb, Sc, Se and Zn were determined. For quality control of the analytical results, certified reference materials were analysed and the results showed good accuracy and precision with relative errors and relative standard deviations lower than 5.1 % and 11.6 %, respectively. Preliminary assays indicated that the contribution due to impurities from plastic involucres used in the irradiation as well as those from nail polishes is very low and could be considered negligible. Results from the nail sample cleaning process using distinct procedures indicated that HNO 3 solution may cause sample dissolution. Sample homogeneity was verified by analysis of a sample in replicate. A

  5. A study on chemical element determinations in human nails by neutron activation analysis

    International Nuclear Information System (INIS)

    Sanches, Thalita Pinheiro

    2012-01-01

    Nail analyses have been the object of study in order to assess the levels of elements accumulated in the human organism and to use this tissue to monitor environmental and occupational exposure, to evaluate the nutritional status, to verify intoxication by toxic metals and to diagnose or to prevent diseases. Nail analyses present advantages due to easy sample collection, storage, transportation and this tissue provides element level accumulation over time. However, there is controversy regarding the application of nail analysis data due to difficulties to establish reliable reference values or element concentration ranges as control values. The objective of this study was to evaluate the factors that can affect nail element concentrations for further sample analyses of a group of individuals by applying neutron activation analysis (NAA). Fingernails and toenails collected from adult individuals of both genders, aged 18 to 71 years, living in the Sao Paulo Metropolitan Region were cut in small fragments, cleaned and dried for analyses. Samples and element standards were irradiated for 16 h under a thermal neutron flux of about 4.5 x 10 12 n cm -2 s -1 at the IEA-R1 nuclear research reactor followed by gamma ray spectrometry. Element concentrations for As, Br, Ca, Co, Cr, Cs, Fe, K, La, Na, Rb, Sb, Sc, Se and Zn were determined. For quality control of the analytical results, certified reference materials were analysed and the results showed good accuracy and precision with relative errors and relative standard deviations lower than 5.1 % and 11.6 %, respectively. Preliminary assays indicated that the contribution due to impurities from plastic involucres used in the irradiation as well as those from nail polishes is very low and could be considered negligible. Results from the nail sample cleaning process using distinct procedures indicated that HNO 3 solution may cause sample dissolution. Sample homogeneity was verified by analysis of a sample in replicate. A

  6. A study on chemical element determinations in human nails by neutron activation analysis

    Energy Technology Data Exchange (ETDEWEB)

    Sanches, Thalita Pinheiro; Saiki, Mitiko, E-mail: thalitapsanches@usp.br, E-mail: mitiko@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2013-07-01

    Nail analyses have been the object of study in order to assess the levels of elements accumulated in the human organism and to use this tissue to monitor environmental and occupational exposure, to evaluate the nutritional status, to verify intoxication by toxic metals and to diagnose or to prevent diseases. Nail analyses present advantages due to easy sample collection, storage, transportation and this tissue provides element level accumulation over time. However, there is controversy regarding the application of nail analysis data due to difficulties to establish reliable reference values or element concentration ranges as control values. The objective of this study was to evaluate the factors that can affect nail element concentrations for further sample analyses of a group of individuals by applying neutron activation analysis (NAA). Fingernails and toenails collected from adult individuals of both genders, aged 18 to 71 years, living in the Sao Paulo Metropolitan Region were cut in small fragments, cleaned and dried for analyses. Samples and element standards were irradiated for 16 h under a thermal neutron flux of about 4.5 x 10{sup 12} n cm{sup -2} s{sup -1} at the IEA-R1 nuclear research reactor followed by gamma ray spectrometry. Element concentrations for As, Br, Ca, Co, Cr, Cs, Fe, K, La, Na, Rb, Sb, Sc, Se and Zn were determined. For quality control of the analytical results, certified reference materials were analysed and the results showed good accuracy and precision with relative errors and relative standard deviations lower than 5.1 % and 11.6 %, respectively. Preliminary assays indicated that the contribution due to impurities from plastic involucres used in the irradiation as well as those from nail polishes is very low and could be considered negligible. Results from the nail sample cleaning process using distinct procedures indicated that HNO{sub 3} solution may cause sample dissolution. Sample homogeneity was verified by analysis of a sample in

  7. Transition-state destabilization reveals how human DNA polymerase β proceeds across the chemically unstable lesion N7-methylguanine

    Science.gov (United States)

    Ouzon-Shubeita, Hala; Lee, Seongmin

    2014-01-01

    N7-Methyl-2′-deoxyguanosine (m7dG) is the predominant lesion formed by methylating agents. A systematic investigation on the effect of m7dG on DNA replication has been difficult due to the chemical instability of m7dG. To gain insights into the m7dG effect, we employed a 2′-fluorine-mediated transition-state destabilzation strategy. Specifically, we determined kinetic parameters for dCTP insertion opposite a chemically stable m7dG analogue, 2′-fluoro-m7dG (Fm7dG), by human DNA polymerase β (polβ) and solved three X-ray structures of polβ in complex with the templating Fm7dG paired with incoming dCTP or dTTP analogues. The kinetic studies reveal that the templating Fm7dG slows polβ catalysis ∼300-fold, suggesting that m7dG in genomic DNA may impede replication by some DNA polymerases. The structural analysis reveals that Fm7dG forms a canonical Watson–Crick base pair with dCTP, but metal ion coordination is suboptimal for catalysis in the polβ-Fm7dG:dCTP complex, which partially explains the slow insertion of dCTP opposite Fm7dG by polβ. In addition, the polβ-Fm7dG:dTTP structure shows open protein conformations and staggered base pair conformations, indicating that N7-methylation of dG does not promote a promutagenic replication. Overall, the first systematic studies on the effect of m7dG on DNA replication reveal that polβ catalysis across m7dG is slow, yet highly accurate. PMID:24966350

  8. Physico-chemical evaluation of bitter and non-bitter Aloe and their raw juice for human consumption.

    Science.gov (United States)

    Azam, M M; Kumar, S; Pancholy, A; Patidar, M

    2014-11-01

    In addition to Aloe vera which is bitter in taste, a non-bitter Aloe is also found in arid part of Rajasthan. This non-bitter Aloe (NBA) is sporadically cultivated as vegetable and for health drink. In spite of its cultivation and various uses, very little information is available about its detailed botanical parameters and chemical characters. This study aims to evaluate the physico-chemical characters of NBA through employing floral morphology, leaf characters and leaf gel and to compare them with those of A. vera. Of eleven floral characters studied, eight characters of NBA were significantly different from that of A. vera. Most visible difference was observed in their reproductive shoots which are highly branched in NBA (5.21 inflorescence/shoot) as compared to A. vera (1.5 inflorescence/shoot). NBA produces less leaf-biomass (-29.32 %) with less leaf-thickness (-31.44 %) but higher leaf length, width, and no. of spine/side by 17.56 %, 21.34 % and 16.11 %, respectively, with significant difference as compared to A. vera. But its polysaccharide content (0.259 %) is at par with that of A. vera. The raw juice from the leaf of NBA has very low aloin content (4.1 ppm) compared to that from A. vera (427.3 ppm) making it a safer health drink compared to the one obtained from A. vera. Thus, NBA raw juice emerged as suitable alternative to A. vera juice for human consumption.

  9. Proteomic Analysis of Human Adipose Derived Stem Cells during Small Molecule Chemical Stimulated Pre-neuronal Differentiation.

    Science.gov (United States)

    Santos, Jerran; Milthorpe, Bruce K; Herbert, Benjamin R; Padula, Matthew P

    2017-11-30

    Adipose derived stem cells (ADSCs) are acquired from abdominal liposuction yielding a thousand fold more stem cells per millilitre than those from bone marrow. A large research void exists as to whether ADSCs are capable of transdermal differentiation toward neuronal phenotypes. Previous studies have investigated the use of chemical cocktails with varying inconclusive results. Human ADSCs were treated with a chemical stimulant, beta-mercaptoethanol, to direct them toward a neuronal-like lineage within 24 hours. Quantitative proteomics using iTRAQ was then performed to ascertain protein abundance differences between ADSCs, beta-mercaptoethanol treated ADSCs and a glioblastoma cell line. The soluble proteome of ADSCs differentiated for 12 hours and 24 hours was significantly different from basal ADSCs and control cells, expressing a number of remodeling, neuroprotective and neuroproliferative proteins. However toward the later time point presented stress and shock related proteins were observed to be up regulated with a large down regulation of structural proteins. Cytokine profiles support a large cellular remodeling shift as well indicating cellular distress. The earlier time point indicates an initiation of differentiation. At the latter time point there is a vast loss of cell population during treatment. At 24 hours drastically decreased cytokine profiles and overexpression of stress proteins reveal that exposure to beta-mercaptoethanol beyond 24 hours may not be suitable for clinical application as our results indicate that the cells are in trauma whilst producing neuronal-like morphologies. The shorter treatment time is promising, indicating a reducing agent has fast acting potential to initiate neuronal differentiation of ADSCs.

  10. Simultaneous analysis of fourteen tertiary amine stimulants in human urine for doping control purposes by liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry

    International Nuclear Information System (INIS)

    Lu Jianghai; Wang San; Dong Ying; Wang Xiaobing; Yang Shuming; Zhang Jianli; Deng Jing; Qin Yang; Xu Youxuan; Wu Moutian; Ouyang Gangfeng

    2010-01-01

    A method for the simultaneous screening and confirmation of the presence of fourteen tertiary amine stimulants in human urine by gas chromatography-mass spectrometry (GC-MS) in combination with liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed and validated. Solid phase extraction (SPE) and liquid-liquid extraction (LLE) approaches were utilized for the pre-treatment of the urine samples. The study indicated that the capillary temperature played a significant role in the signal abundances of the protonated molecules of cropropamide and crotethamide under positive ion electrospray ionization (ESI) conditions. In addition, comparison studies of two different pre-treatment approaches as well as the two ionization modes were conducted. The LODs of the developed method for all the analytes were lower than the minimum required performance limit (MRPL) as set forth in the World Anti-Doping Agency (WADA) technical document for laboratories. The human urine sample obtained after oral administration of prolintane.HCl was successfully analyzed by the developed method, which demonstrated the applicability and reliability of the method for routine doping control analysis.

  11. Analysing of 228Th, 232Th, 228Ra in human bone tissues for the purpose of determining the post mortal interval

    International Nuclear Information System (INIS)

    Kandlbinder, R.; Geissler, V.; Schupfner, R.; Wolfbeis, O.; Zinka, B.

    2009-01-01

    Bone tissues of thirteen deceased persons were analyzed to determine the activity concentration of the radionuclides 228 Ra, 228 Th, 232 Th and 2 30 Th. The activity ratios enable to assess the post-mortem-interval PMI). The samples were prepared for analysis by incinerating and pulverizing. 228 Ra was directly detected by γ-spectrometry. 2 28 Th, 230 Th, 232 Th were detected by α-spectrometry after radiochemical purification and electrodeposition. It is shown that the method s principally suited to determine the PMI. A minimum of 300 g (wet weight) f human bone tissue is required for the analysis. Counting times are in the range of one to two weeks. (author)

  12. A systematic review of Bisphenol A "low dose" studies in the context of human exposure: a case for establishing standards for reporting "low-dose" effects of chemicals.

    Science.gov (United States)

    Teeguarden, Justin G; Hanson-Drury, Sesha

    2013-12-01

    Human exposure to the chemical Bisphenol A is almost ubiquitous in surveyed industrialized societies. Structural features similar to estrogen confer the ability of Bisphenol A (BPA) to bind estrogen receptors, giving BPA membership in the group of environmental pollutants called endocrine disruptors. References by scientists, the media, political entities, and non-governmental organizations to many toxicity studies as "low dose" has led to the belief that exposure levels in these studies are similar to humans, implying that BPA is toxic to humans at current exposures. Through systematic, objective comparison of our current, and a previous compilation of the "low-dose" literature to multiple estimates of human external and internal exposure levels, we found that the "low-dose" moniker describes exposures covering 8-12 orders of magnitude, the majority (91-99% of exposures) being greater than the upper bound of human exposure in the general infant, child and adult U.S. Population. "low dose" is therefore a descriptor without specific meaning regarding human exposure. Where human exposure data are available, for BPA and other environmental chemicals, reference to toxicity study exposures by direct comparison to human exposure would be more informative, more objective, and less susceptible to misunderstanding. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Study of physical, chemical and structural effects caused by ionizing radiation and preservation on human costal cartilage

    International Nuclear Information System (INIS)

    Martinho Junior, Antonio Carlos

    2008-01-01

    Tissue Banks around the world have stored human cartilages obtained from cadaver donors for use in several kinds of reconstructive surgeries. To ensure that such tissues are not contaminated, they have been sterilized with ionizing radiation. However, high doses of gamma radiation may cause undesirable changes in the tissues, decreasing the mechanical properties of the grafts. In this work, we evaluate physical/chemical and structural changes in deep-frozen (-70 deg C) or high concentration of glycerol (> 98%) preserved costal cartilage, before and after sterilization by ionizing radiation at 3 different doses (15, 25 and 50 kGy). Samples of human costal cartilage were obtained from 20 cadaver donors ranging between 18 and 55 years old. A 60 Co irradiator was used as irradiation source. Thermogravimetry (TG), Optical Coherence Tomography (OCT) and mechanical tension and compression tests were carried out to evaluate the changes in the cartilage. Regarding the thermogravimetric results, the obtained data has shown that the TG curves have the same pattern independently of the sample irradiated or not. On the other hand, non-irradiated samples showed great variability of thermogravimetric curves among different donors and for the same donor. Concerning the mechanical tests, when cartilages were irradiated with 15 kGy, their mechanical strength to tension was increased about 24%, in both deep-froze and preserved in glycerol samples. Samples deep-frozen, when irradiated with 25 and 50 kGy, presented a decrease of their mechanical behavior smaller than those preserved in high concentrations of glycerol and irradiated with the same dose. Therefore, deep-frozen cartilages can be sterilized with doses until 50 kGy and cartilages preserved in high concentrations of glycerol can be sterilized with doses until 25 kGy without significant changes in their bio-mechanical properties.(author)

  14. Chemical composition analysis and in vitro biological activities of ten essential oils in human skin cells

    Directory of Open Access Journals (Sweden)

    Xuesheng Han

    2017-12-01

    Full Text Available Research on the biological effects of essential oils on human skin cells is scarce. In the current study, we primarily explored the biological activities of 10 essential oils (nine single and one blend in a pre-inflamed human dermal fibroblast system that simulated chronic inflammation. We measured levels of proteins critical for inflammation, immune responses, and tissue-remodeling processes. The nine single oils were distilled from Citrus bergamia (bergamot, Coriandrum sativum (cilantro, Pelargonium graveolens (geranium, Helichrysum italicum (helichrysum, Pogostemon cablin (patchouli, Citrus aurantium (petitgrain, Santalum album (sandalwood, Nardostachys jatamansi (spikenard, and Cananga odorata (ylang ylang. The essential oil blend (commercial name Immortelle is composed of oils from frankincense, Hawaiian sandalwood, lavender, myrrh, helichrysum, and rose. All the studied oils were significantly anti-proliferative against these cells. Furthermore, bergamot, cilantro, and spikenard essential oils primarily inhibited protein molecules related to inflammation, immune responses, and tissue-remodeling processes, suggesting they have anti-inflammatory and wound healing properties. Helichrysum and ylang ylang essential oils, as well as Immortelle primarily inhibited tissue remodeling-related proteins, suggesting a wound healing property. The data are consistent with the results of existing studies examining these oils in other models and suggest that the studied oils may be promising therapeutic candidates. Further research into their biological mechanisms of action is recommended. The differential effects of these essential oils suggest that they exert activities by different mechanisms or pathways, warranting further investigation. The chemical composition of these oils was analyzed using gas chromatography–mass spectrometry. Keywords: Anti-proliferation, Bergamot, Cilantro, Anti-inflammatory, Spikenard, Wound healing

  15. Cultured human peripheral blood mononuclear cells alter their gene expression when challenged with endocrine-disrupting chemicals

    International Nuclear Information System (INIS)

    Wens, B.; De Boever, P.; Verbeke, M.; Hollanders, K.; Schoeters, G.

    2013-01-01

    Endocrine disrupting chemicals (EDCs) have the potential to interfere with the hormonal system and may negatively influence human health. Microarray analysis was used in this study to investigate differential gene expression in human peripheral blood cells (PBMCs) after in vitro exposure to EDCs. PBMCs, isolated from blood samples of four male and four female healthy individuals, were exposed in vitro for 18 h to either a dioxin-like polychlorinated biphenyl (PCB126, 1 μM), a non-dioxin-like polychlorinated biphenyl (PCB153, 10 μM), a brominated flame retardant (BDE47, 10 μM), a perfluorinated alkyl acid (PFOA, 10 μM) or bisphenol (BPA, 10 μM). ANOVA analysis revealed a significant change in the expression of 862 genes as a result of EDC exposure. The gender of the donors did not affect gene expression. Hierarchical cluster analysis created three groups and clustered: (1) PCB126-exposed samples, (2) PCB153 and BDE47, (3) PFOA and BPA. The number of differentially expressed genes varied per compound and ranged from 60 to 192 when using fold change and multiplicity corrected p-value as filtering criteria. Exposure to PCB126 induced the AhR signaling pathway. BDE47 and PCB153 are known to disrupt thyroid metabolism and exposure influenced the expression of the nuclear receptors PPARγ and ESR2, respectively. BPA and PFOA did not induce significant changes in the expression of known nuclear receptors. Overall, each compound produced a unique gene expression signature affecting pathways and GO processes linked to metabolism and inflammation. Twenty-nine genes were significantly altered in expression under all experimental conditions. Six of these genes (HSD11B2, MMP11, ADIPOQ, CEL, DUSP9 and TUB) could be associated with obesity and metabolic syndrome. In conclusion, microarray analysis identified that PBMCs altered their gene expression response in vitro when challenged with EDCs. Our screening approach has identified a number of gene candidates that warrant

  16. An in vitro method for detecting chemical sensitization using human reconstructed skin models and its applicability to cosmetic, pharmaceutical, and medical device safety testing.

    Science.gov (United States)

    McKim, James M; Keller, Donald J; Gorski, Joel R

    2012-12-01

    Chemical sensitization is a serious condition caused by small reactive molecules and is characterized by a delayed type hypersensitivity known as allergic contact dermatitis (ACD). Contact with these molecules via dermal exposure represent a significant concern for chemical manufacturers. Recent legislation in the EU has created the need to develop non-animal alternative methods for many routine safety studies including sensitization. Although most of the alternative research has focused on pure chemicals that possess reasonable solubility properties, it is important for any successful in vitro method to have the ability to test compounds with low aqueous solubility. This is especially true for the medical device industry where device extracts must be prepared in both polar and non-polar vehicles in order to evaluate chemical sensitization. The aim of this research was to demonstrate the functionality and applicability of the human reconstituted skin models (MatTek Epiderm(®) and SkinEthic RHE) as a test system for the evaluation of chemical sensitization and its potential use for medical device testing. In addition, the development of the human 3D skin model should allow the in vitro sensitization assay to be used for finished product testing in the personal care, cosmetics, and pharmaceutical industries. This approach combines solubility, chemical reactivity, cytotoxicity, and activation of the Nrf2/ARE expression pathway to identify and categorize chemical sensitizers. Known chemical sensitizers representing extreme/strong-, moderate-, weak-, and non-sensitizing potency categories were first evaluated in the skin models at six exposure concentrations ranging from 0.1 to 2500 µM for 24 h. The expression of eight Nrf2/ARE, one AhR/XRE and two Nrf1/MRE controlled gene were measured by qRT-PCR. The fold-induction at each exposure concentration was combined with reactivity and cytotoxicity data to determine the sensitization potential. The results demonstrated that

  17. Quantitative Nuclease Protection Assays (qNPA) as Windows into Chemical-Induced Adaptive Response in Cultures of Primary Human Hepatocytes (Concentration and Time-Response)

    Science.gov (United States)

    Cultures of primary human hepatocytes have been shown to be dynamic in vitro model systems that retain liver-like functionality (e.g. metabolism, transport, induction). We have utilized these culture models to interrogate 309 ToxCast chemicals. The study design characterized both...

  18. Human Stem Cell-Derived Cardiomyocytes: An Alternative Model to Evaluate Environmental Chemical Cardiac Safety and Development of Predictive Adverse Outcome Pathways

    Science.gov (United States)

    Biomonitoring over the last 14 years has shown human exposure to environmental chemicals has increased ~10-fold (1). In addition, mortality and morbidity related cardiovascular disease continues to be the leading national and global public health issue (2, 3). The association bet...

  19. Inter-laboratory study of human in vitro toxicogenomics-based tests as alternative methods for evaluating chemical carcinogenicity : a bioinformatics perspective

    NARCIS (Netherlands)

    Herwig, R; Gmuender, H; Corvi, Raffaella; Bloch, K.M.; Brandenburg, A.; Castell, J; Ceelen, L; Chesne, C; Doktorova, T Y; Jennen, D; Jennings, P; Limonciel, A; Lock, E A; McMorrow, T; Phrakonkham, P; Radford-Smith, G.; Slattery, C; Stierum, R; Vilardell, M; Wittenberger, T; Yildirimman, R; Ryan, M.; Rogiers, Vera; Kleinjans, Jos

    The assessment of the carcinogenic potential of chemicals with alternative, human-based in vitro systems has become a major goal of toxicogenomics. The central read-out of these assays is the transcriptome, and while many studies exist that explored the gene expression responses of such systems,

  20. Seeds of Peganum Harmala L. chemical analysis, antimalarial and antioxidant activities, and cytotoxicity against human breast cancer cells.

    Science.gov (United States)

    Chabir, Naziha; Ibrahim, Hany; Romdhane, Hany; Valentin, Alexis; Moukarzel, Beatrice; Mars, Mohamed; Bouajila, Jalloul

    2014-01-01

    The present study evaluated the levels of total phenolics, flavonoids, tannins and anthocyanins from Peganum harmala L. seeds and determined their antioxidant, antiplasmodial and anticancer potentials. Antioxidant activity was determined by DPPH and ABTS assays. Extracts of P. harmala seeds from Oudref and Djerba (two places in Tunisia) were obtained by successive extraction solvents: petroleum ether, chloroform, ethyl acetate, ethanol and water. Their composition was evaluated for phenolics (gallic acid equivalent 2.48 to 72.52 g/kg), tannins (catechin equivalent 0 to 25.27 g/kg), anthocyanins (cyanidin equivalent 0 to 20.56 mg/kg) and flavonoids (quercetin equivalent 0 to 3.12 g/kg). Ethanolic extract exerted the highest activities against a chloroquine-resistant strain of Plasmodium falciparum (IC₅₀=23 mg/L), against human breast cancer cells MCF7 (IC₅₀=32 mg/L) and against free radical (IC₅₀=19.09±3.07 mg/L). Correlations were studied between each chemical family and the three activities. Total phenolics content exhibited the highest correlation with antiplasmodial activity (R²=0.92) and with anticancer activity (R²=0.86), respectively.

  1. Almond (Prunus dulcis (Mill.) D.A. Webb) polyphenols: from chemical characterization to targeted analysis of phenolic metabolites in humans.

    Science.gov (United States)

    Bartolomé, Begoña; Monagas, María; Garrido, Ignacio; Gómez-Cordovés, Carmen; Martín-Alvarez, Pedro J; Lebrón-Aguilar, Rosa; Urpí-Sardà, Mireia; Llorach, Rafael; Andrés-Lacueva, Cristina

    2010-09-01

    In this paper, a survey of our studies on almond polyphenols including their chemical characterization and further bioavailability in humans is reported. Combination of analytical techniques (LC-DAD/fluorescence, LC/ESI-MS and MALDI-TOF-MS) allowed us, for the first time, the identification of A- and B-type procyanidin, propelargonidin and prodelphinidin polymers in almond skins. Glucuronide, O-methyl glucuronide, sulfate and O-methyl sulfate derivatives of (epi)catechin, as well as the glucuronide conjugates of naringenin and isorhamnetin, and sulfate conjugates of isorhamnetin, together with conjugates of hydroxyphenylvalerolactones were detected in plasma and urine samples after the intake of almond skin polyphenols. In addition, numerous microbial-derived metabolites, including hydroxyphenylpropionic, hydroxyphenylacetic, hydroxycinnamic, hydroxybenzoic and hydroxyhippuric acids were also identified. Depending of the type of metabolite, maximum urinary excretion was attained at different time in comparison to the control group in the course of the 24-h period of urine excretion, allowing us to establish the onset of microbial metabolism. 2010 Elsevier Inc. All rights reserved.

  2. The role of genetic background in susceptibility to chemical warfare nerve agents across rodent and non-human primate models.

    Science.gov (United States)

    Matson, Liana M; McCarren, Hilary S; Cadieux, C Linn; Cerasoli, Douglas M; McDonough, John H

    2018-01-15

    Genetics likely play a role in various responses to nerve agent exposure, as genetic background plays an important role in behavioral, neurological, and physiological responses to environmental stimuli. Mouse strains or selected lines can be used to identify susceptibility based on background genetic features to nerve agent exposure. Additional genetic techniques can then be used to identify mechanisms underlying resistance and sensitivity, with the ultimate goal of developing more effective and targeted therapies. Here, we discuss the available literature on strain and selected line differences in cholinesterase activity levels and response to nerve agent-induced toxicity and seizures. We also discuss the available cholinesterase and toxicity literature across different non-human primate species. The available data suggest that robust genetic differences exist in cholinesterase activity, nerve agent-induced toxicity, and chemical-induced seizures. Available cholinesterase data suggest that acetylcholinesterase activity differs across strains, but are limited by the paucity of carboxylesterase data in strains and selected lines. Toxicity and seizures, two outcomes of nerve agent exposure, have not been fully evaluated for genetic differences, and thus further studies are required to understand baseline strain and selected line differences. Published by Elsevier B.V.

  3. Synthetic surface for expansion of human mesenchymal stem cells in xeno-free, chemically defined culture conditions.

    Directory of Open Access Journals (Sweden)

    Paula J Dolley-Sonneville

    Full Text Available Human mesenchymal stem cells (HMSCS possess three properties of great interest for the development of cell therapies and tissue engineering: multilineage differentiation, immunomodulation, and production of trophic factors. Efficient ex vivo expansion of hMSCs is a challenging requirement for large scale production of clinical grade cells. Low-cost, robust, scalable culture methods using chemically defined materials need to be developed to address this need. This study describes the use of a xeno-free synthetic peptide acrylate surface, the Corning® Synthemax® Surface, for culture of hMSCs in serum-free, defined medium. Cell performance on the Corning Synthemax Surface was compared to cells cultured on biological extracellular matrix (ECM coatings in xeno-free defined medium and in traditional conditions on tissue culture treated (TCT plastic in fetal bovine serum (FBS supplemented medium. Our results show successful maintenance of hMSCs on Corning Synthemax Surface for eight passages, with cell expansion rate comparable to cells cultured on ECM and significantly higher than for cells in TCT/FBS condition. Importantly, on the Corning Synthemax Surface, cells maintained elongated, spindle-like morphology, typical hMSC marker profile and in vitro multilineage differentiation potential. We believe the Corning Synthemax Surface, in combination with defined media, provides a complete synthetic, xeno-free, cell culture system for scalable production of hMSCs.

  4. Probabilistic human health risk assessment of degradation-related chemical mixtures in heterogeneous aquifers: Risk statistics, hot spots, and preferential channels

    Science.gov (United States)

    Henri, Christopher V.; Fernàndez-Garcia, Daniel; de Barros, Felipe P. J.

    2015-06-01

    The increasing presence of toxic chemicals released in the subsurface has led to a rapid growth of social concerns and the need to develop and employ models that can predict the impact of groundwater contamination on human health risk under uncertainty. Monitored natural attenuation is a common remediation action in many contamination cases. However, natural attenuation can lead to the production of daughter species of distinct toxicity that may pose challenges in pollution management strategies. The actual threat that these contaminants pose to human health depends on the interplay between the complex structure of the geological media and the toxicity of each pollutant byproduct. This work addresses human health risk for chemical mixtures resulting from the sequential degradation of a contaminant (such as a chlorinated solvent) under uncertainty through high-resolution three-dimensional numerical simulations. We systematically investigate the interaction between aquifer heterogeneity, flow connectivity, contaminant injection model, and chemical toxicity in the probabilistic characterization of health risk. We illustrate how chemical-specific travel times control the regime of the expected risk and its corresponding uncertainties. Results indicate conditions where preferential flow paths can favor the reduction of the overall risk of the chemical mixture. The overall human risk response to aquifer connectivity is shown to be nontrivial for multispecies transport. This nontriviality is a result of the interaction between aquifer heterogeneity and chemical toxicity. To quantify the joint effect of connectivity and toxicity in health risk, we propose a toxicity-based Damköhler number. Furthermore, we provide a statistical characterization in terms of low-order moments and the probability density function of the individual and total risks.

  5. Cumulative effects of prenatal-exposure to exogenous chemicals and psychosocial stress on fetal growth: Systematic-review of the human and animal evidence.

    Science.gov (United States)

    Vesterinen, Hanna M; Morello-Frosch, Rachel; Sen, Saunak; Zeise, Lauren; Woodruff, Tracey J

    2017-01-01

    Adverse effects of prenatal stress or environmental chemical exposures on fetal growth are well described, yet their combined effect remains unclear. To conduct a systematic review on the combined impact and interaction of prenatal exposure to stress and chemicals on developmental outcomes. We used the first three steps of the Navigation Guide systematic review. We wrote a protocol, performed a robust literature search to identify relevant animal and human studies and extracted data on developmental outcomes. For the most common outcome (fetal growth), we evaluated risk of bias, calculated effect sizes for main effects of individual and combined exposures, and performed a random effects meta-analysis of those studies reporting on odds of low birthweight (LBW) by smoking and socioeconomic status (SES). We identified 17 human- and 22 animal-studies of combined chemical and stress exposures and fetal growth. Human studies tended to have a lower risk of bias across nine domains. Generally, we found stronger effects for chemicals than stress, and these exposures were associated with reduced fetal growth in the low-stress group and the association was often greater in high stress groups, with limited evidence of effect modification. We found smoking associated with significantly increased odds of LBW, with a greater effect for high stress (low SES; OR 4.75 (2.46-9.16)) compared to low stress (high SES; OR 1.95 (95% CI 1.53-2.48)). Animal studies generally had a high risk of bias with no significant combined effect or effect modification. We found that despite concern for the combined effects of environmental chemicals and stress, this is still an under-studied topic, though limited available human studies indicate chemical exposures exert stronger effects than stress, and this effect is generally larger in the presence of stress.

  6. The punishment's purpose

    Directory of Open Access Journals (Sweden)

    Gheorghe DIACONU

    2012-12-01

    Full Text Available The repressive reaction involves, as any human action, a certain finality. As the punishment's essence is the suffering, then, in the course of time it has been arisen the question regarding the goal for which the society utilizes the suffering and for what the society punishes. According to the classic penal doctrine that bases on the idea of retribution, the repressive reaction was limited to a simple revenge and it didn't existed any concern in order to influence the doer's future behaviour. In the positivist conception, the punishment's purpose was to shelter the society against the offender's new attacks. Going up to an extreme point with this idea, the positivists equated the punishment with the curative treatment at which the patients in the hospitals were submitted and which it was adequate to each category of offender. For the positivists, the penal sanction, it was meant to combat the organic or the psychological anomalies or the dysfunctions of the social environment that have influenced the offender and that determined him to commit antisocial deeds. In the modern vision, the punishment cannot have a goal on its own and that is to answer to bad with bad because it doesn't come from an abstract desire for revenge, but from a concrete necessity of hindering the repetition of the antisocial deeds and of defending the fundamental social values.

  7. 5-(2-Aminopropyl)indole (5-IT): a psychoactive substance used for recreational purposes is an inhibitor of human monoamine oxidase (MAO).

    Science.gov (United States)

    Herraiz, Tomás; Brandt, Simon D

    2014-01-01

    5-(2-Aminopropyl)indole (5-IT) is a psychoactive compound that has recently been associated with several fatal and non-fatal intoxications in a number of European countries. There are indications that acute effects may include symptoms of monoaminergic (e.g. serotonin) toxicity and one mechanism involved in the increase of serotonin levels includes the inhibition of monoamine oxidase. This study investigated the effect of 5-IT on human MAO-A and -B isozymes using kynuramine as the substrate. Substrate conversion to 4-hydroxyquinoline was monitored by high-performance liquid chromatography coupled to diode array detection. This method was employed to determine the extent of MAO inhibition (IC50 and Ki ) and it was found that 5-IT was a selective, competitive and reversible inhibitor of MAO-A. 5-IT revealed a relatively potent ability to inhibit MAO-A (IC50  =1.6 μM and Ki  =0.25 μM) while MAO-B inhibition was not observed (0-500 μM 5-IT). Under identical experimental conditions, other established inhibitors of MAO-A and antidepressants provided the following IC50 values: clorgyline 16 nM, harmaline 20 nM, toloxatone 6.7 μM and moclobemide >500 μM. These data indicated that 5-IT was less potent than clorgyline and harmaline but more potent than toloxatone and moclobemide under the in-vitro conditions studied. The inhibition of MAO-A suggests that 5-IT by itself or in combination with other substances may be able to potentiate serotonergic/monoaminergic effects and further studies are needed to clarify its relevance to the adverse effects reported for 5-IT. Copyright © 2013 John Wiley & Sons, Ltd.

  8. Military chemical warfare agent human subjects testing: part 2--long-term health effects among participants of U.S. military chemical warfare agent testing.

    Science.gov (United States)

    Brown, Mark

    2009-10-01

    Military chemical warfare agent testing from World War I to 1975 produced thousands of veterans with concerns about how their participation affected their health. A companion article describes the history of these experiments, and how the lack of clinical data hampers evaluation of long-term health consequences. Conversely, much information is available about specific agents tested and their long-term health effects in other populations, which may be invaluable for helping clinicians respond effectively to the health care and other needs of affected veterans. The following review describes tested agents and their known long-term health consequences. Although hundreds of chemicals were tested, they fall into only about a half-dozen pharmaceutical classes, including common pharmaceuticals; anticholinesterase agents including military nerve agents and pesticides; anticholinergic glycolic acid esters such as atropine; acetylcholine reactivators such as 2-PAM; psychoactive compounds including cannabinoids, phencyclidine, and LSD; and irritants including tear gas and riot control agents.

  9. Combining Purpose With Profits

    DEFF Research Database (Denmark)

    Julian Birkinshaw, Julian; Foss, Nicolai Juul; Lindenberg, Siegwart

    2014-01-01

    A sense of purpose that transcends making money can motivate employees. But to sustain both a sense of purpose and a solid level of profitability over time, companies need to pay attention to several fundamental organizing principles....

  10. Purpose and Professional Writers.

    Science.gov (United States)

    Blyler, Nancy Roundy

    1989-01-01

    Describes a protocol study of 10 professional writers which examined the meaning and influence of purpose on writers in the workplace. Explores the interactions of various purpose considerations derived from situation, reader, and text. Suggests that professional writers have a range of meanings in mind when they think about purpose. (MM)

  11. The Role of Faculty in Connecting Canadian Undergraduate Arts and Humanities Students to Scholarly Inquiries into Teaching: A Case for Purposeful Experiential Learning

    Directory of Open Access Journals (Sweden)

    Ginny R. Ratsoy

    2016-06-01

    Full Text Available Increasingly, various sectors of Canadian universities are advocating an assortment of beyond-the-classroom learning models – from research assistantships through service learning and cooperative education placements. At the same time, faculty who engage in the Scholarship of Teaching and Learning (SoTL and related inquiries into teaching and learning are striving to shift attention on their activities from the periphery to a more central position within campus culture – a particular challenge for Arts and Humanities professors, who may find themselves marginalized within SoTL. This article focuses attention on the intersections of experiential learning and SoTL and SoTL-related activity. Students have much to benefit from, and offer to, these activities – beyond their usual role as subjects of studies. I present a framework based on examples from research and my own experiences – with a focus on undergraduate Arts students, who, arguably, have the fewest opportunities for Experiential Learning in general – that illustrates varying degrees of involvement. As Arts faculty attempt to enhance and highlight inquiries into teaching and learning, they would be wise to conjoin them with experiential learning by including students in the process and product. Divers secteurs des universités canadiennes conseillent de plus en plus un assortiment de modèles d’apprentissage hors de la salle de classe – que ce soit par le biais de postes d’assistants à la recherche, de l’apprentissage par le service ou de stages dans le cadre de l’enseignement coopératif. En même temps, les professeurs qui sont actifs dans l’Avancement des connaissances en enseignement et en apprentissage (ACEA et dans des domaines connexes liés à l’enseignement et à l’apprentissage s’efforcent d’attirer l’attention sur leurs activités pour les faire passer de la périphérie à une position plus centrale sur les campus – ce qui s’avère être un

  12. Conceptual Framework To Extend Life Cycle Assessment Using Near-Field Human Exposure Modeling and High-Throughput Tools for Chemicals.

    Science.gov (United States)

    Csiszar, Susan A; Meyer, David E; Dionisio, Kathie L; Egeghy, Peter; Isaacs, Kristin K; Price, Paul S; Scanlon, Kelly A; Tan, Yu-Mei; Thomas, Kent; Vallero, Daniel; Bare, Jane C

    2016-11-01

    Life Cycle Assessment (LCA) is a decision-making tool that accounts for multiple impacts across the life cycle of a product or service. This paper presents a conceptual framework to integrate human health impact assessment with risk screening approaches to extend LCA to include near-field chemical sources (e.g., those originating from consumer products and building materials) that have traditionally been excluded from LCA. A new generation of rapid human exposure modeling and high-throughput toxicity testing is transforming chemical risk prioritization and provides an opportunity for integration of screening-level risk assessment (RA) with LCA. The combined LCA and RA approach considers environmental impacts of products alongside risks to human health, which is consistent with regulatory frameworks addressing RA within a sustainability mindset. A case study is presented to juxtapose LCA and risk screening approaches for a chemical used in a consumer product. The case study demonstrates how these new risk screening tools can be used to inform toxicity impact estimates in LCA and highlights needs for future research. The framework provides a basis for developing tools and methods to support decision making on the use of chemicals in products.

  13. 45 CFR 99.24 - Evidentiary purpose.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Evidentiary purpose. 99.24 Section 99.24 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PROCEDURE FOR HEARINGS FOR THE CHILD CARE AND DEVELOPMENT FUND Hearing Procedures § 99.24 Evidentiary purpose. The purpose of the...

  14. Current Knowledge on Endocrine Disrupting Chemicals (EDCs from Animal Biology to Humans, from Pregnancy to Adulthood: Highlights from a National Italian Meeting

    Directory of Open Access Journals (Sweden)

    Maria Elisabeth Street

    2018-06-01

    Full Text Available Wildlife has often presented and suggested the effects of endocrine disrupting chemicals (EDCs. Animal studies have given us an important opportunity to understand the mechanisms of action of many chemicals on the endocrine system and on neurodevelopment and behaviour, and to evaluate the effects of doses, time and duration of exposure. Although results are sometimes conflicting because of confounding factors, epidemiological studies in humans suggest effects of EDCs on prenatal growth, thyroid function, glucose metabolism and obesity, puberty, fertility, and on carcinogenesis mainly through epigenetic mechanisms. This manuscript reviews the reports of a multidisciplinary national meeting on this topic.

  15. Exposição humana a substâncias químicas potencialmente tóxicas na dieta e os riscos para saúde Chemical dietary exposure and the risks to human health

    Directory of Open Access Journals (Sweden)

    Andréia Nunes Oliveira Jardim

    2009-01-01

    Full Text Available Humans are exposed to a variety of chemicals from the consumption of food, including undesirable compounds such as pesticides and mycotoxins. Chemical human risk assessment is a process intended to estimate the risk to a given population from the exposure to a chemical (or to a chemical group having the same mechanism of action. The process consists of four steps, namely hazard identification, hazard characterization, exposure assessment and risk characterization. Chemical dietary risk assessment is an essential procedure to establish safe food standards. In this review the tools and data sources currently used in the risk assessment process will be discussed.

  16. Estrogenic Endocrine Disrupting Chemicals Influencing NRF1 Regulated Gene Networks in the Development of Complex Human Brain Diseases.

    Science.gov (United States)

    Preciados, Mark; Yoo, Changwon; Roy, Deodutta

    2016-12-13

    During the development of an individual from a single cell to prenatal stages to adolescence to adulthood and through the complete life span, humans are exposed to countless environmental and stochastic factors, including estrogenic endocrine disrupting chemicals. Brain cells and neural circuits are likely to be influenced by estrogenic endocrine disruptors (EEDs) because they strongly dependent on estrogens. In this review, we discuss both environmental, epidemiological, and experimental evidence on brain health with exposure to oral contraceptives, hormonal therapy, and EEDs such as bisphenol-A (BPA), polychlorinated biphenyls (PCBs), phthalates, and metalloestrogens, such as, arsenic, cadmium, and manganese. Also we discuss the brain health effects associated from exposure to EEDs including the promotion of neurodegeneration, protection against neurodegeneration, and involvement in various neurological deficits; changes in rearing behavior, locomotion, anxiety, learning difficulties, memory issues, and neuronal abnormalities. The effects of EEDs on the brain are varied during the entire life span and far-reaching with many different mechanisms. To understand endocrine disrupting chemicals mechanisms, we use bioinformatics, molecular, and epidemiologic approaches. Through those approaches, we learn how the effects of EEDs on the brain go beyond known mechanism to disrupt the circulatory and neural estrogen function and estrogen-mediated signaling. Effects on EEDs-modified estrogen and nuclear respiratory factor 1 (NRF1) signaling genes with exposure to natural estrogen, pharmacological estrogen-ethinyl estradiol, PCBs, phthalates, BPA, and metalloestrogens are presented here. Bioinformatics analysis of gene-EEDs interactions and brain disease associations identified hundreds of genes that were altered by exposure to estrogen, phthalate, PCBs, BPA or metalloestrogens. Many genes modified by EEDs are common targets of both 17 β-estradiol (E2) and NRF1. Some of

  17. Estrogenic Endocrine Disrupting Chemicals Influencing NRF1 Regulated Gene Networks in the Development of Complex Human Brain Diseases

    Directory of Open Access Journals (Sweden)

    Mark Preciados

    2016-12-01

    Full Text Available During the development of an individual from a single cell to prenatal stages to adolescence to adulthood and through the complete life span, humans are exposed to countless environmental and stochastic factors, including estrogenic endocrine disrupting chemicals. Brain cells and neural circuits are likely to be influenced by estrogenic endocrine disruptors (EEDs because they strongly dependent on estrogens. In this review, we discuss both environmental, epidemiological, and experimental evidence on brain health with exposure to oral contraceptives, hormonal therapy, and EEDs such as bisphenol-A (BPA, polychlorinated biphenyls (PCBs, phthalates, and metalloestrogens, such as, arsenic, cadmium, and manganese. Also we discuss the brain health effects associated from exposure to EEDs including the promotion of neurodegeneration, protection against neurodegeneration, and involvement in various neurological deficits; changes in rearing behavior, locomotion, anxiety, learning difficulties, memory issues, and neuronal abnormalities. The effects of EEDs on the brain are varied during the entire life span and far-reaching with many different mechanisms. To understand endocrine disrupting chemicals mechanisms, we use bioinformatics, molecular, and epidemiologic approaches. Through those approaches, we learn how the effects of EEDs on the brain go beyond known mechanism to disrupt the circulatory and neural estrogen function and estrogen-mediated signaling. Effects on EEDs-modified estrogen and nuclear respiratory factor 1 (NRF1 signaling genes with exposure to natural estrogen, pharmacological estrogen-ethinyl estradiol, PCBs, phthalates, BPA, and metalloestrogens are presented here. Bioinformatics analysis of gene-EEDs interactions and brain disease associations identified hundreds of genes that were altered by exposure to estrogen, phthalate, PCBs, BPA or metalloestrogens. Many genes modified by EEDs are common targets of both 17 β-estradiol (E2 and

  18. Genetic k-means clustering approach for mapping human vulnerability to chemical hazards in the industrialized city: a case study of Shanghai, China.

    Science.gov (United States)

    Shi, Weifang; Zeng, Weihua

    2013-06-20

    Reducing human vulnerability to chemical hazards in the industrialized city is a matter of great urgency. Vulnerability mapping is an alternative approach for providing vulnerability-reducing interventions in a region. This study presents a method for mapping human vulnerability to chemical hazards by using clustering analysis for effective vulnerability reduction. Taking the city of Shanghai as the study area, we measure human exposure to chemical hazards by using the proximity model with additionally considering the toxicity of hazardous substances, and capture the sensitivity and coping capacity with corresponding indicators. We perform an improved k-means clustering approach on the basis of genetic algorithm by using a 500 m × 500 m geographical grid as basic spatial unit. The sum of squared errors and silhouette coefficient are combined to measure the quality of clustering and to determine the optimal clustering number. Clustering result reveals a set of six typical human vulnerability patterns that show distinct vulnerability dimension combinations. The vulnerability mapping of the study area reflects cluster-specific vulnerability characteristics and their spatial distribution. Finally, we suggest specific points that can provide new insights in rationally allocating the limited funds for the vulnerability reduction of each cluster.

  19. Genetic k-Means Clustering Approach for Mapping Human Vulnerability to Chemical Hazards in the Industrialized City: A Case Study of Shanghai, China

    Directory of Open Access Journals (Sweden)

    Weihua Zeng

    2013-06-01

    Full Text Available Reducing human vulnerability to chemical hazards in the industrialized city is a matter of great urgency. Vulnerability mapping is an alternative approach for providing vulnerability-reducing interventions in a region. This study presents a method for mapping human vulnerability to chemical hazards by using clustering analysis for effective vulnerability reduction. Taking the city of Shanghai as the study area, we measure human exposure to chemical hazards by using the proximity model with additionally considering the toxicity of hazardous substances, and capture the sensitivity and coping capacity with corresponding indicators. We perform an improved k-means clustering approach on the basis of genetic algorithm by using a 500 m × 500 m geographical grid as basic spatial unit. The sum of squared errors and silhouette coefficient are combined to measure the quality of clustering and to determine the optimal clustering number. Clustering result reveals a set of six typical human vulnerability patterns that show distinct vulnerability dimension combinations. The vulnerability mapping of the study area reflects cluster-specific vulnerability characteristics and their spatial distribution. Finally, we suggest specific points that can provide new insights in rationally allocating the limited funds for the vulnerability reduction of each cluster.

  20. Development of a human corneal epithelium model utilizing a collagen vitrigel membrane and the changes of its barrier function induced by exposing eye irritant chemicals.

    Science.gov (United States)

    Takezawa, Toshiaki; Nishikawa, Kazunori; Wang, Pi-Chao

    2011-09-01

    The brief TEER (trans-epithelial electrical resistance) assay after exposing chemicals to corneal epithelium in vivo is known as a suitable method for evaluating corneal irritancy and permeability quantitatively and continuously. A collagen vitrigel membrane we previously developed is a thin (about 20 μm thick) and transparent membrane composed of high density collagen fibrils equivalent to connective tissues in vivo, e.g. corneal Bowman's membrane. To develop such a TEER assay system in vitro utilizing a human corneal epithelial model, HCE-T cells (a human corneal epithelial cell line) were cultured on the collagen vitrigel membrane substratum prepared in a Millicell chamber suitable for TEER measurement. Human corneal epithelium model possessing 5-6 cell layers sufficient for TEER assay was successfully reconstructed on the substratum in the Millicell chamber by culturing the cells in monolayer for 2 days and subsequently in air-liquid interface for 7 days. The exposure of chemicals to the model induced the time-dependent relative changes of TEER in response to the characteristic of each chemical within a few minutes. These results suggest that the TEER assay using the human corneal epithelial model is very useful for an ocular irritancy evaluation as an alternative to the Draize eye irritation test. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Personal Chemical Exposure informatics

    Science.gov (United States)

    Chemical Exposure science is the study of human contact with chemicals (from manufacturing facilities, everyday products, waste) occurring in their environments and advances knowledge of the mechanisms and dynamics of events that cause or prevent adverse health outcomes. (adapted...

  2. Adult Human Stem Cell-Derived Cardiomyocytes: An Alternative Model for Evaluating Chemical and Environmental Pollutant Cardiotoxicity

    Science.gov (United States)

    Heart disease is increasing globally with a significant percentage of the increase being attributed to chemical and pollution exposures. Currently, no alternative or in vitro testing models exist to rapidly and accurately determine the cardiac effects of chemicals and/or pollutan...

  3. The Special Purpose Vehicle

    DEFF Research Database (Denmark)

    Fomcenco, Alex

    2013-01-01

    The purpose of this article is to investigate whether the situation where two companies appear as originators or sponsors behind a Special Purpose Vehicle (SPV) can be described as a merger, although on micro scale. Are the underlying grounds behind the creation of an SPV much different than those...

  4. An evaluation of human sperm as indicators of chemically induced alterations of spermatogenic function. A report of the U. S. Environmental Protection Agency Gene-Tox Program

    Energy Technology Data Exchange (ETDEWEB)

    Wyrobek, A.J.; Gordon, L.A.; Burkhart, J.G.; Francis, M.W.; Kapp, R.W. Jr.; Letz, G.; Malling, H.V.; Topham, J.C.; Whorton, M.D.

    1983-05-01

    To evaluate the utility of sperm tests as indichangesators of chemical effects on human spermatogenesis, the literature on 4 sperm tests used to assess chemically induced testicular dysfunction was reviewed. The tests surveyed included sperm count, motility, morphology (seminal cytology), and double Y-body (a fluorescence-based test thought to detect Y-chromosomal nondisjunction). There were 132 papers that provided sufficient data for evaluation. These reports encompassed 89 different chemical exposures: 53 were to single agents; 14 to complex mixtures; and 22 to combinations of 2 or more identified agents. Approximately 85% of the exposures were to experimental or therapeutic drugs, 10% were to occupational or environmental agents, and 5% were to drugs for personal use. The most common sperm parameter studied was sperm count. The 89 exposures reviewed were grouped into 4 classes: those which adversely effected spermatogenesis, as measured by one or more of the sperm test; those suggestive of improving semen quality; those showing inconclusive evidence of adverse effects from exposure; and those showing no significant changes. Since the reviewed reports had a large variety of study designs, and since every attempt was made to include all reports with interpretable data, these classifications were based on reviewing committee decisions rather than on uniform statistical criteria. This review gives strong evidence that human sperm tests can be used to identify chemicals that affect sperm production, but because of our limited understanding of underlying mechanisms, the extent to which they can detect mutagens, carcinogens or agents that affect fertility remains uncertain. For the very few agents studied with both human and mouse sperm tests, similar test-responses were seen. An overall comparison of the 4 human sperm tests suggests that no one test is biologically more responsive than another.

  5. Studying the synergistic damage effects induced by 1.8 GHz radiofrequency field radiation (RFR) with four chemical mutagens on human lymphocyte DNA using comet assay in vitro

    International Nuclear Information System (INIS)

    Wang Baohong; He Jiliang; Jin Lifen; Lu Deqiang; Zheng Wei; Lou Jianlin; Deng Hongping

    2005-01-01

    The aim of this investigation was to study the synergistic DNA damage effects in human lymphocytes induced by 1.8 GHz radiofrequency field radiation (RFR, SAR of 3 W/kg) with four chemical mutagens, i.e. mitomycin C (MMC, DNA crosslinker), bleomycin (BLM, radiomimetic agent), methyl methanesulfonate (MMS, alkylating agent), and 4-nitroquinoline-1-oxide (4NQO, UV-mimetic agent). The DNA damage of lymphocytes exposed to RFR and/or with chemical mutagens was detected at two incubation time (0 or 21 h) after treatment with comet assay in vitro. Three combinative exposure ways were used. Cells were exposed to RFR and chemical mutagens for 2 and 3 h, respectively. Tail length (TL) and tail moment (TM) were utilized as DNA damage indexes. The results showed no difference of DNA damage indexes between RFR group and control group at 0 and 21 h incubation after exposure (P > 0.05). There were significant difference of DNA damage indexes between MMC group and RFR + MMC co-exposure group at 0 and 21 h incubation after treatment (P 0.05). The experimental results indicated 1.8 GHz RFR (SAR, 3 W/kg) for 2 h did not induce the human lymphocyte DNA damage effects in vitro, but could enhance the human lymphocyte DNA damage effects induced by MMC and 4NQO. The synergistic DNA damage effects of 1.8 GHz RFR with BLM or MMS were not obvious

  6. Unscheduled DNA synthesis in human hair follicles after in vitro exposure to 11 chemicals: comparison with unscheduled DNA synthesis in rat hepatocytes.

    Science.gov (United States)

    van Erp, Y H; Koopmans, M J; Heirbaut, P R; van der Hoeven, J C; Weterings, P J

    1992-06-01

    A new method is described to investigate unscheduled DNA synthesis (UDS) in human tissue after exposure in vitro: the human hair follicle. A histological technique was applied to assess cytotoxicity and UDS in the same hair follicle cells. UDS induction was examined for 11 chemicals and the results were compared with literature findings for UDS in rat hepatocytes. Most chemicals inducing UDS in rat hepatocytes raised DNA repair at comparable concentrations in the hair follicle. However, 1 of 9 chemicals that gave a positive response in the rat hepatocyte UDS test, 2-acetylaminofluorene, failed to induce DNA repair in the hair follicle. Metabolizing potential of hair follicle cells was shown in experiments with indirectly acting compounds, i.e., benzo[a]pyrene, 7,12-dimethylbenz[a]anthracene and dimethylnitrosamine. The results support the conclusion that the test in its present state is valuable as a screening assay for the detection of unscheduled DNA synthesis. Moreover, the use of human tissues may result in a better extrapolation to man.

  7. Life Cycle Risks for Human Health: A Comparison of Petroleum Versus Bio-Based Production of Five Bulk Organic Chemicals

    NARCIS (Netherlands)

    Roes, A.L.; Patel, M.K.

    2007-01-01

    This article describes the development and application of a generic approach to the comparative assessment of risks related to the production of organic chemicals by petrochemical processes versus white biotechnology. White biotechnology, also referred to as industrial biotechnology, typically uses

  8. Advances in chemical sensing technologies for VOCs in breath for security/threat assessment, illicit drug detection, and human trafficking activity.

    Science.gov (United States)

    Giannoukos, S; Agapiou, A; Taylor, S

    2018-01-17

    On-site chemical sensing of compounds associated with security and terrorist attacks is of worldwide interest. Other related bio-monitoring topics include identification of individuals posing a threat from illicit drugs, explosive manufacturing, as well as searching for victims of human trafficking and collapsed buildings. The current status of field analytical technologies is directed towards the detection and identification of vapours and volatile organic compounds (VOCs). Some VOCs are associated with exhaled breath, where research is moving from individual breath testing (volatilome) to cell breath (microbiome) and most recently to crowd breath metabolites (exposome). In this paper, an overview of field-deployable chemical screening technologies (both stand-alone and those with portable characteristics) is given with application to early detection and monitoring of human exposome in security operations. On-site systems employed in exhaled breath analysis, i.e. mass spectrometry (MS), optical spectroscopy and chemical sensors are reviewed. Categories of VOCs of interest include (a) VOCs in human breath associated with exposure to threat compounds, and (b) VOCs characteristic of, and associated with, human body odour (e.g. breath, sweat). The latter are relevant to human trafficking scenarios. New technological approaches in miniaturised detection and screening systems are also presented (e.g. non-scanning digital light processing linear ion trap MS (DLP-LIT-MS), nanoparticles, mid-infrared photo-acoustic spectroscopy and hyphenated technologies). Finally, the outlook for rapid and precise, real-time field detection of threat traces in exhaled breath is revealed and discussed.

  9. The purpose of adaptation.

    Science.gov (United States)

    Gardner, Andy

    2017-10-06

    A central feature of Darwin's theory of natural selection is that it explains the purpose of biological adaptation. Here, I: emphasize the scientific importance of understanding what adaptations are for, in terms of facilitating the derivation of empirically testable predictions; discuss the population genetical basis for Darwin's theory of the purpose of adaptation, with reference to Fisher's 'fundamental theorem of natural selection'; and show that a deeper understanding of the purpose of adaptation is achieved in the context of social evolution, with reference to inclusive fitness and superorganisms.

  10. The effects of chemical and physical factors on mammalian embryo culture and their importance for the practice of assisted human reproduction.

    Science.gov (United States)

    Wale, Petra L; Gardner, David K

    2016-01-01

    Although laboratory procedures, along with culture media formulations, have improved over the past two decades, the issue remains that human IVF is performed in vitro (literally 'in glass'). Using PubMed, electronic searches were performed using keywords from a list of chemical and physical factors with no limits placed on time. Examples of keywords include oxygen, ammonium, volatile organics, temperature, pH, oil overlays and incubation volume/embryo density. Available clinical and scientific evidence surrounding physical and chemical factors have been assessed and presented here. Development of the embryo outside the body means that it is constantly exposed to stresses that it would not experience in vivo. Sources of stress on the human embryo include identified factors such as pH and temperature shifts, exposure to atmospheric (20%) oxygen and the build-up of toxins in the media due to the static nature of culture. However, there are other sources of stress not typically considered, such as the act of pipetting itself, or the release of organic compounds from the very tissue culture ware upon which the embryo develops. Further, when more than one stress is present in the laboratory, there is evidence that negative synergies can result, culminating in significant trauma to the developing embryo. It is evident that embryos are sensitive to both chemical and physical signals within their microenvironment, and that these factors play a significant role in influencing development and events post transfer. From the viewpoint of assisted human reproduction, a major concern with chemical and physical factors lies in their adverse effects on the viability of embryos, and their long-term effects on the fetus, even as a result of a relatively brief exposure. This review presents data on the adverse effects of chemical and physical factors on mammalian embryos and the importance of identifying, and thereby minimizing, them in the practice of human IVF. Hence, optimizing the

  11. Methodology for national risk analysis and prioritization of toxic industrial chemicals.

    Science.gov (United States)

    Taxell, Piia; Engström, Kerstin; Tuovila, Juha; Söderström, Martin; Kiljunen, Harri; Vanninen, Paula; Santonen, Tiina

    2013-01-01

    The identification of chemicals that pose the greatest threat to human health from incidental releases is a cornerstone in public health preparedness for chemical threats. The present study developed and applied a methodology for the risk analysis and prioritization of industrial chemicals to identify the most significant chemicals that pose a threat to public health in Finland. The prioritization criteria included acute and chronic health hazards, physicochemical and environmental hazards, national production and use quantities, the physicochemical properties of the substances, and the history of substance-related incidents. The presented methodology enabled a systematic review and prioritization of industrial chemicals for the purpose of national public health preparedness for chemical incidents.

  12. Rapid Induction of Cerebral Organoids From Human Induced Pluripotent Stem Cells Using a Chemically Defined Hydrogel and Defined Cell Culture Medium.

    Science.gov (United States)

    Lindborg, Beth A; Brekke, John H; Vegoe, Amanda L; Ulrich, Connor B; Haider, Kerri T; Subramaniam, Sandhya; Venhuizen, Scott L; Eide, Cindy R; Orchard, Paul J; Chen, Weili; Wang, Qi; Pelaez, Francisco; Scott, Carolyn M; Kokkoli, Efrosini; Keirstead, Susan A; Dutton, James R; Tolar, Jakub; O'Brien, Timothy D

    2016-07-01

    Tissue organoids are a promising technology that may accelerate development of the societal and NIH mandate for precision medicine. Here we describe a robust and simple method for generating cerebral organoids (cOrgs) from human pluripotent stem cells by using a chemically defined hydrogel material and chemically defined culture medium. By using no additional neural induction components, cOrgs appeared on the hydrogel surface within 10-14 days, and under static culture conditions, they attained sizes up to 3 mm in greatest dimension by day 28. Histologically, the organoids showed neural rosette and neural tube-like structures and evidence of early corticogenesis. Immunostaining and quantitative reverse-transcription polymerase chain reaction demonstrated protein and gene expression representative of forebrain, midbrain, and hindbrain development. Physiologic studies showed responses to glutamate and depolarization in many cells, consistent with neural behavior. The method of cerebral organoid generation described here facilitates access to this technology, enables scalable applications, and provides a potential pathway to translational applications where defined components are desirable. Tissue organoids are a promising technology with many potential applications, such as pharmaceutical screens and development of in vitro disease models, particularly for human polygenic conditions where animal models are insufficient. This work describes a robust and simple method for generating cerebral organoids from human induced pluripotent stem cells by using a chemically defined hydrogel material and chemically defined culture medium. This method, by virtue of its simplicity and use of defined materials, greatly facilitates access to cerebral organoid technology, enables scalable applications, and provides a potential pathway to translational applications where defined components are desirable. ©AlphaMed Press.

  13. Prediction of the contact sensitizing potential of chemicals using analysis of gene expression changes in human THP-1 monocytes.

    Science.gov (United States)

    Arkusz, Joanna; Stępnik, Maciej; Sobala, Wojciech; Dastych, Jarosław

    2010-11-10

    The aim of this study was to find differentially regulated genes in THP-1 monocytic cells exposed to sensitizers and nonsensitizers and to investigate if such genes could be reliable markers for an in vitro predictive method for the identification of skin sensitizing chemicals. Changes in expression of 35 genes in the THP-1 cell line following treatment with chemicals of different sensitizing potential (from nonsensitizers to extreme sensitizers) were assessed using real-time PCR. Verification of 13 candidate genes by testing a large number of chemicals (an additional 22 sensitizers and 8 nonsensitizers) revealed that prediction of contact sensitization potential was possible based on evaluation of changes in three genes: IL8, HMOX1 and PAIMP1. In total, changes in expression of these genes allowed correct detection of sensitization potential of 21 out of 27 (78%) test sensitizers. The gene expression levels inside potency groups varied and did not allow estimation of sensitization potency of test chemicals. Results of this study indicate that evaluation of changes in expression of proposed biomarkers in THP-1 cells could be a valuable model for preliminary screening of chemicals to discriminate an appreciable majority of sensitizers from nonsensitizers. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  14. In vitro-in vivo extrapolation: estimation of human serum concentrations of chemicals equivalent to cytotoxic concentrations in vitro

    International Nuclear Information System (INIS)

    Guelden, Michael; Seibert, Hasso

    2003-01-01

    In the present study an extrapolation model for estimating serum concentrations of chemicals equivalent to in vitro effective concentrations is developed and applied to median cytotoxic concentrations (EC 50 ) determined in vitro. Nominal concentrations of a chemical in serum and in vitro are regarded as equivalent, if they result in the same aqueous concentration of the unbound form. The algorithm used is based on equilibrium distribution and requires albumin binding data, the octanol-water partition coefficient (K ow ), and the albumin concentrations and lipid volume fractions in vitro and in serum. The chemicals studied cover wide ranges of cytotoxic potency (EC 50 : 2.5-530000 μM) and lipophilicity (log K ow : -5 to 7). Their albumin binding characteristics have been determined by means of an in vitro cytotoxicity test as described previously. The equivalent serum concentrations of 19 of the 33 compounds investigated, having high protein binding and/or lipophilicity, were substantially higher than the EC 50 -values, by factors of 2.5-58. Prominent deviations between the equivalent nominal concentrations in serum and in vitro were largely restricted to chemicals with higher cytotoxic potency (EC 50 ≤1000 μM). The results suggest that estimates of equivalent serum concentrations based on in vitro data are robust for chemicals with low lipophilicity (log K ow ≤2) and low potency (EC 50 >1000 μM). With more potent chemicals or those with higher lipophilicity partitioning into lipids and/or binding to serum proteins have to be taken into account when estimating in vivo serum concentrations equivalent to in vitro effective concentrations

  15. Formation and repair of physically and chemically induced DNA damage in human cells. Final report, September 1, 1976-November 30, 1978

    International Nuclear Information System (INIS)

    Cerutti, P.A.

    1979-01-01

    The major topic was the study of the formation and repair of DNA damage by energy related physical and chemical agents in cultured human cells. Two pathways of damage production were distinguished: (1) indirect action, i.e., attack of DNA by active oxygen species which are formed by the reaction of the primary agent with a non-DNA target; and (2) direct action, i.e., reaction of the primary agent or a chemical derivative of the primary agent with DNA usually resulting in the formation of a covalent adduct. Near-ultraviolet light and ionizing radiation were studied as agents which operate at least in part via indirect action and benzo(a)pyrene as chemical carcinogen operating mostly by direct action. The formation of monomeric thymine damage of the 5,6-dihydroxy-dihydrothymine type by γ-rays and ultraviolet light was investigated. Indirect action of near-ultraviolet light is also responsible for the induction of DNA single strand breaks. Their formation and repair following exposure to 313 nm light was studied in skin fibroblasts from patients with the hereditary disease Xeroderma pigmentosum (XP). Excision repair of γ-ray induced 5,6-dihydroxy-dihydrothymine type lesions was studied in fibroblasts from Ataxia telangiectasia (AT) patients. The formation and repair of covalent purine adducts was studied in actively metabolizing rodent and human cells following treatment with the procarcinogen benzo(a)pyrene and with the ultimate metabolite benzo(a)pyrene-diol-epoxide I

  16. Xenobiotic-Metabolizing Enzyme and Transporter Gene Expression in Primary Cultures of Human Hepatocytes Modulated by Toxcast Chemicals

    Science.gov (United States)

    Primary human hepatocyte cultures are useful in vitro model systems of human liver because when cultured under appropriate conditions the hepatocytes retain liver-like functionality such as metabolism, transport, and cell signaling. This model system was used to characterize the ...

  17. 45 CFR 84.1 - Purpose.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Purpose. 84.1 Section 84.1 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE General Provisions § 84.1 Purpose. The...

  18. 10 CFR 712.31 - Purpose.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Purpose. 712.31 Section 712.31 Energy DEPARTMENT OF ENERGY HUMAN RELIABILITY PROGRAM Medical Standards § 712.31 Purpose. The standards and procedures set forth in... impairment in reliability; (b) Facilitate the early diagnosis and treatment of disease or impairment and...

  19. The chemical juggernaut.

    Science.gov (United States)

    Cadbury, D

    1997-01-01

    Man-made chemicals pervade and support every aspect of modern living. The chemical industry has become such a powerful force in the global economy, sales of synthetic chemicals and products derived from them constitute well in excess of a third of the world's gross national product. But, these man-made chemicals are also 'elixirs of death,' the symbol of human destruction. Laboratory tests have shown that a number of chemicals in common use possess a remarkable property: they can weakly mimic or modify the action of human hormones. It has been proven that some chemicals found in plastics, pesticides, and industrial products are weakly estrogenic, modifying the action of the female hormone. In addition, other chemicals affect the male hormones, androgens, or anti-androgens; others are thought to target different hormone systems, such as thyroid and adrenal glands. Many research studies are being conducted to establish the impact of chemicals on human health. Of special concern are the rising incidence of testicular cancer, decline in human sperm counts, and the sharp rise of breast cancer. In conclusion, although there is a worldwide debate on the effects of chemical exposure on humans, the significance of findings for human health, concerning testicular and breast cancer, are still unknown. An international treaty is called for to control the use of the persistent hormonally active chemicals.

  20. Identification of exposure to environmental chemicals in children and older adults using human biomonitoring data sorted by age

    DEFF Research Database (Denmark)

    Choi, Judy; Knudsen, Lisbeth E.; Mizrak, Seher

    2017-01-01

    /classes of chemicals with potentially higher body burden in children or older adults. Children appear to have higher body burden of bisphenol A (BPA), some phytoestrogens, perchlorate, and some metabolites of polycyclic aromatic hydrocarbons and benzene. On the other hand, older adults appear to have higher body...

  1. Correlation between chemical composition of dental calculus and bone samples in ancient human burials: perspectives in paleonutritional studies

    International Nuclear Information System (INIS)

    Capasso, L.; Di Tota, G.; Bondioli, L.

    1997-01-01

    Full text: The authors describe the results of an assay based on the comparison between chemical composition of dental calculus and bone respectively obtained from teeth and bones of ancient skeletons. The chemical analysis has been performed by synchrotron light. The concentrations of the following oligoelements having paleonutritional correlations were analysed: Fe, Cu, Zn, Pb, Sr and Ca. The authors demonstrate that- in a given individual the concentration of such elements in the bone sample were in the range of those obtained for the same elements in the sample of dental calculus. Such correspondence suggests that the chemical analysis of dental calculus may give paleonutritional indications analogous to those deriving from the analysis of bone samples. The authors underline also that the use of dental calculus has a distinct advantage over the use of bone samples, since it may allow a diachronic investigation. In fact, dental calculus typically presents a concentric pattern of growth, and the chemical composition of each layer may vary in accordance with temporal dietary variations. This is not the case for bone. This fact is the theoretical basis for the possible future development of techniques directed to the reconstruction of variations in the dietary habits of ancient individuals, possibly in relation to environmental seasonal changes

  2. Assessment of 16 chemicals on proliferation and apoptosis in human neuroprogenitor cells using high-content image analysis (HCA).

    Science.gov (United States)

    The need for efficient methods of screening chemicals for the potential to cause developmental neurotoxicity is paramount. We previously described optimization of an HCA assay for proliferation and apoptosis in ReNcell CX cells (ReN), identifying appropriate controls. Utility of ...

  3. Predicting Developmental Toxicity of ToxCast Phase I Chemicals Using Human Embryonic Stem Cells and Metabolomics

    Science.gov (United States)

    EPA’s ToxRefDB contains prenatal guideline study data from rats and rabbits for over 240 chemicals that overlap with the ToxCast in vitro high throughput screening project. A subset of these compounds were tested in Stemina Biomarker Discovery's developmental toxicity platform, a...

  4. Using Alternative Approaches to Prioritize Testing for the Universe of Chemicals with Potential for Human Exposure (WC9)

    Science.gov (United States)

    One use of alternative methods is to target animal use at only those chemicals and tests that are absolutely necessary. We discuss prioritization of testing based on high-throughput screening assays (HTS), QSAR modeling, high-throughput toxicokinetics (HTTK), and exposure modelin...

  5. Diuron-induced rat urinary bladder carcinogenesis: mode of action and human relevance evaluations using the International Programme on Chemical Safety framework.

    Science.gov (United States)

    Da Rocha, Mitscheli Sanches; Arnold, Lora L; De Oliveira, Maria Luiza Cotrim Sartor; Catalano, Shadia M Ihlaseh; Cardoso, Ana Paula Ferragut; Pontes, Merielen G N; Ferrucio, Bianca; Dodmane, Puttappa R; Cohen, Samuel M; De Camargo, João Lauro V

    2014-05-01

    Diuron, a high volume substituted urea herbicide, induced high incidences of urinary bladder carcinomas and low incidences of kidney pelvis papillomas and carcinomas in rats exposed to high doses (2500 ppm) in a 2-year bioassay. Diuron is registered for both occupational and residential uses and is used worldwide for more than 30 different crops. The proposed rat urothelial mode of action (MOA) for this herbicide consists of metabolic activation to metabolites that are excreted and concentrated in the urine, leading to cytotoxicity, urothelial cell necrosis and exfoliation, regenerative hyperplasia, and eventually tumors. We show evidence for this MOA for diuron using the International Programme on Chemical Safety (IPCS) conceptual framework for evaluating an MOA for chemical carcinogens, and the United States Environmental Protection Agency (USEPA) and IPCS framework for assessing human relevance.

  6. A rapid chemical method of labelling human plasma proteins with sup(99m)Tc-pertechnetate at pH 7.4

    International Nuclear Information System (INIS)

    Wong, D.W.; Mishkin, F.; Lee, T.

    1978-01-01

    A successful method for labelling human plasma proteins with sup(99m)Tc-pertechnetate by chemical means is described. The labelling methodology involves the production of Sup(99m)Tc-(Sn)citrate complex species with high protein binding capacity at pH 7.4 condition following initial chemical reduction of sodium sup(99m)Tc-pertechnetate by stannous chloride. A combined labelling efficiency range of 95-99% for sup(99m)Tc-labelled fibrinogen, immune gamma globulin and serum albumin is achieved. The actual amount of labelled protein content in the product is found to be 85-95% when assayed by ITLC and 74-85% by TCAA protein precipitation. In vitro experimental data indicate that sup(99m)Tc-fibrinogen contains an average of 85% clottable protein with an average clottability of 95%. This strongly suggests that the radioactive proteins retain much of their biological and physiological activities after the labelling process. (author)

  7. Combining purpose with profits

    NARCIS (Netherlands)

    Birkinshaw, J.; Foss, N.J.; Lindenberg, S.M.

    2014-01-01

    Is it possible for a company to strive for a higher purpose while also delivering solid profits? Some have argued that pursuing goals other than making money means, by definition, spending on things that aren't profit-maximizing. Others have countered that by investing in worthwhile causes the

  8. JENDL special purpose file

    International Nuclear Information System (INIS)

    Nakagawa, Tsuneo

    1995-01-01

    In JENDL-3,2, the data on all the reactions having significant cross section over the neutron energy from 0.01 meV to 20 MeV are given for 340 nuclides. The object range of application extends widely, such as the neutron engineering, shield and others of fast reactors, thermal neutron reactors and nuclear fusion reactors. This is a general purpose data file. On the contrary to this, the file in which only the data required for a specific application field are collected is called special purpose file. The file for dosimetry is a typical special purpose file. The Nuclear Data Center, Japan Atomic Energy Research Institute, is making ten kinds of JENDL special purpose files. The files, of which the working groups of Sigma Committee are in charge, are listed. As to the format of the files, ENDF format is used similarly to JENDL-3,2. Dosimetry file, activation cross section file, (α, n) reaction data file, fusion file, actinoid file, high energy data file, photonuclear data file, PKA/KERMA file, gas production cross section file and decay data file are described on their contents, the course of development and their verification. Dosimetry file and gas production cross section file have been completed already. As for the others, the expected time of completion is shown. When these files are completed, they are opened to the public. (K.I.)

  9. Meaningful and Purposeful Practice

    Science.gov (United States)

    Clementi, Donna

    2014-01-01

    This article describes a graphic, designed by Clementi and Terrill, the authors of "Keys to Planning for Learning" (2013), visually representing the components that contribute to meaningful and purposeful practice in learning a world language, practice that leads to greater proficiency. The entire graphic is centered around the letter…

  10. New methods for field collection of human skin volatiles and perspectives for their application in the chemical ecology of human-pathogen-vector interactions.

    Science.gov (United States)

    Dormont, Laurent; Bessière, Jean-Marie; McKey, Doyle; Cohuet, Anna

    2013-08-01

    Odours emitted by human skin are of great interest to biologists in many fields, with practical applications in forensics, health diagnostic tools and the ecology of blood-sucking insect vectors of human disease. Convenient methods are required for sampling human skin volatiles under field conditions. We experimentally compared four modern methods for sampling skin odours: solvent extraction, headspace solid-phase micro-extraction (SPME), and two new techniques not previously used for the study of mammal volatiles, contact SPME and dynamic headspace with a chromatoprobe design. These methods were tested and compared both on European subjects under laboratory conditions and on young African subjects under field conditions. All four methods permitted effective trapping of skin odours, including the major known human skin volatile compounds. In both laboratory and field experiments, contact SPME, in which the time of collection was restricted to 3 min, provided results very similar to those obtained with classical headspace SPME, a method that requires 45 min of collection. Chromatoprobe sampling also proved to be very sensitive, rapid and convenient for the collection of human-produced volatiles in natural settings. Both contact SPME and chromatoprobe design may considerably facilitate the study of human skin volatiles under field conditions, opening new possibilities for examining the olfactory cues mediating the host-seeking behaviour of mosquito vectors implicated in the transmission of major diseases.

  11. Saliva Preservative for Diagnostic Purposes

    Science.gov (United States)

    Pierson, Duane L.; Mehta, Satish K.

    2012-01-01

    Saliva is an important body fluid for diagnostic purposes. Glycoproteins, glucose, steroids, DNA, and other molecules of diagnostic value are found in saliva. It is easier to collect as compared to blood or urine. Unfortunately, saliva also contains large numbers of bacteria that can release enzymes, which can degrade proteins and nucleic acids. These degradative enzymes destroy or reduce saliva s diagnostic value. This innovation describes the formulation of a chemical preservative that prevents microbial growth and inactivates the degradative enzymes. This extends the time that saliva can be stored or transported without losing its diagnostic value. Multiple samples of saliva can be collected if needed without causing discomfort to the subject and it does not require any special facilities to handle after it is collected.

  12. Chemical applicability domain of the local lymph node assay (LLNA) for skin sensitisation potency. Part 4. Quantitative correlation of LLNA potency with human potency.

    Science.gov (United States)

    Roberts, David W; Api, Anne Marie

    2018-07-01

    Prediction of skin sensitisation potential and potency by non-animal methods is the target of many active research programmes. Although the aim is to predict sensitisation potential and potency in humans, data from the murine local lymph node assay (LLNA) constitute much the largest source of quantitative data on in vivo skin sensitisation. The LLNA has been the preferred in vivo method for identification of skin sensitising chemicals and as such is potentially valuable as a benchmark for assessment of non-animal approaches. However, in common with all predictive test methods, the LLNA is subject to false positives and false negatives with an overall level of accuracy said variously to be approximately 80% or 90%. It is also necessary to consider the extent to which, for true positives, LLNA potency correlates with human potency. In this paper LLNA potency and human potency are compared so as to express quantitatively the correlation between them, and reasons for non-agreement between LLNA and human potency are analysed. This leads to a better definition of the applicability domain of the LLNA, within which LLNA data can be used confidently to predict human potency and as a benchmark to assess the performance of non-animal approaches. Copyright © 2018. Published by Elsevier Inc.

  13. Does the recommended lymphocyte cytokinesis-block micronucleus assay for human biomonitoring actually detect DNA damage induced by occupational and environmental exposure to genotoxic chemicals?

    Science.gov (United States)

    Speit, Günter

    2013-07-01

    This commentary challenges the paradigm that the cytokinesis-block micronucleus assay (CBMN assay) with cultured human lymphocytes, as it is performed currently, is a sensitive and useful tool for detecting genotoxic effects in populations exposed occupationally or environmentally to genotoxic chemicals. Based on the principle of the assay and the available data, increased micronucleus (MN) frequencies in binucleated cells (BNC) are mainly due to MN produced in vitro during the cultivation period (i.e. MN produced in vivo do not substantially contribute to the MN frequency measured in BNC). The sensitivity of the assay for the detection of induced MN in BNC after an in vivo exposure to a genotoxic chemical is limited because cytochalasin B (Cyt-B) is added relatively late during the culture period and, therefore, the BNC that are scored do not always represent cells that have completed one cell cycle only. Furthermore, this delay means that damaged cells can be eliminated by apoptosis and/or that DNA damage induced in vivo can be repaired prior to the production of a MN in the presence of Cyt-B. A comparison with the in vitro CBMN assay used for genotoxicity testing leads to the conclusion that it is highly unlikely that DNA damage induced in vivo is the cause for increased MN frequencies in BNC after occupational or environmental exposure to genotoxic chemicals. This commentary casts doubt on the usefulness of the CBMN assay as an indicator of genotoxicity in human biomonitoring and questions the relevance of many published data for hazard identification and risk assessment. Thus, it seems worthwhile to reconsider the use of the CBMN assay as presently conducted for the detection of genotoxic exposure in human biomonitoring.

  14. Evaluation of selected biomarkers for the detection of chemical sensitization in human skin: a comparative study applying THP-1, MUTZ-3 and primary dendritic cells in culture.

    Science.gov (United States)

    Hitzler, Manuel; Bergert, Antje; Luch, Andreas; Peiser, Matthias

    2013-09-01

    Dendritic cells (DCs) exhibit the unique capacity to induce T cell differentiation and proliferation, two processes that are crucially involved in allergic reactions. By combining the exclusive potential of DCs as the only professional antigen-presenting cells of the human body with the well known handling advantages of cell lines, cell-based alternative methods aimed at detecting chemical sensitization in vitro commonly apply DC-like cells derived from myeloid cell lines. Here, we present the new biomarkers programmed death-ligand 1 (PD-L1), DC immunoreceptor (DCIR), IL-16, and neutrophil-activating protein-2 (NAP-2), all of which have been detectable in primary human DCs upon exposure to chemical contact allergens. To evaluate the applicability of DC-like cells in the prediction of a chemical's sensitization potential, the expression of cell surface PD-L1 and DCIR was analyzed. In contrast to primary DCs, only minor subpopulations of MUTZ-3 and THP-1 cells presented PD-L1 or DCIR at their surface. After exposure to increasing concentrations of nickel and cinnamic aldehyde, the expression level of PD-L1 and DCIR revealed much stronger affected on monocyte-derived DCs (MoDCs) or Langerhans cells (MoLCs) when compared to THP-1 and MUTZ-3 cells. Applying protein profiler arrays we further identified the soluble factors NAP-2, IL-16, IL-8 and MIP-1α as sensitive biomarkers showing the capacity to discriminate sensitizing from non-sensitizing chemicals or irritants. An allergen-specific release of IL-8 and MIP-1α could be detected in the supernatants of MoDCs and MoLCs and also in MUTZ-3 and THP-1 cells, though at much lower levels. On the protein and transcriptional level, NAP-2 and IL-16 indicated sensitizers most sensitively and specifically in MoDCs. Altogether, we have proven the reciprocal regulated surface molecules PD-L1 and DCIR and the soluble factors MIP-1α, NAP-2 and IL-16 as reliable biomarkers for chemical sensitization. We further show that primary

  15. Utilization of reconstructed cultured human skin models as an alternative skin for permeation studies of chemical compounds

    OpenAIRE

    Kano, Satoshi; 藤堂, 浩明; 杉江, 謙一; 藤本, 英哲; 中田, 圭一; 徳留, 嘉寛; 橋本, フミ惠; 杉林, 堅次

    2010-01-01

    Two reconstructed human skin models, EpiskinSM and EpiDermTM, have been approved as alternative membranes for skin corrosive/irritation experiments due to their close correlation with animal skin. Such reconstructed human skin models were evaluated as alternative membranes for skin permeation experiments. Seven drugs with different lipophilicities and almost the same molecular weight were used as test penetrants. Relationships were investigated between permeability coefficients (P values) of ...

  16. 45 CFR 73.735-101 - Purpose.

    Science.gov (United States)

    2010-10-01

    ... Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION STANDARDS OF CONDUCT General Provisions § 73.735-101 Purpose. To assure that the business of the Department of Health and Human Services... responsibilities. In accord with these principles, the regulations in this part are issued to inform HHS employees...

  17. Fit-for-Purpose

    DEFF Research Database (Denmark)

    Enemark, Stig

    2013-01-01

    ; completeness to cover the total jurisdiction; and credibility in terms of reliable data being trusted by the users. Accuracy can then be incrementally improved over time when relevant and justified by serving the needs of citizen, business and society in general. Such a fit-for-purpose approach is fundamental...... systems act within adopted land policies that define the legal regulatory pattern for dealing with land issues. Land administration systems - whether highly advanced or very basic – require a spatial framework to operate. This framework provides the fundamental information for dealing with land issues...... concepts may well be seen as the end target but not as the point of entry. When assessing the technology and investment choices the focus should be on building a fit-for-purpose framework that will meet the needs of society today and that can be incrementally improved over time....

  18. Purposeful engineering economics

    CERN Document Server

    Chadderton, Ronald A

    2015-01-01

    This textbook/course supplement stands as a unique and highly original complement to the traditional engineering economics curriculum. Its primarily narrative approach conveys the essence of an “Austrian" economic perspective on cash flow analysis and decision making in engineering, without extensive tables and graphs, and requires very little mathematics. The book’s objective is to add a new perspective to the usual study of cash flow analysis and solely econometric engineering decision making. The author draws on the methodology of the Austrian Economists—a school of economic thought that bases its study of economic phenomena on the interpretation and analysis of the purposeful actions of individuals. The book includes an array of illustrative case studies examined in detail by the author and emphasizes the importance of market processes and price signals to coordinate engineering plans. Purposeful Engineering Economics is an ideal resource for students, teaching faculty, and practicing professional ...

  19. Vitalism, purpose and superstition.

    Science.gov (United States)

    Lindeman, Marjaana; Saher, Marieke

    2007-02-01

    Developmental studies have shown that children assign purpose to objects more liberally than adults, and that they explain biological processes in terms of vitalistic causality. This study tested the hypothesis that similar misconceptions can be found among superstitious adults. The results from 116 superstitious and 123 sceptical individuals showed that more than sceptics, superstitious individuals attributed purpose to objects, and explained biological processes in terms of organ intentionality and energy transmission. In addition, they thought of energy as a vital force, attributing life and mental properties to it. These conceptual confusions were positively associated to all types of superstitions as well as belief in alternative medicine. The results support the argument that category mistakes and ontological confusions underlie superstitious and vitalistic thinking.

  20. Analysis of human plasma metabolites across different liquid chromatography/mass spectrometry platforms: Cross-platform transferable chemical signatures.

    Science.gov (United States)

    Telu, Kelly H; Yan, Xinjian; Wallace, William E; Stein, Stephen E; Simón-Manso, Yamil

    2016-03-15

    The metabolite profiling of a NIST plasma Standard Reference Material (SRM 1950) on different liquid chromatography/mass spectrometry (LC/MS) platforms showed significant differences. Although these findings suggest caution when interpreting metabolomics results, the degree of overlap of both profiles allowed us to use tandem mass spectral libraries of recurrent spectra to evaluate to what extent these results are transferable across platforms and to develop cross-platform chemical signatures. Non-targeted global metabolite profiles of SRM 1950 were obtained on different LC/MS platforms using reversed-phase chromatography and different chromatographic scales (conventional HPLC, UHPLC and nanoLC). The data processing and the metabolite differential analysis were carried out using publically available (XCMS), proprietary (Mass Profiler Professional) and in-house software (NIST pipeline). Repeatability and intermediate precision showed that the non-targeted SRM 1950 profiling was highly reproducible when working on the same platform (relative standard deviation (RSD) HPLC, UHPLC and nanoLC) on the same platform. A substantial degree of overlap (common molecular features) was also found. A procedure to generate consistent chemical signatures using tandem mass spectral libraries of recurrent spectra is proposed. Different platforms rendered significantly different metabolite profiles, but the results were highly reproducible when working within one platform. Tandem mass spectral libraries of recurrent spectra are proposed to evaluate the degree of transferability of chemical signatures generated on different platforms. Chemical signatures based on our procedure are most likely cross-platform transferable. Published in 2016. This article is a U.S. Government work and is in the public domain in the USA.

  1. The purpose of astronomy

    OpenAIRE

    Davoust, Emmanuel

    1995-01-01

    This is a presentation of the purpose of astronomy in the context of modern society. After exposing two misconceptions about astronomy, I detail its role in five domains, certified knowledge, incorporated abilities, innovations, collective goods, and popular science; with each domain is associated an institution, an incentive, and a method of evaluation. Finally, I point out the role of astronomy as a source of inspiration in other fields than science.

  2. A comparative study of some physico-chemical properties of human serum albumin samples from different sources--I : Some physico-chemical properties of isoionic human serum albumin solutions

    NARCIS (Netherlands)

    Dröge, J.H.M.; Janssen, L.H.M.; Wilting, J.

    1982-01-01

    Human serum albumin samples from different sources were investigated. The fatty acid content of the albumin before and after deionization on a mixed bed ion-exchange column varied from sample to sample. When an albumin sample from one source was deionized under standard conditions the amount of

  3. Chemical Peels

    Science.gov (United States)

    ... care Kids’ zone Video library Find a dermatologist Chemical peels Overview Chemical peels: Overview Also called chemexfoliation , derma peeling Do ... Overview Chemical peels: FAQs Chemical peels: Preparation FAQs Chemical peels: FAQs To help you decide whether this ...

  4. Chemical Constituents of Propolis from Vietnamese Trigona minor and Their Antiausterity Activity against the PANC-1 Human Pancreatic Cancer Cell Line.

    Science.gov (United States)

    Nguyen, Hai X; Nguyen, Mai T T; Nguyen, Nhan T; Awale, Suresh

    2017-08-25

    The ethanol extract of propolis from the Vietnamese stingless bee Trigona minor possessed potent preferential cytotoxicity against PANC-1 human pancreatic cancer cells in nutrient-deprived medium, with a PC 50 value of 14.0 μg/mL. Chemical investigation of this extract led to the isolation of 15 cycloartane-type triterpenoids, including five new compounds (1-5), and a lanostane-type triterpenoid. The structures of the new compounds were elucidated on the basis of NMR spectroscopic analysis. Among the isolated compounds, 23-hydroxyisomangiferolic acid B (5) and 27-hydroxyisomangiferolic acid (13) exhibited the most potent preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrition-deprived conditions, with PC 50 values of 4.3 and 3.7 μM, respectively.

  5. Identification and quantification of flavonoids in human urine samples by column switching liquid chromatography coupled to atmospheric pressure chemical ionization mass spectrometry

    DEFF Research Database (Denmark)

    Nielsen, S. E.; Freese, R.; Cornett, Claus

    2000-01-01

    A rapid and sensitive high-performance liquid chromatographic mass spectrometric (HPLC-MS) method is described for the determination and quantification of 12 dietary flavonoid glycosides and aglycons in human urine samples. Chromatographic separation of the analytes of interest was achieved...... by column-switching, using the first column (a Zorbax 300SB C-3 column) for sample cleanup and eluting the heart-cut flavonoid fraction onto the second column (a Zorbax SE C-18 column) for separation and detection by ultraviolet and atmospheric pressure chemical ionization MS using single ion monitoring...... of variation for the analysis of the 12 different flavonoids in quality control urine samples were 12.3% on average (range 11.0-13.7%, n = 24, reproducibility) and the repeatability of the assay were 5.0% (mean, range 0.1-14.8%, it = 12). A subset of 10 urine samples from a human dietary intervention study...

  6. Female sexual maturation and reproduction after prepubertal exposure to estrogens and endocrine disrupting chemicals: a review of rodent and human data.

    Science.gov (United States)

    Rasier, G; Toppari, J; Parent, A-S; Bourguignon, J-P

    2006-07-25

    Natural hormones and some synthetic chemicals spread into our surrounding environment share the capacity to interact with hormone action and metabolism. Exposure to such compounds can cause a variety of developmental and reproductive detrimental abnormalities in wildlife species and, potentially, in human. Many experimental and epidemiological data have reported that exposure of the developing fetus or neonate to environmentally relevant concentrations of some among these endocrine disrupters induces morphological, biochemical and/or physiological disorders in brain and reproductive organs, by interfering with the hormone actions. The impact of such exposures on the hypothalamic-pituitary-gonadal axis and subsequent sexual maturation is the subject of the present review. We will highlight epidemiological human studies and the effects of early exposure during gestational, perinatal or postnatal life in female rodents.

  7. A new approach towards biomarker selection in estimation of human exposure to chiral chemicals: a case study of mephedrone.

    Science.gov (United States)

    Castrignanò, Erika; Mardal, Marie; Rydevik, Axel; Miserez, Bram; Ramsey, John; Shine, Trevor; Pantoș, G Dan; Meyer, Markus R; Kasprzyk-Hordern, Barbara

    2017-11-02

    Wastewater-based epidemiology is an innovative approach to estimate public health status using biomarker analysis in wastewater. A new compound detected in wastewater can be a potential biomarker of an emerging trend in public health. However, it is currently difficult to select new biomarkers mainly due to limited human metabolism data. This manuscript presents a new framework, which enables the identification and selection of new biomarkers of human exposure to drugs with scarce or unknown human metabolism data. Mephedrone was targeted to elucidate the assessment of biomarkers for emerging drugs of abuse using a four-step analytical procedure. This framework consists of: (i) identification of possible metabolic biomarkers present in wastewater using an in-vivo study; (ii) verification of chiral signature of the target compound; (iii) confirmation of human metabolic residues in in-vivo/vitro studies and (iv) verification of stability of biomarkers in wastewater. Mephedrone was selected as a suitable biomarker due to its high stability profile in wastewater. Its enantiomeric profiling was studied for the first time in biological and environmental matrices, showing stereoselective metabolism of mephedrone in humans. Further biomarker candidates were also proposed for future investigation: 4'-carboxy-mephedrone, 4'-carboxy-normephedrone, 1-dihydro-mephedrone, 1-dihydro-normephedrone and 4'-hydroxy-normephedrone.

  8. Assumed non-persistent environmental chemicals in human adipose tissue; matrix stability and correlation with levels measured in urine and serum.

    Science.gov (United States)

    Artacho-Cordón, F; Arrebola, J P; Nielsen, O; Hernández, P; Skakkebaek, N E; Fernández, M F; Andersson, A M; Olea, N; Frederiksen, H

    2017-07-01

    The aim of this study was to (1) optimize a method for the measurement of parabens and phenols in adipose tissue, (2) evaluate the stability of chemical residues in adipose tissue samples, and (3) study correlations of these compounds in urine, serum, and adipose tissue. Samples were obtained from adults undergoing trauma surgery. Nine phenols and seven parabens were determined by isotope diluted TurboFlow-LC-MS/MS. The analytical method showed good accuracy and precision. Limits of detection (LOD) for parabens and phenols ranged from 0.05 to 1.83ng/g tissue. Good recovery rates were found, even when biological samples remained defrosted up to 24h. Benzophenone-3 (BP-3; range of values: 70% of adipose tissue samples, while bisphenol-A (BPA; 40% of adipose tissue samples. In general, levels were similar between adipose tissue and serum, while a correlation between adipose tissue and urine was only found for BP-3. In conclusion, adipose tissue samples in this study were found to contain environmental chemicals considered to be non-persistent, whose levels were weakly or not at all correlated with the urine burden. Therefore, adipose tissue may potentially provide additional information to that obtained from other biological matrices. Further investigations are warranted to explore whether adipose tissue might be a suitable matrix for assessment of the consequences for human health of mid/long-term exposure to these chemicals. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Multi purpose research reactor

    International Nuclear Information System (INIS)

    Raina, V.K.; Sasidharan, K.; Sengupta, Samiran; Singh, Tej

    2006-01-01

    At present Dhruva and Cirus reactors provide the majority of research reactor based facilities to cater to the various needs of a vast pool of researchers in the field of material sciences, physics, chemistry, bio sciences, research and development work for nuclear power plants and production of radio isotopes. With a view to further consolidate and expand the scope of research and development in nuclear and allied sciences, a new 20 MWt multi purpose research reactor is being designed. This paper describes some of the design features and safety aspects of this reactor

  10. Purpose of the workshop

    International Nuclear Information System (INIS)

    Brunner, H.

    1998-01-01

    The main purpose of the Workshop is to share the experience on emergency data management and to review various conceptual, technical, organisational and operational aspects and problems. The problems posed by hardware and software, the interplay of software developers and users/operators and the positive and negative experiences both from development and operation of data management systems are discussed. Emergency data management systems and their demonstrations are divided into four classes of possible applications: video games, training and simulation systems, 'history writing' = post-event analysis and documentation systems, real-time operational systems. (author)

  11. Responses of genes involved in cell cycle control to diverse DNA damaging chemicals in human lung adenocarcinoma A549 cells

    Directory of Open Access Journals (Sweden)

    Gooderham Nigel J

    2005-08-01

    Full Text Available Abstract Background Many anticancer agents and carcinogens are DNA damaging chemicals and exposure to such chemicals results in the deregulation of cell cycle progression. The molecular mechanisms of DNA damage-induced cell cycle alteration are not well understood. We have studied the effects of etoposide (an anticancer agent, cryptolepine (CLP, a cytotoxic alkaloid, benzo [a]pyrene (BaP, a carcinogenic polycyclic aromatic hydrocarbon and 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP, a cooked-meat derived carcinogen on the expression of cell cycle regulatory genes to understand the molecular mechanisms of the cell cycle disturbance. Results A549 cells were treated with DMSO or chemicals for up to 72 h and periodically sampled for cell cycle analysis, mRNA and protein expression. DMSO treated cells showed a dominant G1 peak in cell cycle at all times examined. Etoposide and CLP both induced G2/M phase arrest yet the former altered the expression of genes functioning at multiple phases, whilst the latter was more effective in inhibiting the expression of genes in G2-M transition. Both etoposide and CLP induced an accumulation of p53 protein and upregulation of p53 transcriptional target genes. Neither BaP nor PhIP had substantial phase-specific cell cycle effect, however, they induced distinctive changes in gene expression. BaP upregulated the expression of CYP1B1 at 6–24 h and downregulated many cell cycle regulatory genes at 48–72 h. By contrast, PhIP increased the expression of many cell cycle regulatory genes. Changes in the expression of key mRNAs were confirmed at protein level. Conclusion Our experiments show that DNA damaging agents with different mechanisms of action induced distinctive changes in the expression pattern of a panel of cell cycle regulatory genes. We suggest that examining the genomic response to chemical exposure provides an exceptional opportunity to understand the molecular mechanism involved in cellular

  12. Application of cation-exchange solid-phase extraction for the analysis of amino alcohols from water and human plasma for verification of Chemical Weapons Convention.

    Science.gov (United States)

    Kanaujia, Pankaj K; Tak, Vijay; Pardasani, Deepak; Gupta, A K; Dubey, D K

    2008-03-28

    The analysis of nitrogen containing amino alcohols, which are the precursors and degradation products of nitrogen mustards and nerve agent VX, constitutes an important aspect for verifying the compliance to the CWC (Chemical Weapons Convention). This work devotes on the development of solid-phase extraction method using silica- and polymer-based SCX (strong cation-exchange) and MCX (mixed-mode strong cation-exchange) cartridges for N,N-dialkylaminoethane-2-ols and alkyl N,N-diethanolamines, from water. The extracted analytes were analyzed by GC-MS (gas chromatography-mass spectrometry) in the full scan and selected ion monitoring modes. The extraction efficiencies of SCX and MCX cartridges were compared, and results revealed that SCX performed better. Extraction parameters, such as loading capacity, extraction solvent, its volume, and washing solvent were optimized. Best recoveries were obtained using 2 mL methanol containing 10% NH(4)OH and limits of detection could be achieved up to 5 x 10(-3) microg mL(-1) in the selected ion monitoring mode and 0.01 microg mL(-1) in full scan mode. The method was successfully employed for the detection and identification of amino alcohol present in water sample sent by Organization for Prohibition of Chemical Weapons (OPCW) in the official proficiency tests. The method was also applied to extract the analytes from human plasma. The SCX cartridge showed good recoveries of amino alcohols from human plasma after protein precipitation.

  13. Induction of molecular endpoints by reactive oxygen species in human lung cells predicted by physical chemical properties of engineered nanoparticles

    Science.gov (United States)

    A series of six titanium dioxide and two cerium oxide engineered nanomaterials were assessed for their ability to induce cytotoxicity, reactive oxygen species (ROS), and various types of DNA and protein damage in human respiratory BEAS-2B cells exposed in vitro for 72 hours at se...

  14. Studying Human Resource Information Systems Implementation using Adaptive Structuration Theory: The Case of an HRIS Implementation at Dow Chemical Company

    NARCIS (Netherlands)

    Ruel, Hubertus Johannes Maria; Chiemeke, Charles C.; Bondarouk, Tatiana; Ruel, Hubertus Johannes Maria; Guiderdoni-Jourdain, Karine; Oiry, Ewan

    2009-01-01

    Research on Human Resource Information Systems (HRIS) implementation lacks theoretical depth and richness. For that reason this paper applies a theory to HRIS implementation developed by Gerardine DeSanctis and Marshal Scott Poole originally for studying information systems implementation, namely

  15. Eye Irritation Test (EIT) for Hazard Identification of Eye Irritating Chemicals using Reconstructed Human Cornea-like Epithelial (RhCE) Tissue Model.

    Science.gov (United States)

    Kaluzhny, Yulia; Kandárová, Helena; d'Argembeau-Thornton, Laurence; Kearney, Paul; Klausner, Mitchell

    2015-08-23

    To comply with the Seventh Amendment to the EU Cosmetics Directive and EU REACH legislation, validated non-animal alternative methods for reliable and accurate assessment of ocular toxicity in man are needed. To address this need, we have developed an eye irritation test (EIT) which utilizes a three dimensional reconstructed human cornea-like epithelial (RhCE) tissue model that is based on normal human cells. The EIT is able to separate ocular irritants and corrosives (GHS Categories 1 and 2 combined) and those that do not require labeling (GHS No Category). The test utilizes two separate protocols, one designed for liquid chemicals and a second, similar protocol for solid test articles. The EIT prediction model uses a single exposure period (30 min for liquids, 6 hr for solids) and a single tissue viability cut-off (60.0% as determined by the MTT assay). Based on the results for 83 chemicals (44 liquids and 39 solids) EIT achieved 95.5/68.2/ and 81.8% sensitivity/specificity and accuracy (SS&A) for liquids, 100.0/68.4/ and 84.6% SS&A for solids, and 97.6/68.3/ and 83.1% for overall SS&A. The EIT will contribute significantly to classifying the ocular irritation potential of a wide range of liquid and solid chemicals without the use of animals to meet regulatory testing requirements. The EpiOcular EIT method was implemented in 2015 into the OECD Test Guidelines as TG 492.

  16. Chemical engineering aspects in medicine

    Energy Technology Data Exchange (ETDEWEB)

    Chmiel, H

    1981-04-01

    Many basic chemical engineering processes are based on transport processes due, for example, to differences in temperature, pressure, and concentration. Such transport processes abound in the healthy circulatory system. Thus, metabolic processes supply the human body with the necessary warmth. The heart serves as a blood pump to provide optimal blood pressure in all vessels. Highly complex membranes in the kidneys ensure the efficient detoxification of the blood. It is therefore natural that the chemical engineer be involved in the solution of a number of biomedical engineering problems that come up in the field of medicine. Some typical tasks are: the characterization of the flow properties of biological fluids; research on the interaction between blood and foreign substances of the purpose of finding materials suitable for temporary or permanent use in the body and the development of blood pumps and artifical substitutes for the lungs, the liver, and the kidneys.

  17. CON4EI: SkinEthic™ Human Corneal Epithelium Eye Irritation Test (SkinEthic™ HCE EIT) for hazard identification and labelling of eye irritating chemicals.

    Science.gov (United States)

    Van Rompay, A R; Alépée, N; Nardelli, L; Hollanders, K; Leblanc, V; Drzewiecka, A; Gruszka, K; Guest, R; Kandarova, H; Willoughby, J A; Verstraelen, S; Adriaens, E

    2018-06-01

    Assessment of ocular irritancy is an international regulatory requirement and a necessary step in the safety evaluation of industrial and consumer products. Although a number of in vitro ocular irritation assays exist, none are capable of fully categorizing chemicals as a stand-alone assay. Therefore, the CEFIC-LRI-AIMT6-VITO CON4EI (CONsortium for in vitro Eye Irritation testing strategy) project was developed with the goal of assessing the reliability of eight in vitro/alternative test methods as well as establishing an optimal tiered-testing strategy. One of the in vitro assays selected was the validated SkinEthic™ Human Corneal Epithelium Eye Irritation Test method (SkinEthic™ HCE EIT). The SkinEthic™ HCE EIT has already demonstrated its capacity to correctly identify chemicals (both substances and mixtures) not requiring classification and labelling for eye irritation or serious eye damage (No Category). The goal of this study was to evaluate the performance of the SkinEthic™ HCE EIT test method in terms of the important in vivo drivers of classification. For the performance with respect to the drivers all in vivo Cat 1 and No Cat chemicals were 100% correctly identified. For Cat 2 chemicals the liquids and the solids had a sensitivity of 100% and 85.7%, respectively. For the SkinEthic™ HCE EIT test method, 100% concordance in predictions (No Cat versus No prediction can be made) between the two participating laboratories was obtained. The accuracy of the SkinEthic™ HCE EIT was 97.5% with 100% sensitivity and 96.9% specificity. The SkinEthic™ HCE EIT confirms its excellent results of the validation studies. Copyright © 2017. Published by Elsevier Ltd.

  18. Multi-purpose hull

    International Nuclear Information System (INIS)

    Taylor, W.C.; Horgan, J.B.G.; Downie, D.M.

    1982-01-01

    An 18 sided hull approximately 4 metres in diameter formed in prefabricated watertight sections from GRP has been designed for burying underground to withstand an overpressure of 12P.S.I above normal atmospheric pressure for human protection against a nuclear explosion and resultant radioactivity. The pre-fabricated sections are so designed to be stacked together prior to assembling and the assembled hulls can also be stacked together both vertically and horizontally in a honeycomb formation to form a multiple chamber. (author)

  19. Managing major chemical accidents in China: Towards effective risk information

    International Nuclear Information System (INIS)

    He Guizhen; Zhang Lei; Lu Yonglong; Mol, Arthur P.J.

    2011-01-01

    Chemical industries, from their very inception, have been controversial due to the high risks they impose on safety of human beings and the environment. Recent decades have witnessed increasing impacts of the accelerating expansion of chemical industries and chemical accidents have become a major contributor to environmental and health risks in China. This calls for the establishment of an effective chemical risk management system, which requires reliable, accurate and comprehensive data in the first place. However, the current chemical accident-related data system is highly fragmented and incomplete, as different responsible authorities adopt different data collection standards and procedures for different purposes. In building a more comprehensive, integrated and effective information system, this article: (i) reviews and assesses the existing data sources and data management, (ii) analyzes data on 976 recorded major hazardous chemical accidents in China over the last 40 years, and (iii) identifies the improvements required for developing integrated risk management in China.

  20. Differential response of human and rodent cell lines to chemical inhibition of the repair of potentially lethal damage

    Energy Technology Data Exchange (ETDEWEB)

    Little, J.B.; Ueno, A.M.; Dahlberg, W.K.

    1989-07-01

    We have examined the effects of several classes of metabolic inhibitors on the repair of potentially lethal damage in density-inhibited cultures of two rodent and two human cell systems which differ in their growth characteristics. Aphidicolin, 1-..beta..-D-arabinofuranosylcytosine (ara-C) and hydroxyurea showed no effect on PLD repair, whereas the effects of 9-..beta..-D-arabinofuranosyladenine (ara-A) and 3-aminobenzamide (3-AB) were cell line dependent. For example, 3-AB suppressed PLD repair almost completely in CHO cells, but showed no inhibitory effects in human diploid fibroblasts. These results indicate that inhibitors of DNA replication and poly(ADP-ribose) synthesis are not efficient inhibitors of cellular recovery in irradiated cells and, moreover, that such effects may be cell line dependent.

  1. Quaternary structure of the ATPase complex of human 26S proteasomes determined by chemical cross-linking

    DEFF Research Database (Denmark)

    Hartmann-Petersen, R; Tanaka, K; Hendil, K B

    2001-01-01

    and substrate specificity. Among the approximately 18 subunits of PA700 regulator, six are ATPases. The ATPases presumably recognize, unfold, and translocate substrates into the interior of the 26S proteasome. It is generally believed that the ATPases form a hexameric ring. By means of chemical cross......-linking, immunoprecipitation, and blotting, we have determined that the ATPases are organized in the order S6-S6'-S10b-S8-S4-S7. Additionally, we found cross-links between the ATPase S10b and the 20S proteasome subunit alpha6. Together with the previously known interaction between S8 and alpha1 and between S4 and alpha7......, these data establish the relative orientations of ATPases with respect to the 20S proteasome....

  2. The Effects of Chronic Lifelong Activation of the AHR Pathway by Industrial Chemical Pollutants on Female Human Reproduction.

    Directory of Open Access Journals (Sweden)

    Aldo Cavallini

    Full Text Available Environmental chemicals, such as heavy metals, affect female reproductive function. A biological sensor of the signals of many toxic chemical compounds seems to be the aryl hydrocarbon receptor (AHR. Previous studies demonstrated the environmental of heavy metals in Taranto city (Italy, an area that has been influenced by anthropogenic factors such as industrial activities and waste treatments since 1986. However, the impact of these elements on female fertility in this geographic area has never been analyzed. Thus, in the present study, we evaluated the AHR pathway, sex steroid receptor pattern and apoptotic process in granulosa cells (GCs retrieved from 30 women, born and living in Taranto, and 30 women who are living in non-contaminated areas (control group, who were undergoing in vitro fertilization (IVF protocol. In follicular fluids (FFs of both groups the toxic and essential heavy metals, such as chromiun (Cr, Manganese (Mn, iron (Fe, cobalt (Co, nickel (Ni, copper (Cu, zinc (Zn, cadmium (Cd and lead (Pb, were also analyzed. Higher levels of Cr, Fe, Zn and Pb were found in the FFs of the women from Taranto as compared to the control group, as were the levels of AHR and AHR-dependent cytochrome P450 1A1 and 1B1; while CYP19A1 expression was decreased. The anti-apoptotic process found in the GCs of women fromTaranto was associated with the highest levels of progesterone receptor membrane component 1 (PGRMC1, a novel progesterone receptor, the expression of which is subjected to AHR activated by its highest affinity ligands (e.g., dioxins or indirectly by other environmental pollutants, such as heavy metals. In conclusion, decreased production of estradiol and decreased number of retrieved mature oocytes found in women from Taranto could be due to chronic exposure to heavy metals, in particular to Cr and Pb.

  3. Mortality in British military participants in human experimental research into chemical warfare agents at Porton Down: cohort study

    Science.gov (United States)

    Brooks, C; Linsell, L; Keegan, T J; Langdon, T; Fletcher, T; Nieuwenhuijsen, M J; Maconochie, N E S; Doyle, P; Beral, V

    2009-01-01

    Objective To investigate any long term effects on mortality in participants in experimental research related to chemical warfare agents from 1941 to 1989. Design Historical cohort study. Data sources Archive of UK government research facility at Porton Down, UK military personnel records, and national death and cancer records. Participants 18 276 male members of the UK armed forces who had spent one or more short periods (median 4 days between first and last test) at Porton Down and a comparison group of 17 600 non-Porton Down veterans followed to 31 December 2004. Main outcome measures Mortality rate ratio of Porton Down compared with non-Porton Down veterans and standardised mortality ratio of each veteran group compared with the general population. Both ratios adjusted for age group and calendar period. Results Porton Down veterans were similar to non-Porton Down veterans in year of enlistment (median 1951) but had longer military service (median 6.2 v 5.0 years). After a median follow-up of 43 years, 40% (7306) of Porton Down and 39% (6900) of non-Porton Down veterans had died. All cause mortality was slightly greater in Porton Down veterans (rate ratio 1.06, 95% confidence interval 1.03 to 1.10, Pchemical exposure and cause specific mortality. The mortality in both groups of veterans was lower than that in the general population (standardised mortality ratio 0.88, 0.85 to 0.90; 0.82, 0.80 to 0.84). Conclusions Mortality was slightly higher in Porton Down than non-Porton Down veterans. With lack of information on other important factors, such as smoking or service overseas, it is not possible to attribute the small excess mortality to chemical exposures at Porton Down. PMID:19318699

  4. Iris Cryptography for Security Purpose

    Science.gov (United States)

    Ajith, Srighakollapu; Balaji Ganesh Kumar, M.; Latha, S.; Samiappan, Dhanalakshmi; Muthu, P.

    2018-04-01

    In today's world, the security became the major issue to every human being. A major issue is hacking as hackers are everywhere, as the technology was developed still there are many issues where the technology fails to meet the security. Engineers, scientists were discovering the new products for security purpose as biometrics sensors like face recognition, pattern recognition, gesture recognition, voice authentication etcetera. But these devices fail to reach the expected results. In this work, we are going to present an approach to generate a unique secure key using the iris template. Here the iris templates are processed using the well-defined processing techniques. Using the encryption and decryption process they are stored, traversed and utilized. As of the work, we can conclude that the iris cryptography gives us the expected results for securing the data from eavesdroppers.

  5. 7 CFR 2902.37 - General purpose de-icers.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false General purpose de-icers. 2902.37 Section 2902.37... Items § 2902.37 General purpose de-icers. (a) Definition. Chemical products (e.g., salt, fluids) that... preference for qualifying biobased general purpose de-icers. By that date, Federal agencies that have the...

  6. Chemical-based risk assessment and in vitro models of human health effects induced by organic pollutants in soils from the Olona valley

    Energy Technology Data Exchange (ETDEWEB)

    Baderna, Diego, E-mail: diego.baderna@marionegri.it; Colombo, Andrea; Amodei, Giorgia; Cantù, Stefano; Teoldi, Federico; Cambria, Felice; Rotella, Giuseppe; Natolino, Fabrizio; Lodi, Marco; Benfenati, Emilio

    2013-10-01

    Risk assessment of soils is usually based on chemical measurements and assuming accidental soil ingestion and evaluating induced toxic and carcinogenic effects. Recently biological tools have been coupled to chemical-based risk assessment since they integrate the biological effects of all xenobiotics in soils. We employed integrated monitoring of soils based on chemical analyses, risk assessment and in vitro models in the highly urbanized semirural area of the Olona Valley in northern Italy. Chemical characterization of the soils indicated low levels of toxic and carcinogenic pollutants such as PAHs, PCDD/Fs, PCBs and HCB and human risk assessment did not give any significant alerts. HepG2 and BALB/c 3T3 cells were used as a model for the human liver and as a tool for the evaluation of carcinogenic potential. Cells were treated with soil extractable organic matters (EOMs) and the MTS assay, LDH release and morphological transformation were selected as endpoints for toxicity and carcinogenicity. Soil EOMs induced dose-dependent inhibition of cell growth at low doses and cytotoxicity after exposure to higher doses. This might be the result of block of cell cycle progression to repair DNA damage caused by oxidative stress; if this DNA damage cannot be repaired, cells die. No significant inductions of foci were recorded after exposure to EOMs. These results indicate that, although the extracts contain compounds with proven carcinogenic potential, the levels of these pollutants in the analyzed soils were too low to induce carcinogenesis in our experimental conditions. In this proposed case study, HepG2 cells were found an appropriate tool to assess the potential harm caused by the ingestion of contaminated soil as they were able to detect differences in the toxicity of soil EOMs. Moreover, the cell transformation assay strengthened the combined approach giving useful information on carcinogenic potential of mixtures. Highlights: • A combined approach for risk

  7. An international network (PlaNet) to evaluate a human placental testing platform for chemicals safety testing in pregnancy

    DEFF Research Database (Denmark)

    Brownbill, Paul; Chernyavsky, Igor; Bottalico, Barbara

    2016-01-01

    The human placenta is a critical life-support system that nourishes and protects a rapidly growing fetus; a unique organ, species specific in structure and function. We consider the pressing challenge of providing additional advice on the safety of prescription medicines and environmental exposures...... placental function in pregnancy-related pathologies and influx/efflux transporter polymorphisms are a few caveats that could be addressed by HPTSs, not the specific focus of current mammalian reproductive toxicology systems. An international consortium, “PlaNet”, will bridge academia, industry...

  8. Chemical Emergencies

    Science.gov (United States)

    When a hazardous chemical has been released, it may harm people's health. Chemical releases can be unintentional, as in the case of an ... the case of a terrorist attack with a chemical weapon. Some hazardous chemicals have been developed by ...

  9. Drilling for scientific purpose

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Shoichi

    1987-09-01

    Drilling for scientific purpose is a process of conducting geophysical exploration at deep underground and drilling for collecting crust samples directly. This is because earth science has advanced to get a good understanding about the top of the crust and has shifted its main interest to the lower layer of the crust in land regions. The on-land drilling plan in Japan has just started, and the planned drilling spots are areas around the Minami River, Hidaka Mts., kinds of the Mesozoic and Cenozoic granite in outside zone, the extension of Japan Sea, Ogasawara Is., Minami-Tori Is., and active volcanos. The paper also outlines the present situation of on-land drilling in the world, focusing on the SG-3rd super-deep well SG-3 on the Kola Peninsula, USSR, Satori SG-1st well SG-1 in Azerbaidzhan S.S.R, V.S.S.R, Sweden's wells, Cyprus' wells, Bayearn well Plan in West Germany, and Salton Sea Scientific Drilling Program in the U.S. At its end, the paper explains the present situation and the future theme of the Japanese drilling technique and points out the necessity of developing equipment, and techniques. (14 figs, 5 tabs, 26 refs)

  10. OPTIMIZATION OF MARSHMALLOW GELATIN FUNCTIONAL PURPOSE

    Directory of Open Access Journals (Sweden)

    G. O. Magomedov

    2015-01-01

    Full Text Available Marshmallow on gelatin or marshmallow items finely porous foam structure. This product is a popular and widely demanded confectionery products to the public, especially children and students. Urgent by the NE-a method for producing a mini-marshmallow functionality in terms of domestic production with natural-functional ingredient – gum-arabic «Instantgum», which is the source of natural-fiber, improving gastrointestinal function, lowering blood glucose levels that especially important in the use of products of diabetics. The inclusion of gum-arabic in the diet leads to a prebiotic effect, stimulating human immune system and improves the functioning intestines. Technology mini marshmallow gelatin with gum-arabic comprises the following manufacturing steps of: preparing a gelatin solution, an aqueous solution of gum-arabic, sugar syrup, invert syrup, whipped gelatinous mass density of 400-600 kg / m3, molding or pressing off mass fractionation followed by cooling and cutting, exposure and dusting starch and sugar mixture housings mini marshmallows. The optimization formulation mini marshmallows on gelatin with functional ingredients «Instantgum» based on gum-arabic method of multicriteria optimization of op-using desirability function Harrington. The greatest value generalized desirability function had a sample with 10% in-functional ingredient, since it belongs to the best set of parameters optimization. The developed product has high organoleptic, physical and chemical parameters, satisfactory form-retaining ability elastic chewing consistency and a functional purpose by NIJ-containing dietary fiber. Proposed can be recommended for the production on-time with continuous mechanized lines to develop Pastila products.

  11. A study on the discrimination of human skeletons using X-ray fluorescence and chemometric tools in chemical anthropology.

    Science.gov (United States)

    Gonzalez-Rodriguez, J; Fowler, G

    2013-09-10

    Forensic anthropological investigations are often restricted in their outcomes by the resources allocated to them, especially in terms of positively identifying the victims exhumed from commingled mass graves. Commingled mass graves can be defined as those graves that contain a number of disarticulated human remains from different individuals that have been mixed by either natural processes or human interventions. The research developed aimed to apply the technique of non-destructive XRF analysis to test whether there is substantial differentiation within the trace elemental composition and their ratios of individuals to separate them using chemometric analysis. The results of the different atomic spectroscopic analyses combined with the use of multivariate analysis on a set of 5 skeletons produced a series of plots using Principal Component Analysis that helped to separate them with a high percentage of accuracy when two, three or four skeletons needed to be separated. Also, two new elemental ratios, Zn/Fe related to metabolic activities and K/Fe related to blood flow into the bone, have been defined for their use in forensic anthropology for the first time to aid in the separation. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  12. Chemical and Microbial Quality of Groundwater in Siloam Village, Implications to Human Health and Sources of Contamination

    Directory of Open Access Journals (Sweden)

    John Ogony Odiyo

    2018-02-01

    Full Text Available Due to inaccessibility of potable water, rural communities drill boreholes within their homesteads despite vulnerability to groundwater contamination and associated health risks. This study assessed the quality of groundwater, identified potential sources of contamination and potential human health risks in Siloam Village, South Africa. Statistical difference between similar water quality parameters at different sites was determined at a significance level (α of 0.05. Water quality parameters with serious potential health effects on human beings were correlated with selected water quality parameters to understand the nature of correlation and possible sources of contamination. Fluorides and nitrates had excessively high concentrations associated with tooth damage and pronounced skeletal fluorosis, and methaemoglobinaemia in infants and mucous membrane irritation in adults, respectively. There were statistically significant differences between means of most water quality parameters. Contrasting correlation of fluoride with calcium and pH indicated the need to further identify local sources and fluoride control mechanisms. Correlation of nitrate with chloride mostly indicated that faecal contamination is the potential source of high nitrates in groundwater. This requires further verification. Presence of total coliforms and E. coli in most boreholes indicated potential presence of faecal contamination. The need to educate borehole owners’ on possible strategies to minimise groundwater pollution was identified.

  13. The chemical behaviour and ecological transfer in the human food chain of some radionuclides in aqueous ecosystems

    International Nuclear Information System (INIS)

    Furnica, Gh.

    1980-01-01

    The aqueous ecosystem of the Danube has been investigated in the period of 1976-1979. Data on the ecological transfer of radionuclides in the human food chain made an estimation available on the risk of the affected population. In the assessment of population exposure, the internal radiation dose for a period of one year and the continuous external irradiation determined by TLD have been considered. - The results revealed very low Sr-90 and Cs-137 contents in the Danube water and in the drinking water. The radioactivity contents are higher in the sediment and in some biota than in the water. The H-3 content in the Danube water varies in a wider range and higher concentration was found in fish than in the water. Both the Danube sediment and the irrigated sandy soil contain very low concentrations of fission products. During 1976-1979, the radioiodine content in air, milk and cow thyroid around the 679-Km is continuously decreasing. - Based on the data obtained, the corresponding collective dose equivalent value was calculated and the risk on the health of the population was found to be very low from contamination during 1975-1978. The radioactivity concentration values in critical human food chain, however, are not negligible. (author)

  14. Chemical kinetics of multiphase reactions between ozone and human skin lipids: Implications for indoor air quality and health effects.

    Science.gov (United States)

    Lakey, P S J; Wisthaler, A; Berkemeier, T; Mikoviny, T; Pöschl, U; Shiraiwa, M

    2017-07-01

    Ozone reacts with skin lipids such as squalene, generating an array of organic compounds, some of which can act as respiratory or skin irritants. Thus, it is important to quantify and predict the formation of these products under different conditions in indoor environments. We developed the kinetic multilayer model that explicitly resolves mass transport and chemical reactions at the skin and in the gas phase (KM-SUB-Skin). It can reproduce the concentrations of ozone and organic compounds in previous measurements and new experiments. This enabled the spatial and temporal concentration profiles in the skin oil and underlying skin layers to be resolved. Upon exposure to ~30 ppb ozone, the concentrations of squalene ozonolysis products in the gas phase and in the skin reach up to several ppb and on the order of ~10 mmol m -3 . Depending on various factors including the number of people, room size, and air exchange rates, concentrations of ozone can decrease substantially due to reactions with skin lipids. Ozone and dicarbonyls quickly react away in the upper layers of the skin, preventing them from penetrating deeply into the skin and hence reaching the blood. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Multi-purpose reactor

    International Nuclear Information System (INIS)

    1991-05-01

    The Multi-Purpose-Reactor (MPR), is a pool-type reactor with an open water surface and variable core arrangement. Its main feature is plant safety and reliability. Its power is 22MW t h, cooled by light water and moderated by beryllium. It has platetype fuel elements (MTR type, approx. 20%. enriched uranium) clad in aluminium. Its cobalt (Co 60 ) production capacity is 50000 Ci/yr, 200 Ci/gr. The distribution of the reactor core and associated control and safety systems is essentially based on the following design criteria: - upwards cooling flow, to waive the need for cooling flow inversion in case the reactor is cooled by natural convection if confronted with a loss of pumping power, and in order to establish a superior heat transfer potential (a higher coolant saturation temperature); - easy access to the reactor core from top of pool level with the reactor operating at full power, in order to facilitate actual implementation of experiments. Consequently, mechanisms associated to control and safety rods s,re located underneath the reactor tank; - free access of reactor personnel to top of pool level with the reactor operating at full power. This aids in the training of personnel and the actual carrying out of experiments, hence: - a vast water column was placed over the core to act as radiation shielding; - the core's external area is cooled by a downwards flow which leads to a decay tank beyond the pool (for N 16 to decay); - a small downwards flow was directed to stream downwards from above the reactor core in order to drag along any possibly active element; and - a stagnant hot layer system was placed at top of pool level so as to minimize the upwards coolant flow rising towards pool level

  16. Reduction of hexavalent chromium by fasted and fed human gastric fluid. I. Chemical reduction and mitigation of mutagenicity

    Energy Technology Data Exchange (ETDEWEB)

    De Flora, Silvio, E-mail: sdf@unige.it [Department of Health Sciences, University of Genoa, 16132 Genoa (Italy); Camoirano, Anna, E-mail: Anna.Fiorenza.Camoirano@unige.it [Department of Health Sciences, University of Genoa, 16132 Genoa (Italy); Micale, Rosanna T., E-mail: rosannamicale@yahoo.it [Department of Health Sciences, University of Genoa, 16132 Genoa (Italy); La Maestra, Sebastiano, E-mail: lamaestra78@yahoo.it [Department of Health Sciences, University of Genoa, 16132 Genoa (Italy); Savarino, Vincenzo, E-mail: vsavarin@unige.it [Gastroenterology Unit, Department of Internal Medicine, University of Genoa, 16132 Genoa (Italy); Zentilin, Patrizia, E-mail: Patrizia.Zentilin@unige.it [Gastroenterology Unit, Department of Internal Medicine, University of Genoa, 16132 Genoa (Italy); Marabotto, Elisa, E-mail: emarabotto@libero.it [Gastroenterology Unit, Department of Internal Medicine, University of Genoa, 16132 Genoa (Italy); Suh, Mina, E-mail: msuh@toxstrategies.com [ToxStrategies, Mission Viejo, CA 92692 (United States); Proctor, Deborah M., E-mail: dproctor@toxstrategies.com [ToxStrategies, Mission Viejo, CA 92692 (United States)

    2016-09-01

    Evaluation of the reducing capacity of human gastric fluid from healthy individuals, under fasted and fed conditions, is critical for assessing the cancer hazard posed by ingested hexavalent chromium [Cr(VI)] and for developing quantitative physiologically-based pharmacokinetic models used in risk assessment. In the present study, the patterns of Cr(VI) reduction were evaluated in 16 paired pre- and post-meal gastric fluid samples collected from 8 healthy volunteers. Human gastric fluid was effective both in reducing Cr(VI), as measured by using the s-diphenylcarbazide colorimetric method, and in attenuating mutagenicity in the Ames test. The mean (± SE) Cr(VI)-reducing ability of post-meal samples (20.4 ± 2.6 μg Cr(VI)/mL gastric fluid) was significantly higher than that of pre-meal samples (10.2 ± 2.3 μg Cr(VI)/mL gastric fluid). When using the mutagenicity assay, the decrease of mutagenicity produced by pre-meal and post-meal samples corresponded to reduction of 13.3 ± 1.9 and 25.6 ± 2.8 μg Cr(VI)/mL gastric fluid, respectively. These data are comparable to parallel results conducted by using speciated isotope dilution mass spectrometry. Cr(VI) reduction was rapid, with > 70% of total reduction occurring within 1 min and 98% of reduction is achieved within 30 min with post-meal gastric fluid at pH 2.0. pH dependence was observed with decreasing Cr(VI) reducing capacity at higher pH. Attenuation of the mutagenic response is consistent with the lack of DNA damage observed in the gastrointestinal tract of rodents following administration of ≤ 180 ppm Cr(VI) for up to 90 days in drinking water. Quantifying Cr(VI) reduction kinetics in the human gastrointestinal tract is necessary for assessing the potential hazards posed by Cr(VI) in drinking water. - Highlights: • Cr(VI) reduction capacity was greater in post-meal than paired pre-meal samples. • Cr(VI) reduction was rapid, pH dependent, and due to heat stable components. • Gastric fluid attenuates

  17. 57Fe Moessbauer spectroscopic study of Japanese cedar bark - the variation in chemical states of iron due to influence of human activities

    International Nuclear Information System (INIS)

    Matsuo, Motoyuki; Kobayashi, Takaaki; Singh, T.B.; Tsurumi, Makoto; Ichikuni, Masami

    1992-01-01

    Chemical states of iron have been investigated by 57 Fe Moessbauer technique for the barks of Japanese cedar collected from urban and mountainous area of Japan. The Moessbauer spectra of all outer bark samples show two overlapping doublets and one sextet ascribable to paramagnetic ferrous, paramagnetic ferric and magnetic iron, respectively, whereas an inner bark sample consists only of the two doublets. The bark sample from urban area shows the higher relative amount of magnetic component and the smaller ferrous to ferric ratio. These features of iron species in the bark sample indicate that the bark sample can supply a more effective indicator of human activities than airborne particles collected directly by evaluation with an air sampler. (orig.)

  18. Assessment of an in vitro model of human cells to evaluate the toxic and irritating potential of chemical compounds

    Directory of Open Access Journals (Sweden)

    M. Catalano

    2011-01-01

    Full Text Available We attempted to induce differentation in unidifferentiated NCTC2544 human keratinocyte line, by exposure to ZnSO4 and CaCl2. Analysis of specific markers, transglutaminase I, involucrin and loricrin, show that basal NCTC2544 (BL reached spinous- (SL and granular-like (GL phenotypes. BL-, SI- and GL- NCTC were exposed to SDS, as irritant stimulus and Neutral red uptake (NRU and MTT cytoxicity tests evidenced a relatively higher toxicity in SL- and GL cells on lysosomes respect to mitochondria. ILIα cytokine was monitored as early inflammation marker. The complex of data provides evidence for the suitability of our in vitro model to the analysis of cytotoxic/biological effects of topically applied exogenous compounds.

  19. Probing the reactivity of nucleophile residues in human 2,3-diphosphoglycerate/deoxy-hemoglobin complex by aspecific chemical modifications.

    Science.gov (United States)

    Scaloni, A; Ferranti, P; De Simone, G; Mamone, G; Sannolo, N; Malorni, A

    1999-06-11

    The use of aspecific methylation reaction in combination with MS procedures has been employed for the characterization of the nucleophilic residues present on the molecular surface of the human 2,3-diphosphoglycerate/deoxy-hemoglobin complex. In particular, direct molecular weight determinations by ESMS allowed to control the reaction conditions, limiting the number of methyl groups introduced in the modified globin chains. A combined LCESMS-Edman degradation approach for the analysis of the tryptic peptide mixtures yielded to the exact identification of methylation sites together with the quantitative estimation of their degree of modification. The reactivities observed were directly correlated with the pKa and the relative surface accessibility of the nucleophilic residues, calculated from the X-ray crystallographic structure of the protein. The results here described indicate that this methodology can be efficiently used in aspecific modification experiments directed to the molecular characterization of the surface topology in proteins and protein complexes.

  20. Sensitive monitoring of monoterpene metabolites in human urine using two-step derivatisation and positive chemical ionisation-tandem mass spectrometry

    International Nuclear Information System (INIS)

    Schmidt, Lukas; Belov, Vladimir N.; Göen, Thomas

    2013-01-01

    Highlights: •Sensitive monitoring of 10 metabolites of (R)-limonene, α-pinene, and Δ 3 -carene in human urine samples. •Fast and simple sample preparation and derivatisation procedure using two-step silylation for unreactive tertiary hydroxyl groups. •Synthesis of reference substances and isotopically labelled internal standards of (R)-limonene, α-pinene, and Δ 3 -carene metabolites. •Study on (R)-limonene, α-pinene, and Δ 3 -carene metabolite background exposure of 36 occupationally unexposed volunteers. -- Abstract: A gas chromatographic–positive chemical ionisation-tandem mass spectrometric (GC–PCI-MS/MS) method for the simultaneous determination of 10 oxidative metabolites of the monoterpenoid hydrocarbons α-pinene, (R)-limonene, and Δ 3 -carene ((+)-3-carene) in human urine was developed and tested for the monoterpene biomonitoring of the general population (n = 36). The method involves enzymatic cleavage of the glucuronides followed by solid-supported liquid–liquid extraction and derivatisation using a two-step reaction with N,O-bis(trimethylsilyl)-trifluoroacetamide and N-(trimethylsilyl)imidazole. The method proved to be both sensitive and reliable with detection limits ranging from 0.1 to 0.3 μg L −1 . In contrast to the frequent and distinct quantities of (1S,2S,4R)-limonene-1,2-diol, the (1R,2R,4R)-stereoisomer could not be detected. The expected metabolite of (+)-3-carene, 3-caren-10-ol was not detected in any of the samples. All other metabolites were detected in almost all urine samples. The procedure enables for the first time the analysis of trace levels of a broad spectrum of mono- and bicyclic monoterpenoid metabolites (alcohols, diols, and carboxylic acids) in human urine. This analytical procedure is a powerful tool for population studies as well as for the discovery of human metabolism and toxicokinetics of monoterpenes

  1. [Comparison of Physico-chemical Aspects between E. coli and Human Dihydrofolate Reductase: an Equilibrium Unfolding Study].

    Science.gov (United States)

    Thapliyal, Charu; Jain, Neha; Chaudhuri, Pratima

    2015-01-01

    A protein, differing in origin, may exhibit variable physicochemical behaviour, difference in sequence homology, fold and function. Thus studying structure-function relationship of proteins from altered sources is meaningful in the sense that it may give rise to comparative aspects of their sequence-structure-function relationship. Dihydrofolate reductase is an enzyme involved in cell cycle regulation. It is a significant enzyme as.a target for developing anticancer drugs. Hence, detailed understanding of structure-function relationships of wide variants of the enzyme dihydrofolate reductase would be important for developing an inhibitor or an antagonist against the enzyme involved in the cellular developmental processes. In this communication, we have reported the comparative structure-function relationship between E. coli and human dihydrofolate reductase. The differences in the unfolding behaviour of these two proteins have been investigated to understand various properties of these two proteins like relative' stability differences and variation in conformational changes under identical denaturing conditions. The equilibrium unfolding mechanism of dihydrofolate reductase proteins using guanidine hydrochloride as a denaturant in the presence of various types of osmolytes has been monitored using loss in enzymatic activity, intrinsic tryptophan fluorescence and an extrinsic fluorophore 8-anilino-1-naphthalene-sulfonic acid as probes. It has been observed that osmolytes, such as 1M sucrose, and 30% glycerol, provided enhanced stability to both variants of dihydrofolate reductase. Their level of stabilisation has been observed to be dependent on intrinsic protein stability. It was observed that 100 mM proline does not show any 'significant stabilisation to either of dihydrofolate reductases. In the present study, it has been observed that the human protein is relatively less stable than the E.coli counterpart.

  2. Down-regulation of glutaminase C in human hepatocarcinoma cell by diphenylarsinic acid, a degradation product of chemical warfare agents

    International Nuclear Information System (INIS)

    Kita, Kayoko; Suzuki, Toshihide; Ochi, Takafumi

    2007-01-01

    In a poisonous incident in Kamisu, Japan, it is understood that diphenylarsinic acid (DPAA) was a critical contaminant of ground water. Most patients showed dysfunction of the central nervous system. To understand the overall mechanism of DPAA toxicity and to gain some insight into the application of a remedy specific for intoxication, the molecular target must be clarified. As an approach, a high throughput analysis of cell proteins in cultured human hepatocarcinoma HpG2 exposed to DPAA was performed by two-dimensional electrophoresis (2-DE). Four proteins, which were up- and down-regulated by exposure of cultured HepG2 cells to DPAA, were identified. They were chaperonin containing TCP-1 (CCT) beta subunit, aldehyde dehydrogenase 1 (ALDH1), ribosomal protein P0 and glutaminase C (GAC). Of these, GAC was the only protein that was down-regulated by DPAA exposure, and cellular expression levels were reduced by DPAA in a concentration- and time-dependent manner. Decrease in cellular GAC levels was accompanied by decreased activity of the enzyme, phosphate-activated glutaminase (PAG). Decreased expression of GAC by DPAA was also observed in human cervical carcinoma HeLa and neuroblastoma SH-SY5Y cells. By contrast, no significant changes in GAC protein expression were observed when cells were incubated with arsenite [iAs (III)] and trivalent dimethylarsinous acid [DMA (III)]. In the central nervous system, GAC plays a role in the production of the neurotransmitter glutamic acid. Selective inhibition of GAC expression by DPAA may be a cause of dysfunction of glutamatergic neuronal transmission and the resultant neurological impairments

  3. Down-regulation of glutaminase C in human hepatocarcinoma cell by diphenylarsinic acid, a degradation product of chemical warfare agents

    Energy Technology Data Exchange (ETDEWEB)

    Kita, Kayoko [Laboratory of Toxicology, Faculty of Pharmaceutical Sciences, Teikyo University, 1091-1 Sagamiko-chou, Sagamihara, Kanagawa 229-0195 (Japan); Suzuki, Toshihide [Laboratory of Toxicology, Faculty of Pharmaceutical Sciences, Teikyo University, 1091-1 Sagamiko-chou, Sagamihara, Kanagawa 229-0195 (Japan); Ochi, Takafumi [Laboratory of Toxicology, Faculty of Pharmaceutical Sciences, Teikyo University, 1091-1 Sagamiko-chou, Sagamihara, Kanagawa 229-0195 (Japan)

    2007-05-01

    In a poisonous incident in Kamisu, Japan, it is understood that diphenylarsinic acid (DPAA) was a critical contaminant of ground water. Most patients showed dysfunction of the central nervous system. To understand the overall mechanism of DPAA toxicity and to gain some insight into the application of a remedy specific for intoxication, the molecular target must be clarified. As an approach, a high throughput analysis of cell proteins in cultured human hepatocarcinoma HpG2 exposed to DPAA was performed by two-dimensional electrophoresis (2-DE). Four proteins, which were up- and down-regulated by exposure of cultured HepG2 cells to DPAA, were identified. They were chaperonin containing TCP-1 (CCT) beta subunit, aldehyde dehydrogenase 1 (ALDH1), ribosomal protein P0 and glutaminase C (GAC). Of these, GAC was the only protein that was down-regulated by DPAA exposure, and cellular expression levels were reduced by DPAA in a concentration- and time-dependent manner. Decrease in cellular GAC levels was accompanied by decreased activity of the enzyme, phosphate-activated glutaminase (PAG). Decreased expression of GAC by DPAA was also observed in human cervical carcinoma HeLa and neuroblastoma SH-SY5Y cells. By contrast, no significant changes in GAC protein expression were observed when cells were incubated with arsenite [iAs (III)] and trivalent dimethylarsinous acid [DMA (III)]. In the central nervous system, GAC plays a role in the production of the neurotransmitter glutamic acid. Selective inhibition of GAC expression by DPAA may be a cause of dysfunction of glutamatergic neuronal transmission and the resultant neurological impairments.

  4. Point mutation in activated c-Ha-ras gene of a chemically induced transplantable human pancreas carcinoma

    International Nuclear Information System (INIS)

    Maheshwari, K.K.; Parsa, I.

    1986-01-01

    The authors have reported a model of human pancreas carcinogenesis where repeated treatment with MNU of explants results in the development of transplantable carcinoma. This report compares the endonuclease digests of DNAs from normal human pancreas (HP) and MNU-induced transplantable tumor (HP-T1) analyzed with 32 P-labelled Ha-ras probe prepared from clone BS-9. The hybridization patterns of BamHI, BglII, EcoRI and HindIII digests of HP were significantly different from those of HP-T1. In EcoRI digests a 3.0 kb fragments of HP-T1 DNA hybridized with Ha-ras probe instead of a 4.3 kb fragments seen in HP DNA. The pattern for HindIII digests was similar to those of EcoRI. The BgIII digests of HP DNA revealed two hybridizing fragments of 8.0 and 4.3 kb whereas those of HP-T1 DNA fragments measured 8.5 and 4.0 kb. BamHI treated HP DNA showed only hybridizing fragments of 6.6 kb while the HP-T1 DNA showed to hybridizing fragments of 6.8 and 7.2 kb. The digested DNAs by HhaI, HinfI, KpnI, pstI, PvuII, SaII, SstI, TaqI and XbaI showed similar hybridization profiles. The point mutation in c-Ha-ras was examined in the HpaII and MspI double digests of both DNAs by 0.6 Kb SmaI fragments of pEJ. The hybridized fragments measured 412 and 355 bp in DNA digests from tumor and normal pancreas respectively

  5. Monolayer culturing and cloning of human pluripotent stem cells on laminin-521-based matrices under xeno-free and chemically defined conditions.

    Science.gov (United States)

    Rodin, Sergey; Antonsson, Liselotte; Hovatta, Outi; Tryggvason, Karl

    2014-10-01

    A robust method for culturing human pluripotent stem (hPS) cells under chemically defined and xeno-free conditions is an important tool for stem cell research and for the development of regenerative medicine. Here, we describe a protocol for monolayer culturing of Oct-4-positive hPS cells on a specific laminin-521 (LN-521) isoform, under xeno-free and chemically defined conditions. The cells are dispersed into single-cell suspension and then plated on LN-521 isoform at densities higher than 5,000 cells per cm², where they attach, migrate and survive by forming small monolayer cell groups. The cells avidly divide and expand horizontally until the entire dish is covered by a confluent monolayer. LN-521, in combination with E-cadherin, allows cloning of individual hPS cells in separate wells of 96-well plates without the presence of rho-associated protein kinase (ROCK) inhibitors or any other inhibitors of anoikis. Characterization of cells maintained for several months in culture reveals pluripotency with a minimal degree of genetic abnormalities.

  6. Enhancement of chemically induced reactive oxygen species production and DNA damage in human SH-SY5Y neuroblastoma cells by 872 MHz radiofrequency radiation

    Energy Technology Data Exchange (ETDEWEB)

    Luukkonen, Jukka [Department of Environmental Science, University of Kuopio, Bioteknia 2, P.O. Box 1627, FI-70211 Kuopio (Finland)], E-mail: Jukka.Luukkonen@uku.fi; Hakulinen, Pasi; Maeki-Paakkanen, Jorma [Department of Environmental Health, National Public Health Institute, P.O. Box 95, FI-70701 Kuopio (Finland); Juutilainen, Jukka; Naarala, Jonne [Department of Environmental Science, University of Kuopio, Bioteknia 2, P.O. Box 1627, FI-70211 Kuopio (Finland)

    2009-03-09

    The objective of the study was to investigate effects of 872 MHz radiofrequency (RF) radiation on intracellular reactive oxygen species (ROS) production and DNA damage at a relatively high SAR value (5 W/kg). The experiments also involved combined exposure to RF radiation and menadione, a chemical inducing intracellular ROS production and DNA damage. The production of ROS was measured using the fluorescent probe dichlorofluorescein and DNA damage was evaluated by the Comet assay. Human SH-SY5Y neuroblastoma cells were exposed to RF radiation for 1 h with or without menadione. Control cultures were sham exposed. Both continuous waves (CW) and a pulsed signal similar to that used in global system for mobile communications (GSM) mobile phones were used. Exposure to the CW RF radiation increased DNA breakage (p < 0.01) in comparison to the cells exposed only to menadione. Comparison of the same groups also showed that ROS level was higher in cells exposed to CW RF radiation at 30 and 60 min after the end of exposure (p < 0.05 and p < 0.01, respectively). No effects of the GSM signal were seen on either ROS production or DNA damage. The results of the present study suggest that 872 MHz CW RF radiation at 5 W/kg might enhance chemically induced ROS production and thus cause secondary DNA damage. However, there is no known mechanism that would explain such effects from CW RF radiation but not from GSM modulated RF radiation at identical SAR.

  7. Enhancement of chemically induced reactive oxygen species production and DNA damage in human SH-SY5Y neuroblastoma cells by 872 MHz radiofrequency radiation

    International Nuclear Information System (INIS)

    Luukkonen, Jukka; Hakulinen, Pasi; Maeki-Paakkanen, Jorma; Juutilainen, Jukka; Naarala, Jonne

    2009-01-01

    The objective of the study was to investigate effects of 872 MHz radiofrequency (RF) radiation on intracellular reactive oxygen species (ROS) production and DNA damage at a relatively high SAR value (5 W/kg). The experiments also involved combined exposure to RF radiation and menadione, a chemical inducing intracellular ROS production and DNA damage. The production of ROS was measured using the fluorescent probe dichlorofluorescein and DNA damage was evaluated by the Comet assay. Human SH-SY5Y neuroblastoma cells were exposed to RF radiation for 1 h with or without menadione. Control cultures were sham exposed. Both continuous waves (CW) and a pulsed signal similar to that used in global system for mobile communications (GSM) mobile phones were used. Exposure to the CW RF radiation increased DNA breakage (p < 0.01) in comparison to the cells exposed only to menadione. Comparison of the same groups also showed that ROS level was higher in cells exposed to CW RF radiation at 30 and 60 min after the end of exposure (p < 0.05 and p < 0.01, respectively). No effects of the GSM signal were seen on either ROS production or DNA damage. The results of the present study suggest that 872 MHz CW RF radiation at 5 W/kg might enhance chemically induced ROS production and thus cause secondary DNA damage. However, there is no known mechanism that would explain such effects from CW RF radiation but not from GSM modulated RF radiation at identical SAR

  8. Comet assay in reconstructed 3D human epidermal skin models—investigation of intra- and inter-laboratory reproducibility with coded chemicals

    Science.gov (United States)

    Pfuhler, Stefan

    2013-01-01

    Reconstructed 3D human epidermal skin models are being used increasingly for safety testing of chemicals. Based on EpiDerm™ tissues, an assay was developed in which the tissues were topically exposed to test chemicals for 3h followed by cell isolation and assessment of DNA damage using the comet assay. Inter-laboratory reproducibility of the 3D skin comet assay was initially demonstrated using two model genotoxic carcinogens, methyl methane sulfonate (MMS) and 4-nitroquinoline-n-oxide, and the results showed good concordance among three different laboratories and with in vivo data. In Phase 2 of the project, intra- and inter-laboratory reproducibility was investigated with five coded compounds with different genotoxicity liability tested at three different laboratories. For the genotoxic carcinogens MMS and N-ethyl-N-nitrosourea, all laboratories reported a dose-related and statistically significant increase (P 30% cell loss), and the overall response was comparable in all laboratories despite some differences in doses tested. The results of the collaborative study for the coded compounds were generally reproducible among the laboratories involved and intra-laboratory reproducibility was also good. These data indicate that the comet assay in EpiDerm™ skin models is a promising model for the safety assessment of compounds with a dermal route of exposure. PMID:24150594

  9. A novel chemical-defined medium with bFGF and N2B27 supplements supports undifferentiated growth in human embryonic stem cells

    International Nuclear Information System (INIS)

    Liu Yanxia; Song Zhihua; Zhao Yang; Qin Han; Cai Jun; Zhang Hong; Yu Tianxin; Jiang Siming; Wang Guangwen; Ding Mingxiao; Deng Hongkui

    2006-01-01

    Traditionally, undifferentiated human embryonic stem cells (hESCs) are maintained on mouse embryonic fibroblast (MEF) cells or on matrigel with an MEF-conditioned medium (CM), which hampers the clinical applications of hESCs due to the contamination by animal pathogens. Here we report a novel chemical-defined medium using DMEM/F12 supplemented with N2, B27, and basic fibroblast growth factor (bFGF) [termed NBF]. This medium can support prolonged self-renewal of hESCs. hESCs cultured in NBF maintain an undifferentiated state and normal karyotype, are able to form embryoid bodies in vitro, and differentiate into three germ layers and extraembryonic cells. Furthermore, we find that hESCs cultured in NBF possess a low apoptosis rate and a high proliferation rate compared with those cultured in MEF-CM. Our findings provide a novel, simplified chemical-defined culture medium suitable for further therapeutic applications and developmental studies of hESCs

  10. 31P-MR spectroscopy of all regions of the human heart at 1.5 T with acquisition-weighted chemical shift imaging

    International Nuclear Information System (INIS)

    Koestler, H.; Beer, M.; Buchner, S.; Sandstede, J.; Pabst, T.; Kenn, W.; Hahn, D.

    2001-01-01

    Aim: Aim of this study was to show whether or not acquisition-weighted chemical shift imaging (AW-CSI) allows the determination of PCr and ATP in the lateral and posterior wall of the human heart at 1.5 T. Methods: 12 healthy volunteers were examined using a conventional chemical shift imaging (CSI) and an AW-CSI. The sequences differed only in the number of repetitions for each point in k space. A hanning function was used as filter function leading to 7 repetitions in the center of the k space and 0 in the corners. Thus, AW-CSI had the same resolution as the CSI sequence. The results for both sequences were analyzed using identically positioned voxels in the septal, anterior, lateral and posterior wall. Results: The determined averaged AW-CSI signal to noise ratios were higher for PCr by a factor of 1.3 and for ATP by 1.4 than those of CSI. The PCr/ATP ratios were higher by a factor of 1.2 - 1.3 and showed a smaller standard deviation in all locations for AW-CSI. The mean PCr/ATP ratios determined by AW-CSI of septal, lateral and posterior wall were almost identical (1.72 - 1.76), while it was higher in the anterior wall (1.9). Conclusions: The reduced contamination in AW-CSI improves the signal to noise ratio and the determination of the PCr/ATP ratio in cardiac 31 P spectroscopy compared to CSI with the same resolution. The results in volunteers indicate that AW-CSI renders 31 P spectroscopy of the lateral and posterior wall of the human heart feasible for patient studies at 1.5 T. (orig.) [de

  11. Chemical Composition of Moringa oleifera Ethyl Acetate Fraction and Its Biological Activity in Diabetic Human Dermal Fibroblasts

    Science.gov (United States)

    Gothai, Sivapragasam; Muniandy, Katyakyini; Zarin, Mazni Abu; Sean, Tan Woan; Kumar, S. Suresh; Munusamy, Murugan A.; Fakurazi, Sharida; Arulselvan, Palanisamy

    2017-01-01

    Background: Moringa oleifera (MO), commonly known as the drumstick tree, is used in folklore medicine for the treatment of skin disease. Objective: The objective of this study is to evaluate the ethyl acetate (EtOAc) fraction of MO leaves for in vitro antibacterial, antioxidant, and wound healing activities and conduct gas chromatography-mass spectrometry (GC-MS) analysis. Materials and Methods: Antibacterial activity was evaluated against six Gram-positive bacteria and 10 Gram-negative bacteria by disc diffusion method. Free radical scavenging activity was assessed by 1, 1-diphenyl-2-picryl hydrazyl (DPPH) radical hydrogen peroxide scavenging and total phenolic content (TPC). Wound healing efficiency was studied using cell viability, proliferation, and scratch assays in diabetic human dermal fibroblast (HDF-D) cells. Results: The EtOAc fraction showed moderate activity against all bacterial strains tested, and the maximum inhibition zone was observed against Streptococcus pyogenes (30 mm in diameter). The fraction showed higher sensitivity to Gram-positive strains than Gram-negative strains. In the quantitative analysis of antioxidant content, the EtOAc fraction was found to have a TPC of 65.81 ± 0.01. The DPPH scavenging activity and the hydrogen peroxide assay were correlated with the TPC value, with IC50 values of 18.21 ± 0.06 and 59.22 ± 0.04, respectively. The wound healing experiment revealed a significant enhancement of cell proliferation and migration of HDF-D cells. GC-MS analysis confirmed the presence of 17 bioactive constituents that may be the principal factors in the significant antibacterial, antioxidant, and wound healing activity. Conclusion: The EtOAc fraction of MO leaves possesses remarkable wound healing properties, which can be attributed to the antibacterial and antioxidant activities of the fraction. SUMMARY Moringa oleifera (MO) leaf ethyl acetate (EtOAc) fraction possesses antibacterial activities toward Gram-positive bacteria such as

  12. Altered ion transport in normal human bronchial epithelial cells following exposure to chemically distinct metal welding fume particles

    Energy Technology Data Exchange (ETDEWEB)

    Fedan, Jeffrey S., E-mail: jsf2@cdc.gov; Thompson, Janet A.; Meighan, Terence G.; Zeidler-Erdely, Patti C.; Antonini, James M.

    2017-07-01

    Welding fume inhalation causes pulmonary toxicity, including susceptibility to infection. We hypothesized that airway epithelial ion transport is a target of fume toxicity, and investigated the effects of fume particulates from manual metal arc-stainless steel (MMA-SS) and gas metal arc-mild steel (GMA-MS) on ion transport in normal human bronchial epithelium (NHBE) cultured in air-interface. MMA-SS particles, more soluble than GMA-MS particles, contain Cr, Ni, Fe and Mn; GMA-MS particles contain Fe and Mn. MMA-SS or GMA-MS particles (0.0167–166.7 μg/cm{sup 2}) were applied apically to NHBEs. After 18 h transepithelial potential difference (V{sub t}), resistance (R{sub t}), and short circuit current (I{sub sc}) were measured. Particle effects on Na{sup +} and Cl¯ channels and the Na{sup +},K{sup +},2Cl¯-cotransporter were evaluated using amiloride (apical), 5-nitro-2-[(3-phenylpropyl)amino]benzoic acid (NPPB, apical), and bumetanide (basolateral), respectively. MMA-SS (0.0167–16.7 μg/cm{sup 2}) increased basal V{sub t}. Only 16.7 μg/cm{sup 2} GMA-MS increased basal V{sub t} significantly. MMA-SS or GMA-MS exposure potentiated I{sub sc} responses (decreases) to amiloride and bumetanide, while not affecting those to NPPB, GMA-MS to a lesser degree than MMA-SS. Variable effects on R{sub t} were observed in response to amiloride, and bumetanide. Generally, MMA-SS was more potent in altering responses to amiloride and bumetanide than GMA-MS. Hyperpolarization occurred in the absence of LDH release, but decreases in V{sub t}, R{sub t}, and I{sub sc} at higher fume particulate doses accompanied LDH release, to a greater extent for MMA-SS. Thus, Na{sup +} transport and Na{sup +},K{sup +},2Cl¯-cotransport are affected by fume exposure; MMA-MS is more potent than GMA-MS. Enhanced Na{sup +} absorption and decreased airway surface liquid could compromise defenses against infection. - Highlights: • Welding fume particle toxicity was investigated in human bronchial

  13. Quantification of monosialogangliosides in human plasma through chemical derivatization for signal enhancement in LC–ESI-MS

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Qianyang; Liu, Danting [Clinical Chemistry Program, Department of Chemistry, Cleveland State University, 2121 Euclid Avenue, Cleveland, OH 44115 (United States); Xin, Baozhong; Cechner, Karen [DDC Clinic, Center for Special Needs Children, 14567 Madison Road, Middlefield, OH 44062 (United States); Zhou, Xiang [Clinical Chemistry Program, Department of Chemistry, Cleveland State University, 2121 Euclid Avenue, Cleveland, OH 44115 (United States); Wang, Heng, E-mail: Wang@ddcclinic.org [DDC Clinic, Center for Special Needs Children, 14567 Madison Road, Middlefield, OH 44062 (United States); Zhou, Aimin, E-mail: a.zhou@csuohio.edu [Clinical Chemistry Program, Department of Chemistry, Cleveland State University, 2121 Euclid Avenue, Cleveland, OH 44115 (United States); Center for Gene Regulation in Health and Diseases, Cleveland State University, 2121 Euclid Avenue, Cleveland, OH 44115 (United States)

    2016-07-27

    Gangliosides are found in abundance in the central nervous system of vertebrates. Their metabolic disruption and dysfunction are associated with various neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. In order to improve our understanding of the etiology of these diseases, analytical ganglioside assays with sufficient specificity and sensitivity in relevant biological matrices are required. In the present work we have developed and validated a reverse-phase ultra-performance liquid chromatography (UPLC)/tandem mass spectrometry (MS) method for determining monosialogangliosides GM1, GM2, and GM3 present in human plasma. Compared with our previous method, this method enhanced, by 15 fold, MS responses of the analytes by employing 2-(2-Pyridilamino)-ethylamine (PAEA) & 4-(4, 6-Dimethoxy-1, 3, 5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM)-based derivatization. The analytes and internal standards were derivatized with PAEA&DMTMM after extraction from plasma using a protein precipitation procedure. They were then purified using liquid–liquid partitioning. When the samples were then analyzed by UPLC-MS/MS with a multiple reaction monitoring (MRM) mode, we achieved superior sensitivity and specificity. This method was evaluated for extraction recovery, calibration linearity, precision, accuracy, and lower limit of quantification (LLOQ). The validated method was successfully applied to monitor monosialoganglioside levels in the plasma from patients with GM3 synthase deficiency. With significantly increased sensitivity, we have, for the first time, detected a significant amount of GM3 in the affected patients. - Highlights: • A UPLC/MS/MS method for analyzing monosialogangliosides GM1, GM2, and GM3 in human plasma was developed and validated. • PAEA&DMTMM-based derivatization greatly improved the sensitivity. • The method was applied to measure GM1, GM2, and GM3 in the plasma from the patients with GM3 synthase

  14. Electrosprayed calcium phosphate coatings for biomedical purposes.

    OpenAIRE

    Leeuwenburgh, S.C.G.

    2006-01-01

    In this thesis, the suitability of the Electrostatic Spray Deposition (ESD) technique was studied for biomedical purposes, i.e., deposition of calcium phosphate (CaP) coatings onto titanium substrates. Using ESD, which is a simple and cheap deposition method for inorganic and organic coatings, it was possible to obtain thin CaP layers with an extremely wide range of chemical and morphological characteristics. Various CaP phases and phase mixtures were deposited and a broad diversity of coatin...

  15. Epigenetic factors in cancer risk: effect of chemical carcinogens on global DNA methylation pattern in human TK6 cells.

    Directory of Open Access Journals (Sweden)

    Ali M Tabish

    Full Text Available In the current study, we assessed the global DNA methylation changes in human lymphoblastoid (TK6 cells in vitro in response to 5 direct and 10 indirect-acting genotoxic agents. TK6 cells were exposed to the selected agents for 24 h in the presence and/or absence of S9 metabolic mix. Liquid chromatography-mass spectrometry was used for quantitative profiling of 5-methyl-2'-deoxycytidine. The effect of exposure on 5-methyl-2'-deoxycytidine between control and exposed cultures was assessed by applying the marginal model with correlated residuals on % global DNA methylation data. We reported the induction of global DNA hypomethylation in TK6 cells in response to S9 metabolic mix, under the current experimental settings. Benzene, hydroquinone, styrene, carbon tetrachloride and trichloroethylene induced global DNA hypomethylation in TK6 cells. Furthermore, we showed that dose did not have an effect on global DNA methylation in TK6 cells. In conclusion we report changes in global DNA methylation as an early event in response to agents traditionally considered as genotoxic.

  16. Brominated flame retardants and perfluorinated chemicals, two groups of persistent contaminants in Belgian human blood and milk

    Energy Technology Data Exchange (ETDEWEB)

    Roosens, Laurence [Toxicological Centre, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk (Belgium); D' Hollander, Wendy; Bervoets, Lieven [Laboratory for Ecophysiology, Biochemistry and Toxicology, Department of Biology, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp (Belgium); Reynders, Hans; Van Campenhout, Karen [Environment and Health Unit, Department of Environment, Nature and Energy, Flemish Government - Koning Albert II-laan 20, Bus 8, 1000 Brussels (Belgium); Cornelis, Christa; Van Den Heuvel, Rosette; Koppen, Gudrun [Unit Environmental Risk and Health, Flemish Institute of Technological Research (VITO), Boeretang 200, 2400 Mol (Belgium); Covaci, Adrian, E-mail: adrian.covaci@ua.ac.b [Toxicological Centre, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk (Belgium); Laboratory for Ecophysiology, Biochemistry and Toxicology, Department of Biology, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp (Belgium)

    2010-08-15

    We assessed the exposure of the Flemish population to brominated flame retardants (BFRs) and perfluorinated compounds (PFCs) by analysis of pooled cord blood, adolescent and adult serum, and human milk. Levels of polybrominated diphenyl ethers (PBDEs) in blood (range 1.6-6.5 ng/g lipid weight, lw) and milk (range 2.0-6.4 ng/g lw) agreed with European data. Hexabromocyclododecane ranged between <2.1-5.7 ng/g lw in milk. Perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) dominated in blood and ranged between 1 and 171 ng/mL and <0.9-9.5 ng/mL, respectively. Total PFC levels in milk ranged between <0.5-29 ng/mL. A significant increase in PBDE concentrations was detected from newborns (median 2.1) to the adolescents and adults (medians 3.8 and 4.6 ng/g lw, respectively). An identical trend was observed for PFOS, but not for PFOA. We estimated that newborn exposure to BFRs and PFCs occurs predominantly post-natally, whereas placental transfer has a minor impact on the body burden. - The exposure to BFRs and PFCs of general Flemish population has been assessed throughout several age groups.

  17. Difficult Decisions: Chemical Warfare.

    Science.gov (United States)

    Slesnick, Irwin L.; Miller, John A.

    1988-01-01

    Gives the background history and chemistry of modern day chemical warfare from World War I to the present. Provides discussion questions to stimulate deeper thinking on the issue. Contains a discussion activity called "Can New Chemical Weapons Lead to Humane Warfare?" (CW)

  18. Efficient generation of transgene- and feeder-free induced pluripotent stem cells from human dental mesenchymal stem cells and their chemically defined differentiation into cardiomyocytes.

    Science.gov (United States)

    Tan, Xiaobing; Dai, Qingli; Guo, Tao; Xu, Jingshu; Dai, Qingyuan

    2018-01-22

    Advance in stem cell research resulted in several processes to generate induced pluripotent stem cells (iPSCs) from adult somatic cells. In our previous study, the reprogramming of iPSCs from human dental mesenchymal stem cells (MSCs) including SCAP and DPSCs, has been reported. Herein, safe iPSCs were reprogrammed from SCAP and DPSCs using non-integrating RNA virus vector, which is an RNA virus carrying no risk of altering host genome. DPSCs- and SCAP-derived iPSCs exhibited the characteristics of the classical morphology with human embryonic stem cells (hESCs) without integration of foreign genes, indicating the potential of their clinical application. Moreover, induced PSCs showed the capacity of self-renewal and differentiation into cardiac myocytes. We have achieved the differentiation of hiPSCs to cardiomyocytes lineage under serum and feeder-free conditions, using a chemically defined medium CDM3. In CDM3, hiPSCs differentiation is highly generating cardiomyocytes. The results showed this protocol produced contractile sheets of up to 97.2% TNNT2 cardiomyocytes after purification. Furthermore, derived hiPSCs differentiated to mature cells of the three embryonic germ layers in vivo and in vitro of beating cardiomyocytes. The above whole protocol enables the generation of large scale of highly pure cardiomyocytes as needed for cellular therapy. Copyright © 2017. Published by Elsevier Inc.

  19. Insulin-producing Cells from Adult Human Bone Marrow Mesenchymal Stromal Cells Could Control Chemically Induced Diabetes in Dogs: A Preliminary Study.

    Science.gov (United States)

    Gabr, Mahmoud M; Zakaria, Mahmoud M; Refaie, Ayman F; Ismail, Amani M; Khater, Sherry M; Ashamallah, Sylvia A; Azzam, Maha M; Ghoneim, Mohamed A

    2018-01-01

    Ten mongrel dogs were used in this study. Diabetes was chemically induced in 7 dogs, and 3 dogs served as normal controls. For each diabetic dog, 5 million human bone marrow-derived mesenchymal stem cells/kg were differentiated to form insulin-producing cells using a trichostatin-based protocol. Cells were then loaded in 2 TheraCyte capsules which were transplanted under the rectus sheath. One dog died 4 d postoperatively from pneumonia. Six dogs were followed up with for 6 to 18 mo. Euglycemia was achieved in 4 dogs. Their glucose tolerance curves exhibited a normal pattern demonstrating that the encapsulated cells were glucose sensitive and insulin responsive. In the remaining 2 dogs, the fasting blood sugar levels were reduced but did not reach normal values. The sera of all transplanted dogs contained human insulin and C-peptide with a negligible amount of canine insulin. Removal of the transplanted capsules was followed by prompt return of diabetes. Intracytoplasmic insulin granules were seen by immunofluorescence in cells from the harvested capsules. Furthermore, all pancreatic endocrine genes were expressed. This study demonstrated that the TheraCyte capsule or a similar device can provide adequate immunoisolation, an important issue when stem cells are considered for the treatment of type 1 diabetes mellitus.

  20. Understanding the physical and chemical nature of the warfarin drug binding site in human serum albumin: experimental and theoretical studies.

    Science.gov (United States)

    Abou-Zied, Osama K

    2015-01-01

    Human serum albumin (HSA) is one of the major carrier proteins in the body and constitutes approximately half of the protein found in blood plasma. It plays an important role in lipid metabolism, and its ability to reversibly bind a large variety of pharmaceutical compounds makes it a crucial determinant of drug pharmacokinetics and pharmacodynamics. This review deals with one of the protein's major binding sites "Sudlow I" which includes a binding pocket for the drug warfarin (WAR). The binding nature of this important site can be characterized by measuring the spectroscopic changes when a ligand is bound. Using several drugs, including WAR, and other drug-like molecules as ligands, the results emphasize the nature of Sudlow I as a flexible binding site, capable of binding a variety of ligands by adapting its binding pockets. The high affinity of the WAR pocket for binding versatile molecular structures stems from the flexibility of the amino acids forming the pocket. The binding site is shown to have an ionization ability which is important to consider when using drugs that are known to bind in Sudlow I. Several studies point to the important role of water molecules trapped inside the binding site in molecular recognition and ligand binding. Water inside the protein's cavity is crucial in maintaining the balance between the hydrophobic and hydrophilic nature of the binding site. Upon the unfolding and refolding of HSA, more water molecules are trapped inside the binding site which cause some swelling that prevents a full recovery from the denatured state. Better understanding of the mechanism of binding in macromolecules such as HSA and other proteins can be achieved by combining experimental and theoretical studies which produce significant synergies in studying complex biochemical phenomena.

  1. Chemical speciation and human health risk of trace metals in urban street dusts from a metropolitan city, Nanjing, SE China

    Energy Technology Data Exchange (ETDEWEB)

    Li, Huiming; Qian, Xin, E-mail: xqian@nju.edu.cn; Hu, Wei; Wang, Yulei; Gao, Hailong

    2013-07-01

    The modified BCR (the European Community Bureau of Reference) sequential extraction procedure was applied for partitioning and evaluating the mobility, availability and persistence of trace metals (Al, Cd, Co, Cr, Cu, Ni, Pb, Sr, V and Zn) in urban street dusts collected from different areas of Nanjing, China. The mobility sequence based on the sum of the BCR sequential extraction stages was: Sr (91.65%) > Pb (79.16%) > Zn (74.26%) > Cu (68.53%) > Co (45.98%) > Al (40.01%) ≈ V (38.45%) ≈ Ni (37.88%) > Cr (29.35%) > Cd (22.68%). Almost every trace metal had its highest total concentrations in the industrial area, except for Sr which had its highest concentration in the commercial area. Contamination factors (Cf), risk assessment code (RAC) and enrichment factor (Ef) were then calculated to further assess the environmental risk and provide a preliminary estimate of the main sources of trace metals in street dusts. Non-carcinogenic effects and carcinogenic effects due to exposure to urban street dusts were assessed for both children and adults. For non-carcinogenic effects, ingestion was the main route of exposure to street dusts for these metals, followed by dermal contact and inhalation. Hazard index values for all studied metals were lower than the safe level of 1, and Pb exhibited the highest risk value (0.125) in the case of children. The carcinogenic risk for Cd, Co, Cr and Ni were all below the acceptable level (< 10{sup −6}). - Highlights: • This study assesses a comprehensive environmental risk of urban trace metal pollution. • This study evaluates human health risk combined with the speciation of trace metals. • This study points the critical contaminated metals that need to be paid special attention. • This study supplies useful information and reference on the application of BCR SPE method.

  2. Public Laws Authorization and Appropriations Acts 1969-2007 for the U.S. Army Chemical Materials Agency

    Science.gov (United States)

    2006-11-06

    agents, chemical herbicides , smoke and other obscuration materials. (2) The term "lethal chemical agent and munition" means a chemical agent or...military purposes and harmless to human beings under normal circumstances. (k) EFFECTIVE DATE -- The provisions of this section shall take effect on...the ecological and physiological dangers inherent in the use of herbicides , and (B) the 117 ecological and Physiological effects of the defoliation

  3. Health and environmental effects of complex chemical mixtures: proceedings

    Energy Technology Data Exchange (ETDEWEB)

    1985-01-01

    The Office of Health and Environmental Research (OHER) of the Department of Energy supports a broad long-term research program on human health and environmental effects from potential exposure to energy-related complex chemical mixtures. The program seeks basic mechanistic data on the effects of complex mixtures at the cellular, molecular, and whole animal levels to aid in predicting human health effects and seeks ecological data on biological and physical transformations in the mixtures, concentrations of the mixtures in various compartments of the environment, and potential routes for human exposure to these mixtures (e.g., food chain). On June 17-18, 1985, OHER held its First Annual Technical Meeting on the Complex Chemical Mixtures Program in Chicago, IL. The primary purpose of the meeting was to enable principal investigators to report the research status and accomplishments of ongoing complex chemical mixture studies supported by OHER. To help focus future research directions round table discussions were conducted.

  4. Risk assessment of PCDD/Fs levels in human tissues related to major food items based on chemical analyses and micro-EROD assay.

    Science.gov (United States)

    Tsang, H L; Wu, S C; Wong, C K C; Leung, C K M; Tao, S; Wong, M H

    2009-10-01

    Nine groups of food items (freshwater fish, marine fish, pork, chicken, chicken eggs, leafy, non-leafy vegetables, rice and flour) and three types of human samples (human milk, maternal serum and cord serum) were collected for the analysis of PCDD/Fs. Results of chemical analysis revealed PCDD/Fs concentrations (pg g(-1) fat) in the following ascending order: pork (0.289 pg g(-1) fat), grass carp (Ctenopharyngodon idellus) (freshwater fish) (0.407), golden thread (Nemipterus virgatus) (marine fish) (0.511), chicken (0.529), mandarin fish (Siniperca kneri) (marine fish) (0.535), chicken egg (0.552), and snubnose pompano (Trachinotus blochii) (marine fish) (1.219). The results of micro-EROD assay showed relatively higher PCDD/Fs levels in fish (2.65 pg g(-1) fat) when compared with pork (0.47), eggs (0.33), chicken (0.13), flour (0.07), vegetables (0.05 pg g(-1) wet wt) and rice (0.05). The estimated average daily intake of PCDD/Fs of 3.51 pg EROD-TEQ/kg bw/day was within the range of WHO Tolerable Daily Intake (1-4 pg WHO-TEQ/kg bw/day) and was higher than the Provisional Tolerable Daily Intake (PMTL) (70 pg for dioxins and dioxin-like PCBs) recommended by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) [Joint FAO/WHO Expert Committee on Food Additives (JECFA), Summary and conclusions of the fifty-seventh meeting, JECFA, 2001.]. Nevertheless, the current findings were significantly lower than the TDI (14 pg WHO-TEQ/kg/bw/day) recommended by the Scientific Committee on Food of the Europe Commission [European Scientific Committee on Food (EU SCF), Opinions on the SCF on the risk assessment of dioxins and dioxin-like PCBs in food, 2000.]. However, it should be noted that micro-EROD assay overestimates the PCDD/Fs levels by 2 to 7 folds which may also amplify the PCDD/Fs levels accordingly. Although the levels of PCDD/Fs obtained from micro-EROD assay were much higher than those obtained by chemical analysis by 2 to 7 folds, it provides a cost-effective and

  5. 21 CFR 814.2 - Purpose.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Purpose. 814.2 Section 814.2 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PREMARKET..., Apr. 1, 2010, § 814.2 was revised, effective Aug. 16, 2010. For the convenience of the user, the...

  6. 44 CFR 360.1 - Purpose.

    Science.gov (United States)

    2010-10-01

    ... intergovernmental endeavor which combines financial and human resources to fill the unique training needs of local... PREPAREDNESS STATE ASSISTANCE PROGRAMS FOR TRAINING AND EDUCATION IN COMPREHENSIVE EMERGENCY MANAGEMENT § 360.1 Purpose. The Emergency Management Training Program is designed to enhance the States' emergency management...

  7. 21 CFR 516.2 - Purpose.

    Science.gov (United States)

    2010-04-01

    ... designation of minor use or minor species new animal drugs and associated exclusive marketing rights. ... AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES General Provisions § 516.2 Purpose. This...

  8. 5 CFR 9901.501 - Purpose.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Purpose. 9901.501 Section 9901.501 Administrative Personnel DEPARTMENT OF DEFENSE HUMAN RESOURCES MANAGEMENT AND LABOR RELATIONS SYSTEMS (DEPARTMENT... procedures for the recruitment for, and appointment to, positions; and assignment, reassignment, detail...

  9. 42 CFR 93.101 - Purpose.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Purpose. 93.101 Section 93.101 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH ASSESSMENTS AND HEALTH EFFECTS STUDIES OF HAZARDOUS SUBSTANCES RELEASES AND FACILITIES PUBLIC HEALTH SERVICE POLICIES ON RESEARCH MISCONDUCT General...

  10. Investigation and characterization of receptors for pituitary adenylate cyclase-activating polypeptide in human brain by radioligand binding and chemical cross-linking

    International Nuclear Information System (INIS)

    Suda, K.; Smith, D.M.; Ghatei, M.A.; Murphy, J.K.; Bloom, S.R.

    1991-01-01

    Pituitary adenylate cyclase-activating polypeptide (PACAP) is a novel peptide of hypothalamic origin which increases adenylate cyclase activity in rat anterior pituitary cell cultures. The 38-amino acid peptide shows a close sequence homology to vasoactive intestinal peptide (VIP). Binding sites for PACAP in membranes from postmortem human brain tissue were studied using [ 125 I]PACAP27 as the radioligand. High specific binding sites (amount of specific binding measured at 0.25 nM [ 125 I]PACAP27 in femtomoles per mg protein +/- SEM; n = 4) were present in hypothalamus (344.5 +/- 13.0), brain stem (343.0 +/- 29.3), cerebellum (292.0 +/- 21.1), cortex (259.6 +/- 19.8), and basal ganglia (259.2 +/- 50.3). Specific binding sites in pituitary, although present, were less abundant (35.0 +/- 8.9). Binding of [ 125 I]PACAP27 was reversible and time, pH, and temperature dependent. Despite the homology with VIP, VIP was a poor inhibitor of [ 125 I]PACAP27 binding (IC50, greater than 1 microM) compared with PACAP27 (IC50, 0.5-1.3 nM) and PACAP38 (IC50, 0.2-1.3 nM). Scatchard plots of [ 125 I]PACAP27 binding showed the presence of both high and lower affinity sites. Chemical cross-linking of PACAP-binding sites revealed that [ 125 I]PACAP27 was bound to polypeptide chains of 67,000 and 48,000 mol wt. Thus, we have demonstrated the presence of PACAP-specific receptors in human brain which are not VIP receptors. This opens the possibility of PACAP functioning as a novel neurotransmitter/neuromodulator in human brain

  11. Chemical speciation of arsenic species in human blood serum by liquid chromatography using a phosphatidylcholine-coated ODS column with detection by ICP-MS

    International Nuclear Information System (INIS)

    Hasegawa, Takuya; Ishise, Jotaro; Fukumoto, Yasuharu; Matsuura, Hirotaka; Zhu, Yanbei; Umemura, Tomonari; Haraguchi, Hiroki; Yamamoto, Kazuhito; Naoe, Tomoki

    2007-01-01

    Chemical speciation of arsenic species in human blood serum was performed by high-performance liquid chromatography/inductively coupled plasma mass spectrometry (HPLC/ICP-MS) with direct sample injection, where an octadecylsilyl silica (ODS) column coated with phosphatidylcholine (PC) (hereafter known as 'PC-coated ODS column') was used as the separation column. In arsenic species analysis, a citrate buffer solution (pH 4.0) was used as the mobile phase, in which the following reagents were added: sodium 1-dodecanesulfonate (SDS), tetramethylammonium hydroxide (TMAH), which are ion-pair reagents to separate inorganic and organic arsenic species, and 3-[(3-cholamidopropyl)-dimethylammonio]-1-propane sulfonate (CHAPS), which is a protein-solubilizing agent to prevent adsorption of proteins on the column. As a result of optimization, five representative arsenic species spiked in human blood serum reference material could be separated from each other within 5 min on the PC-coated ODS column by elution with a 5 mM citrate buffer (pH 4.0) containing 5 mM SDS, 5 mM THAH, and 0.2 mM CHAPS. The detection limits obtained by ICP-MS were 3.1, 2.7, 4.5, 2.5, and 2.5 ng of As g -1 for arsenate (iAs V ), arsenite (iAs III ), monomethylarsonic acid (MMA), dimethylarsenic acid (DMA), and arsenobetaine (AB), respectively, when the injection volume was 20 μL. The present separation system was also applied to speciation analysis of arsenic species in human blood serum collected from a leukemia patient after therapeutic treatment with arsenic. (author)

  12. Application of SV40 T-transformed human corneal epithelial cells to evaluate potential irritant chemicals for in vitro alternative eye toxicity.

    Science.gov (United States)

    Kim, Cho-Won; Park, Geon-Tae; Bae, Ok-Nam; Noh, Minsoo; Choi, Kyung-Chul

    2016-01-01

    Assessment of eye irritation potential is important to human safety, and it is necessary for various cosmetics and chemicals that may contact the human eye. Until recently, the Draize test was considered the standard method for estimating eye irritation, despite its disadvantages such as the need to sacrifice many rabbits for subjective scoring. Thus, we investigated the cytotoxicity and inflammatory response to standard eye irritants using SV40 T-transformed human corneal epithelial (SHCE) cells as a step toward development of an animal-free alternative eye irritation test. MTT and NRU assays of cell viability were performed to investigate the optimal experimental conditions for SHCE cell viability when cells were exposed to sodium dodecyl sulfate (SDS) as a standard eye irritant at 6.25×10(-3) to 1×10(-1)%. Additionally, cell viability of SHCE cells was examined in response to six potential eye irritants, benzalkonium chloride, dimethyl sulfoxide, isopropanol, SDS, Triton X-100 and Tween 20 at 5×10(-3) to 1×10(-1)%. Finally, we estimated the secretion level of cytokines in response to stimulation by eye irritants in SHCE cells. SHCE cells showed a good response to potential eye irritants when the cells were exposed to potential irritants for 10min at room temperature (RT), and cytokine production increased in a concentration-dependent manner, indicating that cytotoxicity and cytokine secretion from SHCE cells may be well correlated with the concentrations of irritants. Taken together, these results suggest that SHCE cells could be an excellent alternative in vitro model to replace in vivo animal models for eye irritation tests. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. An isotope-labeled chemical derivatization method for the quantitation of short-chain fatty acids in human feces by liquid chromatography–tandem mass spectrometry

    International Nuclear Information System (INIS)

    Han, Jun; Lin, Karen; Sequeira, Carita; Borchers, Christoph H.

    2015-01-01

    Highlights: • 3-Nitrophenylhydrazine was used to derivatize short-chain fatty acids (SCFAs) for LC-MS/MS. • 13 C 6 analogues were produced for use as isotope-labeled internal standards. • Isotope-labeled standards compensate for ESI matrix effects in LC-MS/MS. • Femtomolar sensitivities and 93–108% quantitation accuracy were achieved for human fecal SCFAs. - Abstract: Short-chain fatty acids (SCFAs) are produced by anaerobic gut microbiota in the large bowel. Qualitative and quantitative measurements of SCFAs in the intestinal tract and the fecal samples are important to understand the complex interplay between diet, gut microbiota and host metabolism homeostasis. To develop a new LC-MS/MS method for sensitive and reliable analysis of SCFAs in human fecal samples, 3-nitrophenylhydrazine (3NPH) was employed for pre-analytical derivatization to convert ten C 2 –C 6 SCFAs to their 3-nitrophenylhydrazones under a single set of optimized reaction conditions and without the need of reaction quenching. The derivatives showed excellent in-solution chemical stability. They were separated on a reversed-phase C 18 column and quantitated by negative-ion electrospray ionization – multiple-reaction monitoring (MRM)/MS. To achieve accurate quantitation, the stable isotope-labeled versions of the derivatives were synthesized in a single reaction vessel from 13 C 6 -3NPH, and were used as internal standard to compensate for the matrix effects in ESI. Method validation showed on-column limits of detection and quantitation over the range from low to high femtomoles for the ten SCFAs, and the intra-day and inter-day precision for determination of nine of the ten SCFAs in human fecal samples was ≤8.8% (n = 6). The quantitation accuracy ranged from 93.1% to 108.4% (CVs ≤ 4.6%, n = 6). This method was used to determine the SCFA concentrations and compositions in six human fecal samples. One of the six samples, which was collected from a clinically diagnosed type 2

  14. An isotope-labeled chemical derivatization method for the quantitation of short-chain fatty acids in human feces by liquid chromatography–tandem mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Han, Jun; Lin, Karen; Sequeira, Carita [University of Victoria – Genome BC Proteomics Centre, University of Victoria, Vancouver Island Technology Park, 3101–4464 Markham Street, Victoria, BC V8Z 7X8 (Canada); Borchers, Christoph H., E-mail: christoph@proteincentre.com [University of Victoria – Genome BC Proteomics Centre, University of Victoria, Vancouver Island Technology Park, 3101–4464 Markham Street, Victoria, BC V8Z 7X8 (Canada); Department of Biochemistry and Microbiology, University of Victoria, Petch Building Room 207, 3800 Finnerty Road, Victoria, BC V8P 5C2 (Canada)

    2015-01-07

    Highlights: • 3-Nitrophenylhydrazine was used to derivatize short-chain fatty acids (SCFAs) for LC-MS/MS. • {sup 13}C{sub 6} analogues were produced for use as isotope-labeled internal standards. • Isotope-labeled standards compensate for ESI matrix effects in LC-MS/MS. • Femtomolar sensitivities and 93–108% quantitation accuracy were achieved for human fecal SCFAs. - Abstract: Short-chain fatty acids (SCFAs) are produced by anaerobic gut microbiota in the large bowel. Qualitative and quantitative measurements of SCFAs in the intestinal tract and the fecal samples are important to understand the complex interplay between diet, gut microbiota and host metabolism homeostasis. To develop a new LC-MS/MS method for sensitive and reliable analysis of SCFAs in human fecal samples, 3-nitrophenylhydrazine (3NPH) was employed for pre-analytical derivatization to convert ten C{sub 2}–C{sub 6} SCFAs to their 3-nitrophenylhydrazones under a single set of optimized reaction conditions and without the need of reaction quenching. The derivatives showed excellent in-solution chemical stability. They were separated on a reversed-phase C{sub 18} column and quantitated by negative-ion electrospray ionization – multiple-reaction monitoring (MRM)/MS. To achieve accurate quantitation, the stable isotope-labeled versions of the derivatives were synthesized in a single reaction vessel from {sup 13}C{sub 6}-3NPH, and were used as internal standard to compensate for the matrix effects in ESI. Method validation showed on-column limits of detection and quantitation over the range from low to high femtomoles for the ten SCFAs, and the intra-day and inter-day precision for determination of nine of the ten SCFAs in human fecal samples was ≤8.8% (n = 6). The quantitation accuracy ranged from 93.1% to 108.4% (CVs ≤ 4.6%, n = 6). This method was used to determine the SCFA concentrations and compositions in six human fecal samples. One of the six samples, which was collected from a

  15. Altered ion transport in normal human bronchial epithelial cells following exposure to chemically distinct metal welding fume particles.

    Science.gov (United States)

    Fedan, Jeffrey S; Thompson, Janet A; Meighan, Terence G; Zeidler-Erdely, Patti C; Antonini, James M

    2017-07-01

    Welding fume inhalation causes pulmonary toxicity, including susceptibility to infection. We hypothesized that airway epithelial ion transport is a target of fume toxicity, and investigated the effects of fume particulates from manual metal arc-stainless steel (MMA-SS) and gas metal arc-mild steel (GMA-MS) on ion transport in normal human bronchial epithelium (NHBE) cultured in air-interface. MMA-SS particles, more soluble than GMA-MS particles, contain Cr, Ni, Fe and Mn; GMA-MS particles contain Fe and Mn. MMA-SS or GMA-MS particles (0.0167-166.7μg/cm 2 ) were applied apically to NHBEs. After 18h transepithelial potential difference (V t ), resistance (R t ), and short circuit current (I sc ) were measured. Particle effects on Na + and Cl¯ channels and the Na + ,K + ,2Cl¯-cotransporter were evaluated using amiloride (apical), 5-nitro-2-[(3-phenylpropyl)amino]benzoic acid (NPPB, apical), and bumetanide (basolateral), respectively. MMA-SS (0.0167-16.7μg/cm 2 ) increased basal V t . Only 16.7μg/cm 2 GMA-MS increased basal V t significantly. MMA-SS or GMA-MS exposure potentiated I sc responses (decreases) to amiloride and bumetanide, while not affecting those to NPPB, GMA-MS to a lesser degree than MMA-SS. Variable effects on R t were observed in response to amiloride, and bumetanide. Generally, MMA-SS was more potent in altering responses to amiloride and bumetanide than GMA-MS. Hyperpolarization occurred in the absence of LDH release, but decreases in V t , R t , and I sc at higher fume particulate doses accompanied LDH release, to a greater extent for MMA-SS. Thus, Na + transport and Na + ,K + ,2Cl¯-cotransport are affected by fume exposure; MMA-MS is more potent than GMA-MS. Enhanced Na + absorption and decreased airway surface liquid could compromise defenses against infection. Published by Elsevier Inc.

  16. Transport and Purpose in the Anthropocene

    Science.gov (United States)

    Haff, P. K.

    2012-12-01

    A challenge to a geological, or any scientific, explanation of transport and other fundamental processes of the anthroposphere is the presence of purpose. The proximate force driving the flux of economic goods in a society is clearly physical (e.g., diesel engines), but a higher-level cause or force is human purpose—people want stuff. Large-scale expression of human purpose in the anthroposphere is nonetheless subject to some of the same physical restrictions as apply to physical forcing. Long-distance transport (Haff, 2010) of economic goods in response to human demand, for example, requires a diffusion-to-advection hand-off from producer to transport mode which resembles heat transfer from a thermal boundary layer to a convective roll in a Rayleigh-Benard cell (Haff, 2012) or to the earth's atmosphere. The (inverse) thickness of the boundary layer plays a role analogous to price. However, detailing anthropic mass and energy fluxes even with consideration of human purpose addresses only half the problem of describing transport dynamics in the anthroposphere; this is meant in the same sense that studies of river flow under the influence of gravity address only part of the problem of water transport in the hydrologic cycle. From the point of view of the hydrosphere the purpose of a river is to help maintain hydrospheric function, and from the point of view of the anthroposphere, the purpose of economic flows is not to fulfill human wants but to help maintain anthropospheric function. The role of purpose in the anthroposphere becomes clearer under the (mental) operation of coarse-graining a system, i.e., of spatially decomposing a system according to scale. Self-consistency, or equivalently system longevity, implies the existence of a set of mutual responsibilities and constraints between system and parts. These relationships illustrate the role of purpose as an attribute of complex, steady, dynamical systems, including the anthroposphere. Purpose arises

  17. Gut microbiota in toxicological risk assessment of drugs and chemicals: The need of hour.

    Science.gov (United States)

    Velmurugan, Ganesan

    2018-03-06

    The advent of industrial revolution caused a large inflow of synthetic chemicals for medical, agricultural, industrial and other purposes in the world. In general, these chemicals were subjected to toxicological risk assessment for human health and ecology before release for public use. But today we are witnessing a negative impact of some of these chemicals on human health and environment indicating an underestimation of toxic effects by current risk assessment protocol. Recent studies established gut microbiota as one of the key player in intercession of toxicity of drugs and synthetic chemicals. Hence, the need of the hour is to include the assessment for microbiota specifically gut microbiota in human toxicological risk assessment protocol. Herewith we are proposing a framework for assessment of gut microbiota upon exposure to drugs or chemicals.

  18. Pharmacological modulation of human mesenchymal stem cell chondrogenesis by a chemically oversulfated polysaccharide of marine origin: potential application to cartilage regenerative medicine.

    Science.gov (United States)

    Merceron, Christophe; Portron, Sophie; Vignes-Colombeix, Caroline; Rederstorff, Emilie; Masson, Martial; Lesoeur, Julie; Sourice, Sophie; Sinquin, Corinne; Colliec-Jouault, Sylvia; Weiss, Pierre; Vinatier, Claire; Guicheux, Jérôme

    2012-03-01

    Mesenchymal stem cells (MSCs) are considered as an attractive source of cells for cartilage engineering due to their availability and capacity for expansion and multipotency. Differentiation of MSC into chondrocytes is crucial to successful cartilage regeneration and can be induced by various biological agents, including polysaccharides that participate in many biological processes through interactions with growth factors. Here, we hypothesize that growth factor-induced differentiation of MSC can be increased by chemically oversulfated marine polysaccharides. To test our hypothesis, human adipose tissue-derived MSCs (hATSCs) were cultured in pellets with transforming growth factor (TGF)-β1-supplemented chondrogenic medium containing either the polysaccharide GY785 DR or its oversulfated isoform GY785 DRS. Chondrogenesis was monitored by the measurement of pellet volume, quantification of DNA, collagens, glycosaminoglycans (GAGs), and immunohistological staining. Our data revealed an increase in pellet volume, total collagens, and GAG production with GY785 DRS and chondrogenic medium. The enhanced chondrogenic differentiation of hATSC was further demonstrated by the increased expression of several chondrogenic markers by real-time reverse transcription-polymerase chain reaction. In addition, surface plasmon resonance analyses revealed that TGF-β1 bound GY785 DRS with higher affinity compared to GY785 DR. In association with TGF-β1, GY785 DRS was found to upregulate the phosphorylation of extracellular signal-regulated kinase 1/2, indicating that oversulfated polysaccharide affects the mitogen activated protein kinase signaling activity. These results demonstrate the upregulation of TGF-β1-dependent stem cell chondrogenesis by a chemically oversulfated marine polysaccharide. This polysaccharide of marine origin is easily producible and therefore could be considered a promising additive to drive efficient and reliable MSC chondrogenesis for cartilage tissue

  19. Sensitive monitoring of monoterpene metabolites in human urine using two-step derivatisation and positive chemical ionisation-tandem mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, Lukas [Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, University of Erlangen-Nuremberg, Schillerstrasse 25/29, 91054 Erlangen (Germany); Belov, Vladimir N. [Max Planck Institute for Biophysical Chemistry, Facility for Synthetic Chemistry, Am Fassberg 11, 37077 Göttingen (Germany); Göen, Thomas, E-mail: Thomas.Goeen@ipasum.med.uni-erlangen.de [Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, University of Erlangen-Nuremberg, Schillerstrasse 25/29, 91054 Erlangen (Germany)

    2013-09-02

    Highlights: •Sensitive monitoring of 10 metabolites of (R)-limonene, α-pinene, and Δ{sup 3}-carene in human urine samples. •Fast and simple sample preparation and derivatisation procedure using two-step silylation for unreactive tertiary hydroxyl groups. •Synthesis of reference substances and isotopically labelled internal standards of (R)-limonene, α-pinene, and Δ{sup 3}-carene metabolites. •Study on (R)-limonene, α-pinene, and Δ{sup 3}-carene metabolite background exposure of 36 occupationally unexposed volunteers. -- Abstract: A gas chromatographic–positive chemical ionisation-tandem mass spectrometric (GC–PCI-MS/MS) method for the simultaneous determination of 10 oxidative metabolites of the monoterpenoid hydrocarbons α-pinene, (R)-limonene, and Δ{sup 3}-carene ((+)-3-carene) in human urine was developed and tested for the monoterpene biomonitoring of the general population (n = 36). The method involves enzymatic cleavage of the glucuronides followed by solid-supported liquid–liquid extraction and derivatisation using a two-step reaction with N,O-bis(trimethylsilyl)-trifluoroacetamide and N-(trimethylsilyl)imidazole. The method proved to be both sensitive and reliable with detection limits ranging from 0.1 to 0.3 μg L{sup −1}. In contrast to the frequent and distinct quantities of (1S,2S,4R)-limonene-1,2-diol, the (1R,2R,4R)-stereoisomer could not be detected. The expected metabolite of (+)-3-carene, 3-caren-10-ol was not detected in any of the samples. All other metabolites were detected in almost all urine samples. The procedure enables for the first time the analysis of trace levels of a broad spectrum of mono- and bicyclic monoterpenoid metabolites (alcohols, diols, and carboxylic acids) in human urine. This analytical procedure is a powerful tool for population studies as well as for the discovery of human metabolism and toxicokinetics of monoterpenes.

  20. Human Health Risk Assessment of Artisanal Miners Exposed to Toxic Chemicals in Water and Sediments in the PresteaHuni Valley District of Ghana

    Directory of Open Access Journals (Sweden)

    Samuel Obiri

    2016-01-01

    Full Text Available A human health risk assessment of artisanal miners exposed to toxic metals in water bodies and sediments in the PresteaHuni Valley District of Ghana was carried out in this study, in line with US EPA risk assessment guidelines. A total of 70 water and 30 sediment samples were collected from surface water bodies in areas impacted by the operations of artisanal small-scale gold mines in the study area and analyzed for physico-chemical parameters such as pH, TDS, conductivity, turbidity as well as metals and metalloids such as As, Cd, Hg and Pb at CSIR—Water Research Institute using standard methods for the examination of wastewater as outlined by American Water Works Association (AWWA. The mean concentrations of As, Cd, Hg and Pb in water samples ranged from 15 μg/L to 325 μg/L (As, 0.17 μg/L to 340 μg/L (Cd, 0.17 μg/L to 122 μg/L (Pb and 132 μg/L to 866 μg/L (Hg, respectively. These measured concentrations of arsenic (As, mercury (Hg, cadmium (Cd and lead (Pb were used as input parameters to calculate the cancer and non-cancer health risks from exposure to these metals in surface water bodies and sediments based on an occupational exposure scenario using central tendency exposure (CTE and reasonable maximum exposure (RME parameters. The results of the non-cancer human health risk assessment for small-scale miners working around river Anikoko expressed in terms of hazard quotients based on CTE parameters are as follows: 0.04 (Cd, 1.45 (Pb, 4.60 (Hg and 1.98 (As; while cancer health risk faced by ASGM miners in Dumase exposed to As in River Mansi via oral ingestion of water is 3.1 × 10−3. The hazard quotient results obtained from this study in most cases were above the HQ guidance value of 1.0, furthermore the cancer health risk results were found to be higher than the USEPA guidance value of 1 × 10−4 to 1 × 10−6. These findings call for case-control epidemiological studies to establish the relationship between exposure to the

  1. Human Health Risk Assessment of Artisanal Miners Exposed to Toxic Chemicals in Water and Sediments in the Prestea Huni Valley District of Ghana.

    Science.gov (United States)

    Obiri, Samuel; Yeboah, Philip O; Osae, Shiloh; Adu-Kumi, Sam; Cobbina, Samuel J; Armah, Frederick A; Ason, Benjamin; Antwi, Edward; Quansah, Reginald

    2016-01-18

    A human health risk assessment of artisanal miners exposed to toxic metals in water bodies and sediments in the PresteaHuni Valley District of Ghana was carried out in this study, in line with US EPA risk assessment guidelines. A total of 70 water and 30 sediment samples were collected from surface water bodies in areas impacted by the operations of artisanal small-scale gold mines in the study area and analyzed for physico-chemical parameters such as pH, TDS, conductivity, turbidity as well as metals and metalloids such as As, Cd, Hg and Pb at CSIR-Water Research Institute using standard methods for the examination of wastewater as outlined by American Water Works Association (AWWA). The mean concentrations of As, Cd, Hg and Pb in water samples ranged from 15 μg/L to 325 μg/L (As), 0.17 μg/L to 340 μg/L (Cd), 0.17 μg/L to 122 μg/L (Pb) and 132 μg/L to 866 μg/L (Hg), respectively. These measured concentrations of arsenic (As), mercury (Hg), cadmium (Cd) and lead (Pb) were used as input parameters to calculate the cancer and non-cancer health risks from exposure to these metals in surface water bodies and sediments based on an occupational exposure scenario using central tendency exposure (CTE) and reasonable maximum exposure (RME) parameters. The results of the non-cancer human health risk assessment for small-scale miners working around river Anikoko expressed in terms of hazard quotients based on CTE parameters are as follows: 0.04 (Cd), 1.45 (Pb), 4.60 (Hg) and 1.98 (As); while cancer health risk faced by ASGM miners in Dumase exposed to As in River Mansi via oral ingestion of water is 3.1 × 10(-3). The hazard quotient results obtained from this study in most cases were above the HQ guidance value of 1.0, furthermore the cancer health risk results were found to be higher than the USEPA guidance value of 1 × 10(-4) to 1 × 10(-6). These findings call for case-control epidemiological studies to establish the relationship between exposure to the

  2. Human Health Risk Assessment of Artisanal Miners Exposed to Toxic Chemicals in Water and Sediments in the Prestea Huni Valley District of Ghana

    Science.gov (United States)

    Obiri, Samuel; Yeboah, Philip O.; Osae, Shiloh; Adu-kumi, Sam; Cobbina, Samuel J.; Armah, Frederick A.; Ason, Benjamin; Antwi, Edward; Quansah, Reginald

    2016-01-01

    A human health risk assessment of artisanal miners exposed to toxic metals in water bodies and sediments in the PresteaHuni Valley District of Ghana was carried out in this study, in line with US EPA risk assessment guidelines. A total of 70 water and 30 sediment samples were collected from surface water bodies in areas impacted by the operations of artisanal small-scale gold mines in the study area and analyzed for physico-chemical parameters such as pH, TDS, conductivity, turbidity as well as metals and metalloids such as As, Cd, Hg and Pb at CSIR—Water Research Institute using standard methods for the examination of wastewater as outlined by American Water Works Association (AWWA). The mean concentrations of As, Cd, Hg and Pb in water samples ranged from 15 μg/L to 325 μg/L (As), 0.17 μg/L to 340 μg/L (Cd), 0.17 μg/L to 122 μg/L (Pb) and 132 μg/L to 866 μg/L (Hg), respectively. These measured concentrations of arsenic (As), mercury (Hg), cadmium (Cd) and lead (Pb) were used as input parameters to calculate the cancer and non-cancer health risks from exposure to these metals in surface water bodies and sediments based on an occupational exposure scenario using central tendency exposure (CTE) and reasonable maximum exposure (RME) parameters. The results of the non-cancer human health risk assessment for small-scale miners working around river Anikoko expressed in terms of hazard quotients based on CTE parameters are as follows: 0.04 (Cd), 1.45 (Pb), 4.60 (Hg) and 1.98 (As); while cancer health risk faced by ASGM miners in Dumase exposed to As in River Mansi via oral ingestion of water is 3.1 × 10−3. The hazard quotient results obtained from this study in most cases were above the HQ guidance value of 1.0, furthermore the cancer health risk results were found to be higher than the USEPA guidance value of 1 × 10−4 to 1 × 10−6. These findings call for case-control epidemiological studies to establish the relationship between exposure to the

  3. Depleting high-abundant and enriching low-abundant proteins in human serum: An evaluation of sample preparation methods using magnetic nanoparticle, chemical depletion and immunoaffinity techniques.

    Science.gov (United States)

    de Jesus, Jemmyson Romário; da Silva Fernandes, Rafael; de Souza Pessôa, Gustavo; Raimundo, Ivo Milton; Arruda, Marco Aurélio Zezzi

    2017-08-01

    The efficiency of three different depletion methods to remove the most abundant proteins, enriching those human serum proteins with low abundance is checked to make more efficient the search and discovery of biomarkers. These methods utilize magnetic nanoparticles (MNPs), chemical reagents (sequential application of dithiothreitol and acetonitrile, DTT/ACN), and commercial apparatus based on immunoaffinity (ProteoMiner, PM). The comparison between methods shows significant removal of abundant protein, remaining in the supernatant at concentrations of 4.6±0.2, 3.6±0.1, and 3.3±0.2µgµL -1 (n=3) for MNPs, DTT/ACN and PM respectively, from a total protein content of 54µgµL -1 . Using GeLC-MS/MS analysis, MNPs depletion shows good efficiency in removing high molecular weight proteins (>80kDa). Due to the synergic effect between the reagents DTT and ACN, DTT/ACN-based depletion offers good performance in the depletion of thiol-rich proteins, such as albumin and transferrin (DTT action), as well as of high molecular weight proteins (ACN action). Furthermore, PM equalization confirms its efficiency in concentrating low-abundant proteins, decreasing the dynamic range of protein levels in human serum. Direct comparison between the treatments reveals 72 proteins identified when using MNP depletion (43 of them exclusively by this method), but only 20 proteins using DTT/ACN (seven exclusively by this method). Additionally, after PM treatment 30 proteins were identified, seven exclusively by this method. Thus, MNPs and DTT/ACN depletion can be simple, quick, cheap, and robust alternatives for immunochemistry-based protein depletion, providing a potential strategy in the search for disease biomarkers. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Sampling strategy and analysis of trace element concentrations by inductively coupled plasma mass spectrometry on medieval human bones--the concept of chemical life history.

    Science.gov (United States)

    Skytte, Lilian; Rasmussen, Kaare Lund

    2013-07-30

    Medieval human bones have the potential to reveal diet, mobility and treatment of diseases in the past. During the last two decades trace element chemistry has been used extensively in archaeometric investigations revealing such data. Many studies have reported the trace element inventory in only one sample from each skeleton - usually from the femur or a tooth. It cannot a priori be assumed that all bones or teeth in a skeleton will have the same trace element concentrations. Six different bone and teeth samples from each individual were carefully decontaminated by mechanical means. Following dissolution of ca. 20 mg sample in nitric acid and hydrogen peroxide the assays were performed using inductively coupled plasma mass spectrometry (ICPMS) with quadropole detection. We describe the precise sampling technique as well as the analytical methods and parameters used for the ICPMS analysis. The places of sampling in the human skeleton did exhibit varying trace element concentrations. Although the samples are contaminated by Fe, Mn and Al from the surrounding soil where the bones have been residing for more than 500 years, other trace elements are intact within the bones. It is shown that the elemental ratios Sr/Ca and Ba/Ca can be used as indicators of provenance. The differences in trace element concentrations can be interpreted as indications of varying diet and provenance as a function of time in the life of the individual - a concept which can be termed chemical life history. A few examples of the results of such analyses are shown, which contains information about provenance and diagenesis. Copyright © 2013 John Wiley & Sons, Ltd.

  5. Informing the Human Plasma Protein Binding of Environmental Chemicals by Machine Learning in the Pharmaceutical Space: Applicability Domain and Limits of Predictability

    Science.gov (United States)

    The free fraction of a xenobiotic in plasma (Fub) is an important determinant of chemical adsorption, distribution, metabolism, elimination, and toxicity, yet experimental plasma protein binding data is scarce for environmentally relevant chemicals. The presented work explores th...

  6. 42 CFR 4.3 - Purpose of the Library.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Purpose of the Library. 4.3 Section 4.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS NATIONAL LIBRARY OF MEDICINE § 4.3 Purpose of the Library. The purpose of the Library is to assist the advancement of...

  7. Assessment of skin barrier function and biochemical changes of ex vivo human skin in response to physical and chemical barrier disruption.

    Science.gov (United States)

    Döge, Nadine; Avetisyan, Araks; Hadam, Sabrina; Pfannes, Eva Katharina Barbosa; Rancan, Fiorenza; Blume-Peytavi, Ulrike; Vogt, Annika

    2017-07-01

    Topical dermatotherapy is intended to be used on diseased skin. Novel drug delivery systems even address differences between intact and diseased skin underlining the need for pre-clinical assessment of different states of barrier disruption. Herein, we studied how short-term incubation in culture media compared to incubation in humidified chambers affects human skin barrier function and viability. On both models we assessed different types and intensities of physical and chemical barrier disruption methods with regard to structural integrity, biophysical parameters and cytokine levels. Tissue degeneration and proliferative activity limited the use of tissue cultures to 48h. Viability is better preserved in cultured tissue. Tape-stripping (50×TS) and 4h sodium lauryl sulfate (SLS) pre-treatment were identified as highly reproducible and effective procedures for barrier disruption. Transepidermal water loss (TEWL) values reproducibly increased with the intensity of disruption while sebum content and skin surface pH were of limited value. Interleukin (IL)-6/8 and various chemokines and proteases were increased in tape-stripped skin which was more pronounced in SLS-treated skin tissue extracts. Thus, albeit limited to 48h, cultured full-thickness skin maintained several barrier characteristics and responded to different intensities of barrier disruption. Potentially, these models can be used to assess pre-clinically the efficacy and penetration of anti-inflammatory compounds. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Conformational fluctuation dynamics of domain I of human serum albumin in the course of chemically and thermally induced unfolding using fluorescence correlation spectroscopy.

    Science.gov (United States)

    Yadav, Rajeev; Sengupta, Bhaswati; Sen, Pratik

    2014-05-22

    The present study elucidates the involvement of conformational fluctuation dynamics during chemically and thermally induced unfolding of human serum albumin (HSA) by fluorescence correlation spectroscopic (FCS) study, time-resolved fluorescence measurements, and circular dichroism (CD) spectroscopic methods. Two fluorescent probes, tetramethylrhodamine-5-maleimide (TMR) and N-(7-dimethylamino-4-methylcoumarin-3-yl) iodoacetamide (DACIA) were used to selectively label the domain I of HSA through the reaction with cys-34 for these studies. The guanidine hydrochloride (GnHCl) induced global structural change of HSA is monitored through its hydrodynamic radius (r(H)) and CD response, which is found to be two step in nature. In FCS experiment, along with the diffusion time component we have observed an exponential relaxation time component (τ(R)) that has been ascribed to the concerted chain dynamics of HSA. Unlike in the global structural change, we found that the τ(R) value changes in a different manner in the course of the unfolding. The dependence of τ(R) on the concentration of GnHCl was best fitted with a four state model, indicating the involvement of two intermediate states during the unfolding process, which were not observed through the CD response and r(H) data. The fluorescence lifetime measurement also supports our observation of intermediate states during the unfolding of HSA. However, no such intermediate states were observed during thermally induced unfolding of HSA.

  9. Repeatability of two-dimensional chemical shift imaging multivoxel proton magnetic resonance spectroscopy for measuring human cerebral choline-containing compounds.

    Science.gov (United States)

    Puri, Basant K; Egan, Mary; Wallis, Fintan; Jakeman, Philip

    2018-03-22

    To investigate the repeatability of proton magnetic resonance spectroscopy in the in vivo measurement of human cerebral levels of choline-containing compounds (Cho). Two consecutive scans were carried out in six healthy resting subjects at a magnetic field strength of 1.5 T. On each occasion, neurospectroscopy data were collected from 64 voxels using the same 2D chemical shift imaging (CSI) sequence. The data were analyzed in the same way, using the same software, to obtain the values for each voxel of the ratio of Cho to creatine. The Wilcoxon related-samples signed-rank test, coefficient of variation (CV), repeatability coefficient (RC), and intraclass correlation coefficient (ICC) were used to assess the repeatability. The CV ranged from 2.75% to 33.99%, while the minimum RC was 5.68%. There was excellent reproducibility, as judged by significant ICC values, in 26 voxels. Just three voxels showed significant differences according to the Wilcoxon related-samples signed-rank test. It is therefore concluded that when CSI multivoxel proton neurospectroscopy is used to measure cerebral choline-containing compounds at 1.5 T, the reproducibility is highly acceptable.

  10. Polyphenols from Root, Tubercles and Grains Cropped in Brazil: Chemical and Nutritional Characterization and Their Effects on Human Health and Diseases

    Directory of Open Access Journals (Sweden)

    Diego dos Santos Baião

    2017-09-01

    Full Text Available Throughout evolution, plants have developed the ability to produce secondary phenolic metabolites, which are important for their interactions with the environment, reproductive strategies and defense mechanisms. These (polyphenolic compounds are a heterogeneous group of natural antioxidants found in vegetables, cereals and leguminous that exert beneficial and protective actions on human health, playing roles such as enzymatic reaction inhibitors and cofactors, toxic chemicals scavengers and biochemical reaction substrates, increasing the absorption of essential nutrients and selectively inhibiting deleterious intestinal bacteria. Polyphenols present in some commodity grains, such as soy and cocoa beans, as well as in other vegetables considered security foods for developing countries, including cassava, taro and beetroot, all of them cropped in Brazil, have been identified and quantified in order to point out their bioavailability and the adequate dietary intake to promote health. The effects of the flavonoid and non-flavonoid compounds present in these vegetables, their metabolism and their effects on preventing chronic and degenerative disorders like cancers, diabetes, osteoporosis, cardiovascular and neurological diseases are herein discussed based on recent epidemiological studies.

  11. Polyphenols from Root, Tubercles and Grains Cropped in Brazil: Chemical and Nutritional Characterization and Their Effects on Human Health and Diseases

    Science.gov (United States)

    dos Santos Baião, Diego; Silva de Freitas, Cyntia; da Silva, Davi; Ribeiro Pereira, Patricia

    2017-01-01

    Throughout evolution, plants have developed the ability to produce secondary phenolic metabolites, which are important for their interactions with the environment, reproductive strategies and defense mechanisms. These (poly)phenolic compounds are a heterogeneous group of natural antioxidants found in vegetables, cereals and leguminous that exert beneficial and protective actions on human health, playing roles such as enzymatic reaction inhibitors and cofactors, toxic chemicals scavengers and biochemical reaction substrates, increasing the absorption of essential nutrients and selectively inhibiting deleterious intestinal bacteria. Polyphenols present in some commodity grains, such as soy and cocoa beans, as well as in other vegetables considered security foods for developing countries, including cassava, taro and beetroot, all of them cropped in Brazil, have been identified and quantified in order to point out their bioavailability and the adequate dietary intake to promote health. The effects of the flavonoid and non-flavonoid compounds present in these vegetables, their metabolism and their effects on preventing chronic and degenerative disorders like cancers, diabetes, osteoporosis, cardiovascular and neurological diseases are herein discussed based on recent epidemiological studies. PMID:28930173

  12. Independent effects of the chemical and microstructural surface properties of polymer/ceramic composites on proliferation and osteogenic differentiation of human MSCs.

    Science.gov (United States)

    Sun, Lanying; Danoux, Charlène B; Wang, Qibao; Pereira, Daniel; Barata, David; Zhang, Jingwei; LaPointe, Vanessa; Truckenmüller, Roman; Bao, Chongyun; Xu, Xin; Habibovic, Pamela

    2016-09-15

    Within the general aim of finding affordable and sustainable regenerative solutions for damaged and diseased tissues and organs, significant efforts have been invested in developing synthetic alternatives to natural bone grafts, such as autografts. Calcium phosphate (CaP) ceramics are among widely used synthetic bone graft substitutes, but their mechanical properties and bone regenerative capacity are still outperformed by their natural counterparts. In order to improve the existing synthetic bone graft substitutes, it is imperative to understand the effects of their individual properties on a biological response, and to find a way to combine the desired properties into new, improved functional biomaterials. To this end, we studied the independent effects of the chemical composition and surface microstructure of a poly(lactic acid)/hydroxyapatite (PLA/HA) composite material on the proliferation and osteogenic differentiation of clinically relevant bone marrow-derived human mesenchymal stromal cells (hMSCs). While the molecular weight of the polymer and presence/absence of the ceramic phase were used as the chemical variables, a soft embossing technique was used to pattern the surfaces of all materials with either pits or pillars with identical microscale dimensions. The results indicated that, while cell morphology was affected by both the presence and availability of HA and by the surface microstructure, the effect of the latter parameter on cell proliferation was negligible. The osteogenic differentiation of hMSCs, and in particular the expression of bone morphogenetic protein 2 (BMP-2) and osteopontin (OP) were significantly enhanced when cells were cultured on the composite based on low-molecular-weight PLA, as compared to the high-molecular-weight PLA-based composite and the two pure polymers. The OP expression on the low-molecular-weight PLA-based composite was further enhanced when the surface was patterned with pits. Taken together, within this experimental

  13. Commentary: critical questions, misconceptions and a road map for improving the use of the lymphocyte cytokinesis-block micronucleus assay for in vivo biomonitoring of human exposure to genotoxic chemicals-a HUMN project perspective.

    Science.gov (United States)

    Kirsch-Volders, Micheline; Bonassi, Stefano; Knasmueller, Siegfried; Holland, Nina; Bolognesi, Claudia; Fenech, Michael F

    2014-01-01

    The lymphocyte cytokinesis-block micronucleus (CBMN) assay has been applied in hundreds of in vivo biomonitoring studies of humans exposed to genotoxic chemicals because it allows the measurement of both structural and numerical chromosome aberrations. The CBMN cytome assay version which, apart from measuring micronuclei (MN) already present in cells in vivo or expressed ex vivo, also includes measurement of nucleoplasmic bridges (NPB), nuclear buds (NBUD), necrosis and apoptosis, is also increasingly being used in such studies. Because of the numerous published studies there is now a need to re-evaluate the use of MN and other biomarkers within the lymphocyte CBMN cytome assay as quantitative indicators of exposure to chemical genotoxins and the genetic hazard this may cause. This review has identified some important misconceptions as well as knowledge gaps that need to be addressed to make further progress in the proper application of this promising technique and enable its full potential to be realised. The HUMN project consortium recommends a three pronged approach to further improve the knowledge base and application of the lymphocyte CBMN cytome assay to measure DNA damage in humans exposed to chemical genotoxins: (i) a series of systematic reviews, one for each class of chemical genotoxins, of studies which have investigated the association of in vivo exposure in humans with MN, NPB and NBUD induction in lymphocytes; (ii) a comprehensive analysis of the literature to obtain new insights on the potential mechanisms by which different classes of chemicals may induce MN, NPB and NBUD in vitro and in vivo and (iii) investigation of the potential advantages of using the lymphocyte CBMN cytome assay in conjunction with other promising complementary DNA damage diagnostics to obtain an even more complete assessment of the DNA damage profile induced by in vivo exposure to chemical genotoxins in humans. Copyright © 2014 The Authors. Published by Elsevier B.V. All

  14. Purpose and objectives for international plutonium storage

    International Nuclear Information System (INIS)

    Kupp, R.W.

    1983-01-01

    Separated and decontaminated plutonium - out of a reactor, in a bottle, tank or canister represents an easy target for diversion into possible non-peaceful uses. It also presents a situation that is of concern from a terrorist attack standpoint. Because this special nuclear material has such national and international sensitivity, storage for those quantities which are ''in excess'' of those necessary to be used for peaceful purposes is of concern to the Nations of the World. Recognizing these concerns, Article XII.A.5 of the IAEA Statutes was developed (1956) and the introduction to this Sub-article 5 states ''...that with respect to any Agency Project or other arrangements where the Agency is requested by the parties concerned to apply safeguards, the Agency shall have the following rights and responsibilities to the extent relevant to the project or arrangement....'' Article XII.A.5 then continues: ''To approve the means to be used for chemical processing.... to insure that this chemical processing will not lend itself to diversion of materials for military purposes.... to require that special additional materials recovered or produced as by-product be used for peaceful purposes under continuing Agency safeguards, for research or in reactors.... and to require deposit with the Agency of any excess.... over what is needed for the above stated uses in order to prevent stockpiling of these materials, provided that thereafter, at the request of the member or members concerned.... (plutonium) shall be returned promptly.... for use under the same provisions as stated above.''

  15. Ecological Assembly of Chemical Mixtures

    Science.gov (United States)

    Human-environment interactions have a significant role in the formation of chemical mixtures in the environment and by extension in human tissues and fluids. These interactions, which include decisions to purchase and use products containing chemicals as well as behaviors and act...

  16. Mitigation options for chemicals of emerging concern in surface waters operationalising solutions-focused risk assessment

    NARCIS (Netherlands)

    Van Wezel, Annemarie P.; Ter Laak, Thomas L.; Fischer, Astrid; Bäuerlein, Patrick S.; Munthe, John; Posthuma, Leo

    2017-01-01

    The water system provides many services to society; industries, municipalities and agriculture all withdraw, use and return water and demand a water quality fit for the intended purposes. Both global production of chemicals and global water withdrawal grow faster than human population. This implies

  17. Chemically modified tetracyclines stimulate matrix metalloproteinase-s production by periodontal ligament cells

    NARCIS (Netherlands)

    Bildt, M.M.; Snoek-van Beurden, A.M.P.; Groot, J. de; El, B. van; Kuijpers-Jagtman, A.M.; Hoff, J.W. van den

    2006-01-01

    Background and Objective: The purpose of this study was to investigate the effects of chemically modified tetracyclines (CMTs) on the production of gelatinases [matrix metalloproteinase (MMP)-2 and -9] by human periodontal ligament (PDL) cells, and on the activity of recombinant gelatinases.

  18. Teaching English for Specific Purposes

    Directory of Open Access Journals (Sweden)

    Nijolė Netikšienė

    2011-04-01

    Full T