Health & Environmental Research Online (HERO)


Dioxin (2012 Project Page for Final Report)


2,507 References Were Found:

Archival Material
Archival Material

National Health and Nutrition Survey: NHANES 1999-2000

Author: NCHS (2017) Available online at https://wwwn.cdc.gov/nchs/nhanes/continuousnhanes/default.aspx?BeginYear=1999. (Jul 2, 2017). [Website] HERO ID: 786662

[Less] The National Health and Nutrition Examination Survey (NHANES) is a program of studies designed to assess . . . [More] The National Health and Nutrition Examination Survey (NHANES) is a program of studies designed to assess the health and nutritional status of adults and children in the United States. The survey is unique in that it combines interviews and physical examinations.

Technical Report
Technical Report

Integrated Risk Information System Program

Author: U.S. EPA (2015) Washington, DC: U.S. Environmental Protection Agency, IRIS. HERO ID: 192196

[Less] The U.S. Environmental Protection Agency's (EPA) Integrated Risk Information System (IRIS) Program provides . . . [More] The U.S. Environmental Protection Agency's (EPA) Integrated Risk Information System (IRIS) Program provides health effects information on chemicals to which the public may be exposed, providing a critical part of the scientific foundation for EPA's decisions to protect public health. EPA has made several changes to this important Program over the past few years, streamlining the assessment development process, improving transparency, and creating efficiencies within the Program. In April 2011, the National Research Council (NRC) made several recommendations to EPA for improving the development of IRIS assessments. The N RC's recommendations were focused on the development of draft assessments, and the NRC was clear that their intent was not to delay assessments. EPA has made progress in implementing these recommendations. Consistent with the advice of the NRC, EPA is implementing these recommendations using a phased approach and is making the most extensive changes to documents that are in the earlier steps of the assessment development process. For assessments that are in the later stages of development, including assessments that have been posted on the IRIS database since the release of the NRC report, EPA is implementing the recommendations as feasible without taking the assessments backwards to earlier steps of the process. Phase 1 of implementing the NRC recommendations has focused on editing and streamlining documents and using more tables, figures, and appendices. EPA is now in Phase 2 of implementing the NRC recommendations and will soon publicly release two draft IRIS assessments that represent a major advancement in implementing the NRC recommendations. EPA is using a new document structure for these draft assessments, including an Executive Summary presenting major conclusions, a Preamble describing methods used to develop the assessment, distinct sections on Hazard Identification and Dose-Response Analysis, and more tables and figures to clearly present data. Additionally as part of Phase 2, EPA is addressing all of the short-term recommendations provided by the NRC. As part of this effort, EPA will make several changes to IRIS assessments. Highlights include: evaluating and describing the strengths and weaknesses of critical studies in a more uniform way; including toxicity values for multiple effects associated with the chemical, if applicable and where the data allow; routinely considering the use of multiple data sets of combined multiple responses in deriving toxicity values, where appropriate; and evaluating existing guidelines to establish clearer criteria for study selection. Phase 3 of implementation will incorporate the longer-term scientific recommendations made by the NRC. The U.S. Congress has directed EPA to issue a progress report to the House and Senate Committees on Appropriations and relevant Congressional authorizing committees to describe EPA's implementation of the NRC recommendations. This report provides Congress, stakeholders, and the public with an update on the IRIS Program and EPA's progress toward implementing the NRC recommendations and improving the Program.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Bottom sediment as a source of organic contaminants in Lake Mead, Nevada, USA

Authors: Alvarez, DA; Rosen, MR; Perkins, SD; Cranor, WL; Schroeder, VL; Jones-Lepp, TL (2012) Chemosphere 88:605-611. HERO ID: 1807980

[Less] Treated wastewater effluent from Las Vegas, Nevada and surrounding communities' flow through Las Vegas . . . [More] Treated wastewater effluent from Las Vegas, Nevada and surrounding communities' flow through Las Vegas Wash (LVW) into the Lake Mead National Recreational Area at Las Vegas Bay (LVB). Lake sediment is a likely sink for many hydrophobic synthetic organic compounds (SOCs); however, partitioning between the sediment and the overlying water could result in the sediment acting as a secondary contaminant source. Locating the chemical plumes may be important to understanding possible chemical stressors to aquatic organisms. Passive sampling devices (SPMDs and POCIS) were suspended in LVB at depths of 3.0, 4.7, and 6.7 (lake bottom) meters in June of 2008 to determine the vertical distribution of SOCs in the water column. A custom sediment probe was used to also bury the samplers in the sediment at depths of 0-10, 10-20, and 20-30cm. The greatest number of detections in samplers buried in the sediment was at the 0-10cm depth. Concentrations of many hydrophobic SOCs were twice as high at the sediment-water interface than in the mid and upper water column. Many SOCs related to wastewater effluents, including fragrances, insect repellants, sun block agents, and phosphate flame retardants, were found at highest concentrations in the middle and upper water column. There was evidence to suggest that the water infiltrated into the sediment had a different chemical composition than the rest of the water column and could be a potential risk exposure to bottom-dwelling aquatic organisms.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Evaluation of a multi-endpoint assay in rats, combining the bone-marrow micronucleus test, the Comet assay and the flow-cytometric peripheral blood micronucleus test

Authors: Bowen, DE; Whitwell, JH; Lillford, L; Henderson, D; Kidd, D; Mc Garry, S; Pearce, G; Beevers, C; Kirkland, DJ; Work conducted at Covance Laboratories Ltd., H (2011) Mutation Research 722:7-19. HERO ID: 784746

[Less] With the publication of revised draft ICH guidelines (Draft ICH S2), there is scope and potential to . . . [More] With the publication of revised draft ICH guidelines (Draft ICH S2), there is scope and potential to establish a combined multi-end point in vivo assay to alleviate the need for multiple in vivo assays, thereby reducing time, cost and use of animals. Presented here are the results of an evaluation trial in which the bone-marrow and peripheral blood (via MicroFlow(®) flow cytometry) micronucleus tests (looking at potential chromosome breakage and whole chromosome loss) in developing erythrocytes or young reticulocytes were combined with the Comet assay (measuring DNA strand-breakage), in stomach, liver and blood lymphocytes. This allowed a variety of potential target tissues (site of contact, site of metabolism and peripheral distribution) to be assessed for DNA damage. This combination approach was performed with minimal changes to the standard and regulatory recommended sampling times for the stand-alone assays. A series of eight in vivo genotoxins (2-acetylaminofluorene, benzo[a]pyrene, carbendazim, cyclophosphamide, dimethylnitrosamine, ethyl methanesulfonate, ethyl nitrosourea and mitomycin C), which are known to act via different modes of action (direct- and indirect-acting clastogens, alkylating agents, gene mutagens, cross-linking and aneugenic compounds) were tested. Male rats were dosed at 0, 24 and 45 h, and bone marrow and peripheral blood (micronucleus endpoint), liver, whole blood and stomach (Comet endpoint) were sampled at three hours after the last dose. Comet and micronucleus responses were as expected based on available data for conventional (acute) stand-alone assays. All compounds were detected as genotoxic in at least one of the endpoints. The importance of evaluating both endpoints was highlighted by the uniquely positive responses for certain chemicals (benzo[a]pyrene and 2-acetylaminofluorene) with the Comet endpoint and certain other chemicals (carbendazim and mitomycin C) with the micronucleus endpoint. The data generated from these investigations demonstrate the suitability of the multi-endpoint design.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Endogenous synthesis of corticosteroids in the hippocampus

Authors: Higo, S; Hojo, Y; Ishii, H; Komatsuzaki, Y; Ooishi, Y; Murakami, G; Mukai, H; Yamazaki, T; Nakahara, D; Barron, A; Kimoto, T; Kawato, S (2011) PLoS ONE 6:e21631. HERO ID: 784764

[Less] Brain synthesis of steroids including sex-steroids is attracting much attention. The endogenous synthesis . . . [More] Brain synthesis of steroids including sex-steroids is attracting much attention. The endogenous synthesis of corticosteroids in the hippocampus, however, has been doubted because of the inability to detect deoxycorticosterone (DOC) synthase, cytochrome P450(c21).

The expression of P450(c21) was demonstrated using mRNA analysis and immmunogold electron microscopic analysis in the adult male rat hippocampus. DOC production from progesterone (PROG) was demonstrated by metabolism analysis of (3)H-steroids. All the enzymes required for corticosteroid synthesis including P450(c21), P450(2D4), P450(11β1) and 3β-hydroxysteroid dehydrogenase (3β-HSD) were localized in the hippocampal principal neurons as shown via in situ hybridization and immunoelectron microscopic analysis. Accurate corticosteroid concentrations in rat hippocampus were determined by liquid chromatography-tandem mass spectrometry. In adrenalectomized rats, net hippocampus-synthesized corticosterone (CORT) and DOC were determined to 6.9 and 5.8 nM, respectively. Enhanced spinogenesis was observed in the hippocampus following application of low nanomolar (10 nM) doses of CORT for 1 h.

These results imply the complete pathway of corticosteroid synthesis of 'pregnenolone →PROG→DOC→CORT' in the hippocampal neurons. Both P450(c21) and P450(2D4) can catalyze conversion of PROG to DOC. The low nanomolar level of CORT synthesized in hippocampal neurons may play a role in modulation of synaptic plasticity, in contrast to the stress effects by micromolar CORT from adrenal glands.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Galactosylated cellulosic sponge for multi-well drug safety testing

Authors: Nugraha, B; Hong, X; Mo, X; Tan, L; Zhang, W; Chan, PM; Kang, CH; Wang, Y; Beng, LT; Sun, W; Choudhury, D; Robens, JM; McMillian, M; Silva, J; Dallas, S; Tan, CH; Yue, Z; Yu, H (2011) Biomaterials 32:6982-6994. HERO ID: 784767

[Less] Hepatocyte spheroids can maintain mature differentiated functions, but collide to form bulkier structures . . . [More] Hepatocyte spheroids can maintain mature differentiated functions, but collide to form bulkier structures when in extended culture. When the spheroid diameter exceeds 200 μm, cells in the inner core experience hypoxia and limited access to nutrients and drugs. Here we report the development of a thin galactosylated cellulosic sponge to culture hepatocytes in multi-well plates as 3D spheroids, and constrain them within a macroporous scaffold network to maintain spheroid size and prevent detachment. The hydrogel-based soft sponge conjugated with galactose provided suitable mechanical and chemical cues to support rapid formation of hepatocyte spheroids with a mature hepatocyte phenotype. The spheroids tethered in the sponge showed excellent maintenance of 3D cell morphology, cell-cell interaction, polarity, metabolic and transporter function and/or expression. For example, cytochrome P450 (CYP1A2, CYP2B2 and CYP3A2) activities were significantly elevated in spheroids exposed to β-naphthoflavone, phenobarbital, or pregnenolone-16α-carbonitrile, respectively. The sponge also exhibits minimal drug absorption compared to other commercially available scaffolds. As the cell seeding and culture protocols are similar to various high-throughput 2D cell-based assays, this platform is readily scalable and provides an alternative to current hepatocyte platforms used in drug safety testing applications.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Pregnenolone as a novel therapeutic candidate in schizophrenia: emerging preclinical and clinical evidence

Authors: Marx, CE; Bradford, DW; Hamer, RM; Naylor, JC; Allen, TB; Lieberman, JA; Strauss, JL; Kilts, JD (2011) Neuroscience 191:78-90. [Review] HERO ID: 784769

[Less] Emerging preclinical and clinical evidence suggests that pregnenolone may be a promising novel therapeutic . . . [More] Emerging preclinical and clinical evidence suggests that pregnenolone may be a promising novel therapeutic candidate in schizophrenia. Pregnenolone is a neurosteroid with pleiotropic actions in rodents that include the enhancement of learning and memory, neuritic outgrowth, and myelination. Further, pregnenolone administration results in elevations in downstream neurosteroids such as allopregnanolone, a molecule with neuroprotective effects that also increases neurogenesis, decreases apoptosis and inflammation, modulates the hypothalamic-pituitary-adrenal axis, and markedly increases GABA(A) receptor responses. In addition, pregnenolone administration elevates pregnenolone sulfate, a neurosteroid that positively modulates NMDA receptors. There are thus multiple mechanistic possibilities for pregnenolone as a potential therapeutic agent in schizophrenia, including the amelioration of NMDA receptor hypofunction (via metabolism to pregnenolone sulfate) and the mitigation of GABA dysregulation (via metabolism to allopregnanolone). Additional evidence consistent with a therapeutic role for pregnenolone in schizophrenia includes neurosteroid changes following administration of certain antipsychotics in rodent models. For example, clozapine elevates pregnenolone levels in rat hippocampus, and these increases may potentially contribute to its superior antipsychotic efficacy [Marx et al. (2006a) Pharmacol Biochem Behav 84:598-608]. Further, pregnenolone levels appear to be altered in postmortem brain tissue from patients with schizophrenia compared to control subjects [Marx et al. (2006c) Neuropsychopharmacology 31:1249-1263], suggesting that neurosteroid changes may play a role in the neurobiology of this disorder and/or its treatment. Although clinical trial data utilizing pregnenolone as a therapeutic agent in schizophrenia are currently limited, initial findings are encouraging. Treatment with adjunctive pregnenolone significantly decreased negative symptoms in patients with schizophrenia or schizoaffective disorder in a pilot proof-of-concept randomized controlled trial, and elevations in pregnenolone and allopregnanolone post-treatment with this intervention were correlated with cognitive improvements [Marx et al. (2009) Neuropsychopharmacology 34:1885-1903]. Another pilot randomized controlled trial recently presented at a scientific meeting demonstrated significant improvements in negative symptoms, verbal memory, and attention following treatment with adjunctive pregnenolone, in addition to enduring effects in a small subset of patients receiving pregnenolone longer-term [Savitz (2010) Society of Biological Psychiatry Annual Meeting New Orleans, LA]. A third pilot clinical trial reported significantly decreased positive symptoms and extrapyramidal side effects following adjunctive pregnenolone, in addition to increased attention and working memory performance [Ritsner et al. (2010) J Clin Psychiatry 71:1351-1362]. Future efforts in larger cohorts will be required to investigate pregnenolone as a possible therapeutic candidate in schizophrenia, but early efforts are promising and merit further investigation. This article is part of a Special Issue entitled: Neuroactive Steroids: Focus on Human Brain.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Evaluation of the interaction of coumarins with biomembrane models studied by differential scanning calorimetry and Langmuir-Blodgett techniques

Authors: Sarpietro, MG; Giuffrida, MC; Ottimo, S; Micieli, D; Castelli, F (2011) Journal of Natural Products 74:790-795. HERO ID: 784776

[Less] Three coumarins, scopoletin (1), esculetin (2), and esculin (3), were investigated by differential scanning . . . [More] Three coumarins, scopoletin (1), esculetin (2), and esculin (3), were investigated by differential scanning calorimetry and Langmuir-Blodgett techniques to gain information about the interaction of these compounds with cellular membranes. Phospholipids assembled as multilamellar vesicles or monolayers (at the air-water interface) were used as biomembrane models. Differential scanning calorimetry was employed to study the interaction of these coumarins with multilamellar vesicles and to evaluate their absorption by multilamellar vesicles. These experiments indicated that 1-3 interact in this manner to different extents. The Langmuir-Blodgett technique was used to study the effect of these coumarins on the organization of phospholipids assembled as a monolayer. The data obtained were in agreement with those obtained in the calorimetric experiments.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Can a novel MRI staging system for low rectal cancer aid surgical planning

Authors: Shihab, OC; How, P; West, N; George, C; Patel, U; Quirke, P; Heald, RJ; Moran, BJ; Brown, G (2011) Diseases of the Colon and Rectum 54:1260-1264. HERO ID: 784873

[Less] : Low rectal cancers are associated with worse outcomes in comparison with mid and upper rectal tumors.
[More] : Low rectal cancers are associated with worse outcomes in comparison with mid and upper rectal tumors.

: This study aimed to assess the predictive accuracy of MRI in identifying the correct surgical approach based on the mesorectal and extralevator planes.

: This study involved the retrospective analysis of MRI and histopathology data of 33 patients with low rectal cancer, with the use of an anatomically based staging system. Three radiologists reported on the available surgical planes of excision based on the predicted relationship of tumor to key anatomical features. MRI-predicted planes of excision were then compared with the histopathological planes actually required, with the use of the same staging criteria.

: The study was conducted at 4 English district general hospitals.

: Unselected patients with low rectal cancer, all of whom were participants in a multicenter study, were eligible for this study.

: The main outcome measured was the accuracy of operative plane prediction on MRI.

: On pathological analysis, the mesorectal plane would have been sufficient to achieve a clear margin in 28 of 33 (84.9%) of cases. The extralevator plane was required in 5 of 33 (15.1%). Planes were correctly predicted by MRI in 29 of 33 cases by radiologist 1 and 24 of 33 cases by radiologists 2 and 3 with an accuracy of 87.9% and 72.7%. Overstaging (extralevator plane predicted when a mesorectal plane would have sufficed) occurred in 3 of 33 and 7 of 33 cases. Understaging (mesorectal plane predicted when an extralevator plane was required) occurred in 1 of 33 and 2 of 33 cases. The positive and negative predictive values of MRI in determining the histopathological plane of excision required were 57% and 96% for radiologist 1 and 30% and 91% for radiologists 2 and 3.

: This study was limited by its retrospective nature and its relatively small patient numbers. No account was taken of postoperative function when recommending the surgical plane.

: This supports an anatomically based MRI staging system for low rectal cancer to predict the planes of surgical excision. This may help to reduce margin positivity and to improve outcome in patients with low rectal cancer.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

The role of the spontaneous and evoked k-complex in good-sleeper controls and in individuals with insomnia

Authors: Forget, D; Morin, CM; Bastien, CH (2011) Sleep 34:1251-1260. HERO ID: 784874

[Less] Spontaneous and evoked K-complexes are believed to reflect a mechanism of sleep protection, yet their . . . [More] Spontaneous and evoked K-complexes are believed to reflect a mechanism of sleep protection, yet their functional role remains a subject of debate. Studying the K-complex in primary insomnia, for which sleep protection appears to be of central importance, may provide further insight on its role. The purpose of the present study was to determine the role of spontaneous and evoked K-complexes in good sleepers and to investigate its role in primary insomnia.

Twelve individuals with primary insomnia (mean age = 45.4 years) and 12 good-sleeper controls (mean age = 44.3 years).

Participants underwent 4 consecutive nights of polysomnographic recordings. Spontaneous K-complexes (SKC) were analyzed during continuous stage 2 sleep on the third night, whereas evoked K-complexes (EKC) were elicited by auditory stimuli on the fourth night. Relative spectral power was measured on 1-second electroencephalographic segments prior to and following SKC, EKC, and trials in which auditory stimuli did not elicit a K-complex (EKC-). K-complex amplitudes were also measured.

Measures of relative spectral power showed significant changes following EKC (increase in activity in the delta frequency band and decrease in activity in the theta, sigma, beta, and gamma frequency bands) and SKC (increase in activity in delta frequency band and decrease in activity in theta, alpha, sigma, and beta frequency bands) for good sleepers, whereas there was no such marked change in electroencephalographic activity surrounding EKC-. A similar pattern of electroencephalographic activity was also observed for the insomnia group on trials of each different K-complex. Auditory stimuli elicited the same proportion of EKC for both groups, whereas SKC density was higher for the insomnia group (1.52 SKC/min) than for good sleepers (1.06 SKC/minute)

These results suggest that the SKC and the EKC both promote deeper sleep, further supporting a sleep-protection role. CITATION: Forget D; Morin CM; Bastien CH. The role of the spontaneous and evoked K-complex in good-sleeper controls and in individuals with insomnia. SLEEP 2011;34(9):1251-1260.